[Federal Register Volume 83, Number 242 (Tuesday, December 18, 2018)]
[Notices]
[Pages 64837-64843]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-27361]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Agency for Healthcare Research and Quality


Supplemental Evidence and Data Request on Diagnostic and 
Treatment of Clinical Alzheimer's-Type Dementia (CATD)

AGENCY: Agency for Healthcare Research and Quality (AHRQ), HHS.

ACTION: Request for supplemental evidence and data submissions.

-----------------------------------------------------------------------

SUMMARY: The Agency for Healthcare Research and Quality (AHRQ) is 
seeking scientific information submissions from the public. Scientific 
information is being solicited to inform our review of Diagnostic and 
Treatment of Clinical Alzheimer's-type Dementia (CATD), which is 
currently being conducted by the AHRQ's Evidence-based Practice Centers 
(EPC) Program. Access to published and unpublished pertinent scientific 
information will improve the quality of this review.

DATES: Submission Deadline on or before January 17, 2019.

ADDRESSES: 
    Email submissions: [email protected].
    Print submissions:
    Mailing Address: Center for Evidence and Practice Improvement, 
Agency for Healthcare Research and Quality, ATTN: EPC SEADs 
Coordinator, 5600 Fishers Lane, Mail Stop 06E53A, Rockville, MD 20857.

[[Page 64838]]

    Shipping Address (FedEx, UPS, etc.): Center for Evidence and 
Practice Improvement, Agency for Healthcare Research and Quality, ATTN: 
EPC SEADs Coordinator, 5600 Fishers Lane, Mail Stop 06E77D, Rockville, 
MD 20857.

FOR FURTHER INFORMATION CONTACT: Jenae Benns, Telephone: 301-427-1496 
or Email: [email protected].

SUPPLEMENTARY INFORMATION:  The Agency for Healthcare Research and 
Quality has commissioned the Evidence-based Practice Centers (EPC) 
Program to complete a review of the evidence for Diagnostic and 
Treatment of Clinical Alzheimer's-type Dementia (CATD). AHRQ is 
conducting this systematic review pursuant to Section 902(a) of the 
Public Health Service Act, 42 U.S.C. 299a(a).
    The EPC Program is dedicated to identifying as many studies as 
possible that are relevant to the questions for each of its reviews. In 
order to do so, we are supplementing the usual manual and electronic 
database searches of the literature by requesting information from the 
public (e.g., details of studies conducted). We are looking for studies 
that report on Diagnostic and Treatment of Clinical Alzheimer's-type 
Dementia (CATD), including those that describe adverse events. The 
entire research protocol, including the key questions, is also 
available online at: https://effectivehealthcare.ahrq.gov/topics/alzheimers-type-dementia/protocol.
    This is to notify the public that the EPC Program would find the 
following information on Diagnostic and Treatment of Clinical 
Alzheimer's-type Dementia (CATD) helpful:

    [ssquf] A list of completed studies that your organization has 
sponsored for this indication. In the list, please indicate whether 
results are available on ClinicalTrials.gov along with the 
ClinicalTrials.gov trial number.
    [ssquf] For completed studies that do not have results on 
ClinicalTrials.gov, please provide a summary, including the 
following elements: study number, study period, design, methodology, 
indication and diagnosis, proper use instructions, inclusion and 
exclusion criteria, primary and secondary outcomes, baseline 
characteristics, number of patients screened/eligible/enrolled/lost 
to follow-up/withdrawn/analyzed, effectiveness/efficacy, and safety 
results.
    [ssquf] A list of ongoing studies that your organization has 
sponsored for this indication. In the list, please provide the 
ClinicalTrials.gov trial number or, if the trial is not registered, 
the protocol for the study including a study number, the study 
period, design, methodology, indication and diagnosis, proper use 
instructions, inclusion and exclusion criteria, and primary and 
secondary outcomes.
    [ssquf] Description of whether the above studies constitute ALL 
Phase II and above clinical trials sponsored by your organization 
for this indication and an index outlining the relevant information 
in each submitted file.
    Your contribution will be very beneficial to the EPC Program. 
Materials submitted must be publicly available or able to be made 
public. Materials that are considered confidential; marketing 
materials; study types not included in the review; or information on 
indications not included in the review cannot be used by the EPC 
Program. This is a voluntary request for information, and all costs for 
complying with this request must be borne by the submitter.
    The draft of this review will be posted on AHRQ's EPC Program 
website and available for public comment for a period of 4 weeks. If 
you would like to be notified when the draft is posted, please sign up 
for the email list at: https://www.effectivehealthcare.ahrq.gov/email-updates.
    The systematic review will answer the following questions. This 
information is provided as background. AHRQ is not requesting that the 
public provide answers to these questions.

The Key Questions

    KQ 1: In adults with CATD, what are the efficacy and harms of 
prescription pharmacological interventions versus placebo/inactive 
control for treatment of cognition, function, and quality of life?
    KQ 1a: In adults with CATD, does the efficacy of prescription 
pharmacological interventions versus placebo/inactive control vary 
as a function of patient characteristics (i.e., age, sex, race/
ethnicity, depression, pre-treatment cognitive or functional level/
CATD stage, living setting)?
    KQ 2: In adults with CATD, what are the efficacy and harms of 
nonprescription pharmacological interventions versus placebo/
inactive control for treatment of cognition, function, and quality 
of life?
    KQ 2a: In adults with CATD, does the efficacy of nonprescription 
pharmacological interventions versus placebo/inactive control vary 
as a function of patient characteristics (i.e., age, sex, race/
ethnicity, depression, pre-treatment cognitive or functional level/
CATD stage, living setting)?
    KQ 3: In adults with CATD, what are the comparative 
effectiveness and harms of prescription pharmacological 
interventions versus other active interventions for treatment of 
cognition, function, and quality of life?
    KQ 3a: In adults with CATD, what are the comparative 
effectiveness and harms of prescription pharmacological 
interventions versus other prescription pharmacological 
interventions for treatment of cognition, function, and quality of 
life?
    KQ 3b: In adults with CATD, what are the comparative 
effectiveness and harms of prescription pharmacological 
interventions versus nonprescription pharmacological interventions 
for treatment of cognition, function, and quality of life?
    KQ 3c: In adults with CATD, what are the comparative 
effectiveness and harms of prescription pharmacological 
interventions versus nonpharmacological interventions for treatment 
of cognition, function, and quality of life?
    KQ 3d: In adults with CATD, does the comparative effectiveness 
of prescription pharmacological interventions versus other active 
interventions for treatment of cognition, function, and quality of 
life vary as a function of patient characteristics (i.e., age, sex, 
race/ethnicity, depression, pre-treatment cognitive or functional 
level/CATD stage, living setting)?
    KQ 4: In adults with CATD and behavioral and psychological 
symptoms of dementia (BPSD), what are the efficacy and harms of 
prescription pharmacological interventions versus placebo/inactive 
control for treatment of BPSD?
    KQ 4a: In adults with CATD and BPSD, what are the efficacy and 
harms of prescription pharmacological interventions versus placebo/
inactive control for reducing frequency and severity of future BPSD?
    KQ 4b: In adults with CATD and BPSD, does the efficacy of 
prescription pharmacological interventions versus placebo/inactive 
control for reducing frequency and severity of future BPSD vary as a 
function of patient characteristics (i.e., age, sex, race/ethnicity, 
depression, pre-treatment cognitive or functional level/CATD stage, 
pre-treatment BPSD severity, living setting)?
    KQ 4c: In adults with CATD and BPSD, what are the efficacy and 
harms of prescription pharmacological interventions versus placebo/
inactive control for acute treatment of BPSD?
    KQ 4d: In adults with CATD and BPSD, does the efficacy of 
prescription pharmacological interventions versus placebo/inactive 
control for acute treatment of BPSD vary as a function of patient 
characteristics (i.e., age, sex, race/ethnicity, depression, pre-
treatment cognitive or functional level/CATD stage, pre-treatment 
BPSD severity, living setting)?
    KQ 5: In adults with CATD and BPSD, what are the efficacy and 
harms of nonprescription pharmacological interventions versus 
placebo/inactive control for treatment of BPSD in adults with CATD 
and BPSD?
    KQ 5a: In adults with CATD and BPSD, what are the efficacy and 
harms of nonprescription pharmacological interventions versus 
placebo/inactive control for reducing frequency and severity of 
future BPSD?
    KQ 5b: In adults with CATD and BPSD, does the efficacy of 
nonprescription pharmacological interventions versus placebo/
inactive control for reducing frequency and severity of future BPSD 
vary as a function of patient characteristics (i.e., age, sex, race/
ethnicity, depression, pre-treatment cognitive or functional level/
CATD stage, pre-treatment BPSD severity, living setting)?
    KQ 5c: In adults with CATD and BPSD, what are the efficacy and 
harms of

[[Page 64839]]

nonprescription pharmacological interventions versus placebo/
inactive control for acute treatment of BPSD?
    KQ 5d: In adults with CATD and BPSD, does the efficacy of 
nonprescription pharmacological interventions versus placebo/
inactive control for acute treatment of BPSD vary as a function of 
patient characteristics (i.e., age, sex, race/ethnicity, depression, 
pre-treatment cognitive or functional level/CATD stage, pre-
treatment BPSD severity, living setting)?
    KQ 6: In adults with CATD and BPSD, what are the comparative 
effectiveness and harms of prescription pharmacological 
interventions versus other active interventions for treatment of 
BPSD?
    KQ 6a: In adults with CATD and BPSD, what are the comparative 
effectiveness and harms of prescription pharmacological 
interventions versus other prescription pharmacological 
interventions for reducing frequency and severity of future BPSD?
    KQ 6b: In adults with CATD and BPSD, what are the comparative 
effectiveness and harms of prescription pharmacological 
interventions versus nonprescription pharmacological interventions 
for reducing frequency and severity of future BPSD?
    KQ 6c: In adults with CATD and BPSD, what are the comparative 
effectiveness and harms of prescription pharmacological 
interventions versus nonpharmacological interventions for reducing 
frequency and severity of future BPSD?
    KQ 6d: In adults with CATD and BPSD, does the comparative 
effectiveness of prescription pharmacological interventions versus 
other active interventions for reducing frequency and severity of 
future BPSD vary as a function of patient characteristics (i.e., 
age, sex, race/ethnicity, depression, pre-treatment cognitive or 
functional level/CATD stage, pre-treatment BPSD severity, living 
setting)?
    KQ 6e: In adults with CATD and BPSD, what are the comparative 
effectiveness and harms of prescription pharmacological 
interventions versus other prescription pharmacological 
interventions for acute treatment of BPSD?
    KQ 6f: In adults with CATD and BPSD, what are the comparative 
effectiveness and harms of prescription pharmacological 
interventions versus nonprescription pharmacological interventions 
for acute treatment of BPSD?
    KQ 6g: In adults with CATD and BPSD, what are the comparative 
effectiveness and harms of prescription pharmacological 
interventions versus nonpharmacological interventions for acute 
treatment of BPSD?
    KQ 6h: In adults with CATD and BPSD, does the comparative 
effectiveness of prescription pharmacological interventions versus 
other active interventions for acute treatment of BPSD vary as a 
function of patient characteristics (i.e., age, sex, race/ethnicity, 
depression, pre-treatment cognitive or functional level/CATD stage, 
pre-treatment BPSD severity, living setting)?
    KQ 7: In adults with suspected CATD, what are the accuracy, 
comparative accuracy, and harms of different individual cognitive 
diagnostic tests and their combinations for making the diagnosis of 
CATD as defined by full clinical evaluation and/or 
neuropsychological testing with explicit diagnostic criteria?
    KQ 7a: Do the accuracy and comparative accuracy of cognitive 
tests for making the diagnosis of CATD as defined by full clinical 
evaluation and/or neuropsychological testing with explicit 
diagnostic criteria vary as a function of patient characteristics 
(i.e., age, sex, race/ethnicity, education, pre-testing cognitive or 
functional level CATD stage)?
    KQ 8: In adults with a clinical diagnosis of CATD, what are the 
accuracy, comparative accuracy, and harms of brain imaging, CSF, and 
blood tests for diagnosing pathologically confirmed Alzheimer's 
disease as the underlying etiology?
    KQ 8a: Do the accuracy and comparative accuracy of brain 
imaging, CSF, and blood tests for pathologically confirmed 
Alzheimer's disease as the underlying etiology of CATD vary as a 
function of patient characteristics (i.e., age, sex, race/ethnicity, 
depression, education, pre-testing cognitive or functional level 
CATD stage)?

[[Page 64840]]



                                                                     Table 1--PICOTS
                                   [Populations, interventions, comparators, outcomes, timing, settings/study design]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                       Treatment
                                                                     comparator or
              KQ                  Population       Intervention       diagnostic      Health outcomes       Timing          Setting        Study design
                                                                       reference          & harms
                                                                       standard
--------------------------------------------------------------------------------------------------------------------------------------------------------
KQ 1-3: Drug treatment         Adults with CATD  Prescription      For efficacy      Efficacy and      >=24 weeks.....  Cognitive        Efficacy and
 efficacy, comparative          >=50 years of     pharmacologic     comparisons:      comparative                        outcomes:        comparative
 effectiveness & harms on       age.              (drug)            Placebo, Other    effectiveness:                     Community-       effectiveness:
 cognition, function &         Patient            treatment:        inactive          Change in                          dwelling,        RCT, CCT,
 quality of life.               characteristics   Cholinesterase    control.          patient                            Assisted         systematic
                                to be assessed    inhibitors,      For comparative    cognition                          living.          review of RCTs
                                as possible       NMDA              effectiveness     (global screen,                   Functional &      or CCTs.
                                treatment         antagonists.      comparisons:      multidomain,                       QOL outcomes:   Harms: RCT,
                                effect           Nonprescription    Prescription      memory,                            Community-       CCT,
                                modifiers: Age,   pharmacologic     drug treatment,   executive                          dwelling,        controlled
                                Sex, Race/        (drug)            Nonprescription   function,                          Assisted         prospective
                                ethnicity,        treatment: OTC    drug treatment,   language,                          living,          cohort studies
                                Depression, Pre-  supplements,      Nondrug           attention),                        Nursing home.    with >=1,000
                                treatment         Vitamins,         treatment.        function, or                                        participants,
                                cognitive or      Herbals.                            QOL on                                              systematic
                                functional                                            validated test.                                     review of any
                                level/CATD                                           Change in                                            of these study
                                stage, Living                                         disease stage                                       designs.
                                setting.                                              based on
                                                                                      validated test.
                                                                                     Change in
                                                                                      patient ``at
                                                                                      home'' IADL or
                                                                                      ADL function.
                                                                                     Change in
                                                                                      patient
                                                                                      residence to
                                                                                      different level
                                                                                      of independence.
                                                                                     Harms:
                                                                                     General: FDA
                                                                                      defined SAEs,
                                                                                      Withdrawals due
                                                                                      to AEs.
                                                                                     Psychiatric:
                                                                                      Somnolence,
                                                                                      Confusion/
                                                                                      Delirium.
                                                                                     Nonpsychiatric:
                                                                                      Falls,
                                                                                      Extrapyramidal
                                                                                      symptoms,
                                                                                      Stroke.
                                                                                     Mortality (all-
                                                                                      cause, CVD, non-
                                                                                      CVD).
KQ 4-6: Drug treatment         Adults with CATD  Prescription      Efficacy          Efficacy and      Agitation,       Community-       Efficacy and
 efficacy, comparative          >=50 years of     pharmacologic     comparisons:      comparative       aggression,      dwelling,        comparative
 effectiveness & harms on       age with BPSD     treatment:        Placebo, Other    effectiveness:    psychosis or     Assisted         effectiveness:
 BPSD.                          (studies          Cholinesterase    inactive         Primary: Change    Disinhibited     living,          RCT, CCT,
                                specified BPSD    inhibitors,       control.          in the            sexual           Nursing home.    systematic
                                inclusion         NMDA             Comparative        frequency and/    behavior                          review of RCTs
                                criterion).       antagonists,      effectiveness     or severity of    outcomes: >=2                     or CCTs.
                               Patient            Antipsychotics,   comparisons:      patient BPSD*     weeks.                           Harms: RCT,
                                characteristics   second            Prescription      on validated     Depression or                      CCT,
                                to be assessed    generation        drug treatment,   tests,            anxiety                           controlled
                                as possible       (any) and first   Nonprescription   Agitation/        outcomes: >=24                    prospective
                                treatment         generation        drug treatment,   aggression,       weeks.                            cohort studies
                                effect            (only             Nondrug           Psychosis,                                          >=1,000
                                modifiers: Age,   haloperidol),     treatment.        Depression,                                         participants,
                                Sex, Race/        Antidepressants                     Anxiety,                                            systematic
                                ethnicity, Pre-   , Anti-seizure/                     Disinhibited                                        review of any
                                treatment         mood                                sexual                                              of these study
                                cognitive or      stabilizers,                        behavior,                                           designs.
                                functional        Anxiolytics,                        Change in
                                level/CATD        benzodiazepine,                     patient QoL on
                                stage, Pre-       Anxiolytics,                        validated test,
                                treatment BPSD    other Hormonal                      Change in
                                severity,         agents                              validated
                                Living setting.   (Disinhibited                       general
                                                  sexual behavior                     behavior scale.
                                                  only),                             Secondary:
                                                  Cannabinoids,                       Change in
                                                  Combinations.                       caregiver/staff
                                                 Nonprescription                      outcomes on
                                                  pharmacologic                       validated
                                                  treatment: OTC                      tests,
                                                  supplements,                        Depression,
                                                  Vitamins,                           Global stress/
                                                  Herbals.                            distress, QOL,
                                                                                      Burden.
                                                                                     Harms:..........
                                                                                     General: FDA
                                                                                      defined
                                                                                      composite SAE
                                                                                      outcome,
                                                                                      Withdrawals due
                                                                                      to AE.
                                                                                     Psychiatric:
                                                                                      Somnolence,
                                                                                      Confusion/
                                                                                      Delirium.
                                                                                     Nonpsychiatric:
                                                                                      Falls,
                                                                                      Extrapyramidal
                                                                                      symptoms,
                                                                                      Stroke,
                                                                                      Mortality (all-
                                                                                      cause, CVD, non-
                                                                                      CVD).

[[Page 64841]]

 
KQ 7-8: Diagnostic test        Cognitive tests:  Brief, validated  Cognitive tests:  Accuracy and      Any............  Community-       Accuracy and
 accuracy & harms (also see     Adults >=50       cognitive         Full clinical     comparative                        dwelling,        comparative
 Table 2 below).                years of age      tests: Global     evaluation and/   accuracy (e.g.,                    Assisted         accuracy:
                                with suspected    (brief screens,   or                TP, FP, TN, FN,                    living.          Controlled
                                CATD.             multi-domain      neuropsychologi   sensitivity,                                        observational
                               Biomarker tests    batteries),       cal testing       specificity,                                        studies (i.e.,
                                only: Adults      Single domain     with explicit     PPV, NPV).                                          cross-
                                >=50 years of     tests (memory,    diagnostic       Of cognitive                                         sectional,
                                age with          executive,        criteria.         tests for                                           retrospective
                                clinical          language,        Biomarker tests:   confirming                                          cohort, case
                                syndrome of       attention.        Postmortem        clinical                                            control);
                                CATD.            Biomarker tests:   neuropathologic   syndrome of                                         systematic
                               Patient           Brain imaging:     al confirmation   CATD.                                               review of
                                characteristics   CT/MRI: Medial    of AD.           Of biomarker                                         controlled
                                to be assessed    temporal                            tests for                                           observational
                                as possible       atrophy/                            confirming that                                     studies.
                                effect            hippocampal                         etiology of                                        Harms:
                                modifiers of      volume,                             CATD is AD.                                        Controlled
                                diagnostic test   Cortical                           Harms:..........                                     observational
                                accuracy: Age,    thickness, DTI                     Psychological or                                     studies (i.e.,
                                Sex, Race/        indices.                            behavioral.                                         cross-
                                ethnicity,       PET: \18\F-FDG                      True positive:                                       sectional,
                                Education,        PET, Amyloid                        Labeling stigma.                                    retrospective
                                Depression.       PET, \11\C-PiB                     False positive:                                      cohort, case
                               Pre-test           and fluorinated                     Incorrect                                           control,
                                cognitive or      tracers (e.g.                       diagnosis,                                          prospective
                                functional        florbetapir,                        Labeling                                            cohort);
                                level/CATD        flutemetamol,                       stigma, Side                                        systematic
                                stage.            florbetaben),                       effects of                                          review of
                                                  Tau PET.                            unneeded                                            controlled
                                                 fMRI: Resting                        interventions                                       observational
                                                  state and task                      (e.g.,                                              studies.
                                                  specific                            restrictions on
                                                  activation.                         independence).
                                                 SPECT: Resting                      False negative:
                                                  state cerebral                      Unexplained
                                                  perfusion.                          symptoms,
                                                 CSF tests:                           Failure to make
                                                  A[beta]42,                          appropriate
                                                  A[beta]42/                          interventions
                                                  A[beta]40                           (e.g., safety
                                                  ratio, t-tau, p-                    precautions,
                                                  tau, t-tau/                         future
                                                  A[beta]42                           planning).
                                                  ratio, p-tau/                      Any test result:
                                                  A[beta]42                           Patient or
                                                  ratio,                              caregiver
                                                  neurofilament                       mental distress.
                                                  light protein.                     Physical:
                                                 Blood tests:                         Directly from
                                                  A[beta]42,                          diagnostic
                                                  A[beta]42/                          tests: Pain,
                                                  A[beta]40                           Infection,
                                                  ratio, APP.                         Headache,
                                                 Combinations....                     Radiation.
--------------------------------------------------------------------------------------------------------------------------------------------------------
* For this report, two psychological symptoms that are components of BPSD have been excluded due to their coverage in recent, high quality systematic
  reviews--apathy and sleep disturbances.18 19 In addition, wandering was also eliminated, as this symptom is usually treated with nonpharmacologic
  interventions, which are not covered as interventions in this review.
[dagger] Strength of evidence (SOE) will be evaluated for the 1-2 most commonly reported validated treatment efficacy outcomes for each of the following
  test categories: disease stage, global cognitive screening tests, global multidomain cognitive tests, memory, executive functioning, language,
  attention, function, quality of life, BPSD agitation/aggression, and the harms outcome of serious adverse events. Additional treatment outcomes will
  be considered for SOE grading when available data allow. For diagnostic tests, SOE will be graded for the 1-2 most commonly reported validated tests
  for each of the following categories: global cognitive screening tests, global multidomain cognitive tests, memory, MRI, PET, and CSF tests.
  Additional diagnostic testing outcomes will be considered for SOE grading when available data allow.
A[szlig] = beta amyloid, AD = Alzheimer's dementia, ADL = activities of daily living, AE = adverse events, APOE = apolipoprotein E, APP = amyloid
  precursor protein, BPSD = behavioral and psychological symptoms of dementia, CATD = clinical Alzheimer's-type dementia, CCT = controlled clinical
  trial, CSF = cerebrospinal fluid, CT = computed tomography, CVD = cardiovascular disease, DTI = diffusion tensor imaging, FDG = fluorodeoxyglucose,
  fMRI = functional magnetic resonance imaging, FN = false negative, FP = false positive, IADL = instrumental activities of daily living, MCI = mild
  cognitive impairment, MRI = magnetic resonance imaging, NMDA = N-methyl-D-aspartate, NPV = negative predictive value, OTC = over-the-counter, PET =
  positron emission tomography, PPV = positive predictive value, p-tau = abnormally phosphorylated tau, QOL = quality of life, RCT = randomized clinical
  trial, ROC = receiver operating characteristic, SAE = serious adverse events, SPECT = single-photon emission computed tomography, TN = true negative,
  TP = true positive, t-tau = total tau.


[[Page 64842]]


    Table 2--Prescription Drugs Used for Treatment of CATD Cognition,
                    Function, Quality of Life or BPSD
------------------------------------------------------------------------
             Class of drug                         Drug name(s)
------------------------------------------------------------------------
Cholinesterase inhibitor...............  Donepezil *, rivastigmine *,
                                          galantamine *.
NMDA receptor antagonist...............  Memantine *.
Cholinesterase inhibitor/NMDA receptor   Donepezil/Memantine *.
 antagonist combination.
1st generation (typical) antipsychotic.  only Haloperidol.
2nd generation (atypical) antipsychotic  e.g., Risperidone, quetiapine,
                                          olanzapine, aripiprazole,
                                          clozapine.
Anti-depressant, selective serotonin-    e.g., Citalopram, escitalopram,
 reuptake inhibitor (SSRI).               sertraline, fluoxetine,
                                          fluvoxamine, paroxetine.
Anti-depressant, serotonin-              e.g., Duloxetine, venlafaxine.
 norepinephrine reuptake inhibitor
 (SNRI).
Anti-depressant, other [dagger]........  e.g., Trazodone, bupropion,
                                          mirtazapine.
Anti-seizure/mood stabilizer...........  e.g., Valproate, gabapentin,
                                          carbamazepine, lamotrigine.
Anti-anxiety, benzodiazepine...........  e.g., Clonazepam, diazepam,
                                          lorazepam, temazepam,
                                          alprazolam.
Anti-anxiety, other....................  Buspirone.
Mixed..................................  Dextromethorpan/Quinidine.
Hormones (antiandrogens, estrogens,      e.g., medroxyprogesterone
 gonadotropin-releasing hormone           acetate, cyproterone acetate,
 analogues).                              leuprolide.
Cannabinoids...........................  e.g., medical marijuana.
------------------------------------------------------------------------
* US FDA approved indication for Alzheimer's dementia.
[dagger] Excludes MAO-inhibitor, tricyclic and tetracyclic
  antidepressants.
BPSD = behavioral and psychological symptoms of dementia, CATD =
  clinical Alzheimer's-type dementia, NMDA = N-methyl-D-aspartate, SSRI
  = selective serotonin reuptake inhibitor, SNRI = selective
  norepinephrine reuptake inhibitor.

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Francis D. Chesley, Jr.,
Acting Deputy Director.
[FR Doc. 2018-27361 Filed 12-17-18; 8:45 am]
 BILLING CODE 4160-90-P