Adjunct Treatment to Escitalopram for Depression (Excluding Antipsychotics)
Primary Recommendation
Bupropion is the preferred adjunct to escitalopram for treatment-resistant depression, demonstrating superior efficacy in reducing depression severity compared to buspirone, with lower discontinuation rates due to adverse events. 1
Evidence-Based Augmentation Strategy
First-Line Adjunct: Bupropion
Bupropion augmentation decreases depression severity more effectively than buspirone augmentation when added to SSRI therapy (specifically studied with citalopram, escitalopram's racemic parent). 1
Bupropion combined with escitalopram achieves response rates of 62% and remission rates of 50%, which significantly exceeds typical SSRI monotherapy outcomes. 2
The combination is well-tolerated with only 6% discontinuation due to side effects, demonstrating favorable tolerability. 2
Typical dosing: escitalopram 18-20 mg/day combined with bupropion-SR 300-400 mg/day, with dose escalation completed by weeks 6-8. 2
Alternative Adjunct: Buspirone
Buspirone represents a second-line augmentation option when bupropion is contraindicated or not tolerated. 1
No difference exists between bupropion and buspirone for serious adverse events, but bupropion shows better efficacy outcomes. 1
Cognitive Behavioral Therapy as Adjunct
Low-quality evidence shows no difference in response, remission, or depression severity between augmenting with another antidepressant (bupropion or buspirone) versus augmenting with cognitive therapy. 1
This suggests CBT augmentation is equivalent to pharmacologic augmentation, providing a non-pharmacologic alternative. 1
Important Clinical Considerations
When Augmentation is Indicated
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 be considered after adequate trial duration (6-12 weeks) at therapeutic doses. 1
Alternative Strategy: Switching vs. Augmenting
The STAR*D trial demonstrated that switching to bupropion-SR, sertraline, or venlafaxine-XR produces remission in 1 in 4 patients, with no difference among the three agents. 1
Switching may be preferred over augmentation when tolerability issues exist with escitalopram or when simplifying the regimen is desirable. 1
Common Pitfalls to Avoid
Do not assume augmentation is superior to switching - both strategies have similar success rates, and switching may reduce polypharmacy burden. 1
Avoid premature augmentation - ensure adequate dose and duration of escitalopram monotherapy (at least 6-12 weeks at therapeutic doses) before adding adjunctive treatment. 1
Do not overlook non-pharmacologic augmentation - cognitive therapy shows equivalent efficacy to pharmacologic augmentation and may be preferred in patients concerned about additional medication burden. 1
Monitor for serotonin syndrome when combining serotonergic agents, though the risk with bupropion (which has minimal serotonergic activity) is low. 2
Mechanistic Rationale
Bupropion's dopaminergic and noradrenergic mechanisms complement escitalopram's serotonergic activity, providing multi-neurotransmitter coverage that may address residual symptoms. 2
This combination addresses different symptom domains: escitalopram targets mood and anxiety, while bupropion addresses energy, motivation, and concentration. 2
Bupropion may counteract SSRI-induced sexual dysfunction, a common reason for treatment discontinuation. 3