Can the combination of Abilify (aripiprazole) and Lexapro (escitalopram) cause weight gain?

Can Abilify and Lexapro Cause Weight Gain When Combined?

Yes, the combination of Abilify (aripiprazole) and Lexapro (escitalopram) can cause weight gain, though the risk is relatively modest compared to other antipsychotic-antidepressant combinations, with aripiprazole contributing more to weight gain than escitalopram.

Weight Gain Risk from Aripiprazole (Abilify)

• Aripiprazole causes modest weight gain in adults, with mean weight change of +0.3 kg over 21-25 days in clinical trials, and 8.1% of patients with schizophrenia experienced ≥7% body weight gain compared to 3.2% on placebo 1
• At 24 weeks, aripiprazole-treated adults actually showed mean weight loss of -1.5 kg compared to -0.2 kg in placebo-treated patients, suggesting weight effects may stabilize or reverse with longer-term use 1
• In pediatric and adolescent patients (10-17 years), aripiprazole causes more significant weight gain with mean change of +1.6 kg over 42-43 days and +5.8 kg at 24 weeks, with 5.2% experiencing ≥7% body weight gain versus 1.6% on placebo 1
• Among antipsychotics, aripiprazole has a relatively favorable metabolic profile compared to clozapine and olanzapine, which carry the highest risk of weight gain and metabolic disturbances 2, 3

Weight Gain Risk from Escitalopram (Lexapro)

• Escitalopram is associated with minimal weight change during treatment, with an average increase of only 0.14 kg (0.05-point BMI increase) over 12 weeks of treatment 4
• Among SSRIs, escitalopram is considered relatively weight-neutral, particularly compared to paroxetine which has the highest risk of weight gain among all SSRIs 5, 6
• SSRIs as a class may cause transient weight loss during initial weeks of treatment followed by potential weight gain with long-term use, though escitalopram appears to maintain weight neutrality better than other SSRIs 7, 6

Combined Effect and Clinical Implications

• When medications are combined, the weight gain risk is primarily driven by aripiprazole rather than escitalopram, making this combination relatively favorable from a metabolic standpoint 8, 1
• The American Diabetes Association recommends minimizing medications associated with weight gain whenever possible and monitoring metabolic parameters including BMI, fasting glucose, and lipid profiles at baseline and regularly during treatment 8, 9
• Weight gain during antidepressant treatment that continues despite achieving full remission of depressive symptoms is likely a medication side effect rather than symptom improvement 6

Monitoring and Management Strategy

• Baseline assessment: Measure weight, BMI, fasting glucose, and lipid profile before initiating combination therapy 9
• Early monitoring: Assess weight weekly during the first month, as weight gain with aripiprazole typically commences during the first 6 weeks of treatment 1, 2
• Ongoing monitoring: Check weight monthly for the first 3 months, then quarterly during continued treatment, along with metabolic parameters 5, 9
• Intervention threshold: If weight gain ≥5% occurs within 3 months or metabolic parameters worsen, consider medication adjustment or intensified lifestyle interventions 8

Important Clinical Caveats

• Patients who are underweight at baseline may gain more weight during treatment, which could represent therapeutic benefit if weight loss was a depressive symptom 4
• Weight gain perceived as an undesired adverse effect by patients is a major contributor to medication nonadherence and treatment discontinuation 7, 6
• The combination of aripiprazole and escitalopram is substantially less likely to cause significant weight gain compared to combinations involving olanzapine, clozapine, or risperidone with tricyclic antidepressants or mirtazapine 8, 2
• Pediatric and adolescent patients require special attention as they show greater weight gain with aripiprazole than adults, and weight changes must be assessed using age- and gender-matched z-scores to account for normal growth 1