1. Antipsychotics in Dementia— What’s a Doc to Do? Janis B. Petzel, M.D. Geriatric Psychiatry, Private Practice, Hallowell, ME and Togus VA

2. 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

3. 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

4. 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

5. Overview of Psychosis and BPSD  Symptoms Delusions Hallucinations Aggression  Verbal  Physical Combativeness Sleep Disorder Anxiety Depression  Triggers Individual oPremorbid personality o? Alcohol history o? TBI history Social  Over stimulation  Unwanted cares  Unpleasant experiences Undiagnosed Medical Condition Pain Environment Poor Sleep Delirium

6. BPSD Symptom Clusters Physical Verbal Resistance to Care Pacing Repetitive Actions Undressing Anxiety/Restless Euphoria Pressured Speech Irritability Hallucinations Delusions Misidentification Suspiciousness Sad Tearful Wish to Die Irritable Anxious Screaming Guilty Withdrawn Lack of Interest Amotivation Aggression Agitation Psychosis Mania Depression Apathy McShane et al Int Psychogeriatr 2001

7. Aggression correlates with neuropsychiatric disorders (and consitpation) Adjusted Odds Ratio Physical Aggression Verbal Aggression Depressive3.34.9 Symptoms Delusions2.02.5 Hallucinations1.41.8 Constipation1.31.1 (but not significant) Arch Int Med 166:1295-1300

8. 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

9. Other Studies—Very Limited Case studies for ziprazidone 20 mg i.m. Small studies with aripiprazole 2/3 (-)

10. 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

11. 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

12. Other helpful meds?  Cholinesterase Inhibitors Modest efficacy on behavior Removal--worsening behaviors Most data on donepezil and galantamine Effect shows up in metaanalysis

13. Other Meds?  Memantine 3 studies “post-hoc” analysis Seems to delay emergence of agitation, aggression Seems to reduce caregiver burden

14. Antidepressants for BPSD  Tricyclics—worsen cognition  Citalopram—improved agitation, aggression, psychosis  Trazodone—limited data, mixed results

15. 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

16. Other Meds  Benzodiapepines  Beta Blockers

17. More “Out there” Ideas  Nicotine patches—case studies  Marijuana Speculation only, or computer modeling or receptors. No studies

18. Non-Pharmacologic Considerations

19.  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

21. Sleep Changes over lifespan Time in bed for NH patients In NH, almost no exposure to natural or bright light

22. 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

23. “Core” or “Blue Ribbon” Emotions  Seeking  Rage  Fear  Panic  Lust  Care  Play

24. 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

25. 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

26. 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

27. 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

28. 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.