Comparison of short-term venlafaxine versus lithium monotherapy for bipolar II major depressive episode: a randomized open-label study.

OBJECTIVE: Practice guidelines for the initial treatment of bipolar II (BP II) major depressive episode (MDE) recommend mood stabilizer (MS) monotherapy or combined MS plus antidepressant drug (AD) therapy. We hypothesized that initial AD monotherapy would be superior to MS monotherapy for BP II MDE with a low hypomanic switch rate.

METHODS: Bipolar II MDE patients were randomized to a 12-week open-label treatment with either venlafaxine monotherapy (n = 43) or lithium carbonate monotherapy (n = 40). The primary outcome measure was the 28-item Hamilton Depression Rating Scale (HAM-D 28). The secondary outcome measures included the Young Mania Rating Scale (YMRS), clinical global impressions severity and change ratings, and the proportion of patients classified as responder (with > or = 50% reduction in baseline HAM-D score) or as remitter (final HAM-D score, < or = 8).

RESULTS: Thirty-four venlafaxine-treated patients (79.1%) and 15 lithium-treated patients (37.5%) completed the trial (P < 0.0005). Venlafaxine monotherapy produced a greater reduction in HAM-D 28 scores, with a difference in change of -6.57 points (95% confidence interval, -11.97 to -1.18) (P = 0.017) between treatment conditions. There was a greater proportion of venlafaxine-treated (vs lithium-treated) patients classified either as treatment responder (58.1% vs 20.0%; P < 0.0005) or as treatment remitter (44.2% vs 7.5%; P < 0.0005) for the HAM-D 28 scores. There was no significant increase in mean YMRS scores over time in the venlafaxine (vs lithium) treatment condition, and no significant increase in mean YMRS scores at any study visit compared with baseline for either treatment.

CONCLUSIONS: Results from this study suggest that AD monotherapy with venlafaxine may be an effective initial therapy for BP II MDE with a low hypomanic switch rate.