What antipsychotic medications are most commonly associated with weight gain?

Antipsychotics Associated with Weight Gain

Clozapine and olanzapine cause the most severe weight gain among all antipsychotics, with clozapine leading to approximately 4.45 kg gain after 10 weeks of treatment, followed closely by olanzapine at 4.15 kg. 1

Highest Risk Antipsychotics (Most to Least)

Extreme Weight Gain Risk

• Clozapine: Causes mean weight gain of 4.45 kg at 10 weeks, with 35% of patients experiencing ≥7% body weight increase 2, 1. FDA labeling confirms weight gain occurs with clozapine use and requires monitoring 2.
• Olanzapine: Produces mean weight gain of 4.15 kg at 10 weeks, with 46% of patients experiencing ≥7% body weight increase—the highest proportion among comparators 2, 1.

Moderate Weight Gain Risk

• Risperidone: Associated with mean weight gain of 2.10 kg at 10 weeks, with 14% experiencing ≥7% body weight increase 2, 1.
• Quetiapine: Causes intermediate weight gain effects, with 16% of patients experiencing ≥7% body weight increase 3.
• Sertindole: Produces mean weight gain of 2.92 kg at 10 weeks 1.

Lower Weight Gain Risk

• Aripiprazole: Has a neutral influence on body weight 3.
• Ziprasidone: Minimal weight effect with only 0.04 kg mean gain at 10 weeks and 7% experiencing ≥7% body weight increase 2, 1.

Traditional Antipsychotics

• Thioridazine: Highest weight gain among conventional agents at 3.19 kg mean increase 1.
• Chlorpromazine: Causes weight gain of 0.6 kg at 4 weeks, increasing to modest levels over time, with only 8% experiencing ≥7% body weight increase 2, 1.
• Haloperidol: Associated with 22% of patients experiencing ≥7% body weight increase 4.
• Molindone: Exception among antipsychotics—associated with mean weight reduction of 0.39 kg 1, 5.

Critical Clinical Considerations

Weight gain with atypical antipsychotics may be extreme and represents the most common significant problem associated with their use 6. The American Academy of Child and Adolescent Psychiatry guidelines emphasize this is particularly concerning in pediatric populations 6.

Time Course of Weight Gain

• Weight increases most rapidly during initial treatment weeks 7.
• Patients continue gaining weight long-term with sustained exposure 7.
• Children are particularly vulnerable to antipsychotic-induced weight gain 7.

Clinical Impact

• Weight gain leads to increased cardiovascular and cerebrovascular morbidity and mortality 7.
• Reduces quality of life and causes poor medication compliance 7.
• Lower baseline BMI predicts greater antipsychotic-induced weight gain 4.