Variables as mediators or moderators in predicting relapse to any type of mood episode in a bipolar maintenance study

Division of Mood and Anxiety Disorders, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
The Journal of Clinical Psychiatry (Impact Factor: 5.5). 08/2012; 73(7):e913-7. DOI: 10.4088/JCP.10m06737
Source: PubMed


Post hoc mediator/moderator analyses were designed to identify risk factors and their relationships in predicting relapse in olanzapine- or lithium-treated bipolar patients with an index manic or mixed episode. The aim was to identify moderators that precede and influence other variables to affect relapse and mediators that explain how or why a second variable affects relapse.
We examined DSM-IV-diagnosed bipolar I disorder patients who met symptomatic remission criteria of an index manic or mixed (6.3%) episode after acute (6-12 weeks), open-label, combined therapy with olanzapine (5-20 mg/d; mean dose = 13.5 mg/d) plus lithium (300-1,800 mg/d; mean dose = 1,003.3 mg/d) followed by double-blind randomization to lithium (n = 214) or olanzapine (n = 217) for up to 52 weeks. The study started on August 5, 1999, and finished on June 14, 2002. Mediator/moderator analyses with α cut at .05 were used to understand how variables work together to impact rate of relapse.
For lithium-treated patients, variables identified for relapse were country of residence, smoking status, previous episode history, and previous lithium use. For olanzapine-treated patients, risk factors included smoking status, previous episode history, amount of time patients had a 21-Item Hamilton Depression Rating Scale (HDRS-21) score ≤ 8 at pre-randomization, and HDRS-21 score at randomization. For lithium-treated patients, no mediators/moderators were identified among relapse variables. For olanzapine-treated patients, several baseline variables--such as previous number of mood episodes (manic or depressive)--operate through severity of depressive symptoms prior to remission (mediator) to affect relapse rate. On the other hand, the effect of the patient's pre-remission depressive symptoms on outcome is moderated by the polarity of the first episode, whether manic, depressive, or mixed.
Mediators and moderators may provide valuable information in the treatment planning of patients with bipolar disorder and potentially influence treatment outcomes.

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    • "Smoking strongly predicts treatment dropout [137, 138] and non- adherence [139]. Variables predicting relapse for treatment of manic treatments in BD with olanzapine or lithium include smoking status [140]. Furthermore, individuals with rapid cycling, psychiatric comorbidities and substance abuse presently experiencing an episode of BD are more likely to smoke cigarettes. "
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