Psychotropic Medications

1
Psychotropic Medications

• Broad term encompassing any medication used to
  influence mood, mental status or behavior
• CMS guidelines break them into four categories
• Anti-psychotics
• Anti-anxiety agents
• Hypnotics
• Antidepressants
• Additional important categories
• Cognitive enhancers
• Mood stabilizers

2
QI Domains And Psychoactive Medications
Skin Care
Accidents
Quality of Life
Behavioral/Emotional Problems
QI Domains
Psychotropic Drug Use
Clinical Management
Physical/ Functioning
Cognitive Patterns
Elimination/ Incontinence
Nutrition/Eating
Infection Control
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Paradigm for Comprehensive Assessment

• Dementia
• Frontal lobe impairment
• Delirium
• Medical illness
• Psychotic disorder
• Affective disorder
• Anxiety disorder
• Personality disorder
• Environment/stressors

Cognitive enhancers
Mood Stabilizers
Antipsychotics
Antidepressants
Anxiolytics
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Acetylcholinesterase Inhibitors (AChI)

• Aricept (donepezil)
• Start 5 mg qhs x 4 6 wks, then Increase to 10
  mg qhs
• Exelon (rivastigmine)
• Start 1.5 mg bid w/ meals x 2 - 4 wks
• Target dose 6 mg bid, titrate 1.5 mg q 2 - 4
  weeks
• Reminyl (galantamine)
• Start 4 mg bid
• Target dose is 24 mg qd
• Titrate by 4 mg bid increase q 4 weeks

Treatment goal is to titrate to the highest dose
tolerated
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ACHI Treatment Effects

• Initial improvement may be seen _at_ 2 - 4 weeks
• At 26 wks Approximately 20 of mild/mod pts will
  have significant cognitive improvement
• Approximately 80 will remain above baseline for
  function for 6-10 months
• Cost vs benefit analysis ongoing
• Watch for significant sudden decline when stopped
• Initial data indicates delay in NH placement gt20
  months in those with 4 years of donepezil use

6
Memantine

• Marketed in Germany since 1982 for Organic Brain
  Syndrome and spasticity
• Approved as Namenda in October 2003 for moderate
  to severe Alzheimers Disease
• No significant food interaction, i.e., can be
  administered without regard to meals
• Interactions with highly protein-bound drugs
  unlikely
• No interactions with acetylcholinesterase
  inhibitors

Slide courtesy of Schneider L. Geriatrics.
2003(Aug)Suppl
7
Memantine Study Results

• Memantine treatment was associated with less
  decline vs. placebo on
• Global, CIBIC-plus
• Cognition, Severe Impairment Battery
• Function, ADCS-ADL outcome measures
• Patients switched from placebo to Memantine
  showed significant improvement relative to
  projected decline
• Memantine treatment resulted in reductions in
  caregiver time, institutionalisation rate and
  total costs compared to the placebo group
• Memantine was well-tolerated with dropout rates
  and side effects rates similar or lower than
  placebo

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Paradigm for Comprehensive Assessment

• Dementia
• Frontal lobe impairment
• Delirium
• Medical illness
• Psychotic disorder
• Affective disorder
• Anxiety disorder
• Personality disorder
• Environment/stressors

Cognitive enhancers
Mood Stabilizers
Antipsychotics
Antidepressants
Anxiolytics
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Frontal Lobe Impairment Pharmacologic Management

• Antipsychotics
• Conventionals
• Atypicals
• Risperidone
• Olanzapine
• Quetiapine
• Ziprasidone
• Aripiprazole

• Mood stabilizers
• Carbamazepine
• Divalproex sodium
• Lithium
• Topiramate
• Gabepentin
• Benzodiazepines

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Mood Stabilizers

• These pathways transmit gamma-aminobutyric acid
  (GABA).
• Lower levels of GABA associated with aggressive
  animal behavior.
• NH study of 56 agitated elderly patients given
  Carbamazepine had significant improvement in
  agitation and decreased staff time needed.
• Newer anticonvulsants advantageous due to
  improved side effect profile but have few good
  clinical studies

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Mood Stabilizers
carbamazepine (Tegretol) divalproex sodium
(Depakote)gabapentin (Neurontin)lithium (Lith
ium)topiramate (Topimax)
12
Mood Stabilizers

• Their role is uncertain at present
• No need to monitor serum/blood levels for
  Lamictal or Topimax
• Behavior effects can be seen at low serum levels
• The role of multiple mood stabilizers
  concurrently remains uncertain
• Documentation on the working diagnosis and
  monitoring of benefits and side effects remains
  important

13
Divalproex Study in Dementia

• Randomized, double-blind, placebo-controlled
  trial1
• N172 NH residents met criteria for secondary
  mania
• Target dose 20 mg/kg/day in 10 days
• N100 completers
• Statistically significant improvement on CMAI
  score
• Consistent with antiagitation, not antimanic
  effects
• Study suspended due to side effects (sedation)
• Follow-up indicated with lower doses/slower
  titration

1. Tariot et al, 2000
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Divalproex in Elderly Mania / Dementia
Cohen-Mansfield Agitation Inventory (Total Scores)

Mean Change from Baseline




(SE2.72)
(SE2.65)
0
7
14
21
28
35
42
Days
plt0.05 for group differences
Tariot et al, 2001
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Valproate Summary

• Clinical effects similar to Carbamazepine
• risk of drug interaction
• SE profile
• More definitive controlled trial underway
• Current clinically recommendations
• Initial dose 125-250 mg bid with 125-250 q 5d
• Usual range 500 - 1,250 mg/d
• Usual level 40-90 µg/ml
• Clinical response more important than serum level

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Paradigm for Comprehensive Assessment

• Dementia
• Frontal lobe impairment
• Delirium
• Medical illness
• Psychotic disorder
• Affective disorder
• Anxiety disorder
• Personality disorder
• Environment/stressors

Cognitive enhancers
Mood Stabilizers
Antipsychotics
Antidepressants
Anxiolytics
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OBRA Guidelines Antipsychotics

• Use only if patients exhibit symptoms that impair
  functioning or cause danger to themselves or
  others, and/or interfere with provision of care
• Agitated behavior is an insufficient reason to
  use an antipsychotic medication (i.e. must be
  psychotic or aggressive)
• Considered unnecessary if initiated as treatment
  in the absence of documentation of the approved
  indications
• Use requires approved diagnosis and symptoms

Stoudemire A. Gen Hosp Psych. 19961877-94 The
Long Term Care Survey.ACHA
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Accepted Diagnosis for Antipsychotic Use in LTC

• Schizophrenia
• Schizo-affective Disorder
• Delusional Disorder
• Psychotic Mood Disorder
• Acute Psychotic Episodes
• Brief Reactive Psychosis
• Schizophreniform Disorder
• Atypical Psychosis
• Tourettes Disorder
• Huntingtons Disease
• 11. Organic Mental Syndromes IF certain criteria
  are met

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Treatment with Antipsychotics Requires

• Quantitative and Objective Documentation that
• The behavior requires intervention
• You determined if the behavior is permanent or
  transitory
• The behavior has been evaluated for possible
  social or situational causes
• Environmental causes have been ruled out
• Medical causes have been ruled out
• The symptoms are persistant
• Not caused by preventable reasons

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Treatment with Antipsychotics Requires

• Organic Mental Syndromes with associated
  psychotic and/or agitated behaviors defined by
• Specific Behaviors (biting, kicking, extreme
  fear, etc) that have been quantified AND present
  a danger to themselves or others (including
  staff)
• Continuous crying out, screaming or pacing if
  quantified and cause a functional impairment or
  actually interfere with the staffs ability to
  provide care
• Psychotic symptoms (AH, VH, PI, delusions) that
  are not dangerous but cause distress or an
  impairment in functional capacity

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Antipsychotics Should NOT be used if

• the following symptoms are the ONLY criteria
• Wandering
• Poor self-care
• Anxiety/Restlessness
• Impaired memory
• Uncomplicated Depression
• Unsociability
• Fidgeting
• Nervousness
• Uncooperativeness
• Agitation without any danger to resident or others

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Antipsychotic Medication Guidelines

• F-tag 330 Use only as necessary to treat a
  specific condition as diagnosed documented in
  the clinical record
• F-tag 331 Gradual dose reductions behavioral
  interventions, unless clinically contraindicated,
  are required in an effort to discontinue these
  drugs
• Currently, only IM Zyprexa is approved by the FDA
  for the treatment of acute agitation in dementia
• Usually reserved for dangerous or very distressed
  psychotic symptoms such as aggression, delusions
  or hallucinations

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Antipsychotic Medication Guidelines

• The cause of the psychosis indicates the
  treatment duration
• For psychosis as a symptom of dementia,
  stabilizing behavior may take as long as 12 weeks
  and may require treatment for at least several
  months and up to a year
• For Schizophrenia, antipsychotic treatment is
  lifelong although the dose may decrease with age
• For Bipolar illness, antipsychotics are used
  during acute mania or long term to prevent
  relapse
• For psychotic depression, antipsychotics are
  typically needed for a few months in addition to
  a longer term antidepressant
• For delirium, antipsychotics are needed for a few
  days to a few weeks (even after medical problem
  is cleared)

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Antipsychotics

• Typicals
• Haldol (haloperidol )
• Thorazine (chlorpromazine)
• Many others
• Atypicals
• Clozaril (clozapine)
• Risperdal (risperidone)
• Zyprexa/Zydis (olanzapine)
• Seroquel (quetiapine)
• Geodon (ziprasidone)
• Abilify (aripiprazole)

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Atypical Antipsychotics and Increased Stroke Risk

• Data from four International studies revealed
  increased incidence of CVA TIA in Risperidone
  treated pts 1
• In 2003, the FDA changed the Risperdal label
  warning that the use of Risperidone dementia
  patients has an increased risk of stroke
• Currently a similar label is pending for Zyprexa
• Perhaps increased stroke risk is a class effect
• Stroke risk should be included in the
  risk/benefit assessment

1. Web site address http//www.hc-sc.gc.ca/hpb-dg
ps/therapeut/zfiles/english/advisory/industry/risp
erdal
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Antipsychotics Summary

• Atypicals are effective in the management of
  psychosis in the elderly
• In elders, atypicals offer improved safety and
  tolerability compared with conventional agents
• Differences in tolerability/side effect profiles
  between atypicals impact treatment selection
• It is critical to evaluate for Parkinsons
  symptoms before choosing the atypical to avoid
  worsening motor symptoms.

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Paradigm for Comprehensive Assessment

• Dementia
• Frontal lobe impairment
• Delirium
• Medical illness
• Psychotic disorder
• Affective disorder
• Anxiety disorder
• Personality disorder
• Environment/stressors

Cognitive enhancers
Mood Stabilizers
Antipsychotics
Antidepressants
Anxiolytics
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Treatment of Major Depression

• There is no good reason for depression to ever
  go untreated
• Start low, go slow, but go!
• Strive for maximum recovery/function
• Compare GDS or Cornell
• Treat the sleep disturbance initially then change
  to a prn after 2-3 wks
• The dose that gets them well, keeps them well
• Continue for 6-12 months or perhaps even
  lifelong?

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Common Antidepressants

• SSRIs
• Fluoxetine (Prozac)
• Paroxetine (Paxil)
• Sertraline (Zoloft)
• Citalopram (Celexa)
• Escitalopram (Lexipro)
• SNRIs
• Bupropion (Wellbutrin)
• Mirtazapine (Remeron)
• Venlafaxine (Effexor)
• Trazodone (Desyrel)
• too sedating to treat depression

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Depression Therapy

• TCAs vs. SSRIs vs. SNRIs
• Select the drug based on target symptoms and the
  side effects wanted, for example
• Dep. anorexia mirtazapine
• Dep. lethargy activating antidepressant
• Dep. constipation sertraline
• Dep. psychosis - cymbiax

Insomnia can be effectively treated with the
addition of Trazodone, Ambien, or Sonata
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Paradigm for Comprehensive Assessment

• Dementia
• Frontal lobe impairment
• Delirium
• Medical illness
• Psychotic disorder
• Affective disorder
• Anxiety disorder
• Personality disorder
• Environment/stressors

Cognitive enhancers
Mood Stabilizers
Antipsychotics
Antidepressants
Anxiolytics
34
Anxiolytic Therapy Guidelines

• F-tag 329 Guidance to Surveyors
• Short-acting maximum doses indicated
• Behavioral monitoring charts needed
• Does not indicate how to monitor
• Gradual dose reduction al least twice within one
  year before can conclude dose reduction is
  clinically contraindicated per regulations

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Anxiolytic Therapy Guidelines

• Indications for use
• - other reasons for the distress have been
  considered eliminated
• - use results in maintenance/improvement of
  residents functional status
• - reduction must be attempted by 4 months
• - specific diagnoses (anxiety disorder, organic
  mental syndromes, panic disorder, anxiety in
  concert with another psychiatric disorders)

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lorazepam (Ativan) 0.25 2.0 mg /d
alprazolam (Xanax) 0.25 1.5 mg / d oxazepam
(Serax) 7.5 30 mg / d buspirone (BuSpar) 10
45 mg / d temazepam (Serax)klonzepam (Klonopi
n) 0.25 -3.0 mg / d
Anxiolytic
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Benzodiazepines

• Minimal efficacy data
• Sedating
• Further inhibit learning and memory
• Ataxic gait is episodic - difficult to assess
• Associated with falls
• Paradoxical disinhibition possible
• Avoid long acting benzodiazepines in the elderly

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Anxiety Disorder Treatment

• Short-acting benzodiazepines
• sedating, inhibit learning, increases fall risk
• Trazodone
• check orthostatic BP and Pulse
• Buspirone?
• If paranoid or psychotic component, consider
  Atypicals
• Consider antidepressants, may need empiric trial

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Insomnia - Hypnotics

• F-tag 329 Unnecessary drugs GTS
• Address sleep hygiene issues
• Daily dose 10 or more continuous days requires
  documentation of necessity for maintenance or
  improvement of functional status.
• Maximum hypnotic dosages
• Dose reduction attempts at least 3 times within 6
  mo. before declaring further reductions are
  contraindicated.

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Insomnia Hypnotics - 2

• Trazodone 25-200 mg _at_hs
• Mirtazepine (Remeron) 7.5-45 mg _at_hs
• Short-acting benzodiazepine
• Zolpidem (Ambien) 5-10 mg _at_hs
• Zalepion (Sonata) 5-10 mg _at_hs
• Melatonin 3 mg _at_ 6 pm

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Remember, Psychotherapy Can Also Help Some
Residents
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Summary

• Distressed behaviors are only symptoms
• Unless urgent, a complete assessment to
  determine/develop a working diagnoses should
  guide the long term treatment approach.
• Consider nonpharmacologic management in every
  case.
• Monitor treatment benefits MMSE, GDS, FAST,
  Cornell dementia in depression scale, Behave AD,
  Cohen Mansfield Agitation Inventory
• Optimal care requires teamwork, education, and
  respect.