Does Aripiprazole (Abilify) cause weight gain?

From the Guidelines

Aripiprazole (Abilify) is generally considered to have a lower risk of weight gain compared to other antipsychotic medications, with studies suggesting it is one of the few weight-neutral options in its class. According to the evidence from [1@], aripiprazole, along with lurasidone and ziprasidone, appears to have a lower risk for weight gain. The study notes that olanzapine, clozapine, quetiapine, and risperidone are consistently associated with weight gain, whereas aripiprazole demonstrates a lower risk [1@].

Key Points to Consider

• Aripiprazole's unique mechanism as a partial dopamine agonist may contribute to its lower risk of weight gain [1@].
• Individual responses to aripiprazole can vary, with some patients experiencing no weight change, others gaining weight, and some losing weight.
• Regular monitoring of weight, especially during the first few months of treatment, is crucial.
• Lifestyle factors such as diet and exercise remain important while taking this medication.
• If weight gain becomes problematic, discussing possible dose adjustments or alternative medications with a healthcare provider is recommended.

Comparison with Other Antipsychotics

• Aripiprazole's weight gain risk is significantly lower than medications like olanzapine (Zyprexa) or quetiapine (Seroquel), which can cause substantial weight gains [1@].
• The choice of antipsychotic medication should be guided by the individual patient's circumstances, considering factors beyond just weight gain risk.

Given the available evidence, the use of aripiprazole is recommended for patients where weight gain is a concern, due to its relatively favorable weight profile compared to other antipsychotic medications [1

From the FDA Drug Label

Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of weight is recommended.

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.

Table 14: Percentage of Patients From Placebo-Controlled Trials in Adult Patients with Weight Gain ≥7% of Body Weight

Indication Treatment Arm N Patients n (%) Weight gain≥ 7% of body weight

Schizophrenia * Aripiprazole Tablets 852 69 (8.1) Placebo 379 12 (3. 2)

In an analysis of two placebo-controlled trials in adolescents with schizophrenia (13 to 17 years) and pediatric patients with another indication (10 to 17 years) with median exposure of 42 to 43 days, the mean change in body weight in aripiprazole-treated patients was +1.6 kg (N=381) compared to +0. 3 kg (N=187) in placebo-treated patients.

Table 15 shows the percentage of pediatric and adolescent patients with weight gain ≥7% of body weight by indication

Table 15: Percentage of Patients From Placebo-Controlled Monotherapy Trials in Pediatric and Adolescent Patients with Weight Gain ≥7% of Body Weight

Indication Treatment Arm N Patients n (%) Weight gain ≥7% of body weight

Pooled Schizophrenia and another indication * Aripiprazole Tablets 381 20 (5.2) Placebo 187 3 (1. 6)

Weight Gain with Aripiprazole:

• Aripiprazole may cause weight gain, as observed with other atypical antipsychotics.
• Clinical monitoring of weight is recommended.
• The mean change in body weight in aripiprazole-treated patients was +0.3 kg compared to -0.1 kg in placebo-controlled patients.
• 8.1% of adult patients with schizophrenia treated with aripiprazole experienced weight gain ≥7% of body weight.
• 5.2% of pediatric and adolescent patients treated with aripiprazole experienced weight gain ≥7% of body weight.
• Patients should be monitored for weight gain, and their healthcare provider should assess their weight regularly 1.

From the Research

Weight Gain Associated with Aripiprazole

• Aripiprazole is considered to have a lower likelihood of metabolic abnormalities, including weight gain, compared to other atypical antipsychotics 2.
• A systematic review and meta-analysis found that all antipsychotics, including aripiprazole, led to significantly more weight gain compared to placebo 3.
• A study on pediatric antipsychotic-related overweight/obesity found that switching to aripiprazole, a lower risk antipsychotic, can reduce weight gain 4.
• A review of real-world data on the effects of aripiprazole on weight and metabolic outcomes in adults found that aripiprazole may be associated with a lower risk of metabolic adverse events, including weight gain, compared to other atypical antipsychotics 2.
• A study on weight gain changes in patients with aripiprazole monotherapy compared to aripiprazole-antidepressant polypharmacy found that patients on aripiprazole monotherapy showed statistically significant weight gain, but there was no significant difference in weight gain between the monotherapy and combination therapy groups 5.

Comparison to Other Antipsychotics

• Aripiprazole has been found to have a comparable or lower impact on weight gain compared to other atypical antipsychotics 2.
• A meta-analysis found that metformin, a medication used to manage weight gain, can decrease weight in children and adolescents treated with second-generation antipsychotics, including aripiprazole 6.
• The American Diabetes Association and the American Psychiatric Association have categorized aripiprazole as an atypical antipsychotic with a lower likelihood of metabolic abnormalities, including weight gain 2.

Clinical Implications

• Clinicians should be aware of the potential for weight gain with aripiprazole and monitor patients accordingly 3, 5.
• Metformin may be considered as an adjunctive therapy to manage weight gain in patients treated with aripiprazole, particularly in pediatric populations 6.
• Healthy lifestyle education may not be sufficient to prevent ongoing weight gain in patients treated with aripiprazole, and other interventions may be necessary 4.