Table 1
Typical antipsychotics: Safer than atypicals for older patients?
| Study | Population | Summarized results |
|---|---|---|
| Mortality | ||
| Nasrallah et al6 | VA patients age ≥65 taking haloperidol or an atypical antipsychotic (n=1,553) | Approximately 4 times higher rate of death in those receiving haloperidol compared with those receiving atypicals |
| Wang et al8 | Pennsylvania adults age ≥65 with prescription coverage taking antipsychotics (n=22,890) | Typicals had higher relative risk (RR) of death at all time points over 180 days (RR 1.27 to 1.56), both in persons with and without dementia; higher risk associated with increased typical doses |
| Gill et al10 | Canadians age >65 with dementia (n=27,259 matched pairs) | Mortality rate was higher for users of typical vs atypical antipsychotics (RR 1.26 to 1.55) |
| Kales et al11 | VA patients age >65 prescribed psychotropics after a dementia diagnosis (n=10,615) | Risk of death similar for atypical and typical antipsychotics |
| Schneeweiss et al7 | Cancer-free Canadians age ≥65 taking antipsychotics (n=37,241) | Higher mortality rates for those taking typical antipsychotics than those taking atypicals (RR 1.47); higher mortality associated with higher typical doses |
| Trifirò et al9 | Adults age >65 with dementia receiving antipsychotics in Italy (n=2,385) | Equivalent rates of mortality in those taking typical and atypical antipsychotics |
| Stroke | ||
| Gill et al12 | Canadians age ≥65 with dementia receiving antipsychotics (n=32,710) | Equivalent rates of ischemic stroke in those taking atypical and typical agents compared with those receiving atypicals |
| Liperoti et al13 | Nursing home residents with dementia hospitalized for stroke or TIA and matched controls (n=4,788) | Rates of cerebrovascular adverse events equivalent between users of atypical and typical antipsychotics |
| VA: Veterans Affairs; TIA: transient ischemic attack | ||
CASE CONTINUED: Moderate relief from risperidone
After the psychiatrist explains the data on atypical vs typical antipsychotics in dementia—and the lack of FDA-approved treatments—Mr. B consents to the use of risperidone. He believes his wife would have wanted to try a medication with a moderate chance of relieving her internal distress and preventing her from harming anyone.
Risperidone provides moderate relief of Mrs. B’s aggression and paranoia. The next day Mr. B visits the unit and asks to speak with the psychiatrist. Although he appreciates the staff’s caring attitude, he says, “There must be safer or better ways to deal with these symptoms than medications like risperidone. I just don’t want the guilt of causing my wife to have a stroke or pass away.” He also asks, “How long will she have to take this medication?”
Evidence for efficacy
In addition to discussing antipsychotics’ risk in dementia, we also need to highlight their efficacy and effectiveness. A recent meta-analysis of 15 randomized controlled trials of atypical antipsychotics for agitation and/or psychosis in dementia included studies with risperidone, olanzapine, aripiprazole, and quetiapine.3 Most study participants were institutionalized, female, and had AD.
Psychosis scores improved in pooled studies of risperidone, whereas global neuropsychiatric disturbance improved with risperidone and aripiprazole. Effects were more notable in:
- persons without psychosis
- those living in nursing homes
- patients with severe cognitive impairment.
Subsequent placebo-controlled trials of risperidone, quetiapine, and aripiprazole—most focusing on patients with AD—reveal that atypical and typical antipsychotics have modest efficacy in reducing aggression and psychosis.15-19 However, to some extent the National Institute of Mental Health Clinical Antipsychotic Trial of Intervention Effectiveness Study for Alzheimer’s Disease (CATIE-AD)—the largest nonindustry-funded study conducted to address this question—called this conclusion into question.20 Risperidone and olanzapine (but not quetiapine) were efficacious in that fewer patients taking them vs placebo dropped out because of lack of efficacy. Antipsychotics were not effective overall, however, because the primary outcome—all-cause discontinuation rate—was similar for all 3 drugs and placebo. This indicates that on average these medications’ side effect burden may offset their efficacy, though individual patients’ responses may vary.
Alternatives to antipsychotics
Mr. B also raised the issue of treatment alternatives, such as no treatment, other psychotropics (Table 2),5,21 and nonpharmacologic methods (Table 3).22
“No treatment” does not imply a lack of assessment or intervention. Always examine patients for iatrogenic, medical, psychosocial, or other precipitants of behavioral symptoms. No treatment may be viable in mild to moderate cases but is impractical for patients with severe psychosis or agitation. Untreated, these symptoms could compromise safety or leave the patient without housing options.
Although possibly underused because of time constraints, reimbursement issues, or lack of training, nonpharmacologic strategies to treat aggression and psychosis in dementia are appealing alternatives to antipsychotics. Little empiric evidence supports nonpharmacologic strategies, however.22
Treatment decisions need to consider patients’ and caregivers’ value systems. Proxy decision-makers should examine treatment decisions in terms of how they believe the patient would view the alternatives. Without a specific advance directive, however, even well-intentioned decision-makers are likely to “contaminate” decisions with their own values and interests.