OBJECTIVE: To compare the efficacy and safety of adjunctive treatment with paroxetine or amitriptyline in patients with bipolar disorder who relapsed into a depressive episode during lithium maintenance therapy.

METHODS: Data from a randomized, double-blind trial comparing paroxetine (N=18) or amitriptyline (N=22) as adjunctive treatment for an episode of depression during lithium maintenance therapy were reanalyzed. Only patients with a diagnosis of bipolar disorder were included. The primary endpoint was the change in Hamilton Rating Scale for Depression (HAM-D21) from randomization to study end (week 6).

RESULTS: There was a significant reduction of HAM-D21 total score from randomization to study end in both treatment groups. The mean change in HAM-D21 score in the paroxetine and amitriptyline groups at study end was -14.9 and -15.5 (p=0.798), and the mean HAM-D21 at study end was 8.2 vs. 9.9 (p=0.420), respectively. The patients treated with paroxetine showed a more rapid improvement with lower HAM-D21 scores between weeks 3 and 5. Tolerability was similar in both groups.

LIMITATIONS: No placebo comparator group and relatively small study sample size.

CONCLUSIONS: Adjunctive treatment with either paroxetine or amitriptyline is a viable option for breakthrough depression during lithium maintenance therapy.