
- Vol 40, Issue 6
Clozapine-Induced Weight Gain: Is It Dependent on Dose?
Check out the evidence for a modest effect over 1 year of clozapine dose on weight.
CASE VIGNETTE
“Mrs Green” is a 55-year-old African American woman with a history of chronic schizoaffective disorder, bipolar type. She experienced the onset of her psychosis at age 40 years. At 45 years, after several inpatient psychiatric hospitalizations, she was started on
When she returned for another outpatient visit 6 weeks later, Mrs Green had gained 40 lb. Through improved nutrition and
Clozapine is the gold-standard antipsychotic for treatment-resistant psychosis; however, it is associated with considerable risk of cardiometabolic adverse effects.1 It is unclear whether clozapine’s adverse effects are dose-dependent,2 and findings regarding its effects on weight,3-5 glucose, and lipids6-8 are mixed.
The Current Study
Piras and colleagues9 analyzed the effects of clozapine dose on weight, blood pressure, and metabolic parameters in a prospective cohort of psychiatric patients in Switzerland. Data were obtained from the PsyMetab and PsyClin cohorts, which included patients who had started clozapine between 2007 and 2020 and had at least 2 weight observations and 3 weeks of clinical follow-up. Data on weight, waist circumference, blood pressure, glucose, and lipids were obtained at baseline, 3 months, and 12 months. Weight was also available at 2 and 6 months. Data on clozapine dose and comedications were also obtained. The study included 115 participants.
The authors compared clinical variables between patients who were taking at least 200 mg and patients who were taking less than 200 mg of clozapine (median dose). Dose effects on weight change were evaluated using linear mixed-effects models, adjusting for age, sex, baseline weight, treatment duration and setting (inpatient vs outpatient),
Patients taking 200 mg of clozapine or more were more likely to be younger, to be smokers, to have a diagnosis of schizophrenia/schizoaffective disorder, and to have a higher baseline weight. Treatment duration and dose were significantly associated with weight change over 1 year, with a 0.5% increase in weight for each additional month and a 0.5% increase in weight for each additional 100-mg dose over 1 year of treatment. Weight increase was greater for treatment duration 3 months or less versus greater than 3 months (+0.84% and +0.47% per month, respectively).
Dose increments of 100 mg were associated with weight increases in adults (+0.71%), the elderly (+1.91%), and men (+1.32%) but not in women. There were no significant effects of clozapine dose on blood pressure, glucose, or lipids. Furthermore, baseline weight was not a predictor of weight change with clozapine.
Study Conclusions
Using a 1-year naturalistic design, the authors found a positive association between clozapine dose and weight change, independent of baseline weight. They also found that the percentage of weight increase after each 100-mg increase in clozapine dose was predictable.
Study strengths include the fact that the influence of multiple covariates could be integrated into the model. Study limitations include the modest sample size and absence of data on diet and physical activity. History of previous psychotropic medications, which could have included clozapine, was also unavailable.
The Bottom Line
There is evidence for a modest effect over 1 year of clozapine dose on weight but not on other metabolic parameters, with differences based on age and sex.
Dr Miller is a professor in the Department of Psychiatry and Health Behavior at Augusta University in Augusta, Georgia. He is on the editorial board of Psychiatric Times® and serves as schizophrenia section chief. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and the Stanley Medical Research Institute.
References
1. Pillinger T, McCutcheon RA, Vano L, et al.
2. Simon V, van Winkel R, De Hert M.
3. de Leon J, Diaz FJ, Josiassen RC, et al.
4. Jalenques I, Tauveron I, Albuisson E, et al.
5. Lau SL, Muir C, Assur Y, et al.
6. Wysokiński A.
7. Henderson DC, Nguyen DD, Copeland PM, et al.
8. Kamil Gharab KM, Onmaz DE, Abusoglu S, et al.
9. Piras M, Chahma J, Ranjbar S, et al.
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