Dr. Carpenter, as Editor-in-Chief of Schizophrenia Bulletin and a long-time researcher in the field, I’m sure you’ve seen trends come and go. Lately, we’ve been hearing a lot about how the older, conventional antipsychotics may be just as good as the newer atypicals. What’s your take?

We often see teenagers with co-occurring bipolar disorder and aggressive/impulsive behaviors. While Depakote is often effective, we also often prescribe atypical antipsychotics. A new post-hoc analysis provides some
evidence to bolster that practice.

Atypical antipsychotics can cause significant weight gain in adolescents. In this study, 39 kids between 10 and 18 years of age were randomized to receive either the antidiabetic drug Glucophage (metformin) or a matched placebo; each was added to their primary antipsychotic medication (Risperdal, Seroquel, or Zyprexa) for 16 weeks.

The latest results from the CATIE trial indicate that treatment with Trilafon (perphenazine) is not only much cheaper than treatment with SGAs (second generation antipsychotics), but leads to superior overall quality of life for patients.

Only after thinking long and hard about it, according to the long anticipated results from the CATIE-AD trial. In this study, 421 patients with Alzheimer’s Disease were randomized to double-blind treatment with Zyprexa (mean dose, 3.2 mg/day), Seroquel (34.1 mg/day), Risperdal (0.7 mg/day), or placebo.

Few clinical trials have ever generated as much buzz as the series of trials known as CATIE. CATIE stands for “Clinical Antipsychotic Trials of Intervention Effectiveness,” and is the only set of trials ever done comparing the major second-generation antipsychotics. And because CATIE is funded entirely by NIMH, its results are thought to be quite trustworthy (NEJM 2005;353:1209-1223).

Those of us who completed residency anytime during the last 10 years were indoctrinated against the use of conventional neuroleptics because of their array of side effects, particularly extrapyramidal syndromes (EPS) and tardive dyskinesia (TD).

Dr. Hsiao, you were NIMH’s project officer for the CATIE trial. What was your goal when you came up with the idea for CATIE?

Following the introduction of the first neuroleptics in the 1950s, pharmaceutical companies continued screening compounds for psychoactive properties. In 1959, at Wander Laboratories (ultimately purchased by Sandoz), researchers were surprised to discover a chemical similar to tricyclic antidepressants that had antipsychotic properties. They named it clozapine.

Dr. Janicak, you've had a long career in research and academia, and I was hoping you could help shed some light on the various contentious issues surrounding the use of atypical antipsychotics, including the issue of whether there is clearly a difference in metabolic profile among the different medications.