Weight Gain Among Patients on Clozapine

To the Editor: Some studies have investigated the correlation of weight gain and response to clozapine treatment (1,2,3,4), but the findings have been inconclusive. In our clinical practice, we noticed that female patients with better clinical response seemed to gain weight, but a similar weight gain was not so obvious among male patients. We decided to study the association between weight gain and treatment response to clozapine among male and female patients.

Our sample consisted of 96 patients with chronic schizophrenia who were hospitalized at a psychiatric hospital in a suburban area of east Taiwan and consecutively started on clozapine between May 1995 and March 1997. Patients with major medical illness were excluded from the study. Study participants were hospitalized throughout the study period, assuring their compliance with clozapine treatment.

All patients received the same daily meal and were weighed monthly by nurses. The psychiatrists-in-charge evaluated the patients' improvement on clozapine using the Clinical Global Impression Scale (CGI). Patients who received a CGI score of 1, very much improved, and 2, much improved, were considered to have a significant clinical response to clozapine treatment. The other patients were considered not to have a significant response.

Forty-six of the patients were female, and 50 were male. Their mean± SD age was 38.3±8 years. Their mean clozapine dosage was 385.9±139.5 mg per day, and the mean duration of treatment with clozapine was 14±6.2 months.

For the 46 female patients, their mean initial body weight was 57.4±12.8 kg. The mean body mass index (BMI) was 23.8±5, which is within the ideal BMI range of 21 to 24. For the 50 male patients, the mean initial body weight was 66±2.6 kg, and the mean BMI was 22.6±3.8.

No significant difference was found between male and female patients in their clinical response to clozapine. Seventeen, or 37 percent, of the female patients had a significant clinical response. Those who responded to the drug gained more weight than those who did not, 10.9±6.9 kg compared with 4.3±6.3 kg (t=3.32, df=44, p=.002). The two groups did not differ significantly in initial body weight, clozapine dosage, and duration of clozapine treatment.

Eleven, or 22 percent, of the male patients had a significant clinical response to clozapine. No significant difference in weight gain was noted between male patients who responded and those who did not (7.10±2.14 kg for the responders, compared with 7.10±1.14 kg for the nonresponders).

Few studies have explored gender differences in neuroleptic-induced obesity in human subjects. Our preliminary study found that among patients who were taking clozapine, a bigger weight gain was related to a significant clinical response among female patients, but not among male patients. Animal studies have suggested that impaired ovarian steroidogenesis related to neuroleptic-induced hyperprolactinemia is a factor in weight gain (5). The phenomenon is interesting, and the question needs further study using a more precise scale for rating response to clozapine treatment, such as the Brief Psychiatric Rating Scale or the Positive and Negative Syndrome Scale.