Article

Comparison of fluoxetine, olanzapine, and combined fluoxetine plus olanzapine initial therapy of bipolar type I and type II major depression--lack of manic induction.

Depression Research Unit, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, United States.
Journal of Affective Disorders (Impact Factor: 3.71). 07/2005; 87(1):121-30. DOI: 10.1016/j.jad.2005.02.018
Source: PubMed

ABSTRACT 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.

0 Followers
 · 
51 Views
  • Source
    • "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. "
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Bipolar depression remains a major unresolved challenge for psychiatric therapeutics. It is associated with significant disability and mortality and represents the major proportion of the approximately half of follow-up time spent in morbid states despite use of available treatments. Evidence regarding effectiveness of standard treatments, particularly with antidepressants, remains limited and inconsistent. We reviewed available clinical and research literature concerning treatment with antidepressants in bipolar depression and its comparison with unipolar depression. Research evidence concerning efficacy and safety of commonly used antidepressant treatments for acute bipolar depression is very limited. Nevertheless, an updated meta-analysis indicated that overall efficacy was significantly greater with antidepressants than with placebo-treatment and not less than was found in trials for unipolar major depression. Moreover, risks of non-spontaneous mood-switching specifically associated with antidepressant treatment are less than appears to be widely believed. The findings encourage additional efforts to test antidepressants adequately in bipolar depression, and to consider options for depression in types I vs. II bipolar disorder, depression with subsyndromal hypomania and optimal treatment of mixed agitated-dysphoric states - both short- and long-term. Many therapeutic trials considered were small, varied in design, often involved co-treatments, or lacked adequate controls.
    The International Journal of Neuropsychopharmacology 02/2013; 16(07):1-13. DOI:10.1017/S1461145713000023 · 5.26 Impact Factor
  • Source
    • "In a 2005 randomized clinical trial consisting of 34 bipolar patients, 32 of which of the bipolar I subtype, treatment with 10–30 mg of fluoxetine showed comparable results to treatment with either olanzapine or an olanzapine-fluoxetine combination. Over the course of the 8-week trial, a significant reduction in both HAM-D 28 and MADRS ratings was observed, with no evidence of an increase in treatment-emergent manic symptoms , as measured by the Young Mania Rating Scale (YMRS) [13]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: While studies in the past have focused more on treatment of the manic phase of bipolar disorder (BD), recent findings demonstrate the depressive phase to be at least as debilitating. However, in contrast to unipolar depression, depression in bipolar patients exhibits a varying response to antidepressants, raising questions regarding their efficacy and tolerability. Methods. We conducted a MEDLINE and Cochrane Collaboration Library search for papers published between 2005 and 2011 on the subject of antidepressant treatment of bipolar depression. Sixty-eight articles were included in the present review. Results. While a few studies did advocate the use of antidepressants, most well-controlled studies failed to show a robust effect of antidepressants in bipolar depression, regardless of antidepressant class or bipolar subtype. There was no significant increase in the rate of manic/hypomanic switch, especially with concurrent use of mood stabilizers. Prescribing guidelines published in recent years rely more on atypical antipsychotics, especially quetiapine, as a first-line therapy. Conclusions. Antidepressants probably have no substantial role in acute bipolar depression. However, in light of conflicting results between studies, more well-designed trials are warranted.
    Depression research and treatment 01/2012; 2012:684725. DOI:10.1155/2012/684725
Show more