In adult patients, which antipsychotic causes less weight gain, aripiprazole (Abilify) or lurasidone (Latuda)?

Lurasidone (Latuda) Causes Less Weight Gain Than Aripiprazole (Abilify)

Lurasidone is the preferred choice when minimizing weight gain is a priority, as it demonstrates superior weight neutrality compared to aripiprazole. 1, 2

Evidence-Based Comparison

Guideline Recommendations

• The American Gastroenterological Association explicitly recommends lurasidone and ziprasidone as the preferred alternatives to aripiprazole for weight-concerned patients, as they demonstrate significantly lower weight gain liability. 1
• Aripiprazole is considered among the lower-risk antipsychotics for weight gain compared to olanzapine, clozapine, quetiapine, and risperidone, but it is not weight-neutral despite common misconceptions. 2
• If weight gain is severe (≥10% of baseline) and refractory to interventions, guidelines suggest switching from aripiprazole to ziprasidone or lurasidone, which are the most weight-neutral antipsychotics. 2

FDA-Approved Drug Label Data

Aripiprazole (Abilify): 3

• In adult monotherapy trials (median exposure 21-25 days), mean weight change was +0.3 kg versus -0.1 kg for placebo
• 8.1% of patients with schizophrenia gained ≥7% body weight (versus 3.2% placebo) in 4-6 week trials
• In pediatric patients at 24 weeks, 32.8% gained ≥7% body weight

Lurasidone (Latuda): 4

• In adult bipolar depression monotherapy, mean weight change was +0.29 kg versus -0.04 kg for placebo
• Only 2.4% of patients gained ≥7% body weight (versus 0.7% placebo)
• In adjunctive therapy trials, mean weight change was +0.11 kg with only 3.1% gaining ≥7% body weight
• Pediatric patients showed minimal deviation from normal growth curves (z-score change of -0.06 SD at 104 weeks)

Real-World Evidence

• A large retrospective study of 15,323 adults with schizophrenia found that lurasidone was associated with the smallest proportion of patients experiencing clinically relevant weight gain and the greatest proportion with clinically relevant weight loss. 5
• The risk of ≥7% weight gain was significantly higher with olanzapine versus lurasidone (HR=1.541, p=0.0078), and the likelihood of ≥7% weight loss was significantly greater with lurasidone versus all antipsychotics except ziprasidone. 5
• A 2014 clinical pharmacology review concluded that lurasidone appears best in terms of minimizing unwanted alterations in body weight and metabolic variables among second-generation antipsychotics. 6

Clinical Decision Algorithm

When weight gain is a primary concern: 1, 2

1. First-line choice: Lurasidone or ziprasidone (most weight-neutral)
2. Second-line choice: Aripiprazole (lower risk than olanzapine/clozapine/quetiapine/risperidone, but not weight-neutral)
3. Avoid: Olanzapine, clozapine, quetiapine, risperidone (highest weight gain risk)

Important Clinical Caveats

• Aripiprazole's "weight-neutral" reputation is a misconception that can lead to inadequate monitoring and intervention. 2
• Weight gain ≥7% should trigger consideration of adding pharmacotherapy (GLP-1 agonists, metformin) or switching antipsychotics. 2
• Implement lifestyle interventions immediately at treatment start, not after weight gain occurs—this is critical for prevention. 2
• Monitor weight at baseline, monthly for the first 3 months, then quarterly during continued treatment. 1
• A dose-response meta-analysis showed that most antipsychotics, including aripiprazole, demonstrate an initial dose-related increase in weight that plateaus at higher doses. 7