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 personality       o o ? Alcohol history ? TBI history Social  Over stimulation   Unwanted cares Unpleasant experiences Undiagnosed Medical Condition Pain Environment Poor Sleep Delirium

BPSD Symptom Clusters

Aggression Agitation Apathy

Physical Verbal Resistance to Care Withdrawn Lack of Interest Amotivation

Depression

Sad Tearful Wish to Die Irritable Anxious Screaming Guilty Pacing Repetitive Actions Undressing Anxiety/Restless Euphoria Pressured Speech Irritability

Mania

Hallucinations Delusions Misidentification Suspiciousness

Psychosis

McShane et al Int Psychogeriatr 2001

Aggression correlates with neuropsychiatric disorders (and consitpation) Depressive Symptoms Delusions Hallucinations Constipation

Adjusted Odds Ratio

Physical Aggression Verbal Aggression 3.3

4.9

2.0

1.4

1.3

2.5

1.8

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, 1999 Metaanalysis 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.