Evidence-Based Reviews

Using antipsychotics in patients with dementia

Current Psychiatry. 2004 February;3(2):55-64

References

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Most patients who experienced cerebrovascular events had one or more stroke risk factors, including diabetes, hypertension, atrial fibrillation, heart arrhythmia, atherosclerosis, or heart failure. They did not show a pattern of reduced blood pressure or orthostatic changes.^12,29

Table 2

Antipsychotic side effects and dosages in older patients with dementia*

Side effect	Clozapine (6.25 to 100 mg/d)	Risperidone (0.5 to 1.5 mg/d)	Olanzapine (5 to 10 mg/d)	Quetiapine (25 to 350 mg/d)
Orthostasis	++++	++++	+++	++
Sedation	+++++	++	+++	++
Prolactin increase	0	+++	+	0
Weight gain	++++	+	+++	+
EPS	0/+	++	+	0/+
Tardive dyskinesia	0	+	+	?
Anticholinergic effects	++++	+	+	0
Seizure risk	+++	+	+	+
Hematologic effects	+++	+	+	+
Source: Adapted from references 15 and 16.
* Side-effect profiles and recommended dosages of ziprasidone and aripiprazole in older patients are not yet established.
EPS: Extrapyramidal symptoms
Key:
0 = none
+ = slight
+++ = mild
+++++ = marked
0/+ = none to slight
++ = very mild
++++ = moderate

Dosing. For older patients with dementia and psychosis, start risperidone at 0.25 to 0.5 mg/d and increase by no more than 0.25 to 0.5 mg once or twice per week. Do not exceed 3 mg/d. For agitation, a 1998 Expert Consensus Guideline Series panel² recommended starting risperidone at 0.25 to 0.5 mg/d and increasing to an average of 0.5 to 1.5 mg/d.

Olanzapine. Two double-blind, placebo-controlled studies have examined olanzapine in treating agitation associated with dementia.

Saterlee et al³⁰ compared olanzapine, mean 2.4 mg/d, with placebo in outpatients (mean age 79) with Alzheimer’s disease and psychosis. No significant differences were noted in hepatic transaminase levels, leukopenia, EPS, or orthostatic changes.

In a later study,¹³ nursing home patients (mean age 83) with Alzheimer’s disease, psychosis, and agitation were randomly assigned to receive olanzapine—5, 10, or 15 mg/d—or placebo. After 6 weeks, patients receiving olanzapine, 5 or 10 mg/d, showed significant improvement in Neuropsychiatric Inventory (NPI) total core scores. Olanzapine, 15 mg/d, was not significantly more effective than placebo.

Adverse events such as somnolence and abnormal gait occurred more often with olanzapine than placebo. The somnolence rate with olanzapine was 14% for 5 mg/d and 13% for 10 mg/d, compared with 3% for placebo. For abnormal gait, the rate with olanzapine was 11% for 5 mg/d and 7% for 10 mg/d, compared with 1% for placebo.

Dosing. Start olanzapine at 2.5 mg/d, and increase after 1 to 3 days to 5 mg/d. If symptoms are not adequately controlled, titrate by 2.5-mg increments to 10 mg/d.

Quetiapine. One open-label study¹⁴ examined using quetiapine in older patients with psychotic disorders. The study enrolled 184 patients (mean age 76) with Alzheimer’s disease, Parkinson’s disease, schizophrenia, vascular dementia, schizoaffective disorder, bipolar disorder, or major depression. Before the trial, patients were taking various conventional and atypical antipsychotics.

Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impressions (CGI) scores improved significantly after 52 weeks of quetiapine, median 137.5 mg/d. BPRS scores improved 20% in 49% of patients who completed the study.

Less than one-half (48%) of enrolled patients completed the study. Reasons for withdrawal included lack of efficacy (19%), adverse events or illness (15%; adverse events alone, 11%), lost to follow-up (13%), protocol noncompliance (3%), or diminished need for treatment (2%).

EPS occurred in 13% of patients. Mean total scores on the Simpson-Angus Rating Scale for Extrapyramidal Side Effects decreased 1.8 points, indicating reduced parkinsonian symptoms.

Dosing. Start quetiapine at 25 mg once at bedtime or bid; increase in 25-mg increments until the lowest effective dosage is achieved.

Ziprasidone. Little data exist on using ziprasidone in long-term care. In one recent study,³¹ ziprasidone (mean 100 mg/d) was given to 62 patients ages 64 to 92 with medical illnesses plus major depression, bipolar disorder, schizoaffective disorder, Alzheimer’s disease, or multi-infarct dementia. A retrospective chart review of 10 patients showed decreased agitation, as mean NPI scores declined from 76 to 33.

Sedation was the most common side effect. QTc findings, postural hypotension, and syncope rates did not change. Despite its limitations, this study suggests that ziprasidone is safe and effective in treating psychosis associated with dementia or other disorders.

Aripiprazole. As with ziprasidone, little data exist to guide the use of aripiprazole in older patients. In a randomized preliminary trial,³² 192 noninstitutionalized patients with Alzheimer’s disease and psychosis were treated for 10 weeks with aripiprazole, mean 10 mg/d, or placebo.

At 8 and 10 weeks, BPRS psychosis subscale scores improved significantly in patients taking aripiprazole, compared with placebo. EPS and akathisia improved, and somnolence was the most common side effect. Although this study enrolled noninstitutionalized patients with dementia, the results suggest that aripiprazole may help treat long-term care residents with neurodegenerative disorders and behavioral disturbances.

Related resources

Zaraa AS. Dementia update: Pharmacologic management of agitation and psychosis in older demented patients. Geriatrics 2003;58(10):48-53.
Mills EJ, Chow TW. Randomized controlled trials in long-term care of residents with dementia: a systematic review. J Am Med Dir Assoc 2003;4(6):302-7.
Alzheimer’s Association. Treating agitation. www.alz.org/PhysCare/Treating/agitation.htm