Lurasidone Has the Lowest Weight Gain Risk
Lurasidone is associated with the lowest risk of weight gain and the highest likelihood of clinically relevant weight loss compared to aripiprazole (Abilify) and other commonly used antipsychotics. 1
Evidence-Based Weight Comparison
Lurasidone's Superior Weight Profile
Lurasidone demonstrates the smallest proportion of patients experiencing clinically relevant (≥7%) weight gain and the greatest proportion achieving clinically relevant weight loss among all antipsychotics studied. 1
In a real-world study of 15,323 adults with schizophrenia, lurasidone was associated with an estimated weight reduction of 0.77 kg at 1-year follow-up, with even greater weight loss (1.68 kg) in patients switching from medium/high-risk antipsychotics. 2
Lurasidone appears to be the best antipsychotic in terms of minimizing unwanted alterations in body weight and metabolic variables. 3
Aripiprazole's Weight Profile
Aripiprazole is classified among antipsychotics with a "low risk" of weight gain, but this still represents higher risk than lurasidone. 1
The likelihood of ≥7% weight loss was significantly greater with lurasidone versus all antipsychotics (p<0.05), with the sole exception being ziprasidone. 1
Clinical Implications for Practice
When to Prioritize Lurasidone
For patients with schizophrenia where metabolic side effects are a primary concern, lurasidone should be the first-line choice over aripiprazole. 4
Patients switching to lurasidone from other antipsychotics (including aripiprazole) may experience weight reduction and improvements in ability to focus/concentrate. 4
The American Gastroenterological Association recognizes weight gain as a common adverse effect of antipsychotics that impacts treatment acceptability and long-term health, particularly regarding metabolic syndrome and cardiovascular risk. 5
Comparative Risk Stratification
Olanzapine carries significantly higher risk of clinically relevant weight gain versus lurasidone (hazard ratio=1.541; 95% CI=1.121-2.119; p=0.0078). 1
Medium-high risk antipsychotics (clozapine, olanzapine, quetiapine, risperidone, paliperidone) all demonstrate numerically higher weight gain risk than lurasidone. 1
Aripiprazole, while in the "low risk" category alongside ziprasidone and first-generation antipsychotics, still shows statistically significant differences favoring lurasidone for weight loss outcomes. 1
Important Clinical Caveats
Managing Side Effects
Most side effects with lurasidone (such as somnolence) are transitory and easily managed through dose adjustment. 4
Akathisia and extrapyramidal symptoms may occur in a minority of patients but can be managed effectively with dose adjustment, adjunctive therapy, and/or psychosocial intervention. 4
Long-Term Considerations
Lurasidone demonstrates sustained weight benefits over 12-month periods in both clinical trials and real-world settings, making it suitable for long-term management. 2, 6
Lurasidone 40-160 mg/d was noninferior to quetiapine extended-release on relapse outcomes while demonstrating superior outcomes for avoidance of hospitalization (NNT 8) and remission (NNT 7), with lower long-term weight gain risk. 6