Current guidelines for the initial treatment of bipolar type I (BP I) and bipolar type II (BP II) major depressive episode (MDE) recommend avoiding the use of antidepressant drugs due to concerns over drug-induced manic switch episodes. However, recent evidence suggests that the manic switch rate during SSRI therapy of BP MDE may be lower than previously thought. This preliminary, placebo-controlled study examines the relative rates of treatment-emergent manic symptoms during fluoxetine monotherapy, olanzapine monotherapy, and combined fluoxetine plus olanzapine therapy of BP I and BP II MDE.
32 BP I and 2 BP II MDE patients were randomized to receive double-blind therapy with fluoxetine monotherapy 10-30 mg daily, olanzapine monotherapy 5-20 mg daily, combined therapy with fluoxetine 10-40 mg plus olanzapine 5-15 mg daily, or placebo for up to 8 weeks. Outcome measures included the 17-item HAM-D, 17-item HAM-D "atypical" symptom profile (HAM-D 17-R), 28 item HAM-D, Montgomery-Asberg Depression Rating Scale (MADRS), and the Young Mania Rating (YMR) scale.
There were significant reductions over time in mean HAM-D 28 and MADRS ratings for all treatment groups (p<0.006). However, there were no differences among treatment conditions (p=ns). There was no significant increase in YMR scores over time in any treatment group. In contrast, there was a significant reduction in the mean YMR score in the fluoxetine-treated patients over time (p=0.008). No patient met DSM IV criteria for a manic episode.
Cohort sizes were limited and the study was not powered to detect statistical differences in efficacy or mania symptoms among treatment conditions. The dose of fluoxetine was modest and the treatment duration was limited to 8 weeks.
These observations support earlier findings of a low manic switch rate during fluoxetine monotherapy of BP I and BP II MDE, and suggest that fluoxetine may be a safe initial treatment of BP MDE alone or in combination with olanzapine.
"treatments are generally effective for the reversal of 60 manic episodes and preventing future episodes, these 61 medications have limited, if any, efficacy on their own in 62 the acute treatment of depressive episodes (McInerney 63 and Kennedy, 2014). Moreover, standard antidepressant 64 medications used either as monotherapies, or in conjunc- 65 tion with mood stabilizers or antipsychotics, are generally 66 ineffective for treating depressive episodes, and may 67 induce mood switching in a subset of patients with rapid 68 cycling BD (De Wilde and Doogan, 1982; Himmelhoch 69 et al., 1982; Gijsman et al., 2004; Amsterdam and 70 Shults, 2005; Sachs et al., 2007; McElroy et al., 2010; 71 Sidor and Macqueen, 2011; McInerney and Kennedy, 72 2014). Although there are a few studies suggesting ther- 73 apeutic efficacy of antidepressant monotherapy for bipo- 74 lar depression, current recommendations indicate 75 antidepressants be used only in combination with mood 76 stabilizers if those first-line medications fail (McInerney 77 and Kennedy, 2014). "
"Switching to mania: Four studies     had defined switching to mania as DSM-III-R mania or hypomania, or a score ≥ 8 on YMRS, or HAMD ≥ 14. There was no significant difference in an increased risk of switching to mania [four randomized controlled trials, n = 462, RR = 1.06, 95%CI: 0.63, 1.78, P = 0.84]     . Long-term data also failed to show a significant difference [three randomized controlled trials, n = 433, RR = 0.81, 95%CI: 0.50, 1.32, P = 0.40]    (Figure 3). "
"Tohen et al. (2003) found an olanzapine–fluoxetine combination to be superior to olanzapine monotherapy (responders : 46/82 vs. 137/351 ; p=0.005 ; this arm was excluded from meta-analysis as not comparing an antidepressant to placebo). Amsterdam and Shults (2005) compared three treatments to placebo in a small trial (eight or nine subjects/arm) involving types I and II, depressed BD patients : fluoxetine monotherapy ; olanzapine monotherapy ; their combination ; placebo. Changes in depression ratings did not differ statistically but lacked statistical power. "
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