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September 2009

Prenatal Valproate Lowers IQ
Valproate may adversely affect fetal cognitive development throughout pregnancy.

Stimulant Augmentation for Treatment-Resistant OCD?
In one study, amphetamine was not superior to caffeine as an augmentation strategy for patients with obsessive compulsive disorder.

Antipsychotics in Alzheimer's Patients: New Evidence on Metabolic Effects
Second-generation antipsychotic drugs increase the risk of weight gain and metabolic effects in patients with Alzheimer’s disease.

In Brief
Contraception Use in Female Bipolar Patients Suboptimal; CBT Available over Internet for Insomnia

SSRIs and Gestational Hypertension
Use of a serotonin selective reuptake inhibitor beyond the first trimester of pregnancy is associated with an increased risk of hypertension and preeclampsia.

Antipsychotics in Alzheimer's Patients: New Evidence on Metabolic Effects

September 2009

We've reported frequently in recent years on the dilemma presented by behavioral problems in patients with Alzheimer's disease. Patients' anger and aggressive behaviors take a much greater toll on caregivers than the cognitive impairment. But current treatments are inadequate. In particular, antipsychotics are frequently employed to control behavior in these patients, but evidence of their efficacy is limited, and they increase the risk of death. Apparently, antipsychotics also increase the risk of weight gain and adverse metabolic effects.

Zheng and coauthors analyzed weight and metabolic effects of three second-generation antipsychotic drugs in outpatients with Alzheimer's disease participating in the Clinical Antipsychotic Trials of Intervention Effectiveness - Alzheimer's Disease (CATIE-AD).1 Subjects in this multicenter, randomized, double-blind, placebo-controlled trial took olanzapine (Zyprexa), quetiapine (Seroquel), or risperidone (Risperdal and others).

About 20% of subjects gained a clinically significant amount of weight (at least a 7% increase from baseline), which increased over 36 weeks of antipsychotic drug treatment. Both male and female subjects gained more weight on antipsychotics than on placebo, but the gain was only statistically significant in the females. Baseline weight did not seem to influence weight gain. In other words, it was not only the slender patients who gained weight during treatment.

Olanzapine and quetiapine in particular were associated with weight gain. As well, olanzapine significantly decreased HDL cholesterol (the "good cholesterol") and increased abdominal girth.

These further results from the CATIE-AD trial underscore an adverse effect of second-generation antipsychotics that is now familiar in younger psychotic populations. It appears that Alzheimer's patients also are subject to the adverse metabolic effects of second-generation agents, with some drugs more likely to cause these problems than others. In addition, the CATIE-AD trial suggests women may be more vulnerable than men, although this observation requires replication.

It is a cliché in medicine to say that the risks and benefits of every treatment have to be individually assessed for each patient. But this appears to be a particularly valid caution in the vulnerable population with Alzheimer's. If a specific antipsychotic at a given dose is effective in decreasing troublesome behavior in a patient with Alzheimer's disease, the family may decide that the morbidity and mortality risks are worth the benefit. In these cases, the behavioral improvement and the discussion between doctor and family should be well documented.

1Zheng L, Mack WJ, Dagerman KS, Hsiao JK, Lebowitz BD, Lyketsos CG, Stroup TS, Sultzer DL, Tariot PN, Vigen C, Schneider LS: Metabolic changes associated with second-generation antipsychotic use in Alzheimer's disease patients: The CATIE-AD study. Am J Psychiatry 2009;166:583–590.