Treatment-Resistant Major Depressive Disorder (MDD)
The combination of Abilify (aripiprazole) and Lexapro (escitalopram) is specifically used for treatment-resistant major depressive disorder—when an initial trial of an SSRI antidepressant alone has failed to produce adequate improvement after 6-8 weeks at therapeutic doses. 1, 2
Clinical Context and Rationale
This combination represents an augmentation strategy rather than initial monotherapy for depression. The evidence demonstrates that:
- 38% of patients fail to respond and 54% fail to achieve remission with initial SSRI monotherapy after 6-12 weeks, establishing the high prevalence of treatment-resistant depression 1
- Augmentation should only be considered after an adequate trial duration of 6-12 weeks at therapeutic doses of the initial antidepressant 1
- Escitalopram (Lexapro) serves as the foundational SSRI antidepressant, while aripiprazole (Abilify) is added as an augmenting agent to enhance response 2, 3
Evidence for Efficacy
The combination demonstrates robust clinical benefits in treatment-resistant MDD:
- Remission rates are doubled with aripiprazole augmentation (36.8%) compared to continuing antidepressant monotherapy alone (18.9%) 2
- Response rates reach 58-62.5% when aripiprazole is added to SSRIs in patients who failed initial antidepressant trials 4, 3
- Clinically significant improvements in depressive symptoms (measured by MADRS scores) are substantially greater with adjunctive aripiprazole (-10.1 points) than placebo (-6.4 points) 2
Dosing Algorithm
When implementing this combination:
- Escitalopram: Flexibly dosed up to 20 mg/day 4
- Aripiprazole: Start at 2-5 mg/day and titrate to 15-30 mg/day based on response and tolerability 4, 5, 3
- Some patients show early response within 1-5 weeks of aripiprazole augmentation 5
- Full therapeutic assessment should occur by week 12 or later, as both medications demonstrate logarithmic response models 6
Safety and Tolerability Profile
The combination is generally well-tolerated with manageable side effects:
- Completion rates are high (83% with aripiprazole augmentation vs 87% with placebo) 2
- Discontinuation due to adverse events is low (6.2% vs 1.7% for placebo) 2
- Akathisia is the most common side effect, occurring in approximately 63% of patients, but typically resolves with dose adjustment or propranolol treatment 4
- Escitalopram has the lowest propensity for drug-drug interactions among SSRIs due to minimal effects on CYP450 enzymes 6, 7
Important Clinical Caveats
Common pitfalls to avoid:
- Do not use this combination as first-line therapy—it is specifically indicated for treatment-resistant depression after adequate SSRI monotherapy trial 1, 2
- Ensure adequate initial SSRI trial before augmentation: minimum 6-8 weeks at therapeutic doses 8, 1
- Monitor closely for akathisia, especially during the first weeks of aripiprazole initiation, and be prepared to adjust dose or add propranolol 4
- Consider switching rather than augmenting if tolerability issues exist with escitalopram, as switching to bupropion-SR, sertraline, or venlafaxine-XR produces remission in 1 in 4 patients with similar efficacy 1
Alternative Augmentation Strategies
When aripiprazole is contraindicated or not tolerated:
- Bupropion is the preferred alternative augmentation agent to escitalopram, demonstrating superior efficacy compared to buspirone with lower discontinuation rates 1
- Cognitive therapy shows equivalent efficacy to pharmacologic augmentation and may be preferred in patients concerned about additional medication burden 1
Treatment Duration
Once remission is achieved with this combination: