Can Depakote (valproate) cause weight gain in a patient with bipolar disorder, particularly one with a history of Prozac (fluoxetine)-induced mania and currently being treated with Abilify (aripiprazole)?

Can Depakote Cause Weight Gain?

Yes, Depakote (valproate) consistently causes weight gain, which is one of its most problematic side effects, particularly in patients with bipolar disorder. 1

Evidence for Weight Gain with Valproate

• Weight gain is a particular concern with valproate, especially in younger patients with bipolar disorder. 2
• Weight gain and pharmacokinetic interactions are perhaps the most consistent problems in clinical use of valproate. 3
• The American Academy of Child and Adolescent Psychiatry explicitly recommends monitoring body mass index monthly for 3 months and then quarterly for patients on mood stabilizers like valproate. 1

Clinical Context for Your Patient

Given your patient's history of bipolar disorder currently treated with Abilify (aripiprazole), the weight gain risk with Depakote becomes particularly relevant:

• Aripiprazole has a favorable metabolic profile compared to other atypical antipsychotics, with lower risk of weight gain and metabolic side effects. 1
• If combination therapy is needed, the aripiprazole-valproate combination may be particularly promising for patients with comorbid anxiety, substance use disorders, obsessive-compulsive disorder, or mixed depressive features. 4
• However, combining valproate with aripiprazole will add the weight gain risk of valproate to the regimen. 2, 3

Alternative Considerations

Lithium presents a different metabolic profile: while lithium is also consistently associated with weight gain, it is NOT associated with significant sedation, making it potentially superior to valproate when sedation is a primary concern. 1

Proactive Weight Management

Regardless of medication choice, proactive weight management counseling is essential:

• Baseline body mass index, waist circumference, blood pressure, fasting glucose, and fasting lipid panel should be obtained before starting valproate. 1
• Monthly BMI monitoring for 3 months, then quarterly monitoring is required. 1
• Blood pressure, glucose, and lipids should be reassessed at 3 months then yearly. 1