Can Clomipramine Cause Weight Gain?
Yes, clomipramine is associated with significant weight gain, with 18% of patients experiencing weight gain in controlled trials and 28% gaining at least 7% of their initial body weight—substantially higher than the 4% seen with placebo. 1
Evidence from FDA Drug Labeling
The FDA-approved drug label for clomipramine provides the most authoritative data on this adverse effect:
- In controlled OCD studies, weight gain occurred in 18% of clomipramine-treated patients versus only 1% on placebo 1
- 28% of clomipramine patients gained ≥7% of their initial body weight, compared to just 4% on placebo 1
- Several patients experienced weight gains exceeding 25% of their initial body weight 1
- Conversely, only 5% of clomipramine patients lost ≥7% of body weight versus 1% on placebo 1
Comparative Risk Among Antidepressants
Clomipramine carries a higher weight gain risk than many other antidepressant options:
- Among tricyclic antidepressants, amitriptyline carries the greatest weight gain risk, though clomipramine is also problematic 2
- In a 2.5-year prospective study of OCD patients, clomipramine was associated with the highest weight increase among all serotonin reuptake inhibitors studied, with 34.8% of patients gaining ≥7% body weight 3
- This contrasts sharply with sertraline (4.5%) and fluoxetine (8.7%) in the same study 3
- Bupropion is the only antidepressant consistently associated with weight loss rather than weight gain and should be considered when weight is a primary concern 2
Clinical Context and Mechanism
The weight gain with clomipramine appears dose-related and occurs during long-term treatment:
- Adverse effects of clomipramine, including weight gain, appear to be dose-related 4
- At the 2.5-year endpoint in OCD treatment, patients on clomipramine gained a mean of 2.5% body weight (1.58 kg) 3
- The mechanism likely involves hypothalamic effects on hunger and appetite regulation 5, 6
Important Clinical Caveats
Weight gain with clomipramine poses risks to both health and treatment compliance 7:
- Weight gain is associated with reduced insulin sensitivity and can trigger polycystic ovary syndrome in predisposed women 4
- Clinicians should monitor weight regularly during clomipramine treatment 1
- Consider switching to more weight-neutral alternatives (fluoxetine, sertraline) or weight-loss promoting options (bupropion) if excessive weight gain occurs 2, 3