Dr. Jibson, there have been several meta-analyses comparing atypical antipsychotics published over the last few years. They are all long, complicated papers, and the conclusions are often controversial. Can you help us understand this literature?

Tamoxifen, an estrogen blocker that is approved for the treatment of breast cancer, successfully treated patients with mania in a placebo-controlled trial.

Dr. Jeste, I know that you were responsible for some of the original research demonstrating that tardive dyskinesia is a possible side effect of antipsychotics. Why were you interested in the topic?

In a multi-center study conducted in Great Britain and Australia, 86 adults with mental retardation (IQ < 75) and aggressive behavior were randomized to double-blind treatment with Risperdal (mean dose, 1.8 mg/day), Haldol (mean dose, 2.9 mg/day), or placebo. The primary outcome was score on the modified overt aggression scale (MOAS) at 4 weeks.

Although we tend to feel comfortable counseling patients to continue antidepressants during pregnancy, because most of them do not appear to cause congenital abnormalities, mood stabilizers are trickier.

Because standard antipsychotics don’t do much for the negative symptoms of schizophrenia (such as affective flattening and paucity of speech), there has been a fair amount of interest in the so-called “hypoglutaminergic hypothesis” of schizophrenia.

In 2005, the FDA issued a health advisory saying that antipsychotics appear to increase the risk of death in elderly patients with dementia. That advisory was based on data from placebo-controlled trials of antipsychotics conducted by industry. Now, a new study based on a completely different, and much larger, dataset, appears to confirm these dangers.

One of the final major questions that the NIMH-funded CATIE trials promised to answer was whether atypical antipsychotics are better at improving cognition in schizophrenia than conventional agents, as some smaller studies implied.

Why don’t we start with the issue of agitation? The question in many psychiatrists’ minds is how seriously we should take the FDA advisory about the dangers of atypical antipsychotics?

We’ve known for some time now that clozapine and Zyprexa (olanzapine) cause the most weight gain of any antipsychotic, but we didn’t know the actual mechanism – until now.