Since its introduction, Zyprexa has been prescribed for an estimated 26 million patients worldwide, according to Lilly’s January 15 press statement. In the US, the drug is indicated for the short- and long-term treatment of schizophrenia, acute mixed or manic episodes of bipolar I disorder, and maintenance treatment of bipolar disorder. Zyprexa is not approved for patients younger than 18 years or for patients with dementia-related psychosis.
Yet, behavioral and psychiatric symptoms develop in as many as 60% of community-dwelling patients who have dementia and in more than 80% of patients with dementia living in nursing homes, according to a 2008 paper prepared by Jeste and colleagues.1 The prevalence of specific symptoms in patients with Alzheimer disease varies: for delusions, the prevalence is 9% to 63%; for hallucinations, 4% to 41%; for physical aggression, 11% to 46%; and for agitation, 20% to 80%.
Randomized controlled trials of antipsychotics for psychosis and/or agitation associated with dementia, “in aggregate,” suggest modest efficacy in symptom reduction with active treatment compared with placebo, according to Jeste and colleagues. These researchers added, however, that several individual trials have yielded negative results.
The NIMH sponsored the CATIE-AD trial (Clinical Antipsychotic Trials of Intervention Effectiveness—Alzheimer’s Disease) of atypical antipsychotics for psychosis or agitation/aggression in people with dementia. In this 42-site, double-blind, placebo-controlled trial, 421 outpatients with Alzheimer disease and psychosis, aggression, or agitation, were randomly assigned to receive flexible dose olanzapine(Drug information on olanzapine) (mean dose, 5.5 mg/d), quetiapine (Seroquel; mean dose, 56.5 mg/d), risperidone(Drug information on risperidone) (Risperdal; mean dose, 1.0 mg/d), or placebo. Doses were adjusted as needed, and patients were monitored for up to 9 months.
The main outcomes were the time from initial treatment to the discontinuation of treatment for any reason and the number of patients with at least minimal improvement on the Clinical Global Impression of Change (CGIC) scale at 12 weeks. Researchers found that olanzapine, quetiapine(Drug information on quetiapine), and risperidone were no better than placebo for the primary outcome (time to discontinuation for any reason).2