Fluoxetine monotherapy of bipolar type II and bipolar NOS major depression: A double-blind, placebo-substitution, continuation study

Depression Research Unit, Department of Psychiatry bCenter for Clinical Epidemiology and Bio-statistics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
International Clinical Psychopharmacology (Impact Factor: 2.46). 09/2005; 20(5):257-64. DOI: 10.1097/01.yic.0000171519.64080.c9
Source: PubMed


Current guidelines for the treatment of bipolar type II (BP II) major depressive episode (MDE) recommend using either mood stabilizer monotherapy or the combination of a mood stabilizer with a selective serotonin reuptake inhibitor (SSRI). These guidelines are the result of concern over SSRI-induced manic switch episodes. We previously showed that fluoxetine monotherapy may be effective as an initial treatment for BP II and BP NOS MDE with a low manic switch rate. We now present the results of a double-blind, placebo-substitution continuation study of fluoxetine monotherapy in BP II and BP NOS patients who have recovered from their MDE. This was a two-phase study. In study phase I, patients received open-label fluoxetine monotherapy 20 mg daily for up to 8 weeks. Responders with a final 17-item Hamilton Rating Scale for Depression (HAM-D) score < or =9 were enrolled into study phase II which consisted of double-blind, placebo-substitution continuation therapy with fluoxetine 20 mg daily for up to 6 months. Outcome measures included the 17-item HAM-D and Young Mania Rating (YMR) scales. Changes in YMR scores were assessed using generalized estimating equation analysis. Relapse was assessed using Kaplan-Meier survival analysis and Fisher's exact test. In study phase II, 43% of fluoxetine-treated patients and 100% of placebo-treated patients relapsed during continuation therapy (P=0.08). The mean increase in YMR score in study phase II was slightly higher in the fluoxetine-treated patients (3.0+/-1.8) versus placebo-treated patients (0.2+/-0.4) (P=0.01). However, this difference was not clinically meaningful. No hypomanic switch episodes were observed during study phase II. Despite the limited sample size resulting in insufficient power to detect statistical significance in relapse rates or change in YMR scores between treatment conditions, these preliminary data appear to support previous observations demonstrating that initial and continuation fluoxetine monotherapy may be safe and effective for some patients with BP II or BP NOS MDE with a low manic switch rate. Larger-scale studies are needed to confirm these findings.

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    • "Long-term data did not show a significant difference [two randomized controlled trials, n = 421, RR = 1.41, 95%CI: 0.97, 2.05, P = 0.07] [41] [48] . There was no significant difference in an increased risk of relapse depression during long-term treatment between the antidepressant and placebo groups [two randomized controlled trials, n = 67, RR = 0.61, 95%CI: 0.37, 1.02, P = 0.06] [39] [41] . "
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    ABSTRACT: To examine the efficacy and safety of short-term and long-term use of antidepressants in the treatment of bipolar disorder.
    Neural Regeneration Research 11/2013; 8(31):2962-74. DOI:10.3969/j.issn.1673-5374.2013.31.009 · 0.22 Impact Factor
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    • "One bipolar II and two unmatched unipolar patients taking fl uoxetine had a TEAS. Two more studies by the same group (Amsterdam and Shults 2005, 2010) also support the effi cacy and low switch risk of fl uoxetine in bipolar II patients. It appears that fl uoxetine monotherapy is relatively safe in bipolar II patients which is in line with other analyses of rates of short-term TEAS (Parker et al. 2006; Bond et al. 2008). "
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    ABSTRACT: Abstract Objectives. These guidelines are based on a first edition that was published in 2004, and have been edited and updated with the available scientific evidence up to October 2012. Their purpose is to supply a systematic overview of all scientific evidence pertaining to the long-term treatment of bipolar disorder in adults. Methods. Material used for these guidelines are based on a systematic literature search using various data bases. Their scientific rigor was categorised into six levels of evidence (A-F) and different grades of recommendation to ensure practicability were assigned. Results. Maintenance trial designs are complex and changed fundamentally over time; thus, it is not possible to give an overall recommendation for long-term treatment. Different scenarios have to be examined separately: Prevention of mania, depression, or an episode of any polarity, both in acute responders and in patients treated de novo. Treatment might differ in Bipolar II patients or Rapid cyclers, as well as in special subpopulations. We identified several medications preventive against new manic episodes, whereas the current state of research into the prevention of new depressive episodes is less satisfactory. Lithium continues to be the substance with the broadest base of evidence across treatment scenarios. Conclusions. Although major advances have been made since the first edition of this guideline in 2004, there are still areas of uncertainty, especially the prevention of depressive episodes and optimal long-term treatment of Bipolar II patients.
    The World Journal of Biological Psychiatry 04/2013; 14(3):154-219. DOI:10.3109/15622975.2013.770551 · 4.18 Impact Factor
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    • "Fluoxetine was reported to be effective during the maintenance phase for bipolar II patients [100,101,106]. "
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    ABSTRACT: Anecdotal reports suggests that most clinicians treat medications as belonging to a class with regard to all therapeutic indications; this means that the whole 'class' of drugs is considered to possesses a specific therapeutic action. The present article explores the possible existence of a true 'class effect' for agents available for the treatment of bipolar disorder. We reviewed the available treatment data from randomized controlled trials (RCTs) and explored 16 'agent class'/'treatment issue' cases for bipolar disorder. Four classes of agents were examined: first-generation antipsychotics (FGAs), second-generation antipsychotics (SGAs), antiepileptics and antidepressants, with respect to their efficacy on four treatment issues of bipolar disorder (BD) (acute mania, acute bipolar depression, maintenance against mania, maintenance against depression). From the 16 'agent class'/' treatment issue' cases, only 3 possible class effects were detected, and they all concerned acute mania and antipsychotics. Four effect cases have not been adequately studied (FGAs against acute bipolar depression and in maintenance protection from depression, and antidepressants against acute mania and protection from mania) and they all concern treatment cases with a high risk of switching to the opposite pole, thus research in these areas is poor. There is no 'class effect' at all concerning antiepileptics. The available data suggest that a 'class effect' is the exception rather than the rule in the treatment of BD. However, the possible presence of a 'class effect' concept discourages clinicians from continued scientific training and reading. Focused educational intervention might be necessary to change this attitude.
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