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Antipsychotic-Induced Weight Gain: A Newsmaker Interview With David Henderson, MD

Robert Kennedy

Feb. 13, 2004 (Sydney) Editor's Note: Weight gain and diabetes in patients treated with antipsychotic agents is gaining more recognition as a serious problem in this population. Medscape also recently published a news article for CME credit on this topic (Joint Panel Urges Increased Surveillance for Adverse Effects of Antipsychotic Drugs)

To discuss the latest research in this area, Medscape's Robert Kennedy interviewed David C. Henderson, MD, here at the International Congress of Biological Psychiatry. Dr. Henderson is associate director of the Schizophrenia Program at Massachusetts General Hospital and assistant professor of psychiatry at Harvard Medical School, both in Boston.

Medscape: You presented a number of studies at this meeting pertaining to weight gain and antipsychotic medications. Why did you choose this area to study?
Dr. Henderson: The issue regarding weight gain and glucose metabolism is an important one that we began looking at 10 years ago when we opened a clozapine clinic and found some of the patients were putting on a lot of weight as well as developing diabetes. As a result, we set out not only to monitor these patients for these problems but to also develop interventions to reverse and to prevent these problems.

Medscape: A number of the major antipsychotics have associated weight gain and glucose issues. When you design the studies, do you design it from a pharmacologic point of view or patient care perspective?
Dr. Henderson: We recognized that some drugs were worse than others and we chose to focus on those drugs, in particular clozapine, because it is a drug reserved for the treatment-resistant population. The drug is the most effective drug in that population so a lot of the work has been with that drug. We also recognize that olanzapine caused similar problems in weight, lipid metabolism, and glucose metabolism so we focused on this drug as well.

Medscape: You presented a study about sibutramine. Can you discuss it?
Dr. Henderson: Sibutramine is [Food and Drug Administration]approved weight loss agent that goes under the brand name of Meridia. It works with the serotonin system that is designed for weight loss and has been examined in long-term studies of up to one year. We chose to do this because it is our general feeling that exercise and behavioral weight programs are not going to be effective in this population because they entail taking drugs that impair satiety and cause sedation. It is unrealistic to expect that behavioral changes are going to reverse these problems.

We studied sibutramine in the study that we presented with olanzapine-treated patients who gained a significant amount of weight. It is a 12-week study in conjunction with a behavioral nutrition program and we found that patients did lose weight with this drug. It was statistically significant and their weight was reduced. Their [body mass index] went down and their waist circumference went down as well. It appeared to be an effective agent for weight loss in olanzapine-treated patients without any major side effects.

Medscape: You also presented a study with aripiprazole. Can you discuss this one as well?
Dr. Henderson: Aripiprazole is the newest atypical antipsychotic agent. We decided to add aripiprazole to clozapine-treated patients. Initially, we hypothesized that we would see some improvement in psychopathology, but also because the drug is more activating, we thought we would see some improvement in activity level. We were surprised to find out that patients lost a significant amount of weight (up to 10 pounds, some patients even more), and more striking was a reduction in lipids, particularly the triglyceride levels came down dramatically in a majority of patients.

It is important to note that this is a six-week, open-label, 10-patient study, and you would need a larger sample to continue to confirm the data. When looking at other data that we had in other weight-loss studies with clozapine, where we could get patients to lose some weight, the results were not this dramatic and we did not find any significant change in lipids as we did in the aripiprazole study. This represents something that needs to be studied further in placebo-controlled trials, but it raises some interesting questions mechanistically.... It can be a clinically useful intervention for clozapine patients that are at a high risk for medical disorders because of the drug.

Medscape: Were the results a surprise to you?
Dr. Henderson: The weight loss and the lipid findings were extremely surprising.

Medscape: You were initially looking for reduction in symptomatology?
Dr. Henderson: We were looking for reductions in psychotic symptoms, maybe some improvement in depression symptoms, but not weight loss.

Medscape: I know it is a small study, but the findings are dramatic. How are the patients reacting?
Dr. Henderson: When patients participate in a drug trial, they want to come off the drug when the study is completed and they are usually happy that the study is over. But for this study, the majority of patients (8 out of 10) absolutely demanded to be continued on the drug. Overall they felt better, partly to the decrease in sedation, they were more active, they were more social, and overall the quality of life was significantly better for them. In that study we continued eight patients with the combination of medications and they continued to state what the drug does for them and how it makes them feel better.

Dr. Henderson receives research funding from the National Institute of Health, Squibb, Bristol-Myer

This interview focuses on an issue that has been discussed extensively on the board. The reasons leading to the weight gain and a commonly used med as solution is proposed.

anna22

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