Objective: Post hoc analyses were designed to identify risk factors and their relationships in predicting relapse in olanzapine-treated or lithium-treated bipolar mania/mixed patients using mediator/moderator analyses. Moderators and mediators are both risk factors. We aimed to identify moderators that precede and influence other risk factors to affect relapse and mediators that explain how/why a second risk factor affect the relapse.
Methods: We examined a total of 431 bipolar patients (mixed=6.3%) in remission after acute (6-12 weeks), open-label, combined therapy with olanzapine (5-20 mg/day; mean dose of 13.5 mg/day) plus lithium (300-1800 mg/day; mean dose of 1003.3 mg/day) followed by double-blind randomization to lithium (n=214) or olanzapine (n=217). Mediator/moderator analyses with alpha cut at 0.05 were used to understand how the risk factors work together to impact rate of relapse.
Results: For lithium-treated patients, the risk factors identified for relapse of any mood episode were country, smoking status, previous episode history, and previous lithium use. For olanzapine-treated patients, the risk factors identified included smoking status, previous episode history, amount of time that patients remain in Hamilton Rating Scale for Depression (HAMD-21) ≤8 stage at pre-randomization; and HAMD-21 score at randomization.
Conclusions: For olanzapine-treated patients, a number of baseline risk factors such as previous number of bipolar episodes (manic/depressive) work through pre-remission depressive symptoms (mediator) to affect relapse rate. Alternatively, the effect of a patient’s pre-remission depressive symptoms on the outcome is moderated by the patient’s disease history, such as whether the patient’s first episode was manic, depressive, or mixed.