Clozapine Dosage and Duration of Use Contribute to Weight Gain

The dosage and duration of clozapine treatment were found to modestly increase weight and to affect age groups and genders differently. These findings were published in the Schizophrenia Bulletin.

Data for this analysis were sourced from the PsyMetab and PsyClin cohort studies which were launched starting in 2007 and are ongoing. Data were collected between 2007 and 2015, respectively, at the University Hospital of Lausanne in Switzerland. The aim of this study was to evaluate fluctuations in body weight and metabolic markers over the course of 12 months of clozapine treatment.

The study cohort comprised 115 patients taking a median clozapine dose of 180 (IQR, 98-290) mg, they were aged 51 (IQR, 31-73) years, 50.4% were women, 47.0% were diagnosed with schizophrenia, 69.6% were treated in the inpatient setting, and 42.6% were receiving concomitant benzodiazepines, 36.5% psychotropics, 35.7% antidepressants, 29.6% antihypertensives, 9.6% lipid-lowering medications, and 8.7% antidiabetic drugs.

At baseline, the median BMI was 24 (IQR, 21-27) kg/m² and bodyweight was 70 (IQR, 59-81) kg.

Over 1 year, each additional month of clozapine receipt increased weight by 0.50% (P <.001) and each additional 100 mg in daily dose increased weight by 0.48% (P =.004).

With a cutoff of 3 months, as clozapine can be associated with rapid weight gain in the first 3 months, each additional month of treatment increased weight by 0.84% up to month 3 and by 0.47% for treatment durations greater than 3 months (P <.001). For each additional 100 mg in dose for treatment durations greater than 3 months, weight increased by 0.54% (P =.004).

Stratified by concomitant medications, those who were taking antihypertensive drugs gained 2.77% more weight than patients not on antihypertensives (P =.03).

Stratified by patient characteristics, the greatest weight gain for every additional month of treatment was observed among young adults (0.77%; P <.001) compared with older patients (0.46%; P <.001) or adults (0.30%; P <.001) whereas the greatest weight change with every additional 100 mg dose was observed among older patients (1.91%; <.001) compared with adults (0.71%; =.001) or young adults (-1.19%; =.01).

For genders, significant changes in weight among women were observed with every additional month of treatment (0.65%; P <.001) whereas higher doses (100 mg/day) increased weight among men (1.32%; P <.001).

No significant changes in metabolic outcomes in 4 months were reported.

The findings of this study may have been biased by not having access to data about food intake or physical activity.

Study authors concluded, “The present study reports a modest effect of clozapine dose increment on weight increase over [1] year, with differences among age categories and sexes, and no dose effect on other metabolic parameters over [4] months.”