Weight Gain Comparison: Quetiapine (Seroquel) vs Aripiprazole (Abilify)
Quetiapine causes substantially more weight gain than aripiprazole, with approximately 23% of quetiapine-treated adults gaining ≥7% body weight compared to only 8% with aripiprazole in short-term trials. 1, 2
Direct Comparative Evidence
The most definitive evidence comes from head-to-head trials:
In a 26-week randomized controlled trial comparing aripiprazole versus olanzapine, aripiprazole resulted in mean weight loss of 1.37 kg while olanzapine caused mean weight gain of 4.23 kg (p<0.001), with only 14% of aripiprazole patients experiencing ≥7% weight gain versus 37% with olanzapine. 3 While this compares aripiprazole to olanzapine rather than quetiapine directly, it establishes aripiprazole's favorable metabolic profile among atypicals.
In a pediatric head-to-head trial (ages 12-17), quetiapine-ER caused significantly more rapid weight gain than aripiprazole (p=0.0008), with an adjusted mean weight difference of 3.33 kg favoring aripiprazole at 12 weeks (effect size 0.64, p<0.0001). 4
FDA-Labeled Weight Gain Data
Quetiapine (Seroquel)
- In adults with schizophrenia (up to 6 weeks), 23% of quetiapine patients gained ≥7% body weight versus 6% with placebo. 1
- In pediatric patients with schizophrenia (6 weeks), 21% gained ≥7% body weight versus 7% with placebo; in bipolar mania (3 weeks), 12% versus 0%. 1
- After 26 weeks of open-label treatment in pediatric patients, 45% gained ≥7% body weight, with mean increase of 4.4 kg. 1
Aripiprazole (Abilify)
- In adults with schizophrenia (4-6 weeks), only 8.1% of aripiprazole patients gained ≥7% body weight versus 3.2% with placebo. 2
- In pediatric patients (pooled schizophrenia and bipolar mania, 4-6 weeks), 5.2% gained ≥7% body weight versus 1.6% with placebo. 2
- Mean weight change in adults at 24 weeks was -1.5 kg with aripiprazole versus -0.2 kg with placebo. 2
Metabolic Considerations Beyond Weight
Quetiapine causes significantly worse lipid profile changes than aripiprazole, with higher rates of triglyceride elevations (28% vs 9% in pediatric patients). 1, 4
The pediatric head-to-head trial showed quetiapine caused significantly worse insulin resistance (HOMA-IR) than aripiprazole (adjusted mean log-transformed difference 0.259, effect size 0.35, p=0.0060). 4
Aripiprazole demonstrates minimal impact on cholesterol and triglycerides, with rates similar to placebo in FDA trials. 2
Clinical Context from Guidelines
Guidelines recommend prioritizing glucose-lowering medications with beneficial effects on weight in patients with diabetes and obesity, and specifically advise minimizing medications associated with weight gain for comorbid conditions. 5
Among antipsychotics, weight gain is recognized as a common adverse effect that impacts treatment acceptability and long-term health, particularly regarding metabolic syndrome and cardiovascular risk. 5
Important Caveats
Aripiprazole causes significantly more akathisia than quetiapine, particularly in the first 2 weeks (60% vs 30%, p=0.0021), though this difference diminishes over time. 4
Both medications cause sedation, but aripiprazole paradoxically showed higher overall sedation rates (97.1%) than quetiapine (89.2%) in the pediatric head-to-head trial (p=0.012), contrary to typical expectations. 4
Long-term data (>1 year) suggests quetiapine may have a "weight-neutral or normalizing effect" in some patients, particularly those who are underweight or severely obese at baseline, though this does not negate the substantial weight gain risk in most patients. 6
Weight gain with both medications is most pronounced in pediatric populations, where 32.8% of aripiprazole-treated patients gained ≥7% body weight after 26 weeks versus 45% with quetiapine. 2, 1