Differing Tolerability Profiles Among Atypical Antipsychotics

To the Editor: We read with interest the article by David B. Allison, Ph.D., et al. (1) in which they reported weight gain over 10 weeks’ treatment with a number of antipsychotics. Unfortunately, data for the atypical antipsychotic quetiapine were not included. Jones et al. (2) reported at the recent Biennial Winter Workshop on Schizophrenia a mean weight gain of 2.16 kg (4.75 lb) in patients with schizophrenia and other psychoses after 10 weeks’ treatment with quetiapine at a mean dose of 480 mg/day. After 6 months’ treatment, the mean weight gain was 1.85 kg (4.07 lb) in a sample of 556 patients, whereas after 1 year, the increase was 2.77 kg (6.09 lb) (N=360).

This suggests that with quetiapine, weight gain with short-term treatment does not necessarily presage continued weight gain over the longer term. Concomitant antipsychotic medication was, however, permitted during the open-label extension phase of these studies, thus making difficult any definitive attribution of weight gain to any particular agent. However, Brecher and Melvin (3) recently reported that in a separate population in whom quetiapine was used as monotherapy, a median weight gain of only 1 kg was seen after treatment periods of between 53 and 78 weeks.

Dr. Allison and colleagues highlighted clozapine and olanzapine as being associated with more weight gain than other atypicals and suggested that they may, as a result, also contribute to the development of type II diabetes (4, 5). It is intriguing that Reinstein et al. (6) reported on a case series in which quetiapine appeared to normalize weight and diabetes control in patients who had previously both gained weight and developed diabetes while taking clozapine.

Although the atypical antipsychotics appear to have a more favorable side effect profile than do the conventional agents, their differing tolerability relative to one another (for example, in extrapyramidal side effects, prolactin, and weight effects) also should be considered when selecting treatments for patients with schizophrenia and other related disorders.

The authors have received research grants, sponsorship to attend conferences, consultancy payments, and lecture fees from AstraZeneca and other companies involved in the development of antipsychotics.