Pharmacological interventions for the prevention of relapse in bipolar disorder: A systematic review of controlled trials

Centre for Reviews and Dissemination, University of York, York YO10 5DD, UK.
Journal of Psychopharmacology (Impact Factor: 3.59). 07/2009; 23(5):574-91. DOI: 10.1177/0269881108093885
Source: PubMed


We conducted a systematic review and meta-analysis of randomised and quasi-randomised controlled trials evaluating all clinically relevant pharmacological interventions for the prevention of relapse in people with bipolar disorder. Thirty-four trials were included in the review. Direct comparisons with placebo and with lithium were available for most drugs. In addition, there were direct comparisons of valproate vs. olanzapine, imipramine vs. lithium plus imipramine, olanzapine plus mood stabilisers vs. mood stabilisers and perphenazine plus mood stabilisers vs. mood stabilisers. Methodological quality varied across studies and the strength of evidence was not equal for all treatments or for all comparisons. There is evidence from placebo-controlled trials for the efficacy of lithium, valproate and lamotrigine as maintenance therapy for the prevention of relapse in bipolar disorder. Three drugs have a significant effect in the prevention of manic relapses (lithium, olanzapine and aripiprazole) and three in the prevention of depressive symptoms (valproate, lamotrigine and imipramine). Imipramine is little used in practice, because of concern about adverse effects. The significant effects of olanzapine and aripiprazole were demonstrated in selected responsive bipolar I patients only. Despite widespread use in clinical practice, there is little evidence to support the efficacy of combination therapy.

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Available from: John R Geddes, Dec 25, 2013
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    • "While there is evidence that maintenance pharmacological treatment decreases the risk of recurrence, continuing treatment in women actively seeking a pregnancy bears a potential teratogenic risk for the foetus and is also associated with adverse effects. These concerns are particularly challenging in women who have been stable on maintenance treatment without manic or depressive episodes for several years, as after five years it becomes less clear if treatment continues to exert a protective effect [2]. Another challenge is that maintenance treatment with lithium may be particularly problematic to discontinue, with high rates of recurrence upon discontinuation [3] "
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    ABSTRACT: After ten years of successful maintenance treatment with lithium and olanzapine, a 40-year-old woman with bipolar disorder expressed concerns about continuing the use of medicines, as she was planning a pregnancy. In the past, she had suffered from five severe manic episodes with hospital admissions. After consultations with the treating psychiatrist, gynaecologist, and family doctor, olanzapine was stopped and lithium was gradually withdrawn. After few months, the patient, still in treatment with lithium 300 mg/die, experienced a new manic episode with hospital admission. Treatment with lithium and olanzapine was restored, and she progressively recovered. This case suggests that the risk of manic recurrence after ten years of maintenance treatment may be as high as the well-known risk of recurrence after few years of maintenance treatment, a consideration that doctors may find useful in the light of a complete absence of evidence on treatment choices after five years of successful maintenance treatment.
    Full-text · Article · Oct 2013
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    • "There will never be clinical trials of all possible combination therapies for bipolar disorder. Although controlled studies of polypharmacy are increasing , only limited evidence of effectiveness and safety is available to assist the clinician (Lin et al. 2006; Malhi et al. 2012; Beynon et al. 2009; Ghaemi and Ko, 2002). Further complicating drug selection, patients often have comorbid psychiatric and medical illnesses (Kupfer 2005; McIntyre et al. 2006), including those related to psychotropic drug use (McIntyre et al. 2006; Fagiolini et al. 2005). "
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    ABSTRACT: Background The objective of this study is to investigate drug treatment patterns in bipolar disorder using daily data from patients who received treatment as usual. Methods Patients self-reported the drugs taken daily for about 6 months. Daily drug use and drug combinations were determined for each patient, both by the specific drugs and by medication class. The drug load was calculated for all drugs taken within a medication class. Results and discussion Four hundred fifty patients returned a total of 99,895 days of data (mean 222.0 days). The most frequently taken drugs were mood stabilizers. Of the 450 patients, 353 (78.4%) took a stable drug combination for ≥50% of days. The majority of patients were taking polypharmacy, including 75% of those with a stable combination. Only a small number of drugs were commonly taken within each medication class, but there were a large number of unique drug combinations: 52 by medication class and 231 by specific drugs. Eighty percent of patients with a stable combination were taking three or less drugs daily. Patients without a stable combination took drugs but made frequent changes. Taking more than one drug within a medication class greatly increased the drug load. To summarize, (1) patients were more likely to take a mood stabilizer than any other drug; (2) although most patients were taking polypharmacy, there were no predominant drug regimens even among those taking a stable combination; and (3) most patients with a stable combination take a relatively small number of drugs daily. The wide variation in drug regimens and numerous possible drug combinations suggest that more evidence is needed to optimize treatment of bipolar disorder.
    Full-text · Article · May 2013
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