Improving the design of maintenance studies for bipolar disorder.
ABSTRACT In contrast to the trial design of acute mania studies, there is no standard design for bipolar maintenance studies. Over the past 15 years, the design of monotherapy maintenance studies in bipolar disorder has evolved significantly, but recent study designs continue to differ in important ways.
We reviewed the design of recent controlled bipolar maintenance studies, using PubMed, from August 2006 to August 2009, examining the strengths and weaknesses of different study design features.
Design differences are sufficiently important that the disparate results across maintenance studies may reflect either true differences in medication efficacy or the effects of these design differences on outcome. Design elements such as recent episode polarity, stabilization criteria, using enriched versus nonenriched samples, length of stabilization before randomization, length of experimental phase, and recurrence outcome criteria are critical factors that differ widely across studies and likely play a role in study outcome.
As consensus for trial designs for bipolar maintenance therapy is developed, it will be easier to develop algorithms for maintenance treatment based on results from studies as opposed to clinical opinions.
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ABSTRACT: Background Ziprasidone, adjunctive to either lithium or valproate, has previously been shown to be associated with a significantly lower risk of relapse in bipolar disorder compared with lithium or valproate treatment alone.Methods This placebo-controlled outpatient trial with ziprasidone adjunctive to lithium or valproate or lithium and valproate alone, for subjects with a recent or current manic or mixed episode of bipolar I disorder, comprised a 2.5- to 4-month, open-label stabilization period, followed by a 6-month, double-blind maintenance period. These post hoc analyses characterize the relapse outcomes by dose, relapse types and timing as well as all-reason discontinuations during the maintenance period.ResultsTime to relapse and all-reason discontinuation were both statistically significant in favor of the ziprasidone 120 mg/day group compared with placebo (p=0.004 and 0.001, respectively) during the 6-month double-blind period. There was no difference in time to relapse in the 80 and 160 mg/day dose groups compared with placebo (p=0.16 and 0.40, respectively) and, likewise, for time to all-reason discontinuation (p=0.20 for both doses). The majority of relapses in each group occurred prior to week 8, and most were depressive in nature.LimitationsThe primary study was not designed to compare relapse rates by dose groups.Conclusions These analyses confirm the effectiveness of ziprasidone (80–160 mg/day) in preventing relapses in subjects with bipolar disorder, with the 120 mg/day dosage appearing to have the highest relapse prevention rate.Journal of Affective Disorders 01/2013; 144(s 1–2):171–175. DOI:10.1016/j.jad.2012.04.024 · 3.76 Impact Factor
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ABSTRACT: IntroductionMood stabilization is an important goal in the treatment of bipolar disorder. In addition to well-established mood stabilizers (lithium, certain anticonvulsants), atypical antipsychotic drugs, including aripiprazole and quetiapine, have also been assessed for this purpose.Quaderni Italiani di Psychiatria 12/2011; DOI:10.1016/j.quip.2011.09.001
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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 · 3.57 Impact Factor