[Federal Register Volume 83, Number 246 (Wednesday, December 26, 2018)]
[Rules and Regulations]
[Pages 66103-66124]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-27809]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 882

[Docket No. FDA-2014-N-1210]


Neurological Devices; Reclassification of Electroconvulsive 
Therapy Devices; Effective Date of Requirement for Premarket Approval 
for Electroconvulsive Therapy Devices for Certain Specified Intended 
Uses

AGENCY: Food and Drug Administration, HHS.

ACTION: Final order.

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SUMMARY: The Food and Drug Administration (FDA) is issuing a final 
order to reclassify the electroconvulsive therapy (ECT) device for use 
in treating catatonia or a severe major depressive episode (MDE) 
associated with major depressive disorder (MDD) or bipolar disorder 
(BPD) in patients age 13 years and older who are treatment-resistant or 
who require a rapid response due to the severity of their psychiatric 
or medical condition, which is a preamendments class III device, into 
class II (special controls). FDA is also issuing this final order to 
require the filing of a premarket approval application (PMA) or a 
notice of completion of a product development protocol (PDP) for the 
preamendments class III ECT devices for all other uses that are not 
being reclassified to class II (product code GXC).

DATES: This order is effective on December 26, 2018. See further 
discussion in section V, Implementation Strategy.

FOR FURTHER INFORMATION CONTACT: Carlos Pe[ntilde]a, Center for Devices 
and Radiological Health, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 66, Rm. 2680, Silver Spring, MD 20993, 301-796-
6610, [email protected].

SUPPLEMENTARY INFORMATION:

Table of Contents

I. Table of Abbreviations/Commonly Used Acronyms in This Document
II. Background
    A. Reclassification
    B. Requirement for Premarket Approval
    C. Valid Scientific Evidence
III. Public Comments in Responding to the Proposed Order
    A. Comments in Support of Reclassifying ECT Into Class II
    B. Comments on Reclassifying ECT Based on Safety and 
Effectiveness
    C. Comments on Patient Concerns
    D. Comments on Regulatory Process of the Proposed Order
    E. Comments on Labeling Concerns
    F. Comments Outside the Scope of This Final Order
IV. The Final Order
V. Implementation Strategy
    A. Date To File a PMA
    B. Compliance With Special Controls
VI. Codification of Orders
VII. Analysis of Environmental Impact
VIII. Paperwork Reduction Act of 1995
IX. References

I. Table of Abbreviations/Commonly Used Acronyms in This Document

                   Table of Abbreviations and Acronyms
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      Abbreviation  or acronym                  What it means
------------------------------------------------------------------------
510(k).............................  Premarket Notification.
2011 Panel.........................  2011 Neurological Devices Panel
                                      Meeting.
AACAP..............................  American Academy of Child and
                                      Adolescent Psychiatry.
APA................................  American Psychiatric Association.
BPD................................  Bipolar Disorder.
CANTAB.............................  Cambridge Neuropsychological Test
                                      Automated Battery.
CFR................................  Code of Federal Regulations.
CGI-I..............................  Clinical Global Impressions-
                                      Improvement scale.
ECT................................  Electroconvulsive Therapy Device.
FDA................................  Food and Drug Administration.
FDARA..............................  FDA Reauthorization Act of 2017.
FDASIA.............................  Food and Drug Administration Safety
                                      and Innovation Act.
FD&C Act...........................  Federal Food, Drug, and Cosmetic
                                      Act.
FR.................................  Federal Register.
IDE................................  Investigational Device Exemption.
MAUDE..............................  Manufacturer and User Facility
                                      Device Experience.
MDD................................  Major Depressive Disorder.
MDE................................  Major Depressive Episode.
MDR................................  Medical Device Reporting.
M-ECT..............................  Maintenance ECT.
MMSE...............................  Mini Mental State Exam.
OMB................................  Office of Management and Budget.
PDP................................  Product Development Protocol.
PMA................................  Premarket Approval Application.
PRA................................  Paperwork Reduction Act of 1995.
Ref................................  Reference
RWD................................  Real-World Data.
RWE................................  Real-World Evidence.
SE.................................  Safety and Effectiveness.
U.S.C..............................  United States Code.
WFSBP..............................  World Federation of Societies of
                                      Biological Psychiatry.
------------------------------------------------------------------------

II. Background

    The Federal Food, Drug, and Cosmetic Act (FD&C Act), establishes a 
comprehensive system for the regulation of medical devices intended for 
human use. Section 513 of the FD&C Act (21 U.S.C. 360c) established 
three categories (classes) of devices, reflecting the regulatory 
controls needed to provide reasonable assurance of their safety and 
effectiveness (SE). The three categories of devices are class I 
(general controls), class II (special controls), and class III 
(premarket approval).
    Under section 513(d) of the FD&C Act, devices that were in 
commercial distribution before the enactment of the 1976 amendments, 
May 28, 1976 (generally referred to as preamendments devices) are 
classified after FDA has: (1) Received a recommendation from a device 
classification panel (an FDA advisory committee); (2) published the 
panel's recommendation for comment, along with a proposed regulation 
classifying the device; and (3) published a final regulation 
classifying the device. FDA has classified most preamendments devices 
under these procedures.
    Devices that were not in commercial distribution prior to May 28, 
1976 (generally referred to as postamendments devices) \1\ are 
automatically classified by section 513(f) of the FD&C Act into class 
III without any FDA rulemaking process. Those devices remain in class 
III and require premarket approval unless, and until, the device is 
reclassified into class I or II or FDA issues an order finding the 
device to be substantially equivalent, in accordance with section 
513(i) of the FD&C Act, to a predicate device that does not require 
premarket approval. The Agency determines whether new devices are 
substantially equivalent to predicate devices by means of premarket 
notification procedures in section 510(k) of the FD&C Act (21

[[Page 66104]]

U.S.C. 360(k)) and part 807 (21 CFR part 807).
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    \1\ ECT devices with intended uses outside the scope of those 
listed in paragraphs 21 CFR 882.5940(b)(1) and (2) are considered 
postamendments device, that are subject to classification under 
section 513(f)(1) of the FD&C Act or, if the relevant requirements 
are met, under section 513(f)(2) of the FD&C Act.
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    A preamendments device that has been classified into class III and 
devices found substantially equivalent by means of premarket 
notification (510(k)) procedures to such a preamendments device or to a 
device within that type (both the preamendments and substantially 
equivalent devices are referred to as preamendments class III devices) 
may be marketed without submission of a PMA until FDA issues a final 
order under section 515(b) of the FD&C Act (21 U.S.C. 360e(b)) 
requiring premarket approval.
    On August 18, 2017, section 513(f) of the FD&C Act was amended by 
the FDA Reauthorization Act of 2017 (FDARA; Pub. L. 115-52). Under 
section 513(f)(6) of the FD&C Act, FDA has authority to issue an 
administrative order classifying an accessory based on the risks of the 
accessory when used as intended and the level of regulatory controls 
necessary to provide a reasonable assurance of SE of the accessory, 
notwithstanding the classification of any other device with which such 
accessory is intended to be used. FDA's ``Medical Device Accessories--
Describing Accessories and Classification Pathways'' guidance describes 
the statutory mechanisms to request: (1) Classification for accessories 
that have been granted marketing authorization as part of a PMA, 
premarket notification (510(k)), or De Novo request for another device 
with which the accessory involved is intended to be used and (2) 
classification for accessories included in a PMA or 510(k) that FDA has 
not classified distinctly from another device under the FD&C Act (Ref. 
1).

A. Reclassification

    Under section 515(i)(2) of the FD&C Act, following publication of a 
proposed order, a meeting of a device classification panel, and 
consideration of the comments of a proposed order, FDA has the 
authority to issue an administrative order revising the classification 
of a device that FDA has classified as a class III device and for which 
no administrative order has been issued calling for PMAs under section 
515(b) of the FD&C Act, so that the device is classified into class I 
or II. In determining whether to revise the classification of a device 
or to require a device to remain in class III, FDA applies the criteria 
set forth in section 513(a) of the FD&C Act. Section 513(a)(1)(B) of 
the FD&C Act defines class II devices as those devices for which the 
general controls in section 513(a)(1)(A) by themselves are insufficient 
to provide reasonable assurance of SE, but for which there is 
sufficient information to establish special controls to provide a 
reasonable assurance of SE of a device.
    FDA published a proposed order in the Federal Register of December 
29, 2015 (80 FR 81223), held a meeting of a device classification panel 
on January 27-28, 2011, as described in section 513(b) of the FD&C Act 
with respect to ECT devices, and considered comments from public 
dockets, and, therefore, has met the requirements under sections 
515(i)(2) of the FD&C Act.

B. Requirement for Premarket Approval

    Section 515(b)(1) of the FD&C Act sets forth the process for 
issuing a final order requiring PMAs. Specifically, prior to the 
issuance of a final order requiring premarket approval for a 
preamendments class III device, the following must occur: (1) 
Publication of a proposed order in the Federal Register; (2) a meeting 
of a device classification panel described in section 513(b) of the 
FD&C Act; and (3) consideration of comments from all affected 
stakeholders. As noted above, FDA has published a proposed order that 
would require PMAs for an electroconvulsive therapy device for certain 
uses other than a severe MDE associated with MDD or BPD, in the Federal 
Register of December 29, 2015. FDA has held a meeting of a device 
classification panel described in section 513(b) of the FD&C Act with 
respect to ECT devices. Finally, FDA has received and has considered 
over 3,400 comments on the proposed order, as discussed in section II. 
Therefore, FDA has met the requirements under section 515(b)(1) of the 
FD&C Act.
    On July 9, 2012, the Food and Drug Administration Safety and 
Innovation Act (FDASIA) (Pub. L. 112-144) was enacted. Section 608(a) 
and (b) of FDASIA amended section 515(b) of the FD&C Act, changing the 
mechanism for requiring premarket approval for a preamendments device 
from rulemaking to an administrative order.
    Although under the FD&C Act a manufacturer of a class III 
preamendments device may respond to the call for PMAs by filing a PMA 
or a notice of completion of a PDP, in practice, the option of filing a 
notice of completion of a PDP has not been used. While corresponding 
requirements for PDPs remain available to manufacturers in response to 
a final order under section 515(b) of the FD&C Act, for simplicity this 
document will refer only to the requirement for the filing and 
receiving approval of a PMA.
    Under section 501(f) of the FD&C Act (21 U.S.C. 351(f)), a 
preamendments class III device may be commercially distributed without 
a PMA until 90 days after FDA issues a final order (or a final rule 
issued under section 515(b) of the FD&C Act prior to the enactment of 
FDASIA) requiring premarket approval for the device, or 30 months after 
final classification of the device under section 513 of the FD&C Act, 
whichever is later. Because ECT devices were classified in 1979, the 
30-month period has expired (44 FR 51776, September 4, 1979), and the 
later of these two time periods is the 90-day period. Therefore, if a 
PMA is not filed for ECT devices for certain specified intended uses 
within 90 days after the issuance of a final order, the device will be 
deemed adulterated under section 501(f) of the FD&C Act.
    Also, a preamendments device subject to the order process under 
section 515(b) of the FD&C Act is not required to have an approved 
investigational device exemption (IDE) (see part 812 (21 CFR part 812)) 
contemporaneous with its interstate distribution until the date 
identified by FDA in the final order requiring the filing of a PMA for 
the device. At that time, an IDE is required only if a PMA has not been 
filed. If the manufacturer, importer, or other sponsor of the device 
submits an IDE application and FDA approves it, the device may be 
distributed for investigational use. If a PMA is not filed within 90 
days after the issuance of a final order, and the device is not 
distributed for investigational use under an IDE, the device is deemed 
to be adulterated within the meaning of section 501(f)(1)(A) of the 
FD&C Act, and subject to seizure and condemnation under section 304 of 
the FD&C Act (21 U.S.C. 334) if its distribution continues. Other 
enforcement actions include, but are not limited to, the following: 
Shipment of devices in interstate commerce will be subject to 
injunction under section 302 of the FD&C Act (21 U.S.C. 332), and the 
individuals responsible for such shipment will be subject to 
prosecution under section 303 of the FD&C Act (21 U.S.C. 333). FDA 
requests that manufacturers take action to prevent the further use of 
devices for which no PMA has been filed.

C. Valid Scientific Evidence

    The evidentiary standard FDA relies on to determine the SE of a 
device is valid scientific evidence. Section 860.7(c)(2) (21 CFR 
860.7(c)(2)) defines valid scientific evidence. As described in section 
III, in finalizing this order, FDA has assessed the totality of the

[[Page 66105]]

valid scientific evidence that was provided in response to the proposed 
order, including several comments that referenced additional clinical 
studies. Several of these studies included SE data for adult as well as 
adolescent patients. FDA also considered randomized controlled clinical 
studies, open-label observational trials, case series reports, 
systematic literature reviews, and practice guidelines that were 
submitted in the comments. Single case reports or opinion-based 
commentary were also submitted to the dockets for consideration; 
however, without well controlled empirical experimentation, these types 
of information are generally not considered valid scientific evidence 
and were not relied upon to support this reclassification.
    FDA received many comments from healthcare professionals describing 
their practices, the length of time they have been practicing, and the 
utilization of ECT devices in treating patients with certain 
conditions. While FDA acknowledges receiving comments in support of the 
proposed reclassification, statements by individual healthcare 
professionals that they have used ECT devices to treat individual 
patients do not constitute valid scientific evidence to demonstrate 
reasonable assurance of SE (see valid scientific evidence discussion in 
48 FR 56778 at 56786-56788, comments 16-21, December 23, 1983, Ref. 2). 
Such comments do not contain sufficient detail to capture the use of 
the device, exposures, and outcomes in the appropriate population and 
are not interpretable using informed clinical and scientific judgement.
    FDA also received many comments from patients, or friends and 
family of patients, in support and against reclassification of ECT 
devices. These comments described the experience of the patient that 
received treatment from an ECT device. FDA acknowledges receiving 
comments from patients and other individuals about their experience 
with the device being considered for reclassification; however, FDA 
does not consider such comments to be valid scientific evidence. 
Because these comments did not contain sufficient detail to capture the 
use of the device, exposures, and outcomes in the appropriate 
population and are not interpretable using informed clinical and 
scientific judgement, such comments are not considered valid scientific 
evidence.
    For medical devices, available evidence is traditionally comprised 
of clinical and non-clinical studies conducted and provided to FDA by 
the device manufacturer or sponsor. However, FDA recognizes that a 
wealth of data covering medical device experience is routinely 
collected in the course of treatment and management of patients. Under 
certain circumstances, these real-world data (RWD) may constitute real-
world evidence (RWE), or clinical evidence regarding the usage and 
potential benefits or risks of a medical product derived from analysis 
of RWD, that may be of sufficient quality to help inform or augment 
FDA's understanding of the benefit-risk profile of devices at various 
points in their life cycle, and could potentially be valid scientific 
evidence used to aid FDA in regulatory decision making. See FDA's 
guidance, ``Use of Real-World Evidence to Support Regulatory Decision-
Making for Medical Devices'' (82 FR 41418, August 31, 2017, Ref. 3), 
which clarifies how FDA evaluates RWD to determine whether it may be 
sufficiently relevant and reliable to generate the types of RWE that 
can be used in FDA regulatory decision making for medical devices, 
including potentially generating valid scientific evidence.
    In identifying a device, the SE of which is questionable, Sec.  
860.7(c)(2) also explains random experience and reports lacking 
sufficient details to permit scientific evaluation may be considered 
valid scientific evidence. Such random experience and reports lacking 
sufficient details to permit scientific evaluation may be early and 
sometimes informal indications of the danger or ineffectiveness of a 
device (43 FR 32988 at 32990, July 28, 1978). Where FDA is considering 
the classification of a device, such random experience and reports are 
not considered valid scientific evidence.

III. Public Comments in Response to the Proposed Order

    On December 29, 2015, FDA published a proposed order to reclassify 
from class III to class II the ECT device for use in treating a severe 
MDE associated with MDD or BPD in patients 18 years of age and older 
who are treatment-resistant or who require a rapid response due to the 
severity of their psychiatric or medical condition and to require the 
filing of a PMA for ECT devices for the intended uses of schizophrenia, 
bipolar manic states, schizoaffective disorder, schizophreniform 
disorder, and catatonia. The comment period on the proposed order 
closed on March 28, 2016.
    In response to the December 29, 2015, proposed order, FDA received 
over 3,400 comments from industry, professional societies, trade 
organizations, and individual consumers by the close of the comment 
period, each containing one or more comments on one or more issues. We 
describe and respond to the comments in this section of the document. 
The over 3,400 comments are grouped based on the common themes listed 
below. We have grouped similar comments together under the same number 
and numbered them sequentially.

A. Comments in Support of Reclassifying ECT Into Class II (Comments 1-
2)
B. Comments on Reclassifying ECT Based on Safety and Effectiveness 
(Comments 3-9)
C. Comments on Patient Concerns (Comments 10-16)
D. Comments on Regulatory Process of the Proposed Order (Comments 17-
23)
E. Comments on Labeling Concerns (Comments 24-29)
F. Comments Outside the Scope of This Final Order (Comments 30-34)

    Please note that in some cases we separated different issues 
discussed by the same commenter and designated them as distinct 
comments for purposes of our responses. The number assigned to each 
group is purely for organizational purposes and does not signify the 
comment's value or importance or the order in which comments were 
received.
    In the proposed order we asked interested persons to submit 
comments on two specific questions. FDA sought comments on whether: (1) 
The term ``treatment resistant'' and the phrase ``require rapid 
response'' provide sufficient clarity to the population for which ECT 
benefits outweigh risks and (2) if 60 days is an appropriate time to 
allow existing manufacturers who do not intend to market their ECT 
device(s) for uses other than use in treating severe MDE associated 
with MDD and BPD in patients 18 years of age and older who are 
treatment-resistant or who require a rapid response due to the severity 
of their psychiatric or medical condition to prepare and submit 510(k) 
amendments for ECT devices. FDA continues to believe the term 
``treatment resistant'' and the phrase ``require rapid response'' 
provide sufficient clarity to the population for which ECT benefits 
outweigh risks. Because there were no comments submitted on the second 
question, FDA's discussion of when 510(k) holders should submit an 
amendment to a 510(k) is in section V.B., Compliance with Special 
Controls, of this final order.

[[Page 66106]]

A. Comments in Support of Reclassifying ECT Into Class II

    (Comment 1) FDA received many comments generally supporting the 
proposed reclassification to class II. Comments included many 
literature references including references published since the 2011 
Neurological Devices Classification Panel meeting (the 2011 Panel). 
Several comments noted that ECT had been used safely and effectively in 
their practice or on themselves as a patient or on a family member or a 
friend.
    (Response 1) After examination of the totality of the scientific 
evidence, FDA continues to believe that there is sufficient evidence to 
establish special controls that, together with general controls, 
provide a reasonable assurance of SE to reclassify ECT to class II for 
use in treating a severe MDE associated with MDD or BPD, as initially 
specified in the proposed order. In addition, FDA has determined that 
there is adequate support for the reclassification of ECT into class II 
for the treatment of catatonia and expanding the adolescent age 
subpopulation from 18 to 13 years of age. FDA has made this 
determination based upon a reassessment of the following sources of 
information: (1) Published literature referenced in the Executive 
Summary to the 2011 Panel; (2) comments and literature received in 
public dockets including the call for SE information for all 
preamendments class III devices (74 FR 16214, April 9, 2009), the call 
for ECT SE information in a separate docket (74 FR 46607, September 10, 
2009), the 2011 Panel (75 FR 72832, November 26, 2010), the ECT Draft 
Guidance (80 FR 81330, December 29, 2015) and the proposed order 
(December 29, 2015) (these five dockets are to be referred to as ``ECT 
public dockets'' in this document, discussed below in response 2); (3) 
clinical practice guidelines; and (4) review of medical device reports 
(MDRs) in the FDA Manufacturer and User Facility Device Experience 
(MAUDE) database. The reevaluation of the scientific evidence presented 
to and discussed at the 2011 Panel meeting, and the review of 
additional post-2011 scientific information that was provided to FDA in 
comments to the proposed order, further supports this finding.
    (Comment 2) Several comments supported the reclassification of ECT 
to class II for a severe MDE associated with MDD or BPD, but said the 
reclassification was too restrictive in its scope. Several additional 
indications, many of which are outside the scope of this classification 
effort, were mentioned. Comments suggested that classification should 
be expanded to some or all of the following indications and populations 
(ordered alphabetically):

 Adolescents
 Adolescents and children
 Autism
 Catatonia
 Delirium
 Delusional disorders
 Developmental disability
 Maintenance or continuation ECT
 Mania in BPD
 Mania--refractory, intractable, acute
 Neuroleptic malignant syndrome
 Other psychiatric disorders and conditions for which ECT has 
been used
 Parkinson's disease
 Patients with contraindications to drug treatment including 
women who are pregnant/nursing, the elderly, or those who have comorbid 
conditions
 Psychosis--treatment resistant, puerperal
 Schizophrenia--clozapine resistant, refractory
 Schizoaffective disorder
 Severe self-injurious behavior
 Shy-Drager syndrome
 Status epilepticus
 Suicidal patients

    (Response 2) As part of the review of the public comments received 
in response to the proposed order, FDA considered over 400 scientific 
articles cited in comments or attached to comments filed in the ECT 
public dockets. Many of the scientific articles included information 
not within the scope of this order; however, some of the articles 
included studies that investigated the SE of ECT for catatonia, mania, 
schizophrenia, and schizoaffective disorder, and use of ECT in 
children, adolescents, and adults, which are indications within the 
scope of this final order. Many of these articles also provided 
information on research published since 2010, after the literature 
review was conducted for the 2011 Panel on classification of ECT 
devices.
    Of the information submitted in response to the proposed order, FDA 
reviewed many articles containing valid scientific evidence regarding 
the SE of ECT for certain intended uses, which are within the scope of 
this reclassification effect, including catatonia and severe MDE 
associated with MDD or BDP for the indicated populations. In addition, 
29 articles referenced in the ECT public dockets contain valid 
scientific evidence on the SE of ECT in the adolescent subpopulation 
(patients age 13 years to less than 18 years). The sections below 
further discuss FDA's review of this evidence and conclusions.
    Based on evaluation of this evidence, FDA is including in the final 
order to reclassify ECT the indication of catatonia for patients who 
are treatment-resistant or who require a rapid response due to the 
severity of their psychiatric or medical condition in addition to 
treating a severe MDE (associated with MDD or BPD). FDA believes that 
the totality of evidence supports the determination that the special 
controls identified in this final order, along with general controls, 
are sufficient to provide a reasonable assurance of SE for these 
indications. For the other indications cited in the ECT public dockets 
that are within the scope of this classification effort, FDA has 
concluded that there was insufficient scientific evidence to support 
reclassification.
    Several comments posted to the ECT public docket in response to the 
proposed order, including comments from professional societies and 
organizations, physicians, and other ECT practitioners, were supportive 
of a class II recommendation for catatonia or a severe MDE associated 
with MDD or BPD in adolescents, and in some cases, younger children. 
While ECT devices are historically cleared with no specific age 
indicated, the proposed order for ECT recommended that the indications 
for use be limited to use of the device in patients 18 and above. 
Consistent with the cleared indications, FDA's Executive Summary for 
the 2011 Panel to discuss reclassification did not include a review on 
the use of ECT in different age groups; however, substantive comments 
were provided during the open public hearing section both for and 
against the use of ECT in children and adolescents (Ref. 4). In 
response to the comments recommending expansion of the age range of 
adolescent patients, under section 515(i)(2) of the FD&C Act, FDA 
assessed the articles submitted in the ECT public dockets (sources of 
information listed in response to Comment 1 above) to evaluate the SE 
evidence supporting the use of ECT in younger populations (i.e., 
children and adolescents).
    FDA evaluated ECT use in treating a number of psychiatric or 
medical conditions (e.g., a severe MDE associated with MDD or BPD, 
catatonia, schizophrenia, schizoaffective disorder, and mania) in these 
younger populations. Limited experience and only a few reports were 
available for patients less than and including 12 years of age (i.e., 
children). The majority of studies focused on catatonia or a severe MDE 
associated with MDD or BPD in patients age 13 years and older.

[[Page 66107]]

For those studies that did report clinical outcomes in adolescent 
patients, results were generally favorable in treating catatonia or a 
severe MDE associated with MDD or BPD. Treatment approaches (i.e., 
electrode placement, administration, and safeguards) were similar 
between adult and adolescent subpopulations. As such, the literature 
provided in the ECT public dockets supports a reclassification to class 
II for the use of ECT in treating catatonia or a severe MDE associated 
with MDD or BPD, for patients age 13 years and older who are treatment-
resistant and who require a rapid response due to the severity of their 
psychiatric or medical condition, with the establishment of special 
controls (discussed in more detail below in section III.A.3). FDA's 
evaluation is based on a reassessment of the published literature 
referenced in the Executive Summary to the 2011 Panel, comments and 
literature received in the ECT public dockets, and review of the 2011 
Panel meeting transcript.
    Based upon FDA's review of the scientific literature submitted in 
the comments received in the ECT public dockets, and an assessment of 
the totality of the evidence, FDA is reclassifying ECT devices for a 
broader population than identified in the proposed order. The 
reassessment of evidence including scientific articles are organized 
into four subsections consisting of: (1) Safety of ECT in treating 
catatonia or a severe MDE associated with MDD or BPD; (2) effectiveness 
of ECT for catatonia; (3) effectiveness of ECT for patients 13 years 
and older; and (4) effectiveness of ECT for schizophrenia, 
schizoaffective disorder, and mania. The specific indications within 
the scope of this final order include only those for which FDA has 
cleared 510(k) submissions. In this summary, we do not include isolated 
case reports.
1. Safety of ECT in Treating Catatonia or a Severe MDE Associated With 
MDD or BPD
    Overall, the published literature provided since 2010 in the 
comments received in the ECT public dockets and reviewed by FDA 
provided information on over 1,000 patients, and included information 
regarding ECT treatment outcomes in adults, adolescents, and children. 
The reviewed published literature included prospective and 
retrospective studies, randomized patient treatment schedules (e.g., 
number of treatments per week), and either administered unilateral or 
bilateral stimulation. The majority of studies reported the safe use of 
ECT with minimal and reversible adverse events, and in some cases, 
patient memory and mood improved while treating catatonia or a severe 
MDE associated with MDD or BPD; positive results included outcomes in 
both adults and adolescent subpopulations. Six studies (Refs. 5-10) 
provided detailed safety data on patients (N=609) for review and 
further discussion below.
    Fernie et al. (Ref. 5) conducted a retrospective study to evaluate 
the persistence of cognitive side effects of ECT in a retrospective 
case study of 126 patients treated with ECT between June 2010 and 
October 2012 at the Royal Cornhill Hospital, Aberdeen, Scotland. 
Results from validated longitudinal neuropsychological tests (the 
Cambridge Neuropsychological Test Automated Battery spatial recognition 
memory test (CANTAB)) and subjective reports of memory function showed 
that while the performance was poorer compared with baseline for tests 
administered up to 3 months following completion of ECT therapy, these 
effects were transient and improved at 6 months. In some cases, mood 
and subjective memory scores improved following ECT. The Mini Mental 
State Exam (MMSE) demonstrated improvement over baseline starting from 
1 month following therapy. Overall, the application of ECT had 
reversible cognitive deficiencies compared to pre-ECT treatment scores, 
a measure of safety, and in some assessments (CANTAB, subjective 
reports of memory function, and MMSE) showed patient improvement.
    Kirov et al. (Ref. 6) conducted a retrospective review of 10 years 
of cognitive performance data that included 199 patients and 500 
assessments. Cognitive testing consisted of a battery of nine tests 
including backward digit span, word, shape, and face recognition, 
verbal fluency, complex figure immediate recall, and trail making. Not 
all subjects were capable of performing all tests and parts of the 
battery changed over time. Results (linear mixed regression analyses) 
demonstrated that age, severity of depression at the time of testing, 
and number of days since the last ECT session were the major factors 
affecting cognitive performance, but the total number of previous ECT 
sessions did not have a measurable impact on cognitive performance, 
which further supports the safety of ECT in not leading to cumulative 
cognitive deficits.
    Maric et al. (Ref. 7) prospectively studied 30 patients with MDD at 
baseline, shortly after ECT treatment, and at 1 month post treatment 
using the learning and visual, spatial, and figural memory tests of 
CANTAB. Severity of depressive symptoms as measured by healthcare 
professional-rated and self-rated instruments was significantly reduced 
over time with treatment, as a measure of the effectiveness of ECT. At 
the same time, the neuropsychological tests did not detect any 
significant memory impairment and showed improvement on visual memory 
and learning at 1 month and in the immediate post-treatment period, 
indicating no prolonged or significant ECT-related memory deficits. 
These improvements correlated with improvement in depression while 
serious adverse events were not reported.
    Spaans et al. (Ref. 8) compared unilateral brief pulse ECT with 
unilateral ultra-brief pulse ECT for the treatment of major depression. 
In this double-blind randomized study conducted in 3 tertiary 
psychiatric hospitals in the Netherlands, 116 patients entered the 
study and of those, 87 completed the study (until remission or 12 
treatments). Seventy-six (n=76) patients were available with pre- and 
post-ECT assessments. Blinded cognitive assessment was done before ECT 
treatment was started and again within 2 days to a week after all 
treatments were completed. Patients on average received about eight 
treatments (average 7.1 in the brief pulse group vs. 9.2 in the ultra-
brief pulse group). To assess cognitive function, several 
neuropsychological tests were administered including the 
Autobiographical Memory Interview and the Amsterdam Media 
Questionnaire, which is a public event questionnaire with questions 
grouped by decade about events from the decades of the 1970s through 
the 2000s. Other cognitive domain tests were also conducted. No 
significant difference was seen in retrograde amnesia between the two 
treatment groups. Change in recall performance and fluency tests were 
also similar between the two groups. There was not a significant 
difference in performance in the cognitive tests following ECT for any 
of the cognitive tests during the course of study. The authors also 
reported mitigating adverse effects on cognition by lengthening the 
time between treatments to provide patients with more time to 
recuperate, thereby further characterizing how ECT treatment can be 
applied safely.
    Semkovska et al. (Ref. 9) prospectively studied 138 patients with 
major depressive episodes who were treated in a national ECT study in 
which patients were randomly assigned to receive bitemporal (69 
patients) or right-side unilateral ECT (69 patients). This

[[Page 66108]]

study included 3-month and 6-month followup assessments. Adverse events 
were similar for the unilateral and bitemporal groups. Following 
treatment, headache was the most commonly reported adverse physical 
effect (approximately 27 percent of subjects). Nausea (approximately 14 
percent), and muscle pain (approximately 10 percent) were also 
reported. Significant acute adverse events associated with treatment 
included six patients (4 unilateral, 2 bitemporal) who experienced ECT 
related hypertension. Also, one patient developed laryngospasm with 
temporary drop in oxygen saturation, one patient required treatment for 
sinus tachycardia, one patient developed bradyarrhythmia, and one 
patient developed a pulmonary embolus after the fifth treatment. No 
adverse events required patients to discontinue the study, thereby 
enabling patients to continue treatment. Positive responses to the 
treatments were seen in both treatment groups.
    Ghaziuddin et al. (Ref. 10) conducted a retrospective study of 16 
adolescents treated for depression with ECT. Cognitive tests before ECT 
treatment were compared to tests administered an average of 7 days 
following completion of the ECT treatment (immediate testing) and again 
at an average of 8.5 months following completion of ECT treatment. The 
comparison of pre-ECT and the immediate post-ECT testing demonstrated 
significant impairments of concentration and attention, verbal and 
visual-delayed recall, and verbal fluency. A complete recovery of these 
functions was noted in the cognitive testing conducted at 8.5 months. 
There was no deficit in the ability to problem solve during the initial 
or the subsequent testing. Cognitive parameters found to be impaired 
during the first few days of ECT were recovered over several months 
following the treatment. Therefore, there was no evidence of long-term 
damage to concentration, attention, verbal and visual memory, or verbal 
fluency. There were also no impairments of motor strength and executive 
processing, even during the early (within 7 to 10 days) post-ECT 
period.
    Considering the studies summarized above as well as the additional 
literature referenced in the ECT public dockets and the deliberation of 
the 2011 Panel, there is sufficient scientific evidence demonstrating, 
with the establishment of special controls in combination with general 
controls, a reasonable assurance of the SE for the use of ECT in 
treating a severe MDE associated with MDD or BPD and safety for 
treating catatonia in patients who are treatment-resistant or who 
require a rapid response due to the severity of their psychiatric or 
medical condition (see effectiveness of ECT for catatonia discussion in 
following subsection). ECT in the indicated populations provides a 
treatment option for serious diseases where other treatments are less 
or minimally effective. Based on the totality of available evidence, 
FDA has determined that the designated special controls mitigate the 
risks associated with use of ECT in this patient population and provide 
a reasonable assurance of SE.
2. Effectiveness of ECT for Catatonia
    The 2011 Panel was evenly split regarding their recommendation for 
the reclassification of the use of ECT for catatonia. Several members 
of the 2011 Panel who recommended class II for catatonia pointed out 
that this psychiatric disorder is among the most severe and potentially 
life-threatening and requires a rapid response.
    In the public comments in response to the proposed order, 24 
published articles were submitted as attachments related to the use of 
ECT for catatonia. Of these, 14 were published after FDA's systematic 
literature review performed for the 2011 Panel meeting (Refs. 11-25). 
As was the case at the 2011 Panel, there remain no randomized 
controlled trials of ECT in catatonia. The articles published after the 
2011 Panel are primarily case series reports, retrospective chart 
reviews, and systematic literature reviews. All the studies reported on 
patient outcomes, with the majority of studies reporting favorable SE 
data.
    The systematic review from 2015 by Luchini et al. (Ref. 18) 
identified 8 retrospective or observational studies that included at 
least 10 or more subjects. Collectively, these 8 studies represented 
346 catatonic patients who received ECT. Response rates ranged from 80 
percent to 100 percent. Rates for adverse events were not provided, but 
with regard to safety, the authors cite the transient cardiovascular 
events that need to be monitored and managed, including parasympathetic 
mediated bradycardia or temporary asystole and post-seizure sympathetic 
stimulation that can lead to sinus tachycardia, bigeminy or trigeminy, 
or ventricular arrhythmia in as many as 80 percent of patients with 
known cardiovascular risk. Other risks are those associated with 
administration of anesthesia in a catatonic patient. These side effects 
are generally transient and resolve without adverse sequelae.
    A noteworthy series of the case series reports (Refs. 19 and 20) 
all consistently found ECT to be very effective for the treatment of 
catatonia with relatively few adverse events reported in the treated 
patients. Given the clinical presentation of patients with catatonia, 
including the lack of verbal and motor response due to the etiology of 
the disease, the positive clinical outcome is unlikely to be 
susceptible to placebo effects; therefore, FDA believes the well-
documented case series and open-label trials for the use of ECT in 
catatonia support the recommendation to include catatonia in class II.
    The valid scientific evidence evaluated has enabled FDA to 
determine that ECT for catatonia can be classified as class II because 
general controls, in combination with special controls, are sufficient 
to provide a reasonable assurance of SE. Based on a review of the 
published literature to date, the recommendations from the 2011 Panel 
meeting, and comments received in the ECT public dockets, FDA has 
determined that sufficient evidence exists to establish special 
controls and support a revision of the proposed classification of ECT 
for the treatment of catatonia to class II. ECT for catatonia presents 
the same types of risks to health and would be subject to the same 
types of special controls identified for a severe MDE associated with 
MDD or BPD in patients who are treatment-resistant or who require a 
rapid response due to the severity of their psychiatric or medical 
condition. Further, clinical guidelines for schizophrenia published in 
2012 from the World Federation of Societies of Biological Psychiatry 
(WFSBP) (Ref. 26) recommend consideration of ECT for catatonia as an 
alternative when rapid resolution is necessary or when an initial trial 
of benzodiazepines has failed. Therefore, instead of calling for PMAs 
for ECT devices for the treatment of catatonia, FDA has satisfied the 
requirements under section 515(i)(2) of the FD&C Act for revising the 
proposed classification from class III to class II (special controls) 
following reassessment of the published literature referenced in the 
Executive Summary to the 2011 Panel, and comments and literature 
received in the ECT public dockets.
3. Age Limitations on Adolescent Subpopulation for Use of ECT
    In the 2015 proposed order, FDA proposed that ECT devices should be 
classified as class II (special controls) when used for treating adults 
and adolescents 18 years and older with a severe MDE associated with 
MDD or BPD, who are treatment-resistant or who require a rapid response 
due to the severity of their psychiatric or medical

[[Page 66109]]

condition. In response to the proposed order, public comments included 
submission of 29 articles regarding the use of ECT in children and 
adolescents. Some of these comments recommended the age for using ECT 
should be lower than 18 years of age. Half of these articles (Refs. 13-
17, 21, 25 and 27-31) were published after the 2011 meeting. Articles 
published after the 2011 Panel meeting included children and 
adolescents with a variety of psychiatric conditions, including 
catatonia, a severe MDE associated with MDD or BPD and childhood 
schizophrenia.
    Because the current labeling of legally marketed ECT devices does 
not include specific age limitations for any indication within the 
scope of this classification and FDA received public comments 
advocating expansion to include the adolescent age range, FDA believed 
it was important to reassess the evidence and conduct a systematic re-
review of valid scientific evidence for the use of ECT in catatonia or 
a severe MDE associated with MDD or BPD in different age groups. 
Accordingly, similar to the treatment of catatonia, FDA conducted a 
reevaluation of the SE of ECT for use in the adolescent subpopulation 
by reassessing the published literature referenced in the Executive 
Summary to the 2011 Panel, and in comments and literature received in 
the ECT public dockets relating to the adolescent age range for using 
ECT under section 515(i)(2) of the FD&C Act. Unlike the evidence 
reported for the adolescent population, limited experience and only a 
few isolated reports were available for patients less than or including 
12 years of age. Therefore, this age range was not re-evaluated.
    With regard to safety of ECT in treating catatonia or a severe MDE 
associated with MDD or BPD, specifically in individuals under the age 
of 18, Jacob et al. (Ref. 17) conducted a 10-year retrospective chart 
review of all adolescents and children who had received at least one 
session of ECT therapy in the Child and Adolescent Psychiatry Centre, 
National Institute of Mental Health and Neurosciences. Twenty-two 
patients, most who were severely ill, received therapy in the 10-year 
window. In this group, the majority of patients had no adverse effects; 
four patients (18.4 percent) experienced headache immediately after the 
ECT procedure, and three of eight monitored patients had prolonged 
seizures (greater than 2 minutes). At discharge, approximately 80 
percent were rated as ``much improved'' or ``very much improved'' based 
on the Clinical Global Impressions-Improvement (CGI-I) scale.
    Cohen et al. (Ref. 32) investigated cognitive impairment at long-
term followup in adolescents treated with ECT for severe mood disorders 
and compared the neuropsychological test results of the ECT-treated 
subjects with psychiatric comparison subjects matched for sex, age, and 
diagnosis. This study found that cognitive test scores of the subjects 
treated with ECT were similar to those subjects who did not receive 
ECT. In the ECT treated group 6 of the 10 subjects reported having had 
memory losses immediately after ECT treatment and 1 reported long-term 
subjective memory impairment. In the long-term followup study (3.5 
years average), the cognitive tests of anterograde memory in the ECT 
treated group showed no measurable difference compared to the matched 
group.
    A systematic review by Lima et al. (Ref. 28) published in 2013 
found 212 published studies on the use of ECT in children and 
adolescents. Of these, 39 studies met the authors' criteria for 
inclusion in their systematic review. The reviewed studies specified 
indications of ECT use in adolescents, evaluated the effectiveness of 
this therapy in producing remission, and explored the potential risks 
and complications of the procedure. Overall, the results of this 
systematic review found that the use of ECT in adolescents is 
considered a highly effective option for treating several psychiatric 
disorders including MDE and catatonia, achieving high remission rates, 
and presenting few and relatively benign adverse effects. These authors 
conclude that the risks to adolescents can be mitigated by the correct 
use of the technique and are considered minimal when compared to the 
treatment benefit.
    Consoli et al. (Ref. 33) investigated the use of ECT in adolescents 
with a primary diagnosis of catatonia. These authors reviewed the 
published literature (1985-2009) on the use of ECT in child and 
adolescent patients with catatonia. In their meta-analysis of studies 
that included 10 patients or more, only 1 study of 12 patients included 
subjects below the age of 13 (it included patients in the age range of 
12 to 18). This review found that ECT is used as a second-line 
management after high-dose benzodiazepine trials and that ECT is an 
effective, safe, and useful procedure in the treatment of catatonic 
adolescents (n=59).
    The largest systematic review of the use of ECT in young people was 
reported by Rey and Walter (Ref. 34). This 1997 review assessed 60 
studies comprising nearly 400 patients, with the majority of patients 
between the ages of 13 and 18 years and found rates of improvement 
across studies, including 63 percent for depression and 80 percent for 
catatonia. Serious complications were very rare, whereas minor, 
transient side effects appeared common. These authors concluded that 
ECT in young people appears to be similar in SE to that found in 
adults, but note that these results are limited by the lack of 
controlled clinical trials.
    FDA's review of other retrospective studies submitted as comments 
to the proposed order have found similar results. Walter and Rey (Ref. 
35) studied 42 patients aged 14 to 18 with a variety of psychiatric 
diagnoses who received ECT therapy and observed marked improvement or 
resolution of symptoms in about half of the patients who completed the 
therapy. Ghaziuddin et al. (Ref. 36) observed clinically significant 
improvement in 11 of 11 adolescent patients in the 13- to 18-year range 
with major depressive episode. Of these 11 adolescents 7 achieved 
euthymia, which is defined as a Children Depression Rating Scale-
Revised (CDRS-R) of 40 or less. Strober et al. (Ref. 37) reviewed the 
treatment of 10 adolescents (13-17 years) with major depression or BPDs 
and observed complete remission in 6 patients and partial remission in 
the other 4. Cohen et al. (Ref. 38) studied 21 adolescents (age 14-19) 
and observed 100 percent response in major depression and 75 percent 
response in bipolar-mania. In one of a few studies with a control arm, 
Kutcher and Robertson (Ref. 39) studied 32 bipolar patients and 
compared 16 subjects who received ECT to 16 (serving as controls) who 
were offered ECT but refused it. The ECT group improved significantly 
more than the group who did not receive ECT and the duration of their 
hospitalization was cut in half (74 vs. 176 days on average). Taken as 
a whole, these reports are consistent in reporting effectiveness of ECT 
in treating depressive episodes and catatonia in young adolescents.
    In addition, the American Academy of Child and Adolescent 
Psychiatry (AACAP) has published guidelines for the use of ECT in 
adolescents and children. In the AACAP publication on practice 
parameters (Ref. 40), they reviewed selected publications since 1990. 
While the use of ECT in adolescents is uncommon within the age of 13 to 
17 (representing about 1.5 percent (Ref. 40) of the total population of 
individuals who receive ECT), the benefits of therapy are acknowledged. 
This publication also indicates that while the use of ECT in patients 
12 years of age or younger is rare and necessitates further study, the 
guidelines identify risk mitigations of

[[Page 66110]]

the technique. Overall the AACAP recommends that patients 13 years of 
age and older are appropriate for considering use of ECT in treating 
catatonia or a severe MDE associated with MDD or BPD.
    While the discussion at the 2011 Panel meeting of ECT use in 
treating adolescents with catatonia or a severe MDE associated with MDD 
or BPD was limited, the 2011Panel did hear and discuss comments during 
the open public hearing both on adolescent age groups as well as 
considerations as it relates to ECT (Ref. 41). Although a primary 
emphasis was upon adult populations towards the conclusion of the 2011 
Panel proceedings, sufficient and compelling discussion was heard 
regarding adolescent response to ECT, especially during the opening 
public hearing comments. In summary, there was the 2011 Panel 
discussion focused on adolescent patient use of ECT, as well as many 
comments including literature references addressing inclusion and 
exclusion on the basis of age for specific indications for use of ECT 
(e.g. schizophrenia, bipolar manic states, schizoaffective disorder, 
and schizophreniform disorder).
    Additionally, FDA conducted a review of the MAUDE database from 
August 2016 to December 2017. The additional MDRs from the MAUDE 
database do not appear to be significantly different from those 
compiled for the 2011 Panel meeting and the small number of MDRs is 
consistent with the safety record reported in the literature for ECT.
    As stated previously, FDA has reevaluated the valid scientific 
evidence for use of ECT in treating adolescents and, in the case of 
catatonia or a severe MDE associated with MDD or BPD, we believe the 
requirements under section 515(i)(2) of the FD&C Act for revising the 
classification of the age limitation for the adolescent subpopulation 
are satisfied. Based upon the assessment of the totality of evidence, 
FDA believes that special controls, along with general controls, can 
provide a reasonable assurance of SE of the use of ECT for all 
adolescent age groups (13-21 years) and, therefore, is modifying the 
designation for class II for the indications of catatonia or a severe 
MDE associated with MDD or BPD in the adolescent subpopulation to 
include individuals 13 years and older who are treatment resistant or 
require a rapid response.
4. Effectiveness of ECT for Schizophrenia, Schizoaffective Disorder, 
and Mania
    During the 2011 Panel meeting, members expressed diverse opinions 
on the effectiveness of ECT for treatment of schizophrenia, 
schizoaffective disorders, and mania, but the majority of the 2011 
Panel members supported class III designation for these indications. A 
number of published articles on the use of ECT to treat schizophrenia 
and schizoaffective disorder were submitted and reviewed as attachments 
to the ECT public dockets. Of these, approximately 15 were published 
after the 2011 Panel meeting. The majority of these articles published 
after the 2011 Panel meeting review were either isolated case reports 
or retrospective chart reviews. SE data, including clinical outcomes, 
for both adults and adolescents with a primary diagnosis of 
schizophrenia or schizoaffective disorder (Refs. 14, 23, 30, 42, and 
43-47) resulted in variable patient outcomes, while mania had more 
positive outcomes. However, the available evidence across patients for 
these conditions was limited when compared to the available evidence 
for other conditions presented in this final order for which class II 
is designated.
    There was one published practice guideline (Ref. 48) that provided 
updated treatment recommendations for the acute treatment of 
schizophrenia and the management of treatment resistance. This 
guideline concludes that there is limited evidence for general efficacy 
of ECT in treatment-resistant schizophrenia, but that in certain cases 
ECT as an adjunct to antipsychotic therapy may be appropriate. This is 
in contrast to the guideline recommendation for catatonia where ECT is 
considered an important therapeutic alternative (see above discussion 
in section III.A.2, Effectiveness of ECT for Catatonia).
    Iancu et al. (Ref. 44) conducted a retrospective chart review of 20 
consecutive patients with schizophrenia or schizoaffective disorder who 
were individually treated with at least 30 ECT sessions at the Tel Aviv 
University. All of these patients had been hospitalized for most or all 
of the previous 3 years. In this group of chronically hospitalized 
patients, the authors conclude that ECT treatment improves general 
function and reduces verbal aggression and self-harm. This patient 
group had a mean age of 65 and the average age at disease onset was 22 
years. Patients were selected for treatment based on inadequate 
response to medications, history of a good response to ECT in the past, 
aggression, self-injury, and refusal to eat or drink. Improvement was 
seen on all assessed scales including the Global Assessment of 
Functioning, Clinical Global Impression-Severity and Overt Aggression 
Scale but most changes before and after ECT were not clinically 
meaningful or statistically significant.
    Kristensen et al. (Ref. 45) reviewed the treatment of 72 
consecutive hospitalized patients between 2003 and 2008 from two 
hospitals in the Copenhagen area. Fifty-five had a diagnosis of 
schizophrenia and 17 a diagnosis of schizoaffective disorder. All 
patients had been hospitalized for at least a week and the indication 
for ECT was an increase in acute episodes or symptom severity leading 
to hospitalization. The patient ages ranged from 18 to 79 and the 
disease duration ranged from 1 to 40 years. The duration of the 
patients' psychotic behavior ranged from a few weeks to over 5 years. 
ECT was effective in this severely ill population as reflected by a 
measure of relief from psychosis and disruptive behavior as described 
in the patient charts. Using information about the size of the 
catchment area for the involved hospitals, the authors were able to 
estimate that only about 1.5 percent of patients with schizophrenia 
received ECT over the 6-year study period in this area of Copenhagen. 
Because this represents a select and small fraction of the population 
with schizophrenia, it is not possible to generalize these results to 
the general population of schizophrenic individuals.
    Petrides et al. (Ref. 47) studied patients with clozapine-resistant 
schizophrenia in a single-blind study where 20 clozapine-resistant 
patients received ECT as an adjunct to the clozapine treatment and 19 
received usual (clozapine) care. Response was defined as a 40 percent 
or greater reduction in symptoms based on the psychotic symptom 
subscale of the Brief Psychotic Rating Scale, a Clinical Global 
Ratings-Severity (CGI-S) rating of less than 3, and a CGI improvement 
rating less than or equal to 2 following an 8-week course of treatment. 
Fifty percent of patients in the treatment group that received the ECT 
met the response criteria compared to none of the patients in the 
control group. FDA believes that these results, while promising, have 
significant limitations. The Denmark Study represents a population of 
hospitalized patients who may not be representative of the general 
population of schizophrenic individuals. The Petrides study was small 
and focused on the subpopulation of clozapine resistant patients and 
again cannot be

[[Page 66111]]

extrapolated to the general schizophrenic patient population. The 
available valid scientific data on the schizophrenic patient population 
are limited and insufficient to demonstrate that the use of ECT in 
schizophrenia patients can be safe and effective with the use of 
special controls.
    Other studies have focused on the use of maintenance ECT in the 
treatment of patients with schizophrenia and schizoaffective disorders 
(Refs. 23, 27, and 46). In each of these studies, the patient 
populations are highly selected and represent a small minority of the 
schizophrenic or schizoaffective populations. Also, a number of 
additional therapies were given to patients, with limited use of ECT in 
some cases. While the results are promising in these selected patient 
populations, the evidence available is limited. Moreover, practice 
guidelines have not called out schizophrenia and schizoaffective 
disorders for treatment with ECT. With limited data on different select 
subpopulations, FDA believes that there is insufficient evidence, at 
this time, to establish special controls for the subpopulations that 
might benefit from the treatment. Therefore, FDA believes that the use 
of ECT to treat schizophrenia or schizoaffective disorder is 
appropriately currently regulated in class III.
    Ten published articles were submitted to the ECT public dockets 
regarding the SE of ECT for mania. All the articles were published 
prior to the 2011 Panel meeting and no ``new information'' on the SE of 
mania was submitted to the ECT public dockets that were not available 
to the 2011 Panel. In reviewing the ECT public dockets, FDA did not 
identify additional scientific information since the 2011 Panel meeting 
supportive of reclassifying mania to class II. The published reports on 
using ECT for the treatment of mania are relatively few, have small 
numbers of patients, and acknowledge that there are viable alternative 
treatments in this population.
    In one study, Black et al. (Ref. 49) systematically reviewed 
records of patients treated with ECT for mania or depression over a 12-
year period at the University of Iowa Hospital Center. Patient outcome 
was divided into five categories based on patient discharge notes with 
the category ``marked improvement'' applied to patients where the 
discharge notes suggested there was complete resolution of depressive 
or manic symptoms. In this review, there was marked improvement in a 
substantial majority of the patients with depression and with mania. 
However, the total numbers of patients treated included 422 patients 
treated for depression but only 37 patients treated for mania. As a 
result of the differences in numbers of patients treated, there is 
greater uncertainty in the significance of this retrospective study in 
mania compared with depression.
    Mukherjee et al. (Ref. 50) reviewed the treatment of 30 manic 
patients at a psychiatric institute in India treated for mania with 
ECT. They observed remission of mania in 26 of 30 patients. Results are 
confounded though by the concurrent prescription of neuroleptics at the 
time of admission for treatment.
    Small et al. (Ref. 51) compared ECT with lithium maintenance 
therapy to lithium treatment in 34 patients hospitalized for mania. 
Although the patients who underwent ECT improved more than the lithium 
treatment patients during the first 8 weeks, the study found no 
differences in clinical ratings after 8 weeks and no differences in 
rates of relapse, recurrence, or re-hospitalization in the followup 
period, when compared to pharmacotherapy.
    FDA concluded that based on the published literature referenced in 
the Executive Summary to the 2011 Panel, comments and literature 
received in the ECT public dockets, the small number of patients 
treated and limited outcomes reported, the existence of confounding 
factors in studies, and the availability of alternative therapies with 
similar reported effectiveness, that special controls cannot be 
established to provide a reasonable assurance of SE, and, therefore, it 
is appropriate to maintain ECT to treat mania in class III.

B. Comments on Reclassifying ECT Based on Safety and Effectiveness

    In this section, comments regarding the SE of ECT are categorically 
grouped together so that FDA's responses could be addressed by topic 
instead of each comment considered independently.
    (Comment 3) Several comments indicated that ECT was not safe and/or 
not effective, particularly in the long term. Several comments noted 
that ECT had not been used safely and/or effectively in their practice, 
or on themselves as a patient, or on a family member or a friend. 
Several comments stated ECT injures patients and is not therapy. 
Several comments also noted long-term memory, cognitive, or functional 
impairment following ECT administration. Instead of using ECT, several 
comments recommended alternative treatments, including acupuncture, 
transcranial magnetic stimulation, or nutritional or solar therapy.
    (Response 3) Comment 3 reflects significant concern on the part of 
some patients and caregivers about the risks of ECT. Table 1 shows how 
FDA believes that the risks to health associated with ECT for treatment 
of catatonia or a severe MDE associated with MDD or BPD can be 
mitigated by the designated special controls.

   Table 1--Identified Risks to Health and Mitigation Measures for ECT
------------------------------------------------------------------------
       Identified risks to health             Mitigation measure(s)
------------------------------------------------------------------------
Adverse reaction to anesthetic agents/   Labeling
 neuromuscular blocking agents.
Adverse skin reactions.................  Biocompatibility Labeling
Cardiovascular complications...........  Labeling
Cognitive and memory impairment........  Technical parameters, Non-
                                          clinical test data, Labeling
Death..................................  Labeling
Dental/oral trauma.....................  Labeling
Device malfunction.....................  Performance data,
                                          Electromagnetic compatibility,
                                          Software verification,
                                          validation, and hazard
                                          analysis
Manic symptoms.........................  Labeling
Pain/discomfort........................  Labeling
Physical trauma........................  Labeling
Prolonged or tardive seizures..........  Labeling
Pulmonary complications................  Labeling
Skin burns.............................  Performance data, Labeling
Worsening of psychiatric symptoms......  Labeling
------------------------------------------------------------------------


[[Page 66112]]

    FDA acknowledges that the individuals for whom ECT therapy may be 
prescribed are at significant risk for complications including death 
from their underlying conditions. Milstein et al. (Ref. 52) completed a 
retrospective study of 1,494 psychiatric subjects followed for 5 to 7 
years following hospitalization for a psychiatric condition. They found 
76 deaths in this group of patients with 16 of the deaths being by 
suicide. In this group, ECT was not protective but also did not 
increase the risk for death. Labeling will be required to explain the 
potential risks and benefits to ensure that patients, caregivers, and 
family members understand the magnitudes of the risks and the benefits 
of ECT. FDA acknowledges the important role of patient preference and 
patient choice in selecting treatments. Patient preference is important 
in balancing the individuals' assessment of risk and benefit, 
especially in the presence of serious and potentially life-threatening 
disorders. This classification is concerned with the use of ECT for 
certain specified uses and does not address the potential use of other 
treatments that patients may consider. FDA believes that for certain 
indications, special controls as established in this final order, along 
with general controls, provide a reasonable assurance of SE of ECT by 
mitigating the identified risks to health. As such, FDA disagrees with 
the comments that ECT should not be reclassified for any indications to 
class II.
    FDA reclassifies devices under section 515(i)(2) of the FD&C Act in 
accordance with the criteria in section 513(a) of the FD&C Act. The 
primary purpose of reclassification is to apply the appropriate level 
of regulatory controls for a device based on the most current 
information regarding its SE. FDA notes that reclassification does not 
imply that ECT is a preferred form of treatment. FDA recommends that 
patients consult with their healthcare providers to determine if ECT is 
the best treatment option for them or if there are suitable alternative 
treatments. FDA notes that the patient labeling is required to list 
alternative treatments (see Sec.  882.5940(b)(1)(ix)(E) (21 CFR 
882.5940(b)(1)(ix)(E))).
    (Comment 4) Some comments stated that FDA did not consider animal 
studies and death data in proposing to reclassify these devices.
    (Response 4) FDA does not agree with these comments. Information 
about adverse events, including death, was carefully considered 
regarding the reclassification action. Section 4.8 of the safety review 
in the FDA Executive Summary prepared for the 2011 Panel meeting 
specifically addresses the risk of death. Data for deaths from MDR 
analyses was also considered and made part of the risks identified in 
the proposed order. FDA acknowledges that there is uncertainty in the 
estimate of risk of death from these sources of information and that 
the risks are likely changing as a result of evolution in the practice 
of medicine. In light of this risk, the labeling is required to include 
death (Sec.  882.5940(b)(1)(ix)(H)(3)(viii)) as a risk of the use of 
ECT. In some cases where human experience is limited, animal studies 
can be of significant value in predicting outcomes in humans.\2\ 
However, in this case where there is a significant and substantive 
experience with the use of these devices to treat humans, FDA believes 
that the human study data are the primary sources for review and 
consideration.
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    \2\ FDA supports the principles of the ``3Rs,'' to reduce, 
refine, and replace animal use in testing when feasible. We 
encourage sponsors to consult with us if it they wish to use a non-
animal testing method they believe is suitable, adequate, validated, 
and feasible. We will consider if such an alternative method could 
be assessed for equivalency to an animal test method.
---------------------------------------------------------------------------

    (Comment 5) Several comments opposed the reclassification saying 
that ECT should remain in class III for all indications. Several 
comments indicated that current safety or effectiveness information was 
insufficient to ensure patient protection. Several comments indicated 
that proof of SE should be required before the device enters the 
market. Several comments indicated that the 510(k) clearance pathway 
was not sufficient for ECT devices.
    (Response 5) FDA disagrees with these comments that ECT should not 
be reclassified to class II as specified in this final order for 
certain indications. As established in section 513(a)(1)(C) of the FD&C 
Act and 21 CFR 860.3(c)(3), a device is in class III if insufficient 
information exists to determine that general controls and/or special 
controls are sufficient to provide reasonable assurance of its SE. 
Based on FDA's independent review of the scientific evidence, FDA has 
determined that the special controls established in this final order, 
including performance data, technical parameters of the device, and 
extensive labeling requirements, along with general controls, can 
provide reasonable assurance of SE of ECT for the specified class II 
indications. ECT devices for indications in class II will require a 
510(k) (or an amendment to a previously cleared 510(k) if already 
legally marketed) that demonstrates compliance with these special 
controls. ECT devices for indications other than those being classified 
into class II will require premarket approval as insufficient evidence 
currently exists to establish adequate special controls for these uses.
    (Comment 6) Several comments indicated that ECT did not treat the 
biological basis of depression or other mental disorders. Several 
comments indicated that electricity did not treat the underlying 
cause(s) and could exacerbate mental disorders. Several comments 
indicated that there is no evidence that mental disorders are 
neurobiological. Several comments indicated that ECT may be used in 
patients who are misdiagnosed.
    (Response 6) For a device to be determined to have a reasonable 
assurance of SE, FDA evaluates the device's performance outcomes 
relative to the indications for use and not necessarily the 
mechanism(s) of action of the device, which may not be well understood 
in some cases. For ECT, the clinical data reflecting the device's 
performance in relation to the indications for use have been discussed 
above in response to Comment 2. Additionally, knowledge of the 
underlying causes of mental disorders is not required to evaluate a 
reasonable assurance of the SE of a device type for a specified 
intended use. Therefore, the biological basis or cause of the 
underlying mental disorder is outside of the scope of this 
reclassification.
    (Comment 7) Several comments suggested that reclassification would 
increase acceptance of ECT. Several comments indicated that ECT is not 
as safe or effective when compared to other available treatments. 
Several comments opposed the reclassification saying that 
reclassification indicated that ECT is a preferred method of treatment.
    (Response 7) The primary purpose of reclassification is to apply 
the appropriate level of regulatory controls for a device type based on 
the ability to reasonably assure SE. FDA notes that reclassification 
does not imply that ECT is a preferred form of treatment. This order is 
neither a recommendation of ECT treatment nor a determinant of whether 
ECT is safer or more effective than alternative treatments. The purpose 
of the proposed and final order process is to identify the regulatory 
controls necessary to reasonably assure SE for ECT and to provide the 
evidence supporting this determination. Based upon FDA's assessment, 
special controls, in combination with general controls, are necessary 
and sufficient to provide a reasonable assurance of SE for the use of 
ECT in treating catatonia or

[[Page 66113]]

a severe MDE associated with MDD or BPD in patients age 13 years and 
older who are treatment-resistant or who require a rapid response due 
to the severity of their psychiatric or medical condition. ECT devices 
for indications other than those identified in the previous sentence, 
including schizophrenia, schizoaffective disorders, schizophreniform 
disorder, bipolar manic states, and catatonia or a severe MDE 
associated with MDD or BPD in patients under 13 years or patients 13 
years or older who are not treatment-resistant or who do not require a 
rapid response due to the severity of their psychiatric or medical 
condition, will require premarket approval. FDA believes that 
insufficient evidence currently exists to establish special controls to 
mitigate the risks to health and provide a reasonable assurance of SE 
for those uses.
    (Comment 8) Several comments indicated that ECT should be banned. 
Several comments characterized ECT as inhumane. Commenters indicated 
that the United Nations Special Rapporteur on Torture and Other Cruel 
Inhuman or Degrading Treatment or Punishment February 16, 2013, defined 
ECT without consent as torture.
    (Response 8) FDA disagrees that ECT should be banned. Section 516 
of the FD&C Act (21 U.S.C. 360f) authorizes FDA to ban a device when, 
based on all available data and information, FDA finds that the device 
``presents substantial deception or an unreasonable and substantial 
risk of illness or injury.'' During review of the scientific evidence, 
FDA did not identify sufficient evidence to ban ECT. FDA determined 
that special controls, in combination with general controls, can 
mitigate the identified risks of ECT for certain intended uses and 
mitigate risks associated with ECT use. FDA determined that there is a 
reasonable assurance of SE for ECT treatment for the identified 
indications for use and patient populations. Therefore, FDA has 
determined that ECT does not present substantial deception or an 
unreasonable and substantial risk of illness or injury.
    As noted, we acknowledge the February 1, 2013, United Nations 
Report of the Special Rapporteur on torture and other cruel, inhuman or 
degrading treatment or punishment by Juan E. M[eacute]ndez does 
recommend banning the administration of non-consensual electrical 
stimulation against persons with disabilities (Ref. 53). Persons with 
disabilities include persons with long-term intellectual or sensory 
impairments. The report does not address the use of electrical 
stimulation to treat conditions such as a severe MDE associated with 
MDD or BPD, schizophrenia, bipolar manic states, schizoaffective 
disorder, schizophreniform disorder, or catatonia. As noted in the 
proposed order and adopted in this final order, appropriate directions 
for use and specific labeling special controls (Sec.  
882.5940(b)(1)(viii) and (ix)) are required for the safe use of ECT.
    (Comment 9) Several comments were concerned that reclassification 
would make it easier for either healthcare professionals or non-
healthcare professionals to overly or inappropriately use ECT. Comments 
indicated that ECT may be used to shorten hospital stays without regard 
for patient outcomes. Comments indicated that ECT may be used to 
control patients or reduce unwanted behavior such as screaming rather 
than as treatment for a medical condition. Several comments questioned 
the regulation of ECT use in other indications not included in class II 
in the split classification.
    (Response 9) FDA does not regulate the practice of medicine (see 
section 1006 of the FD&C Act (21 U.S.C. 396)). Diagnosis and treatment 
of patients are clinical decisions that fall within the practice of 
medicine. Rather, FDA regulates the use of a device as indicated by the 
person or entity offering the device for interstate commerce. The 
classification of indications for use for ECT devices are specified in 
the identification language in the codified classification regulation 
(see Sec.  882.5940). Through the classification process, FDA has 
determined the level of regulatory control necessary to provide a 
reasonable assurance of SE of ECT devices for these indications. ECT is 
a prescription only device that is not safe for use except under the 
supervision of a practitioner licensed by law to direct the use of the 
device and for which prescription labeling requirements must be met 
(see 21 CFR 801.109). The labeled uses of the device must conform to 
the indications that have been cleared or approved by FDA through the 
premarket review process. FDA does not regulate off-label use of ECT by 
physicians.

C. Comments on Patient Concerns

    In this subsection, comments on patient concerns with using ECT are 
categorically grouped together so that FDA's responses could be 
addressed by topic instead of each comment considered independently.
    (Comment 10) Several comments state that FDA's call for PMA 
applications is disingenuous because PMA applications have not been 
required for ECT devices since they were originally classified. 
Comments indicate that because the proposed order states ECT devices 
for some indications will be in class II, device manufacturers will not 
have an incentive to apply for additional indications through the PMA 
process, because, under the practice of medicine, healthcare 
professionals can use class II ECT devices for indications beyond those 
cleared via 510(k) for indications that are in class III.
    (Response 10) FDA disagrees with these comments. Finalizing the 
classification of ECT includes a requirement that PMA applications be 
submitted prior to marketing of ECT devices for indications other than 
those identified as class II within this final order, and it is the 
responsibility of the manufacturer to ensure that a PMA application is 
submitted in such circumstances. However, FDA is not permitted to limit 
or interfere with the authority of a healthcare professional to 
administer any legally marketed device to a patient for any condition 
or disease within a legitimate clinician-patient relationship.
    (Comment 11) Several comments raised concerns about a split 
classification and the conditions under which devices could be used 
under either classification. Several comments indicated that a split 
classification could restrict the use of ECT for indications not 
included in class II and thereby limit treatment options for patients. 
Comments asked if there is evidence of patients not receiving treatment 
when ECT devices are in class III. Comments asked for guidance on 
whether class II ECT devices can be used on patients with a severe MDE 
associated with MDD accompanied by another condition. Comments also 
stated concern that class II ECT devices will be used as predicate 
devices for other devices with different current or voltage strength, 
or different pulse length, pattern or waveform, saying such differences 
could impact safety including cognitive side effects and/or 
effectiveness of ECT treatment.
    (Response 11) FDA's reclassification of ECT to class II for the 
indications specified in the final order is an effort to make ECT 
available for the benefit of patients with conditions for which general 
and special controls can provide a reasonable assurance of SE. For 
these indications, sufficient scientific evidence exists for FDA to 
establish special controls that, in combination with general controls, 
provide reasonable assurance of SE of ECT. For other indications, 
sufficient scientific evidence does not currently exist to be

[[Page 66114]]

able to establish special controls to mitigate the risks to health at 
this time. The indications for which there is currently insufficient 
evidence to develop special controls will remain class III and require 
a PMA pursuant to section 513(a)(1)(C) of the FD&C Act. Because of the 
differing levels of scientific evidence currently available to 
establish special controls for the various uses of ECT, a split 
classification was warranted in this case. If warranted by new 
scientific evidence, FDA could reclassify ECT for other indications to 
class II in the future.
    Under section 1006 of the FD&C Act, FDA is prohibited from 
interfering with the authority of a healthcare professional to 
prescribe or administer any legally marketed device to a patient within 
a legitimate clinician-patient relationship. As such, FDA does not 
regulate the practice of medicine. Rather, FDA regulates the use of a 
device as indicated by the person or entity offering the device for 
interstate commerce. The indications for which FDA has determined ECT 
devices have a reasonable assurance of SE based on the general controls 
and the identified special controls are in the codified classification 
regulation (see Sec.  882.5940). Once a product is approved or cleared, 
a healthcare professional is able to prescribe the device based on a 
patient's condition. ECT is a prescription device and FDA relies on 
licensed practitioners to direct its use. Treatment of patients remains 
under the clinical discretion of their healthcare practitioner. While 
treatment of patients falls under the practice of medicine, healthcare 
professionals should carefully consider all ECT device labeling, 
including potential adverse events, warnings, and medical conditions 
that can increase patient risk when deciding if ECT is appropriate for 
their patients, including those with comorbid conditions. The 
healthcare professional is responsible for providing appropriate 
ongoing medical management to mitigate any patient specific risks 
associated with comorbid conditions.
    If ECT devices are used as predicate devices for subsequent ECT 
devices, any differences in the technical parameters (e.g., waveform, 
output mode, pulse duration, maximum charge, and energy as identified 
in Sec.  882.5940(b)(1)(i)) between the predicate device and the new 
device must be characterized and will be considered as part of FDA's 
substantial equivalence determination to ensure that such differences 
do not raise different questions of SE.
    (Comment 12) Several comments were concerned that adequate, well-
informed consent may not take place prior to ECT treatment. Several 
comments indicated concern over the use of ECT without consent or 
without full disclosure of risks. Several comments were concerned with 
involuntary treatment and its outcomes. Comments indicated that 
conversations about potential benefits, potential risks, alternative 
treatments, and the typical experience and course of ECT treatment 
should occur over several sessions prior to ECT treatment. Comments 
asked that FDA provide additional guidance and recommendations to 
healthcare professionals on the procedures for informing patients and 
on obtaining written informed consent from patients or their legally 
authorized representatives prior to ECT treatment. Comments indicated 
that family members or other caregivers should be included in the 
informed consent process and should provide input on how the patient is 
responding to ECT treatment including any adverse events. Several 
comments indicated that ECT should only be used in settings of formal 
informed consent, such as with a documented checklist or when it is 
specified in a psychiatric advance directive. A comment suggests that 
FDA develop a patient decision aid related to ECT that considers key 
clinical variables and alternative therapeutic options as well as 
incorporating patient values, concerns, and preferences. Several 
comments indicated that the order should specify that consent is an 
ongoing process, that information should be provided throughout 
treatment, and that at any time during the course of ECT treatment, 
patients can request that treatment be stopped and can withdraw consent 
for further treatment. Several comments indicated that some patients 
may not be able to give consent due to their medical condition.
    (Response 12) These comments are focused on how patients are 
informed about the risks, benefits, and alternatives to ECT. FDA agrees 
that ECT informational material, including information about benefits 
and risks, should be discussed with the patient and, if applicable, 
with a designated family member or other individual. In Sec.  
882.5940(b)(1)(ix), FDA requires that certain information be provided 
in the patient labeling for a class II ECT device. The appropriate 
treatments for a patient with catatonia or a severe MDE associated with 
MDD or BPD is a complex matter that requires the supervision of a 
practitioner licensed by law to direct the use of the device. In 
selecting the appropriate treatment, the practitioner should consider 
many factors, such as the patient's medical history and the severity of 
their psychiatric or medical condition. FDA believes that the device 
labeling required per the special controls will provide patients and 
healthcare professionals with information that will improve their 
understanding of the ECT device and assist in selecting the appropriate 
treatment for patients. ECT is a prescription device, and FDA and 
licensed practitioners are relied upon to direct its use.
    Informed consent procedures may differ across each State agency, 
institution, hospital, clinic, and practice. For ECT treatment, FDA 
expects review boards and State agencies to have the appropriate 
requirements for medical professionals to provide the appropriate 
informed consent to patients and family members, and to take action 
when necessary. The patient labeling is required to include information 
on ECT use, potential benefits, warnings regarding risks of ECT, and 
alternative treatments. The information required in the patient 
labeling will help patients make an informed decision about ECT 
treatment. Patients may also discuss ECT and other treatment options 
with their healthcare professionals, family members, or other 
individuals. Patients, or their legally authorized representative, may 
withdraw consent and request that ECT treatment be stopped at any time.
    According to the Surgeon General, involuntary ECT treatment is 
uncommon in the United States. In every State in the United States, the 
administration of ECT on an involuntary basis requires a judicial 
proceeding (Ref. 54). At this time, FDA declines to recommend the 
development of patient decision aids related to ECT that considers key 
clinical variables and alternative therapeutic options as well as 
incorporating patient values, concerns, and preferences. FDA is 
concerned that including such information may be more confusing than 
helpful given the complexity of treating a number of different 
psychiatric disorders. FDA also requires patients consult a 
practitioner licensed by law to administer or use the ECT device.
    (Comment 13) Several comments indicated training or education 
should be required for healthcare professionals to be eligible to 
administer ECT. Several comments indicated that the order should 
specify what type of healthcare professional should be able to 
administer ECT. Several comments indicated that healthcare 
professionals

[[Page 66115]]

other than physicians should be able to administer ECT.
    (Response 13) FDA is in agreement that there is a need for ongoing 
training for healthcare professionals who administer ECT. ECT is a 
complex procedure that requires specialty training for reasonably safe 
and effective administration. As stated in the proposed order and 
adopted in this final order, FDA is requiring device labeling to 
specify the clinical training that is needed by those using the ECT 
device to ensure appropriate use and appropriate ongoing medical 
management of the patient.
    (Comment 14) Several comments indicated that those who administer 
and/or study ECT have conflicts of interest. Several commenters noted 
that the doctors recommending ECT treatment profit financially from 
administering ECT. Commenters asked if FDA considers possible conflict 
of interests for researchers when assessing the validity of ECT 
research used to support the reclassification.
    (Response 14) The potential for conflict of interest of healthcare 
professionals administering ECT is outside the scope of this final 
order and does not bear upon FDA's careful evaluation of the valid 
scientific evidence on the SE of ECT. FDA's Federal conflict of 
interest provisions are directed toward the potential for conflict of 
interest on the part of FDA employees and outside experts used on FDA's 
advisory committees (see 5 CFR 2640 and 18 U.S.C. 208).
    FDA defines valid scientific evidence in Sec.  860.7(c)(2). 
Isolated case reports, random experience, and unsubstantiated opinions 
are not regarded as valid scientific evidence. In standard clinical 
practice as in ECT treatment, healthcare professionals are compensated 
for providing treatment to patients. Institutional review boards assess 
potential conflicts of interest for healthcare professionals conducting 
clinical research on ECT. Under 21 CFR part 54, FDA assesses potential 
financial conflicts of interest for healthcare professionals conducting 
clinical research on ECT. Scientific journals typically require 
disclosure of funding and potential conflicts of interest when 
publishing research findings.
    (Comment 15) Several comments were concerned about the benefit-risk 
ratio for ECT treatment. Comments raised concerns that the risks of ECT 
may be higher in vulnerable populations, including the elderly, who 
could have hemorrhaging from increased intracranial pressure, pregnant 
women, and patients with multiple disorders, cancer, or multiple 
medications. Comments indicated that the risks of ECT are higher than 
acknowledged because adverse reactions are mischaracterized so that 
they are not associated with ECT. Comments also expressed concern that 
patient-reported outcomes differ from reported adverse events and study 
outcomes. Comments said some adverse effects of ECT, such as emotional 
trauma, have had limited scientific study but are evidenced by many 
subjective patient accounts and should be considered further. Comments 
noted that the benefit-risk ratio could change over the course of an 
ECT treatment. Comments said the benefit could decrease and the risks 
could increase because higher stimulation is needed for effectiveness 
over the course of treatment, leading to a higher risk of adverse 
events. In addition, comments said the repeated use of general 
anesthesia for ECT over a relatively short period of time could 
increase the risk of side effects.
    (Response 15) FDA believes there is reasonable assurance that with 
the special controls codified in the final order, in combination with 
general controls, the benefit of ECT outweighs the risk for the 
indicated populations whose condition is treatment-resistant or who 
require a rapid response due to the severity of their psychiatric or 
medical condition. The practitioner administering ECT is responsible 
for ongoing medical management and disclosure of changes in the risks 
for individual patients during a course of ECT treatment. In 
considering the benefits and risks, FDA took into consideration all 
available information, including the existing published scientific 
literature, practice guidelines published by major psychiatric and lay 
mental health organizations, input from the external classification 
panel, and reports of adverse events contained in the MAUDE database. 
Based upon all of this information, FDA has determined that the 
probable benefits to health from use of the device outweigh the 
probable risks for the class II indications and, furthermore, the risks 
associated with the use of ECT for the class II indications can be 
mitigated with the proposed special controls.
    (Comment 16) Several comments indicated that the special controls 
were inadequate to properly mitigate severe risks such as the risk of 
cognitive impairment and death. Comments indicated that special 
controls cannot be developed for unknown risks. For example, it is not 
known whether ECT patients return to baseline memory functioning after 
6 months. A comment asserts that FDA must use scientific evidence to 
evaluate risk to memory and it is not enough for FDA ``to believe'' the 
potential benefits of ECT outweigh the risk of memory impairment. The 
comment also indicates that FDA presents no evidence verifying that the 
special controls are effective at mitigating risk or that the special 
controls will ensure patients understand the benefits-risks of ECT.
    (Response 16) FDA identified sufficient scientific information to 
establish special controls, including adequate instructions for use and 
appropriate precautionary language. The special controls along with 
general controls provide a reasonable assurance that ECT can be used 
safely and effectively for the indications being reclassified to class 
II. Regarding the use of the word, believe, by FDA in the proposed 
order, FDA's use is of the word believe is a term of art to indicate 
its current understanding of an issue in administrative orders. The 
term, believe, is also used in both the FD&C Act and FDA's regulations.
    The risk of memory impairment following ECT treatment is addressed 
in the special controls. The risk of cognitive and memory impairment 
can be mitigated by establishing the technical parameters for the 
device along with non-clinical testing data to confirm the electrical 
characteristics of the output waveform. The existing clinical 
performance data for ECT in treating catatonia or a severe MDE 
associated with MDD or BPD provides evidence that the cognitive 
impairment and related effects are transient (Refs. 5 and 34) and 
supports a reasonable assurance of SE. This risk is further mitigated 
by providing information to both the user and patient, in the form of 
labeling, on the potential adverse effects of the device, alternative 
treatments, and a prominent warning that ECT device use may be 
associated with: disorientation, confusion, and memory problems and is 
limited in its long-term effectiveness (greater than 3 months). These 
risks can also be mitigated by providing instructions to the user that 
include recommendations on cognitive status monitoring prior to 
beginning ECT and during the course of treatment. Providing this 
information helps patients and healthcare professionals to make 
informed choices about how and when to use ECT to maximize benefits and 
minimize potential adverse effects.

D. Comments on Regulatory Process of the Proposed Order

    In this section, comments on process concerns of the order are 
categorically grouped together so that the responses could be addressed 
by topic instead of

[[Page 66116]]

each comment considered independently.
    (Comment 17) Several comments provided recommendations on 
additional sources of information that FDA should consider in regards 
to reclassification of ECT. Comments suggested that FDA should review 
State ECT registries for information on use and outcomes. Comments 
suggested FDA should require new clinical trials, additional postmarket 
surveillance, and/or establish patient registries for the purposes of: 
(1) Establishing long-term risks, such as the potential for shortened 
life; (2) monitoring and assessing memory and cognitive functioning 
over a period of a year or more to determine if memory loss is 
permanent; and (3) determining if patients experienced any long-term 
benefit. A comment indicates that MDR data should be used in the 
classification determination for ECT. The comment attaches an analysis 
of the FDA MDR database search showing that most patients report 
lasting memory and cognition impairment, and other side effects that 
affect work, education, and social relationships. The comment indicates 
that FDA's MDR database shows systematic discrepant reporting of ECT 
adverse events (e.g., description of burns coded with event type, 
malfunction). Comments requested that FDA hold another public meeting 
about the classification of ECT that includes testimony from ECT 
patients because of the ``new information'' provided in the public 
comments.
    (Response 17) FDA agrees that State or national registries may play 
a role in medical device surveillance to provide additional detailed 
information about patients, procedures, and devices not routinely 
collected by electronic health records and administrative or claims 
data. The State of Texas has for several years maintained a registry of 
all ECT treatments in the State in a given year. Data on these 
treatments are provided in an annual report to the governor (see 
https://www.dshs.texas.gov/mhsa/bhmd/ect/, Ref. 55). The most recent 
report provides data for fiscal year 2016. This report summarizes 
17,006 treatments given to 2,675 patients. Severe complications 
included 0 fractures, 0 episodes of apnea, 0 cases of cardiac arrest 
without death, and 1 death within 14 days of treatment that was 
reported to be the result of a drug overdose. This report concludes 
that, overall, patients experienced less severe symptomology after ECT 
treatment, which demonstrates the overall effectiveness of treatment. 
These data are consistent with the published literature and do not 
provide ``new information'' that would change the recommendation in the 
final order.
    FDA requires manufacturers to submit MDRs of adverse events when 
their device may have caused or contributed to a death, serious injury, 
or in certain situations when their device has malfunctioned. FDA 
acknowledges that there are limitations to the use of MDR reports for 
determining the cause and frequency of adverse events. Confirming 
whether a device caused a specific event can be difficult based solely 
on information provided in a given MDR report. Establishing a cause-
and-effect relationship is especially difficult if circumstances 
surrounding the event have not been verified or if the device in 
question has not been directly evaluated. FDA does not typically have 
complete information on the number of times devices of a certain type 
are used from which to calculate adverse event rates. MDR data does not 
represent all known safety information for a medical device and should 
be interpreted in the context of other available information when 
making device-related or treatment decisions. Healthcare professionals, 
patients, caregivers, and consumers are encouraged to submit voluntary 
reports detailing treatment parameters and outcomes to MedWatch: The 
FDA Safety Information and Adverse Event Reporting Program, for serious 
adverse events that may be associated with a medical device, as well as 
use errors, product quality issues, and therapeutic failures (Ref. 56). 
Reports of adverse events are monitored by FDA for safety signals that 
may warrant changes to device regulation.
    Despite the limitations of MDR data described above, as part of its 
review of the comments submitted to the ECT public dockets, FDA 
conducted an updated review of the MDR database covering the period 
from February 2011 through December 2017. This review identified an 
additional 27 reports, all of which are voluntary reports. No reports 
for individuals less than 18 years of age were reported to the MDR 
database. Similar to the reports included in the Executive Summary for 
the classification panel, the most commonly cited adverse event type 
was cognitive changes, notably memory loss (52 percent). Other commonly 
reported adverse events included general emotional/psychiatric (e.g., 
anxiety, emotional changes), general motor (e.g., shaking/tremors), and 
four reports of either tissue damage (not specified) or burns. Thus, 
FDA concluded that no new types of adverse events have been identified 
that would warrant changes to the proposed reclassification order.
    (Comment 18) Several comments raised concern with how the ECT 2011 
classification panel was conducted. Several comments indicated that the 
proposed reclassification was not supported by the panel, because the 
classification panel did not reach consensus regarding whether any of 
the indications should be class II. Comments said that FDA 
misrepresented the classification panel results regarding consensus on 
classification of ECT. Another comment alleges that FDA improperly 
influenced the makeup and deliberations of the classification panel.
    (Response 18) FDA considers the deliberations as well as the 
recommendations by the classification panel meeting in determining the 
appropriate classification of a device under section 513(a) of the FD&C 
Act. The classification panel discussions and recommendations are 
considered as part of FDA's decision whether to revise classification 
of a device (see section 515(i)(2) of the FD&C Act). Although the panel 
provides recommendations with respect to the classification of devices, 
FDA is also not required to follow the classification panel 
recommendations. Regarding ECT, the panel did not reach a consensus on 
its classification for any of the proposed conditions for 
reclassification. There were a variety of opinions and judgments 
provided both in support of and in opposition to reclassification. The 
opinions expressed by the classification panel were carefully reviewed 
and considered along with other information including professional 
organization practice guidelines, MDR reports, and published scientific 
studies.
    Based on this evidence from multiple sources, FDA has determined 
that special controls, in combination with general controls, establish 
a reasonable assurance of SE by mitigating the risks associated with 
ECT for the uses being reclassified (as discussed in section X, 80 FR 
81223 at 81230, December 29, 2015). In accordance with section 
515(i)(2) of the FD&C Act, based on valid scientific evidence with 
respect to the device and taking into account the public health 
benefit(s) of the use of the device and the nature and known incidence 
of the risk(s) of the device, FDA is also now revising the 
classification of ECT for treatment of catatonia or a severe MDE 
associated with MDD or BPD who are treatment-resistant or who require a 
rapid response due to the severity of their psychiatric or medical 
condition in patients ages 13 years and older, from class III to class 
II (special controls) (see subsections A and B of this section).

[[Page 66117]]

    FDA disagrees with the comment that FDA improperly influenced the 
2011 classification panel. On January 27-28, 2011, FDA held a meeting 
of the Neurological Devices Classification Panel to discuss the 
classification of ECT devices for treatment of several disorders. FDA 
has standard procedures in place for establishing a classification 
panel meeting consistent with the requirements of the Federal Advisory 
Committee Act, other relevant statutes (e.g., the FD&C Act), 
regulations (e.g., 21 CFR 14.25 and 14.29), and Agency guidance. As 
required for all classification panel meetings, FDA conducted the 
proper screening and vetting of classification panel members for the 
2011 Panel meeting. FDA ensured the classification panel included 
representatives with expertise in several relevant mental health 
disciplines. The ECT classification panel meeting meets the requirement 
under section 513(b)(1) of the FD&C Act for a device classification 
panel meeting.
    The conduct of the 2011 Panel meeting is described in the 
transcript of the meeting and the 24 Hour Summary (Ref. 57). FDA 
presented the general regulatory background, brief clinical history of 
ECT use, and ECT-specific regulatory history. This was followed by an 
open public hearing. Then, FDA presented the FDA's safety analysis, 
which included a review of responses to a public docket on ECT 
reclassification, manufacturer docket responses, and an adverse event 
database review. In addition, FDA presented a focused review of 
specific adverse events, including cognitive and memory adverse events, 
neuropathological changes, and death. Following the safety review, FDA 
presented a review of the effectiveness of ECT. The classification 
panel then proceeded to their deliberations regarding the questions 
posed by FDA. The classification panel agreed that the list of risks 
provided by FDA were appropriate for inclusion with some minor 
modifications and deletions. The classification panel recommended 
physician labeling for pre-ECT assessment, including pertinent history, 
physical examination, other clinically relevant studies, appropriate 
procedure monitoring and administration, and appropriate clinical 
management. When presented with potential regulatory controls that FDA 
could apply to ECT to mitigate risks of adverse cognitive and memory 
effects, especially with respect to anterograde and retrograde memory 
functioning, the classification panel agreed that cognitive function 
should be monitored prior to ECT and throughout the course of 
treatment. The classification panel agreed that the existing clinical 
data do not provide evidence that ECT treatment is associated with 
neuropathological changes. Finally, the classification panel provided 
overall recommendations for the class II or III classification of ECT 
devices for specific indications for use, including depression 
(unipolar and bipolar), schizophrenia, bipolar manic (and mixed) 
states, schizoaffective disorder and schizophreniform disorder, and 
catatonia. There was classification panel consensus recommending class 
III for schizophrenia, bipolar manic states, and schizoaffective and 
schizophreniform disorder. The classification panel did not reach 
consensus on the classification of ECT for depression (unipolar and 
bipolar) and catatonia.
    (Comment 19) Several comments related to the information used to 
support reclassification. Several comments indicated that the 
scientific evidence, medical studies, meta-analyses and literature 
reviews cited in the proposed order do not constitute new evidence or 
reinterpret previously published evidence and are insufficient to 
justify the reclassification. Comments say FDA ignored the 2010 meta-
analysis from Read and Bentall that found, after reviewing hundreds of 
studies, no evidence that ECT treatment had any benefit for any 
population lasting beyond a few days and did not prevent suicide.
    (Response 19) In accordance with section 515(i)(2) of the FD&C Act, 
FDA is reclassifying the ECT device from class III to II (special 
controls) for use in treating catatonia or a severe MDE associated with 
MDD or BPD in patients age 13 years and older who are treatment-
resistant or who require a rapid response due to the severity of their 
psychiatric or medical condition. FDA has made this reclassification 
decision based on FDA's evaluation of the following sources of 
information: (1) Published literature referenced in the Executive 
Summary to the 2011 Panel; (2) comments and literature received in the 
ECT public dockets, as discussed above; (3) clinical practice 
guidelines; (4) review of MDRs in the FDA MAUDE database); and (5) the 
additional post-2011 scientific information that was provided to FDA in 
comments to the 2015 proposed order. Based on FDA's evaluation of the 
totality of the evidence under the criteria set forth in section 513(a) 
of the FD&C Act, FDA believes that there is valid scientific evidence 
to support FDA's decision to reclassify the ECT device from class III 
to II (special controls) for the intended uses described previously.
    FDA disagrees with the conclusions of the 2010 Read and Bentall 
analysis. Specifically, FDA conducted an independent review and several 
publications, as well as reviews of the published literature, support 
the use of ECT in treating catatonia or a severe MDE associated with 
MDD or BPD in patients age 13 years and older who are treatment-
resistant or who require a rapid response due to the severity of their 
psychiatric or medical condition (Ref. 33, 34 and 58-60). Observations 
from these individual studies, retrospective reviews, and meta-analyses 
consistently reported favorable SE clinical outcomes for the 
indications being reclassified by this final order. In addition, as 
part of the preparations for the 2011 Classification Panel Meeting, FDA 
conducted a systematic review of the scientific literature regarding 
the SE of ECT for a variety of psychiatric conditions. FDA conducted a 
meta-analysis of the data provided in all studies that met criteria for 
inclusion in this systematic review. Based upon this review and meta-
analysis, and the totality of evidence, FDA determined that there was 
reasonable assurance of the SE of ECT for the class II indications in 
this final order.
    (Comment 20) Several concerns were raised about the process for the 
proposed order. Comments indicated the guidance should not be used or 
issued prior to finalization of the final order. Comments indicated 
there was inadequate time to comment on the proposed order due to 
timing of the comment period coinciding with holidays at the end of the 
year, and weekends being included in the 90-day response time. Comments 
indicated that two dockets (one for the proposed order and one for the 
draft guidance) on ECT made commenting more difficult. Commenters 
objected to elimination of mass mail in campaigns and duplicative or 
near-duplicative letters.
    (Response 20) FDA agrees with the comment that guidance should not 
be used or issued prior to finalization of the final order. Final 
guidance will not be issued prior to issuance of the final order. FDA 
believes the correct process was followed for the proposed order issued 
for ECT. FDA determined it was beneficial to publish the proposed order 
and draft guidance on ECT concurrently to ensure that all relevant 
information pertinent to the potential reclassification of ECT, along 
with a recommended strategy for demonstrating substantial equivalence 
for ECT devices subject to 510(k), was available to the public at the 
same time.

[[Page 66118]]

FDA believes that a 90-day comment period was ample time to allow the 
public to comment on the proposed order and concurrently released draft 
guidance and is consistent with the timeframes for other classification 
and reclassification efforts. Commenting on two dockets related to ECT 
rather than one docket does require additional effort by commenters. 
However, FDA had taken two different actions related to ECT (proposing 
a reclassification and issuing draft guidance), such that two dockets 
were made available to provide the option of commenting on one or both 
of these proposed actions. Documents that are in ``draft'' form are not 
implemented by FDA unless and until finalized.
    Information submitted as part of a mass campaign was also reviewed. 
However, while the content of these letters is considered and responded 
to, FDA does not individually respond to the same information contained 
in mass campaign letters and duplicative letters. This allows FDA to 
efficiently utilize resources when reviewing comments. As noted 
previously, although over 3,400 comments were received, comments were 
categorically grouped together so that responses are addressed by topic 
instead of responding independently to each individual comment.
    (Comment 21) Several comments argue that the terms ``treatment 
resistant'' and ``require rapid response'' are vague, particularly to 
non-clinicians. Several comments asked for clarification on the number 
and types of treatments, as well as the duration of treatment that 
should be tried prior to being labeled treatment-resistant. Several 
comments indicated that there was not consensus from the literature and 
professional organizations on the meaning of treatment-resistant. A 
comment indicates that defining treatment-resistant depression as the 
failure of two antidepressants is not appropriate because 
antidepressants are not effective for every patient and there are other 
treatments that may be effective that should be used prior to ECT. 
Several comments indicated that psychotherapy or other non-medical 
treatments should be tried prior to ECT. Several comments were 
concerned that the lack of clarity of these terms would lead to misuse 
of ECT. Several other comments indicated that the terms ``treatment-
resistant'' and ``require rapid response'' were well understood and 
described in applicable medical literature and the Diagnostic and 
Statistical Manual of Mental Disorders (Ref. 61).
    (Response 21) FDA identifies the intended population in which ECT 
is classified in class II as patients who are treatment-resistant 
because ECT is not a currently established first-line treatment, except 
when rapid response is needed due to the severity of the patient's 
psychiatric or medical condition. FDA acknowledges that these terms may 
not be entirely clear to patients. However, comments by healthcare 
professionals generally indicated that the terms are well understood by 
the staff who would be prescribing or using this therapy. The need for 
rapid response and the criteria for treatment-resistant can be based on 
clinical judgment. The information on the intended patient population 
that, as part of the special controls, must be listed on the device 
label (Sec.  882.5940(b)(1)(viii)(D)) is directed toward the 
practitioner licensed by law to administer or use the device.
    (Comment 22) A comment asks FDA to delete the recommendation in 
Sec.  882.5940(b)(1)(viii)(B)(7) for ``formal neuropsychological 
assessment'' from the labeling because it is not the norm and would 
create barriers to the availability and timeliness of care in that such 
assessments are costly and difficult to access.
    (Response 22) FDA recognizes that not all ECT practitioners have 
access to neuropsychologists who conduct formal neuropsychological 
assessment. However, FDA believes that the known risk of cognitive 
adverse events can be mitigated by the special controls that require 
user instructions recommending cognitive status monitoring prior to 
beginning ECT and throughout the course of treatment via a formal 
neuropsychological assessment. If cognitive abilities decline during 
the course of treatment, steps can be taken to avoid further decline.
    (Comment 23) A comment stated depression is sometimes associated 
with cognitive problems and urges FDA to require that all providers of 
ECT assess patients' cognitive and memory functioning when they first 
become patients before ECT begins, soon after ECT ends, and at longer 
term followup after ECT treatment.
    (Response 23) FDA includes a special control (Sec.  
882.5940(b)(1)(viii)(B)(7)) that requires user instructions that 
recommend cognitive status monitoring prior to beginning ECT and during 
the course of treatment via formal neuropsychological assessment for 
evaluating specific cognitive functions (e.g., orientation, attention, 
memory, and executive function). FDA acknowledges that autobiographical 
memory loss following ECT treatment can occur, so this adverse event 
has been included in the labeling for ECT. FDA also acknowledges that 
the ``long-term safety and effectiveness of ECT treatment has not been 
demonstrated,'' and therefore has included this risk as a warning in 
the ECT device labeling that long-term followup may be needed.

E. Comments on Labeling Concerns

    In this section, comments on labeling concerns in using ECT are 
categorically grouped together so that the responses could be addressed 
by topic instead of each comment considered independently.
    (Comment 24) A comment requested that FDA delete the proposed 
warning in Sec.  882.5940(b)(1)(viii)(J) and (ix)(G) (``When used as 
intended this device provides short-term relief of symptoms. The long-
term safety and effectiveness of ECT treatment has not been 
demonstrated.'') because it is understood that cessation of active 
treatment will be associated with cessation of treatment benefits.
    (Response 24) Based upon all available evidence and FDA's own 
analysis of the published scientific literature, FDA concluded that the 
long-term SE of ECT has not been demonstrated. However, FDA recognizes 
that ECT healthcare professionals often conduct longer term treatment 
strategies with ECT. The reclassification of ECT does not specifically 
address the issue of maintenance or continual ECT, which would be at 
the discretion of the healthcare professional. However, as described in 
the special controls, results from longer term performance data should 
be considered for inclusion in the healthcare professional and patient 
labeling, if warranted.
    (Comment 25) A comment asks FDA to replace the word 
``contraindications'' in proposed Sec.  882.5940(b)(1)(ix)(A) with the 
phrase ``conditions associated with substantially increased risk'' 
because describing these conditions as contraindications is likely to 
restrict access to needed ECT in very rare but life-threatening 
situations.
    (Response 25) The use of the word ``contraindications'' here refers 
specifically to medical conditions other than psychiatric disorders in 
which the use of ECT has been demonstrated to result in serious adverse 
events, some of which might be life-threatening. These include unstable 
cardiac and pulmonary conditions (e.g., recent heart attack, asthma, 
pneumonia) and history of neurological conditions (e.g., stroke, 
tumors, increased pressure in the brain). Contraindications are defined 
as situations in which the device should not be used because the risk 
of use clearly outweighs any benefit. (Ref. 62).

[[Page 66119]]

Therefore, FDA believes it is appropriate to keep the language as 
initially written in the proposed order.
    (Comment 26) A comment disagrees with definitions of short-term and 
long-term memory in Sec.  882.5940(b)(1)(ix)(H)(1). The comment says 
equating short-term to anterograde memory loss and long-term to 
autobiographical memory loss is unusual in the psychiatric field and 
confusing for patients. The comment says short-term could mean: (1) 
Lasting for a short period before returning; (2) affecting short-term 
memory, i.e., the type of memory where information is held onto for a 
few seconds to a few minutes; or (3) anterograde memory, which is the 
ability to form new memories. The comment says this labeling does not 
clearly describe the range of deficits that patients might experience. 
The comment says there is a similar lack of clarity in the use of the 
term ``long-term''. The comment says long-term memory typically 
includes many different types of information storage, stored for an 
extended period of time that could range from more than a few minutes 
to years. The comment says many types of cognitive problems can occur 
following ECT in addition to anterograde verbal memory and retrograde 
autobiographical memory, including retrograde loss of non-personal, 
non-rote information (such as knowledge used in daily work tasks), and 
impairments in working memory, processing speed, attention, and 
executive function. The comment also indicates that there are 
discrepancies within the order on the definition of long-term, which is 
defined as 1 month in some instance and as 3 months in other instances.
    (Response 26) FDA recognizes that there are a variety of terms used 
in the scientific literature with respect to memory function. The 
multiple descriptions and definitions of various memory functions such 
as ``short-term'' or ``long-term'' memory contributes to significant 
confusion both among healthcare professionals and lay persons. FDA will 
require the inclusion of the following in the labeling: ``ECT treatment 
may be associated with disorientation, confusion and memory loss, 
including short-term (anterograde) and long-term (autobiographical) 
memory loss following treatment. These side effects tend to go away 
within a few days to a few months after the last treatment with ECT. 
However, some patients have reported a permanent loss of memories of 
personal life events (i.e., autobiographical memory).'' In addition, 
because of the complexity of memory loss, cognitive status monitoring 
prior to beginning ECT and during the course of treatment via formal 
neuropsychological assessment for evaluating specific cognitive 
functions (e.g., orientation, attention, memory, executive function) is 
included as a special control.
    (Comment 27) A comment asks FDA to change the proposed labeling by 
deleting from the list of known risks the phrase, ``a worsening of the 
psychiatric symptoms they are being treated for,'' in Sec.  
882.5940(b)(1)(ix)(H)(2). The comment notes symptoms may worsen if ECT 
is not effective but argues that this is not the same as saying that 
symptoms worsen as a known risk of ECT. The comment notes that the 
possibility of precipitating a manic episode with ECT treatment is 
documented in the scientific literature but is already included in the 
listing of potential risks.
    (Response 27) FDA recognizes that worsening of an underlying 
medical condition can occur either by: (1) An ineffective treatment or 
(2) the treatment itself, particularly when it exacerbates the 
symptoms. Without additional scientific evidence to distinguish between 
these two causes for the use of ECT, this language is included as a 
potential risk.
    (Comment 28) Several comments indicated that labeling was not a 
sufficient mitigation for the risks associated with ECT. Several 
comments indicated that labeling was not a sufficient mitigation 
because the label might not be read, understood, or followed.
    (Response 28) FDA notes that regardless of the classification and 
the risk presented by medical devices, they have the potential to cause 
harm to patients if the labeling is not read, understood, or followed. 
FDA has purposefully included, per the special controls, specific 
mitigations in the required labeling to ensure patient protections and 
transparency related to the benefit-risk profile of ECT. Labeling 
directed to healthcare professionals and patients further help to 
mitigate the risks of ECT because it must include instructions for use 
and a description of the known risks.
    (Comment 29) A comment asks FDA to delete in Sec.  
882.5940(b)(1)(ix)(H)(3)(v) the phrase ``insufficient, or lack of 
breathing'' as a pulmonary complication and add a new item ``prolonged 
action of anesthetic agents associated with insufficient or lack of 
breathing.'' The comment says the proposed text implies that 
insufficient or lack of breathing may be a long-term complication of 
ECT, whereas apnea is an expected effect of neuromuscular blocking 
agents. The comment notes insufficient or lack of breathing may be 
prolonged in some individuals but can be addressed through continued 
ventilation and oxygenation by an anesthesia provider.
    (Response 29) FDA agrees that the warnings related to pulmonary 
risks were unclear and has revised Sec.  882.5940(b)(1)(ix)(H)(3)(v) to 
identify these pulmonary risks associated with the use of general 
anesthesia and neuromuscular blocking agents.

F. Comments Outside of the Scope of This Final Order

    There were several comments submitted that were outside the scope 
of this Final Order and in this section we explain why. Also, in this 
section comments are categorically grouped together so that the 
responses are by topic.
    (Comment 30) A number of comments recommended that FDA take action 
to not allow the American Psychiatric Association (APA) to use the 
phrase ``safe, effective treatment'' and to prevent the APA and the 
National Institute for Mental Health from explicitly using some of the 
claims on ECT treatment.
    (Response 30) FDA generally does not have the authority to direct 
medical associations and other government agencies on how to phrase 
their scientific evaluation of medical devices. Therefore, the requests 
are outside the scope of this final order.
    (Comment 31) Several comments raised concerns regarding insurance 
coverage with different indications in different regulatory classes. 
Several comments indicated that coverage issues may reduce patient 
options for treatment.
    (Response 31) FDA has no authority over commercial health insurance 
carriers. Under section 513(e) of the FD&C Act, FDA has no authority to 
consider as part of a classification decision whether an indication or 
a device is covered by commercial health insurance companies. FDA 
recommends that patients check with their insurance company regarding 
coverage before receiving ECT treatment.
    (Comment 32) Some comments claim that ECT devices for specific 
intended uses are being reclassified for financial reasons and the 
Agency was influenced by the pharmaceutical industry in making its 
determination. A comment also asked FDA to provide reparations for ECT 
patients.
    (Response 32) As stated previously in this section, FDA based its 
determination of reclassification of ECT devices for use in treating 
catatonia or a severe MDE associated with MDD or BPD to class II 
(special controls) on valid scientific evidence, including the

[[Page 66120]]

classification panel recommendations, evaluation of scientific 
literature, clinical practice guidelines, and comments submitted to the 
ECT public dockets. These comments and the request for reparations are 
outside the scope of this final order.
    (Comment 33) A comment claimed that there is discriminatory use of 
ECT including in women, people of color, elderly, and economically 
struggling patients. Another comment stated that many people are 
receiving ECT treatment out of desperation.
    (Response 33) FDA understands the concerns of possible 
discriminatory actions by sub-populations in the treatment of ECT and 
possible treatment out of desperation; however, these comments are 
outside the scope of this final order in determining the classification 
of ECT devices.
    (Comment 34) A comment stated that the advertising of ECT devices 
directed at consumers promotes ``risk-taking behavior.''
    (Response 34) This is also outside the scope of this final order in 
determining the classification of ECT devices.
    Under the FD&C Act, FDA has regulatory authority over the labeling 
of medical devices (21 CFR part 801). However, FDA's regulation of 
medical device advertising is limited to a subset of restricted medical 
devices, which ECT is not. The Federal Trade Commission regulates the 
advertising, as opposed to the labeling, of most medical devices under 
sections 12-15 of the Federal Trade Commission Act, which prohibit 
false or misleading advertising of certain products that FDA regulates 
(15 U.S.C. 52-55).

IV. The Final Order

    Under section 515(b) and (i) of the FD&C Act, FDA is adopting, in 
part, its findings as published in the preamble to the proposed order. 
For the reasons described previously in section II, FDA has made 
revisions in this final order in response to comments submitted in the 
ECT public dockets and information received on the proposed order. The 
revisions modify the ECT class II classification to also reclassify ECT 
devices used for the treatment of catatonia into class II. The 
revisions further modify the ECT class II classification by changing 
the requirement that the patient be ``18 years of age and older'' to 
the requirement that the patient be ``age 13 years and older.'' The 
revisions modify the ECT class III classification by removing the 
catatonia intended use.
    In response to comments, FDA also made some changes to the patient 
labeling special control requirement that addresses statements on the 
physical risks of ECT and additional age-related precautions. The 
patient labeling provides a list of physical risks, including pulmonary 
(affecting lungs) complications. FDA removes ``insufficient or lack of 
breathing'' as a pulmonary complication and revised the complication 
list to include potential pulmonary complications of general anesthesia 
and neuromuscular blocking agents (muscle relaxants) given as part of 
ECT. FDA added language to clarify that the pulmonary risks of ECT 
include hypoxemia, hypoventilation, aspiration, and upper-airway 
obstruction (see Sec.  882.5940(b)(1)(ix)(H)(3)(v)).
    FDA separately considered the risk of the accessory electrodes as 
part of this classification (see Sec.  882.5940(b)(1)(iii)). No other 
accessories are considered part of this classification.
    Section 510(m) of the FD&C Act provides that FDA may exempt a class 
II device from the premarket notification requirements under section 
510(k), if FDA determines that premarket notification is not necessary 
to provide reasonable assurance of the SE of the device. For these ECT 
devices classified as class II, FDA has determined that premarket 
notification is necessary to provide reasonable assurance of the SE of 
the device. Therefore, this device type is not exempt from premarket 
notification requirements. Persons who intend to market this type of 
device must submit to FDA a premarket notification, prior to marketing 
the device, which contains information about the device they intend to 
market.
    Under section 515(i)(2) of the FD&C Act, FDA has the authority to 
issue an administrative order revising the classification of a device 
for which FDA has classified as a class III device and for which no 
administrative order has been issued calling for PMAs under section 
515(b) of the FD&C Act, so that the device is classified into class I 
or class II, after issuance of a proposed order, a meeting of a device 
classification panel, and consideration of the comments on a proposed 
order.
    FDA published a proposed order to require the reclassification of 
ECT devices for intended uses specified in the proposed order and to 
require the filing of a PMA for ECT devices for other intended uses 
specified in the proposed order in the Federal Register of December 29, 
2015. Moreover, as explained in section II of the proposed order, on 
January 27-28, 2011, FDA held a classification meeting of the 2011 
Panel to discuss classification of ECT devices for treatment of several 
disorders. FDA received and has considered all the comments received in 
response to all the ECT public dockets, including the proposed order, 
as discussed in section II. Therefore, FDA has met the requirements 
under sections 515(b)(1) and 515(i)(2) of the FD&C Act.

V. Implementation Strategy

A. Date To File a PMA

    In accordance with section 515(b) of the FD&C Act, ECT devices 
indicated for schizophrenia, bipolar manic states, schizoaffective 
disorder, schizophreniform disorder, and catatonia or a severe MDE 
associated with MDD or BPD in patients under 13 years who are 
treatment-resistant or who require a rapid response due to the severity 
of their psychiatric or medical condition must have a PMA or a notice 
of completion of a PDP filed with the Agency by March 26, 2019. An 
applicant whose device was legally in commercial distribution before 
May 28, 1976, or whose device has been found to be substantially 
equivalent to such a device, will be permitted to continue marketing 
such class III devices during FDA's review of the PMA provided that the 
PMA is timely filed. FDA intends to review any PMA for the device 
within 180 days of the date of filing. FDA cautions that under section 
515(d)(1)(B)(i) of the FD&C Act, the Agency may not enter into an 
agreement to extend the review period for a PMA beyond 180 days unless 
the Agency finds that ``the continued availability of the device is 
necessary for the public health.''
    Under Sec.  [thinsp]812.2(d) (21 CFR 812.2(d)), the exemptions from 
the requirements of the IDE regulations for preamendments class III 
devices in Sec.  [thinsp]812.2(c)(1) and (2) will cease to apply to ECT 
devices indicated for schizophrenia, bipolar manic states, 
schizoaffective disorder, schizophreniform disorder, and catatonia or a 
severe MDE associated with MDD or BPD in patients that are under 13 
years, or patients of any age who are not treatment-resistant or who do 
not require a rapid response due to the severity of their psychiatric 
or medical condition that are: (1) Not legally on the market on or 
before March 26, 2019 or (2) legally on the market on or before March 
26, 2019 but for which a PMA or notice of completion of a PDP is not 
filed by March 26, 2019, or for which PMA approval has been denied or 
withdrawn.
    If a PMA for a class III device is not filed with FDA by March 26, 
2019, the device will be deemed adulterated under section 501(f) of the 
FD&C Act. The device may be distributed for

[[Page 66121]]

investigational use only if the requirements of the IDE regulations are 
met. The requirements for significant risk devices include submitting 
an IDE application to FDA for its review and approval. An approved IDE 
is required to be in effect before an investigation of the device may 
be initiated or continued under Sec.  [thinsp]812.30. FDA, therefore, 
cautions that IDE applications should be submitted to FDA at least 30 
days before March 26, 2019 to avoid interrupting investigations.

B. Compliance With Special Controls

    Following the effective date of this final order, ECT devices 
intended for use in treating catatonia or a severe MDE associated with 
MDD or BPD in patients age 13 years and older who are treatment-
resistant or who require a rapid response due to the severity of their 
psychiatric or medical condition must comply with the special controls. 
FDA notes that a firm whose ECT device was legally in commercial 
distribution before May 28, 1976, or whose device was found to be 
substantially equivalent to such a device and who does not intend to 
market such device for uses other than use in treating catatonia or a 
severe MDE associated with MDD or BPD in patients age 13 years and 
older who are treatment-resistant or who require a rapid response due 
to the severity of their psychiatric or medical condition, may remove 
such intended uses from the device's labeling.
    The special controls identified in this final order are effective 
as of the date of publication of this order, December 26, 2018. ECT 
devices intended for use in treating catatonia or a severe MDE 
associated with MDD or BPD in patients age 13 years and older who are 
treatment-resistant or who require a rapid response due to the severity 
of their psychiatric or medical condition must comply with the special 
controls following the effective date of this order. Manufacturers who 
wish to continue to legally market an ECT device for treatment of 
catatonia or a severe MDE associated with MDD or BPD in patients age 13 
years and older who are treatment-resistant or who require a rapid 
response due to the severity of their psychiatric or medical condition 
must submit an amendment to their previously cleared 510(k) that 
demonstrates compliance with the special controls by June 24, 2019. 
Because FDA has modified the class II indications and the class II 
patient population from the proposed order, FDA is extending the time 
period for submitting an amendment to the 510(k), from 60 days to 180 
days, to provide additional preparation time to submit a 510(k) 
amendment. Such amendment will be added to the 510(k) file but will not 
serve as a basis for a new substantial equivalence review. A submitted 
510(k) amendment in this context will be used solely to demonstrate to 
FDA that an ECT device is in compliance with the special controls. If a 
510(k) amendment is not submitted by June 24, 2019 or if FDA determines 
that the amendment does not demonstrate compliance with the special 
controls, the device may be considered adulterated under section 
501(f)(1)(B) of the FD&C Act.
    For ECT devices that are not in class III as designated in this 
final order, that have not been legally marketed prior to December 26, 
2018, or models that have been legally marketed but are required to 
submit a new 510(k) under 21 CFR 807.81(a)(3) because the device is 
about to be significantly changed or modified, manufacturers must 
obtain 510(k) clearance, among other relevant requirements, and 
demonstrate compliance with the special controls included in this final 
order, before marketing the new or changed device.

VI. Codification of Orders

    Section 515(b), as amended by FDASIA, and 515(i)(2) of the FD&C Act 
require FDA to issue final orders rather than regulations to reclassify 
devices. Therefore, FDA will continue to codify reclassifications and 
requirements for approval of an application for premarket approval, 
resulting from changes issued in final orders, in the Code of Federal 
Regulations. Accordingly, under section 515(i)(2) of the FD&C Act, as 
amended by FDASIA, in this final order, we are codifying the 
reclassification of ECT devices for use in treating catatonia or a MDE 
associated with MDD or BPD in patients age 13 years and older who are 
treatment-resistant or who require a rapid response due to the severity 
of their psychiatric or medical condition into class II by amending 
Sec.  882.5940. Further, we are codifying the requirement for approval 
of an application for premarket approval for ECT devices for the 
intended uses of schizophrenia, bipolar manic states, schizoaffective 
disorder, schizophreniform, and catatonia or a severe major depressive 
episode associated with MDD or BPD in patients under 13 years, or 
patients 13 years and older who are not treatment-resistant or who do 
not require a rapid response due to the severity of their psychiatric 
or medical condition, by amending the language in Sec.  882.5940.

VII. Analysis of Environmental Impact

    The Agency has determined under 21 CFR 25.34(b) that this action is 
of a type that does not individually or cumulatively have a significant 
effect on the human environment. Therefore, neither an environmental 
assessment nor an environmental impact statement is required.

VIII. Paperwork Reduction Act of 1995

    This final order refers to previously approved collections of 
information that are subject to review by the Office of Management and 
Budget (OMB) under the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 
3501-3520). The collections of information in part 807, subpart E, have 
been approved under OMB control number 0910-0120. The collections of 
information in part 812 have been approved under OMB control number 
0910-0078. The collections of information in 21 CFR part 814 have been 
approved under OMB control number 0910-0231. The collections of 
information in 21 CFR part 801 have been approved under OMB control 
number 0910-0485.
    The device and patient warning labeling provisions in this final 
order are not subject to review by OMB because they do not constitute a 
``collection of information'' under the PRA. Rather, the recommended 
labeling is a ``public disclosure of information originally supplied by 
the Federal government to the recipient for the purpose of disclosure 
to the public'' (5 CFR 1320.3(c)(2)).

IX. References

    The following references marked with an asterisk (*) are on display 
at the Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, and 
are available for viewing by interested persons between 9 a.m. and 4 
p.m., Monday through Friday; they also are available electronically at 
https://www.regulations.gov. References without asterisks are not on 
public display at https://www.regulations.gov because they have 
copyright restriction. Some may be available at the website address, if 
listed. References without asterisks are available for viewing only at 
the Dockets Management Staff. FDA has verified the website addresses, 
as of the date this document publishes in the Federal Register, but 
websites are subject to change over time.

* 1. FDA, ``Medical Device Accessories--Describing Accessories and 
Classification Pathways; Guidance for Industry and Food and Drug 
Administration Staff.'' December 20, 2017.
* 2. FDA, ``Reclassification of Daily Wear Spherical Contact Lenses 
Consisting of Rigid Gas Permeable Plastic Materials;

[[Page 66122]]

Withdrawal of Proposed Rule.'' 48 FR 56778.
* 3. FDA, ``Use of Real-World Evidence to Support Regulatory 
Decision-Making for Medical Devices; Guidance for Industry and Food 
and Druge Administration Staff.'' August 31, 2017.
* 4. FDA, ``FDA Executive Summary, Prepared for the January 27-28, 
2011, meeting of the Neurological Devices Panel, Meeting to Discuss 
the Classification of Electroconvulsive Therapy Devices (ECT).'' 
2011.
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9. Semkovska, M., et al., ``Bitemporal Versus High-Dose Unilateral 
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12. England, M.L., et al., ``Catatonia in Psychotic Patients: 
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16. Haq, A.U. and N. Ghaziuddin, ``Maintenance Electroconvulsive 
Therapy for Aggression and Self-Injurious Behavior in Two 
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and Clinical Neurosciences, 2014. 26(1): pp. 64-72.
17. Jacob, P., et al., ``Review of Electroconvulsive Therapy 
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Psychiatry, 2015. 5(2): pp. 182-192.
19. Medda, P., et al., ``Catatonia in 26 Patients with Bipolar 
Disorder: Clinical Features and Response to Electroconvulsive 
Therapy.'' Bipolar Disorders, 2015. 17(8): pp. 892-901.
20. Medda, P., et al., ``Electroconvulsive Therapy in 197 Patients 
with a Severe, Drug-Resistant Bipolar Mixed State: Treatment Outcome 
and Predictors of Response.'' Journal of Clinical Psychiatry, 2015. 
76(9): pp. 1168-1173.
21. Raffin, M., et al., ``Treatment Use in a Prospective 
Naturalistic Cohort of Children and Adolescents with Catatonia.'' 
European Child and Adolescent Psychiatry, 2015. 24(4): pp. 441-449.
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425-430.
23. Shelef, A., et al., ``Acute Electroconvulsive Therapy Followed 
by Maintenance Electroconvulsive Therapy Decreases Hospital Re-
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Journal of ECT, 2015. 31(2): pp. 125-128.
24. Sienaert, P., et al., ``A Clinical Review of the Treatment of 
Catatonia.'' Frontiers in Psychiatry, 2014. 5: p. 181.
25. Unal, A., et al., ``Effective Treatment of Catatonia by 
Combination of Benzodiazepine and Electroconvulsive Therapy.'' 
Journal of ECT, 2013. 29(3): pp. 206-269.
26. Hasan, A., et al., ``World Federation of Societies of Biological 
Psychiatry (WFSBP) Guidelines for Biological Treatment of 
Schizophrenia, Part 1: Update 2012 on the Acute Treatment of 
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Journal of Biologial Psychiatry, 2012. 13(5): pp. 318-378.
27. Ghaziuddin, N., et al., ``Use of Continuation or Maintenance 
Electroconvulsive Therapy in Adolescents with Severe Treatment-
Resistant Depression.'' Journal of ECT, 2011. 27(2): pp. 168-174.
28. Lima, N.N., et al., ``Electroconvulsive Therapy Use in 
Adolescents: A Systematic Review.'' Annals of General Psychiatry, 
2013. 12(1): p. 17.
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Adolescent Psychopharmacology, 2016. 26(7): pp. 632-636.
30. de la Serna, E., et al., ``Two-Year Follow-Up of Cognitive 
Functions in Schizophrenia Spectrum Disorders of Adolescent Patients 
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Term Follow-Up in Adolescents Treated with ECT for Severe Mood 
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33. Consoli, A., et al., ``Electroconvulsive Therapy in Adolescents 
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of ECT in Adolescents.'' Journal of the American Academy of Child 
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* 41. FDA, Transcript of January 27-28, 2011, Meeting of the 
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Electroconvulsive Therapy Devices (ECT). 2011.
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Schizoaffective

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Disorders With Electroconvulsive Therapy: A Case Series of 264 
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Therapy Sessions: Characteristics, Indications, and Results.'' 
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Schizophrenia: A Chart Review of Patients from Two Catchment 
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49. Black, D.W., et al., ``ECT in Unipolar and Bipolar Disorders: A 
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50. Mukherjee, S., et al., ``Unmodified Electroconvulsive Therapy of 
Acute Mania: A Retrospective Naturalistic Study.'' Convulsion 
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51. Small, J.G., et al., ``Electroconvulsive Treatment Compared with 
Lithium in the Management of Manic States.'' Archives of General 
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52. Milstein, V., et al., ``Does Electroconvulsive Therapy Prevent 
Suicide?'' Convulsion Therapy, 1986. 2(1): pp. 3-6.
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Treatment or Punishment.'' 2008.
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* 55. Texas Department of State Health Services, ``Electroconvulsive 
Therapy (ECT) Reports.'' 2018.
* 56. FDA, ``MedWatch: The FDA Safety Information and Adverse Event 
Reporting Program.''
** 57. FDA, ``Neurological Devices Panel--ECT,'' January 2011, 24 
Hour Summary. 2011.
58. Brown, E.D., et al., ``Efficacy of Continuation/Maintenance 
Electroconvulsive Therapy for the Prevention of Recurrence of a 
Major Depressive Episode in Adults with Unipolar Depression: A 
Systematic Review.'' Journal of ECT, 2014. 30(3): pp. 195-202.
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Depressive Disorder: A Roadmap for Improved Therapeutics.'' Current 
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1991.

List of Subjects in 21 CFR Part 882

    Medical devices, Neurological devices.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR part 
882 is amended as follows:

PART 882--NEUROLOGICAL DEVICES

0
1. The authority citation for part 882 continues to read as follows:

    Authority:  21 U.S.C. 351, 360, 360c, 360e, 360j, 360l, 371.


0
2. Revise Sec.  882.5940 to read as follows:


Sec.  882.5940   Electroconvulsive therapy device.

    (a) Identification. An electroconvulsive therapy device is a 
prescription device, including the pulse generator and its stimulation 
electrodes, used for treating severe psychiatric disturbances by 
inducing in the patient a major motor seizure by applying a brief 
intense electrical current to the patient's head.
    (b) Classification. (1) Class II (special controls) when the device 
is intended to treat catatonia or a severe major depressive episode 
(MDE) associated with major depressive disorder (MDD) or bipolar 
disorder (BPD) in patients age 13 years and older who are treatment-
resistant or who require a rapid response due to the severity of their 
psychiatric or medical condition. The special controls for this device 
are:
    (i) The technical parameters of the device, including waveform, 
output mode, pulse duration, frequency, train delivery, maximum charge 
and energy, and the type of impedance monitoring system must be fully 
characterized to ensure that the device performance characteristics are 
consistent with existing clinical performance data.
    (ii) Non-clinical testing data must confirm the electrical 
characteristics of the output waveform.
    (iii) Components of the device that come into human contact must be 
demonstrated to be biocompatible.
    (iv) Performance data must demonstrate electrical and mechanical 
safety and the functioning of all safety features built into the device 
including the static and dynamic impedance monitoring system.
    (v) Appropriate analysis/testing must validate electromagnetic 
compatibility.
    (vi) Appropriate software verification, validation, and hazard 
analysis must be performed.
    (vii) Performance data must demonstrate electrical performance, 
adhesive integrity, and physical and chemical stability of the 
stimulation electrodes.
    (viii) The labeling for the device must include the following:
    (A) Information related to generic adverse events associated with 
electroconvulsive therapy device (ECT) treatment;
    (B) Instructions must contain the following specific 
recommendations to the user of the device:
    (1) Conduct of pre-ECT medical and psychiatric assessment 
(including pertinent medical and psychiatric history, physical 
examination, anesthesia assessment, dental assessment, and other 
studies as clinically appropriate);
    (2) Use of patient monitoring during the procedure;
    (3) Use of general anesthesia and neuromuscular blocking agents;
    (4) Use of mouth/dental protection during the procedure;
    (5) Use of EEG monitoring until seizure termination;
    (6) Instructions on electrode placement, including adequate skin 
preparation and use of conductive gel; and
    (7) Cognitive status monitoring prior to beginning ECT and during 
the course of treatment via formal neuropsychological assessment for 
evaluating specific cognitive functions (e.g., orientation, attention, 
memory, executive function).
    (C) Clinical training needed by users of the device;
    (D) Information on the patient population in which the device is 
intended to be used;
    (E) Information on how the device operates and the typical course 
of treatment;

[[Page 66124]]

    (F) A detailed summary of the clinical testing, which includes the 
clinical outcomes associated with the use of the device, and a summary 
of adverse events and complications that occurred with the device;
    (G) A detailed summary of the device technical parameters;
    (H) Where appropriate, validated methods and instructions for 
reprocessing of any reusable components;
    (I) The following statement, prominently placed: ``Warning: ECT 
device use may be associated with: disorientation, confusion, and 
memory problems''; and
    (J) Absent performance data demonstrating a beneficial effect of 
longer term use, generally considered treatment in excess of 3 months, 
the following statement, prominently placed: ``Warning: When used as 
intended this device provides short-term relief of symptoms. The long-
term safety and effectiveness of ECT treatment has not been 
demonstrated.''
    (ix) Patient labeling must be provided and include:
    (A) Relevant contraindications, warnings, precautions;
    (B) A summation of the clinical testing, which includes the 
clinical outcomes associated with the use of the device, and a summary 
of adverse events and complications that occurred with the device;
    (C) Information on how the device operates and the typical course 
of treatment;
    (D) The potential benefits;
    (E) Alternative treatments;
    (F) The following statement, prominently placed: ``Warning: ECT 
device use may be associated with: Disorientation, confusion, and 
memory problems'';
    (G) Absent performance data demonstrating a beneficial effect of 
longer term use, generally considered treatment in excess of 3 months, 
the following statement, prominently placed: ``Warning: When used as 
intended this device provides short-term relief of symptoms. The long-
term safety and effectiveness of ECT treatment has not been 
demonstrated''; and
    (H) The following statements on known risks of ECT, absent 
performance data demonstrating that these risks do not apply:
    (1) ECT treatment may be associated with disorientation, confusion 
and memory loss, including short-term (anterograde) and long-term 
(autobiographical) memory loss following treatment. Based on the 
majority of clinical evidence, these side effects tend to go away 
within a few days to a few months after the last treatment with ECT. 
Although the incidence of permanent cognitive memory loss was not 
supported by the clinical literature, some patients have reported a 
permanent loss of memories of personal life events (i.e., 
autobiographical memory);
    (2) Patients treated with ECT may experience manic symptoms 
(including euphoria and/or irritability, impulsivity, racing thoughts, 
distractibility, grandiosity, increased activity, talkativeness, and 
decreased need for sleep) or a worsening of the psychiatric symptoms 
they are being treated for; and
    (3) The physical risks of ECT may include the following (in order 
of frequency of occurrence):
    (i) Pain/somatic discomfort (including headache, muscle soreness, 
and nausea);
    (ii) Skin burns;
    (iii) Physical trauma (including fractures, contusions, injury from 
falls, dental and oral injury);
    (iv) Prolonged or delayed onset seizures;
    (v) Pulmonary complications (hypoxemia, hypoventilation, 
aspiration, upper-airway obstruction);
    (vi) Cardiovascular complications (cardiac arrhythmias, heart 
attack, high or low blood pressure, and stroke); and
    (vii) Death.
    (2) Classification: Class III (premarket approval) for the 
following intended uses: schizophrenia, bipolar manic states, 
schizoaffective disorder, schizophreniform disorder, and catatonia or a 
severe MDE associated with MDD or BPD in:
    (i) Patients under 13 years or
    (ii) Patients 13 years and older who are not treatment-resistant or 
who do not require a rapid response due to the severity of their 
psychiatric or medical condition.
    (c) Date premarket approval application (PMA) or notice of 
completion of product development protocol (PDP) is required. A PMA or 
notice of completion of a PDP is required to be filed with FDA on or 
before March 26, 2019, for any electroconvulsive therapy device with an 
intended use described in paragraph (b)(2) of this section, that was in 
commercial distribution before May 28, 1976, or that has, on or before 
March 26, 2019, been found to be substantially equivalent to any 
electroconvulsive therapy device with an intended use described in 
paragraph (b)(2) of this section, that was in commercial distribution 
before May 28, 1976. Any other electroconvulsive therapy device with an 
intended use described in paragraph (b)(2) of this section shall have 
an approved PMA or declared completed PDP in effect before being placed 
in commercial distribution.

    Dated: December 18, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-27809 Filed 12-21-18; 8:45 am]
 BILLING CODE 4164-01-P