Is Caplyta (lumateperone) weight neutral?

From the Guidelines

Caplyta (lumateperone) is generally considered weight neutral, meaning it typically does not cause significant weight gain for most patients. This is based on the fact that, unlike many other antipsychotics such as olanzapine, clozapine, quetiapine, and risperidone, which are consistently associated with weight gain 1, Caplyta has a unique receptor binding profile that likely contributes to its weight-neutral effect. Some antipsychotics, like lurasidone and ziprasidone, are also considered weight-neutral, with aripiprazole generally demonstrating a lower risk for weight gain as well 1. However, individual responses can vary, and some patients may still experience weight changes while taking Caplyta. Regular monitoring of weight is still recommended while taking Caplyta, especially during the initial treatment period. Patients with concerns about medication-related weight changes should discuss this with their healthcare provider, as it represents an important consideration in antipsychotic medication selection and adherence to treatment. Key points to consider when evaluating the weight impact of antipsychotics like Caplyta include:

• The medication's receptor binding profile, particularly its interaction with histamine H1 receptors
• The results of clinical trials assessing weight changes in patients taking the medication
• Individual patient factors that may influence weight changes, such as diet, exercise, and other health conditions.

From the FDA Drug Label

Weight Gain Weight gain has been observed with use of antipsychotics. Monitor weight at baseline and frequently thereafter Schizophrenia In pooled data from placebo-controlled trials of adult patients with schizophrenia, mean changes from baseline and the proportion of patients with an increase in weight ≥7% from baseline to end of study was similar in patients treated with CAPLYTA and placebo In an uncontrolled open-label trial of CAPLYTA for up to 1 year in patients with stable schizophrenia, the mean change in body weight was approximately -2 kg (SD 5.6) at Day 175 and approximately - 3.2 kg (SD 7. 4) at Day 350. Bipolar Depression In data from short-term (6-week), placebo-controlled monotherapy and adjunctive therapy bipolar depression trials, mean changes from baseline and the proportion of patients with an increase in weight ≥7% from baseline to end of study were similar in patients treated with CAPLYTA and placebo In an uncontrolled open-label trial of CAPLYTA for up to 6 months in patients with bipolar depression, the mean change in body weight was -0.01 kg (SD 3.1) at Day 175.

Key Points:

• The mean change in body weight for patients with schizophrenia was approximately -2 kg at Day 175 and -3.2 kg at Day 350.
• The mean change in body weight for patients with bipolar depression was -0.01 kg at Day 175.
• The proportion of patients with an increase in weight ≥7% was similar between CAPLYTA and placebo in both schizophrenia and bipolar depression trials. Based on the data, CAPLYTA can be considered weight neutral 2.

From the Research

Caplyta Weight Neutral

• Caplyta, also known as lumateperone, has been studied in terms of its weight gain effects compared to other antipsychotics 3, 4, 5.
• A dose-response meta-analysis found that lumateperone produced mild weight gain in comparison to placebo, with a mean difference at any dose ≤1 kg 3.
• A review of novel antipsychotics, including lumateperone, found that it had a lower risk of weight gain compared to brexpiprazole, but a higher risk of akathisia compared to placebo and other antipsychotics 4.
• A comparison of lumateperone with other atypical antipsychotics, including aripiprazole, brexpiprazole, and cariprazine, found that lumateperone had the lowest rate of weight gain 5.
• Overall, the evidence suggests that Caplyta is weight neutral, with a lower risk of weight gain compared to some other antipsychotics 3, 4, 5.

Comparison to Other Antipsychotics

• Brexpiprazole was found to have a higher rate of weight gain associated with increased appetite compared to lumateperone 5.
• Cariprazine had a higher risk of akathisia compared to lumateperone, but a similar risk of weight gain 4, 5.
• Aripiprazole had a lower rate of extrapyramidal symptoms, but a similar risk of weight gain compared to lumateperone 5.

Clinical Implications

• The weight neutral profile of Caplyta makes it a potentially useful option for patients who are at risk of weight gain or metabolic side effects 3, 4, 5.
• Clinicians should consider the individual patient's risk factors and clinical profile when selecting an antipsychotic medication 4, 5.