Weight Gain with Vraylar (Cariprazine)
Vraylar is associated with minimal weight gain, averaging approximately 0.8-1.4 kg (1.8-3.1 lbs) over 3-12 months in clinical trials, with the majority of patients (82.8%) not experiencing clinically significant weight gain (≥7% of body weight). 1
Clinical Trial Data by Indication
Schizophrenia
- Mean weight change at endpoint in 6-week trials: +0.3 kg (placebo) to +1.0 kg (cariprazine 4.5-6 mg/day) 1
- Proportion with ≥7% weight gain: 5-8% at therapeutic doses (1.5-6 mg/day) versus 5% with placebo 1
- Long-term data: Mean weight increases of 1.2 kg at 12 weeks, 1.7 kg at 24 weeks, and 2.5 kg at 48 weeks 1
Bipolar Mania
- Mean weight change in 3-week trials: +0.5 to +0.6 kg (cariprazine 3-6 mg/day) versus +0.2 kg (placebo) 1
- Proportion with ≥7% weight gain: 1-3% across all doses 1
Bipolar Depression
- Mean weight change in 6-8 week trials: +0.4 to +0.7 kg (cariprazine) versus -0.1 kg (placebo) 1
- Proportion with ≥7% weight gain: 3% at both 1.5 mg and 3 mg doses 1
Major Depressive Disorder (Adjunctive)
- Mean weight change in 6-week trials: +0.7 kg (cariprazine 1.5-3 mg/day) versus +0.2 kg (placebo + antidepressant) 1
- Mean weight change in 8-week trials: +0.9 kg (cariprazine 1-4.5 mg/day) versus 0 kg (placebo + antidepressant) 1
- Proportion with ≥7% weight gain: 2-3% across all doses 1
- Long-term data at 26 weeks: Mean weight increase of 1.7 kg, with 19% experiencing ≥7% weight gain 1
Real-World Evidence
Real-world data demonstrates even more favorable weight outcomes than clinical trials:
- Average predicted weight change: +2.4 kg over the entire follow-up period (average 133.7 days) 2
- Time-specific weight changes: +0.8 kg at 3 months, +1.1 kg at 6 months, and +1.4 kg at 12 months 2
- Clinically significant weight changes: 82.8% did not experience ≥7% weight gain, and 90.5% did not experience ≥7% weight loss 2
- Annual trajectory analysis: Weight gain of +0.91 kg/year during cariprazine treatment, compared to +3.55 kg/year before cariprazine initiation 3
Comparative Context
Vraylar demonstrates a favorable metabolic profile compared to other antipsychotics:
- Olanzapine, clozapine, quetiapine, and risperidone are associated with significantly more weight gain than cariprazine 4
- In direct comparisons with other newer second-generation antipsychotics, cariprazine showed minimal weight gain (4.25 lbs at 1 year, not statistically significant), similar to asenapine and lurasidone, but more favorable than brexpiprazole (5.97 lbs, p=0.01) and iloperidone (5.13 lbs, p=0.02) 5
Metabolic Parameters
Beyond weight, cariprazine shows neutral to favorable effects on metabolic markers:
- HbA1c: Decreased by -0.2%/year during treatment (compared to +0.15%/year increase at baseline) 2
- Triglycerides: Decreased by -0.7 mg/dL/year during treatment (compared to +15.0 mg/dL/year increase at baseline) 2
- Blood pressure: Annual trajectories showed -2.38 mmHg/year for systolic BP and -0.57 mmHg/year for diastolic BP 3
- Cholesterol shifts: 90.2% did not shift from normal/borderline to high total cholesterol, and 61.1% shifted from high to normal/borderline levels 2
Clinical Monitoring Recommendations
The FDA label mandates specific monitoring protocols:
- Monitor weight at baseline and frequently thereafter 1
- Obtain fasting lipid profile at baseline or soon after initiation, then monitor periodically during treatment 1
- Monitor fasting glucose and HbA1c in patients with diabetes or at risk for diabetes 1
Important Caveats
- Weight gain appears dose-dependent in some analyses, though the effect is modest across the therapeutic range 1
- Most weight gain occurs early in treatment and plateaus over time 2, 3
- Individual patient responses vary; approximately 17% of patients may experience ≥7% weight gain at higher doses 1
- Real-world discontinuation rates for metabolic medications were 60.4 per 100 patient-years for antihyperglycemic agents and 87.4 per 100 patient-years for hyperlipidemia medications after starting cariprazine 2