Risperidone is a benzisoxazole derivative indicated for treatment of psychotic disorders. Risperidone’s antipsychotic efficacy is equivalent to that of haloperidol, but it has a much safer side-effect profile. In one multicenter study comparing risperidone and a placebo at single daily dosages of 0.5, 1.0, and 2.0 mg, risperidone was found to be effective in controlling the psychosis and behavioral disturbance associated with dementia. The authors recommended using a dosage of 1.0 mg/d because higher dosages resulted in excessive sedation and EPS.17
Risk of side effects is dose-dependent, especially in the older patient. Risperidone is the only atypical antipsychotic associated with persistent hyperprolactinemia, which may indirectly contribute to increased osteoporosis and atherogenesis.18,19 Orthostatic hypotension, especially with initial dosages greater than 1.5 mg/d and rapid dose escalation (≥ 25% every 24 to 48 hours), may also limit its use in older patients.
Olanzapine is a thiobenzodiazepine derivative indicated for treatment of psychosis and acute bipolar mania. Olanzapine has a receptor profile that is somewhat analogous with that of clozapine. Its antipsychotic efficacy is equivalent to that of risperidone, but it has a more favorable safety profile. Like risperidone, olanzapine is relatively nonsedating, but it is significantly less likely to cause EPS and orthostatic hypotension, and its use is not associated with persistent hyperprolactinemia.
Based on its vitro muscarinic receptor antagonism profile, some clinicians incorrectly assume that olanzapine is highly anticholinergic. In vivo data and clinical experience have not borne out this contention.20,21 Weight gain with olanzapine is relatively infrequent in older persons. A rapid-dissolve preparation can be useful in resistant and noncompliant patients. An IM preparation has been approved by the FDA but has not yet been made available by the manufacturer.
Quetiapine is a dibenzothiazepine derivative indicated for treatment of psychotic disorders. Despite limited data on its efficacy in late-life psychosis, clinical experience would suggest that its antipsychotic efficacy would at least equal that of other drugs in this category.
The need for twice-daily dosing and titration to a therapeutic response can sometimes limit the use of quetiapine. Sedation can be a problem at dosages greater than 200 mg/d. Because quetiapine has a relatively lower potential among the antipsychotics to cause EPS, it may be a first-line choice in patients with Parkinson’s disease and Lewy body dementia.
Ziprasidone is a benzothiazolylpiperazine indicated for treatment of psychosis. Experience with its use in older patients is limited. Ziprasidone should be avoided in patients with significant cardiovascular disease because of its potential to cause QT prolongation and cardiac arrhythmias. Although rare, this cardiac side effect may be life-threatening, and clinicians must be exceptionally vigilant when using ziprasidone in older patients. Risk factors for QT prolongation include older age, female sex, pre-existing cardiac disease, hypokalemia, and hypomagnesemia.
Ziprasidone can be somewhat sedating. An IM preparation is under development but has not been approved for use by the FDA
Neuroleptics and other options
Occasionally a typical neuroleptic may be the most appropriate first-line drug for older patients with psychotic symptoms. For example, a mid-potency neuroleptic such as perphenazine at an IM dose of 2 to 4 mg may be considered when severe agitation and aggression pose a substantial safety risk for the patient or caregiver and require rapid control. Haloperidol, despite its widespread use in both acute and long-term settings, should be used with caution because it has great potential for causing EPS and can immobilize an older patient, resulting in further functional decline. Regardless of which typical neuroleptic is used, switch the patient to an atypical antipsychotic as soon as agitation is under control.
Antidepressants Affective psychoses in older patients may require the addition of an antidepressant to the antipsychotic drug. The selective serotonin reuptake inhibitors fluoxetine and sertraline have proven track records for efficacy and safety and should be considered first-line agents.
Other options Electroconvulsive therapy is safe and effective for older patients with psychotic depression or late-life mania. Late-life mania also may respond well to the anticonvulsant divalproex sodium. Avoid anxiolytics in older patients because of the potential of these agents to cause sedation or disinhibition and their associated risk of falls and confusion. Buspirone in higher dosages (40 to 60 mg/d) can sometimes help manage chronic anxiety states.
Related resource
- Sadavoy J, Lazarus LW, Jarvik LF, Grossman GT (eds). Comprehensive review of geriatric psychiatry (2nd ed). Washington, DC: American Psychiatric Press, 1996.
Drug brand names
- Buspirone • Buspar
- Clozapine • Clozaril
- Divalproex • Depakote
- Fluoxetine • Prozac
- Olanzapine • Zyprexa
- Perphenazine • Trilafon
- Quetiapine • Seroquel
- Risperidone • Risperdal
- Sertraline • Zoloft
- Ziprasidone • Geodon
Disclosure
Dr. Snow reports no affiliation or financial arrangement with any of the companies whose products are mentioned in this article.