Is it okay to add Abilify (aripiprazole) to citalopram (escitalopram) in a patient with unmanaged anxiety and depression?

Adding Aripiprazole to Citalopram for Treatment-Resistant Depression and Anxiety

Yes, adding aripiprazole (Abilify) to citalopram is a reasonable and evidence-supported strategy for your patient with inadequately controlled depression and anxiety. This augmentation approach has demonstrated efficacy in treatment-resistant major depressive disorder, including in patients with prominent anxiety features.

Evidence for Aripiprazole Augmentation

Aripiprazole augmentation of SSRIs like citalopram has shown significant benefit in treatment-resistant depression. In pooled analyses of patients with major depressive disorder who failed initial antidepressant therapy, adjunctive aripiprazole produced significantly greater improvement in depression scores compared to placebo, with benefits emerging as early as week 1-2 and continuing through endpoint 1. Importantly, this benefit was consistent in patients presenting with anxious features at baseline 1.

• Response rates with aripiprazole augmentation range from 59-62.5% in patients with persistent depression and anxiety despite SSRI treatment 2, 3
• Remission rates of 50% have been reported when combining aripiprazole with escitalopram (a close relative of citalopram) 3
• The combination appears effective for both depressive and anxiety symptoms simultaneously 2

Dosing Strategy

Start aripiprazole at a low dose and titrate gradually based on response and tolerability:

• Initial dose: 2-5 mg daily 2, 3
• Therapeutic range: Most patients respond to 15-30 mg daily, though some benefit from doses as low as 2-10 mg 2, 4
• Titration: Increase slowly over several weeks as tolerated
• Some patients show early response (weeks 1-5) while others require sustained treatment 2

Critical Side Effect Considerations

Akathisia is the most important side effect to monitor and manage proactively. In one study, 10 of 16 patients (62.5%) developed akathisia, though 9 of these 10 had resolution or partial resolution with dose adjustment or propranolol treatment 3.

Central Nervous System Effects

• Drowsiness, nervousness, and agitation are the most frequent and severe side effects 4
• Patients with pretreatment anxious depression (GAD-7 ≥10) are at significantly higher risk for nervousness and agitation, particularly in the first 2 weeks 4
• These anxiety-related side effects appear more related to the SSRI than aripiprazole itself 4

Other Notable Side Effects

• Headache, insomnia, dizziness 5
• Weight gain and metabolic effects with long-term use 5
• Lower risk of extrapyramidal symptoms compared to typical antipsychotics 5

Important Drug Interactions

Monitor for cytochrome P450 interactions, as aripiprazole is metabolized by CYP2D6 and CYP3A4:

• Reduce aripiprazole dose in poor CYP2D6 metabolizers 5
• Consult with pharmacy regarding potential drug-drug interactions with other medications metabolized by these pathways 5

Alternative Considerations

Before adding aripiprazole, ensure the citalopram dose is optimized. The American College of Physicians guidelines note that second-generation antidepressants generally show similar efficacy for treating anxiety associated with major depressive disorder 5. However, citalopram has dose limitations due to QT prolongation risk—do not exceed 40 mg daily 5.

If switching rather than augmenting is preferred, consider:

• Venlafaxine may be superior to some SSRIs for treating anxiety 5
• Sertraline has been studied extensively and has lower QTc prolongation risk than citalopram 5

Monitoring Plan

• Assess for akathisia at each visit, especially in the first 4-6 weeks
• Monitor for increased anxiety/agitation, particularly in weeks 1-2 if baseline anxiety is prominent 4
• Use standardized rating scales (e.g., HAM-D, MADRS) to track response 3, 1
• Evaluate response by week 6-8; if inadequate, consider dose adjustment before discontinuing 2, 1