No, treating bipolar II disorder with only Wellbutrin (bupropion) and Lexapro (escitalopram) is not recommended and carries significant risks.
Antidepressant monotherapy or dual antidepressant therapy without a mood stabilizer is inappropriate for bipolar disorder and can precipitate mood destabilization, including manic or hypomanic episodes. The FDA explicitly warns that bupropion can precipitate manic, mixed, or hypomanic episodes, with increased risk in patients with bipolar disorder, and states that Wellbutrin is not approved for treating bipolar depression 1. Guidelines consistently emphasize that antidepressants should only be used as adjuncts to mood stabilizers, never as monotherapy 2.
Why This Regimen Is Problematic
Risk of Mood Switching
Both medications carry substantial risk of triggering hypomania or mania when used without mood stabilization:
Bupropion's switch risk: While historically considered "safer" than tricyclics, recent evidence shows bupropion has similar phase-shifting rates to other antidepressants (not lower as previously thought) 3. Case reports document manic switches even when bupropion was added to mood stabilizers 4.
Escitalopram's switch risk: In an open trial, escitalopram added to mood stabilizers caused manic/hypomanic switches in 15% of patients (3 of 20), with one requiring hospitalization for suicidal ideation and psychosis 5.
Combined risk: Using two antidepressants together without mood stabilization exponentially increases the risk of affective switching and mood destabilization.
Guideline Violations
The consensus from expert guidelines is unequivocal 6:
- Antidepressants should only be prescribed as adjuncts to mood-stabilizing medications in bipolar I disorder
- The risk of mood elevation is greater in bipolar I than bipolar II, but bipolar II still requires caution
- SSRIs and bupropion may have lower switch rates than tricyclics, but this does not make them safe as monotherapy
What Should Be Done Instead
First-Line Approach for Bipolar II Depression
The patient needs a mood stabilizer as the foundation of treatment. Recent evidence specifically for bipolar II depression shows 7:
- Antidepressant monotherapy can be considered in bipolar II (unlike bipolar I), but mood stabilizers remain preferred
- When antidepressants are used, they should ideally be combined with lithium or other mood stabilizers
- Switch rates remain concerning even in bipolar II (up to 19.9% in studies)
Recommended Treatment Algorithm
Add a mood stabilizer immediately: Lithium, valproate, lamotrigine, or quetiapine are evidence-based options 2, 8
Reassess the antidepressant regimen:
- If adding a mood stabilizer, one antidepressant (preferably escitalopram or bupropion) might be continued cautiously
- Using two antidepressants simultaneously is excessive and increases risk without clear benefit
- Monitor closely for emerging hypomanic symptoms
Consider FDA-approved alternatives: The olanzapine-fluoxetine combination is FDA-approved for bipolar depression 2
Critical Caveats
Predictors of higher switch risk that warrant extra caution 9:
- History of rapid cycling
- Mixed features during depression
- Stimulant abuse history
- Bipolar I diagnosis (though bipolar II still carries risk)
Warning signs of mood destabilization to monitor:
- Decreased need for sleep
- Increased energy or goal-directed activity
- Racing thoughts or pressured speech
- Impulsivity or risky behaviors
- Irritability or agitation
The current regimen represents suboptimal and potentially dangerous treatment. While some bipolar II patients may benefit from antidepressants 10, 7, the absence of mood stabilization creates unacceptable risk for mood switching and cycle acceleration. The treatment plan requires immediate modification to include appropriate mood stabilization.