In follow up over 6 months, the addition of an antidepressant did not lead to improved outcomes, although, interestingly, there also was no increase in switching in this group, possibly due to the protection afforded by the mood stabilizer. Thus, even when augmenting another treatment there is little evidence to support the use of antidepressants in bipolar depression. Mood stabilizers Although
drugs such as lithium remain a mainstay of clinical treatment in bipolar depression and a first-line treatment recommended by national guidelines [Taylor et al. 2009; NICE, 2006; DSM-IV, 2000], there have been relatively few high-quality studies of the use of Inhibitors,research,lifescience,medical lithium in its acute or see more long-term role [Van Lieshout and MacQueen, 2010]. Lithium can have long-term beneficial effects in all phases of bipolar depression [Bauer and Mitchner, 2004; Tondo et al. 1998]. A meta-analysis
by Muzina and Calabrese Inhibitors,research,lifescience,medical showed that lithium is effective in reducing suicide and self-harm, but 30% of lithium-treated patients experienced breakthrough depression within 2 years [Muzina and Calabrese, 2005]. Pillhatsch and colleagues conducted a double-blind RCT to compare the efficacy and safety of adjunctive treatment with paroxetine or amitriptyline in 40 patients with BPAD who relapsed into a depressive episode Inhibitors,research,lifescience,medical during lithium maintenance therapy [Pillhatsch et al. 2010]. Although there was no comparator placebo group, patients receiving paroxetine and amitriptyline showed response rates (>50% reduction in the 21-item Hamilton Depression Rating Scale) of Inhibitors,research,lifescience,medical 76.9% and 72.2% respectively. Lamotrigine
has been advocated for bipolar depression since the mid-1990s [Calabrese et al. 2008], although some follow-up monotherapy studies have shown ambivalent results compared with placebo. A meta-analysis of five such RCTs combining more than 1000 patients did confirmed statistically significant efficacy, albeit modest in effect size, with benefits proportional to illness severity: the pooled relative risk for Inhibitors,research,lifescience,medical response compared with placebo was 1.27 (95% CI 1.09–1.47) on the Hamilton Rating Scale for Depression (HRSD) and 1.22 (95% CI 1.06–1.41) on the Montgomery–Asberg Depression Rating Scale (MADRS), but significance for remission was obtained only on the MADRS and not the HRSD [Geddes et al. 2009]. Van der Loos MycoClean Mycoplasma Removal Kit and colleagues undertook a double-blind RCT of lamotrigine compared with placebo in subjects already on lithium (with serum levels between 0.6 and 1.2mmol/l), the LamLit study, which received financial support from GlaxoSmithKline, and showed a statistically significant advantage for the combination therapy in both the primary outcome of MADRS reduction and the secondary measure of response on both the MADRS and the Clinical Global Impression-Bipolar version; there was no significant difference in switching rates between the treatments [Van der Loos et al.
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