Bupropion and Bipolar Depression: Good Idea or Bad Idea 

Bupropion, an atypical antidepressant with dopaminergic and noradrenergic activity, has been evaluated for use in bipolar depression through several studies, including double-blind, randomized controlled trials (RCTs).

1. Sachs et al. (2007) – In this multicenter trial, 179 patients with bipolar disorder (bipolar I or II) and depressive episodes were randomized to receive either bupropion, sertraline, or venlafaxine as adjunctive therapy to mood stabilizers (e.g., lithium, valproate) over 26 weeks. The study found that bupropion had a similar efficacy profile to the other antidepressants, with a response rate of about 40%. Importantly, bupropion had a relatively low rate of inducing manic or hypomanic episodes, which was around 7%, lower than venlafaxine but comparable to sertraline.
2. El-Mallakh et al. (2008) – This smaller study focused on the use of bupropion in bipolar II depression. It suggested that bupropion can effectively reduce depressive symptoms without significantly increasing the risk of switching to mania, although the study size was limited, and larger trials were recommended.
3. Systematic Reviews and Meta-analyses – A review by Gijsman et al. (2004) included a number of RCTs that assessed antidepressants in bipolar depression. While bupropion was included, the overall conclusion was that the risk of treatment-emergent affective switch (TEAS) was lower compared to tricyclic antidepressants, but comparable to other selective serotonin reuptake inhibitors (SSRIs). However, bupropion was noted for having a more favorable side effect profile, especially concerning sexual dysfunction and weight gain.

In general, while double-blind RCTs suggest that bupropion can be effective for bipolar depression, its most notable benefit is its relatively low risk of triggering manic episodes compared to other antidepressants. The data supports its use as an adjunct to mood stabilizers, but careful monitoring is still necessary with a mood stabilizing agent in place, as switching to mania, though less frequent, remains a risk.