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.