Can I start Abilify (aripiprazole) 10 mg with Depakote (valproate) for maintenance?

Starting Abilify 10 mg with Depakote for Maintenance in Bipolar Disorder

Yes, you can start Abilify (aripiprazole) 10 mg with Depakote (valproate) for maintenance treatment of bipolar I disorder—this combination is FDA-approved and guideline-recommended as both monotherapy continuation and adjunctive therapy for preventing mood episode recurrence. 1

Evidence Supporting This Combination

FDA-Approved Maintenance Strategy

• Aripiprazole combined with lithium or valproate demonstrated superiority over placebo in preventing relapse to any mood episode during 52 weeks of maintenance treatment in patients with bipolar I disorder who were initially stabilized on this combination. 1

• The FDA maintenance trial (Study 8) enrolled 337 patients who were first stabilized on aripiprazole (10-30 mg/day) plus lithium or valproate for 12 consecutive weeks, then randomized to continue the combination versus placebo plus mood stabilizer. 1

• The aripiprazole combination group experienced 25 mood events versus 43 in the placebo group, with particular benefit in preventing manic episodes (7 versus 19), though depressive episode prevention was similar (14 versus 18). 1

Guideline Recommendations

• The American Academy of Child and Adolescent Psychiatry recommends combination therapy with valproate plus an atypical antipsychotic as a first-line approach for severe presentations and treatment-resistant mania, with continuation for maintenance. 2

• Aripiprazole is specifically recommended as a first-line option for both acute mania treatment and maintenance therapy in bipolar I disorder, either as monotherapy or adjunctive to mood stabilizers. 2, 3

• The combination of aripiprazole with valproate appears particularly promising for patients with comorbidities including anxiety disorders, substance use disorders, and obsessive-compulsive disorder. 4

Practical Implementation

Dosing Strategy

• Start aripiprazole at 10 mg once daily, which is the FDA-approved dose for adolescents and a reasonable starting dose for adults, with the option to adjust to 15-30 mg/day based on response. 1, 5

• Ensure valproate is at therapeutic levels (40-90 mcg/mL) before adding aripiprazole, as the FDA maintenance trial required patients to be on therapeutic mood stabilizer levels. 6, 1

• Maintain both medications for at least 12-24 months after stabilization, as premature discontinuation is associated with relapse rates exceeding 90% in noncompliant patients. 2

Monitoring Requirements

• Baseline metabolic assessment is essential before starting aripiprazole: BMI, waist circumference, blood pressure, fasting glucose, and lipid panel. 2

• Follow-up monitoring should include BMI monthly for 3 months then quarterly, with blood pressure, glucose, and lipids rechecked at 3 months then yearly. 2

• For valproate, monitor serum drug levels, hepatic function, and hematological indices every 3-6 months once stable. 2, 6

Advantages of This Combination

Metabolic Safety Profile

• Aripiprazole has a favorable metabolic profile compared to other atypical antipsychotics, with lower risk of weight gain, diabetes, and dyslipidemia—particularly important when combined with valproate which itself carries metabolic risks. 2, 3

• The combination presents lower risk of metabolic side effects compared with other antipsychotic-mood stabilizer combinations, though it does increase risk of extrapyramidal symptoms with long-term treatment. 4

Efficacy Benefits

• Aripiprazole's unique mechanism as a partial D2 agonist may complement valproate's mood-stabilizing effects, providing both antimanic efficacy and some protection against depressive symptoms. 7, 3

• The combination is more effective than valproate monotherapy for preventing manic episode recurrence, based on FDA trial data showing 7 manic episodes with combination versus 19 with placebo plus mood stabilizer. 1

Important Caveats

Extrapyramidal Symptoms

• Extrapyramidal symptoms occurred in up to 28% of aripiprazole recipients in clinical trials, though after longer-term treatment (≤100 weeks), symptom severity did not differ significantly from placebo. 3

• Monitor for akathisia, tremor, and rigidity, particularly during the first 12 weeks of treatment, as these are the most common movement-related adverse effects. 5, 3

Limited Depressive Episode Prevention

• While this combination effectively prevents manic episodes, it shows similar rates of depressive episode recurrence compared to mood stabilizer alone (14 versus 18 episodes in the FDA trial). 1

• If depressive symptoms become prominent during maintenance, consider adding lamotrigine or switching strategies, as aripiprazole's primary benefit is antimanic rather than antidepressant. 2

Duration of Stabilization Before Maintenance

• The FDA maintenance trial required 12 consecutive weeks of stability (Y-MRS and MADRS scores ≤12) on the combination before entering the maintenance phase. 1

• Do not prematurely label this as "maintenance therapy" until the patient has demonstrated sustained stability on the combination for at least 12 weeks. 1

Common Pitfalls to Avoid

• Inadequate valproate dosing is a frequent error—ensure therapeutic levels (40-90 mcg/mL) are achieved before concluding the combination is ineffective. 6

• Failure to monitor for metabolic side effects, particularly weight gain, is a significant concern even with aripiprazole's favorable profile. 2

• Premature discontinuation of maintenance therapy leads to high relapse rates—continue treatment for at least 12-24 months after stabilization. 2

• Overlooking the need for psychoeducation and psychosocial interventions, which should accompany pharmacotherapy to improve outcomes. 2