Characterizing weight changes in a long-term open-label study of adjunctive cariprazine for major depressive disorder

Background: People with major depressive disorder (MDD) have an increased risk of obesity, and weight gain has been linked to antipsychotics and antidepressants (ADTs). This underscores the clinical importance of understanding weight change with medication use.

Methods: We conducted post hoc analyses of safety data from a 26-week, open-label, phase 3 study (NCT01838876) of adjunctive cariprazine (flexible-dose, 1.5–4.5 mg/d) in adults with MDD having an inadequate response to ADT to understand the relationship between weight change and baseline BMI, baseline medical conditions, final cariprazine dose, and concomitant medications.

Results: Participants had a mean (standard deviation; sample size) baseline weight of 83.63 kg (18.47 kg; n=345) and a mean increase of 1.66 kg (4.58 kg; n=210) from baseline at week 26. One-third (33.3%) of participants did not experience weight gain from baseline, 41.4% experienced an increase of < 5% of their body weight, and 16.7% experienced a ≥7% increase. After treatment, most participants remained in the same BMI category as baseline. For each baseline BMI category, participants with a lower final dose of cariprazine (1.5 mg/d) tended to have less weight gain than those with a higher dose (4.5 mg/d). Of the 55 participants with ≥7% weight gain, 19.7% had a metabolic/nutrition disorder, and their most common concomitant medications were anti-inflammatories (31.8%), psycholeptics (25.8%), and analgesics (21.2%).

Conclusion: Weight gain with long-term use of cariprazine was modest, with most participants gaining < 5% of their body weight or gaining no weight after 26 weeks.