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Letter to the Editor

Metabolic Syndrome in Inpatients Treated With Clozapine

Takefumi Suzuki, MD, PhD

Published: June 15, 2011

See the reply

Metabolic Syndrome in Inpatients Treated With Clozapine

To the Editor: I read with interest the important study by Dr Bai and coauthors1 of metabolic factors and weight gain in schizophrenia patients treated with clozapine. They found that baseline body mass index (BMI) and BMI change over time were associated with metabolic syndrome and 4 metabolic parameters, with the notable exceptions of hyperglycemia and diabetes mellitus, which were related to duration of clozapine treatment rather than weight gain.

Metabolic syndrome in schizophrenia during antipsychotic treatment is a highly relevant and worrisome topic2 in relation to at least some of the antipsychotics. Nevertheless, Bai and colleagues’ valuable findings should be interpreted with caution in the context of the population studied.

It is important to note that this work studied an inpatient sample for an average period of 57.6 ± 27.3 months (range, 5-96 months). In other words, the study sample would have consisted of patients who were relatively poorly responsive to clozapine (as robustly responsive patients would have been discharged sooner). It appears likely that these inpatients had limited access to foods other than those provided in the hospital compared with outpatients, who would have had much freer access to their favorite foods. While inpatients appear more reliable in terms of anthropometric and biochemical measurements, assessment of nutritional intake, and adherence to medications, these same factors limit generalizability of the results to outpatients.

In fact, it is worthy of note that (as seen in Table 1 of the article) the mean absolute change in BMI was only 1.1 over a substantial length of follow-up time, corresponding to an absolute increase of 3.5 kg (and a 4.9% relative increase) if one assumes a height of 170 cm (although another caution is an SD that is larger than the mean, implying substantial interindividual difference on this issue). These numbers are very conservative in light of previous reports that found more robust increase in BMI3 or body weight4 with clozapine, although confounders such as ethnicity, gender, and smoking habits should be taken into account as well.

Also pertinent is the authors’ previous finding5 of less weight gain in patients who experience less improvement with long-term clozapine treatment. As such, the findings of this study should be replicated, as the authors point out in their discussion, especially among outpatients, who may differ from inpatients in terms of the quality as well as the quantity of their food intake, which is a critical variable in evaluating glucose (as well as other metabolic) dysregulation. The results do not unequivocally rule out the possibility that the contribution of weight on diabetes might have been positive if the magnitude of weight gain were more prominent in the sample studied, which was found to potentially be the case in the general population.6


1. Bai YM, Lin CC, Chen JY, et al. Association of weight gain and metabolic syndrome in patients taking clozapine: an 8-year cohort study [published online ahead of print November 20, 2010]. J Clin Psychiatry. PubMed doi:10.4088/JCP.09m05402yel

2. Stahl SM, Mignon L, Meyer JM. Which comes first: atypical antipsychotic treatment or cardiometabolic risk? Acta Psychiatr Scand. 2009;119(3):171-179. PubMed doi:10.1111/j.1600-0447.2008.01334.x

3. Frankenburg FR, Zanarini MC, Kando J, et al. Clozapine and body mass change. Biol Psychiatry. 1998;43(7):520-524. PubMed doi:10.1016/S0006-3223(97)00488-5

4. Allison DB, Mentore JL, Heo M, et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry. 1999;156(11):1686-1696. PubMed

5. Bai YM, Lin CC, Chen JY, et al. Association of initial antipsychotic response to clozapine and long-term weight gain. Am J Psychiatry. 2006;163(7):1276-1279. PubMed doi:10.1176/appi.ajp.163.7.1276

6. Jacobs-van der Bruggen MA, Spijkerman A, van Baal PH, et al. Weight change and incident diabetes: addressing an unresolved issue. Am J Epidemiol. 2010;172(3):263-270. PubMed doi:10.1093/aje/kwq134

Takefumi Suzuki, MD, PhD

Author affiliation: Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan. Potential conflicts of interest: Within the last 5 years, Dr Suzuki has received fellowship grants from Kanae Foundation, Government of Canada Post-Doctoral Research Fellowships, Mochida Memorial Foundation, Japanese Society of Clinical Neuropsychopharmacology, and manuscript fees from Dainippon Sumitomo and Kyowa Hakko Kirin. Funding/support: None reported.

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