What antipsychotic medications do not cause weight gain?

From the Guidelines

Lurasidone and ziprasidone are the most weight-neutral antipsychotic options, with aripiprazole also demonstrating a lower risk for weight gain. When considering antipsychotics that do not cause significant weight gain, it is essential to look at the most recent and highest quality studies. According to the evidence from [1@], lurasidone and ziprasidone appear to be the most weight-neutral in the class, with aripiprazole generally demonstrating a lower risk for weight gain as well [1@].

Key Considerations

• Lurasidone, ziprasidone, and aripiprazole have lower affinity for histamine H1 and serotonin 5-HT2C receptors, which are associated with increased appetite and metabolic changes [1@].
• These medications are often called "weight-neutral" antipsychotics and are preferred options for patients with weight concerns [1@].
• Regular monitoring of weight, blood glucose, and lipids is still important, even when using these medications [1@].
• Combining medication with healthy lifestyle habits can help minimize any potential weight changes [1@].

Dosage and Administration

• Aripiprazole is typically started at 5-10mg daily [1@].
• Ziprasidone is usually started at 20mg twice daily, with doses adjusted based on response [1@].
• Lurasidone should be taken with food (at least 350 calories) for proper absorption, usually starting at 40mg daily [1@].

Comparison to Other Antipsychotics

• Olanzapine, clozapine, quetiapine, and risperidone are consistently associated with weight gain [1@].
• Studies demonstrate that patients may lose weight and develop improved glucose tolerance when switched from olanzapine to ziprasidone [1

From the FDA Drug Label

Weight Gain Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of weight is recommended. Adults In an analysis of 13 placebo-controlled monotherapy trials, primarily from pooled schizophrenia and another indication, with a median exposure of 21 to 25 days, the mean change in body weight in aripiprazole-treated patients was +0. 3 kg (N=1673) compared to –0.1 kg (N=1100) in placebo-controlled patients. Table 14 shows the percentage of adult patients with weight gain ≥7% of body weight by indication. In an open-label trial that enrolled patients from the two placebo-controlled trials of adolescents with schizophrenia (13 to 17 years) and pediatric patients with another indication (10 to 17 years), 73.2% of patients (238/325) completed 26 weeks of therapy with aripiprazole. After 26 weeks, 32. 8% of patients gained ≥7% of their body weight, not adjusted for normal growth.

Aripiprazole is associated with a mean weight gain of +0.3 kg in adults, and 32.8% of patients gained ≥7% of their body weight after 26 weeks of therapy.

Weight Gain Weight gain has been observed with atypical antipsychotic use. Monitoring of weight is recommended. Pooled data from short-term, placebo-controlled studies in schizophrenia and bipolar disorder are presented in Table 9 and 10 Table 9: Weight Mean Changes in Short-Term (up to 6 weeks), Placebo-Controlled, Fixed-Dose, Oral Ziprasidone Monotherapy Trials in Adult Patients With Schizophrenia The proportions of patients meeting a weight gain criterion of ≥ 7% of body weight were compared in a pool of four 4- and 6-week placebo-controlled schizophrenia clinical trials, revealing a statistically significantly greater incidence of weight gain for ziprasidone (10%) compared to placebo (4%).

Ziprasidone is associated with a statistically significantly greater incidence of weight gain (10%) compared to placebo (4%) in short-term studies.

Considering the available data, Aripiprazole may be a better option for patients who are concerned about weight gain, as it is associated with a lower mean weight gain and a lower percentage of patients with ≥7% weight gain compared to Ziprasidone. However, it is essential to monitor weight in all patients taking atypical antipsychotics. 1 2

From the Research

Antipsychotic Options with Low Weight Gain Risk

• Aripiprazole has been identified as an atypical antipsychotic with a low potential for bodyweight gain 3, 4, 5.
• Studies have shown that aripiprazole is associated with a lower risk of metabolic adverse events, including weight gain, compared to other atypical antipsychotics 4.
• Lurasidone is another antipsychotic that has been found to have a lower risk of clinically relevant weight gain and a higher likelihood of clinically relevant weight loss compared to other antipsychotics 6, 7.

Comparison of Antipsychotics

• Aripiprazole has been compared to other antipsychotics, such as haloperidol and olanzapine, and has been found to have a more favorable profile in terms of weight gain 3, 5.
• Lurasidone has been compared to antipsychotics with a medium-high risk of weight gain, such as olanzapine, and has been found to have a lower risk of clinically relevant weight gain 6.

Real-World Studies

• Real-world studies have consistently shown that aripiprazole and lurasidone are associated with a lower risk of weight gain compared to other antipsychotics 4, 6, 7.
• These studies suggest that aripiprazole and lurasidone may be good options for patients who are concerned about weight gain or who have a history of weight gain with other antipsychotics.