Antipsychotics in Dementia—What’s a Doc to Do?

Janis B. Petzel, M.D.Geriatric Psychiatry,

Private Practice, Hallowell, ME and Togus VA

Psychosis in Dementia

• From outpatient dementia clinic data:

– Delusions in 1/3– Hallucination in 1/14

– Paranoid delusions increased across the stages of the illness

Mizrahi et al Am J Geriatr Psychiatry July, 2006 14(7):573-81

Hallucinations

Peak average onset is later than for delusions

Patients who have hallucinations usually also have delusions (but not visa versa)

Risk for aggression high with either AH or VH, but very high with both

Risk for mortality

Even in France….

¾ of patients had verbal aggressiveness Roughly half (48%) were physically

aggressive 61% of episodes had a “triggering event”

Psychosomatic stress Death of spouse, family, asked to do something

person didn’t want to do eg. toilet “organic”

Med side effects, illness, recent surgery

Leger et al International Psychogeriatrics 14(4) 2002

Overview of Psychosis and BPSD

Symptoms Delusions Hallucinations Aggression

Verbal Physical

Combativeness Sleep Disorder Anxiety Depression

Triggers• Individual

o Premorbid personalityo ? Alcohol historyo ? TBI history

Social Over stimulation Unwanted cares Unpleasant experiences

Undiagnosed Medical Condition

Pain Environment Poor Sleep Delirium

BPSD Symptom Clusters

PhysicalVerbal

Resistance to Care

PacingRepetitive Actions

UndressingAnxiety/Restless

Euphoria Pressured Speech

Irritability

HallucinationsDelusions

MisidentificationSuspiciousness

SadTearful

Wish to DieIrritableAnxious

ScreamingGuilty

WithdrawnLack of Interest

Amotivation

Aggression Agitation

Psychosis

ManiaDepression

Apathy

McShane et al Int Psychogeriatr 2001

Aggression correlates with neuropsychiatric disorders (and consitpation)

Adjusted Odds RatioPhysical Aggression Verbal Aggression

Depressive 3.3 4.9Symptoms

Delusions 2.0 2.5

Hallucinations 1.4 1.8

Constipation 1.3 1.1 (but not significant)

Arch Int Med 166:1295-1300

So, do atypical antipsychotics work?

• Mixed data, high placebo response rates– Better effects in NH population – ST impact > chronic use

• Most data for olanzapine and risperdal– CATIE-AD– LASER-AD

Other Studies—Very Limited

• Case studies for ziprazidone 20 mg i.m.

• Small studies with aripiprazole 2/3 (-)

• Haldol– Response rate 60%, placebo 26%– Significant risk for EPS, PD, TD– Other studies also show increased risk of

mortality with older meds

Lanctot et al J Clin Psychiatry, 1999Metaanalysis 17 RCTs, 500 dementia patients on haldol, 235 placebo

Risk of Antipsychotics

FDA Meta-analyses show a roughly 1%

increase in rates of stroke or death in patients with dementia over baseline

Increasing regulatory push to stop use of these meds

Other helpful meds?

Cholinesterase Inhibitors Modest efficacy on behavior Removal--worsening behaviors Most data on donepezil and

galantamine Effect shows up in metaanalysis

Other Meds?

Memantine 3 studies “post-hoc” analysis Seems to delay emergence of agitation,

aggression Seems to reduce caregiver burden

Antidepressants for BPSD

Tricyclics—worsen cognition

Citalopram—improved agitation, aggression, psychosis

Trazodone—limited data, mixed results

Mood Stabilizers in NH Patients

Valproate—5 RCTs No evidence it helps Many adverse events

Carbemazepine—4 RCTs Good evidence it helps Difficult to use

Limited data for gabapentin, lamotrigine, topiramate

Other Meds

Benzodiapepines Beta Blockers

More “Out there” Ideas

Nicotine patches—case studies Marijuana

Speculation only, or computer modeling or receptors.

No studies

Non-Pharmacologic Considerations

Teaching Person-centered Care and Behavioral techniques to caregivers reduced need for neuroleptic use in NH residents

Withdrawal of neuroleptics did not cause an acute worsening of behavioral symptoms of dementia Fossey et al BMJ 2006

“There was no significant association between psychotropic use, use of services, costs of care and improvements in NPS”

LASER-AD AJGP 2005 Training staff/caregivers shows same reduction in

symptoms as treating with antipsychotics Teri et al Neurology 2000

Sleep

• Changes over lifespan

• Time in bed for NH patients

• In NH, almost no exposure to natural or bright light

Ideas from Temple Grandin

freedom from hunger and thirst

freedom from discomfort

freedom from pain, injury, or disease

freedom to express normal behavior

freedom from fear and distress

“Core” or “Blue Ribbon” Emotions

Seeking Rage Fear Panic

Lust Care Play

Behaviors not amenable to medication

Wandering Inappropriate

urination/ defecation

Undressing Annoying activities

(pulling on doors, etc)

Frequent repetition

Hoarding Pushing other

patients Eating inedibles Isolating Tugging at/

removal of restraints

Lack of ability to interpret non-verbal emotional cues

Shirokawa Brain Cogn 2001 Behavior may be tied to a decreased

ability to discern or interpret emotional states in others

Kohler AJGP 2005 AD patients misidentified fear as anger

and neutral as sadness Caregivers had difficulty identifying

anger of mild intensity

Approaches to BPSD Prevention/Psychosocial

• Staff/Caregiver education• Environmental interventions Prevent boredom Prevent over stimulation Pay attention to noise, light, sleep

“Cognitive enhancers” (ChEIs and Memantine)

Look for depression or psychosis—for aggression

Treat constipation aggressively—for aggression

Consider PTSD as an etiology

Look for unrecognized medical—for agitation UTI Pain Polypharmacy

When is it “OK” to Use Antipsychotics in Dementia?

Patients with Bipolar Mania or Schizophrenia who have not responded to other treatment

Short term or limited prn use for psychosis or aggression

Reassess frequently—daily to weekly Delirium

Most data for haldol, risperidone and olanzapine PTSD flashbacks that don’t respond to other

treatments When safety is an issue

Conclusions Aggression and agitation continue to be of clinical concern in dementia

patients. However, it is not clear if neuropsychiatric symptoms in dementia have the same biological basis as psychiatric symptoms in the general population. Psychosis is very common and linked to behavior changes.

Antipsychotic medications do have short term efficacy in treating psychosis in nursing home patients with dementia, but they also have an increased risk of stroke and mortality. Older neuroleptics are more dangerous than the newer atypicals. As with any medication, risks have to be balanced with potential benefit.

Current pharmacologic interventions have some impact on symptoms but little impact on reducing disability or cost. Short-term treatment of aggression with atypical neuroleptics may be a necessary intervention to preserve safety at times since alternative acute treatments are limited. Cholinesterase inhibitors and memantine have a modest but real impact in preventing BPSD. Few studies have been done with antidepressants, but citalopram did show positive results, and did carbemazapine.

Environmental modifications and caregiver interventions may be more cost effective and humane.