To evaluate the efficacy and safety of ziprasidone adjunctive to a mood stabilizer for the maintenance treatment of bipolar mania.
Subjects with DSM-IV bipolar I disorder with a Mania Rating Scale score > or = 14 were enrolled. Subjects achieving > or = 8 consecutive weeks of stability with open-label ziprasidone (80-160 mg/d) and lithium or valproate (period 1) were randomly assigned in the 6-month, double-blind maintenance period (period 2) to ziprasidone plus mood stabilizer or placebo plus mood stabilizer. The primary and key secondary end points were the time to intervention for a mood episode and time to discontinuation for any reason, respectively. Inferential analysis was performed using a Kaplan-Meier product-limit estimator (log-rank test). The study was conducted from December 2005 to May 2008.
A total of 127 and 113 subjects were randomly assigned to ziprasidone and placebo, respectively. Intervention for a mood episode was required in 19.7% and 32.4% of ziprasidone and placebo subjects, respectively. The time to intervention for a mood episode was significantly longer for ziprasidone than placebo (P = .0104). The median time to intervention for a mood episode among those requiring such an intervention (n = 61) was 43.0 days for ziprasidone versus 26.5 days for placebo. The time to discontinuation for any reason was significantly longer for ziprasidone (P = .0047). Adjunctive ziprasidone treatment was well tolerated. Among treatment-emergent adverse events occurring in > or = 5% of subjects in either treatment group during period 2, only tremor occurred more frequently in the ziprasidone versus placebo group (6.3% vs 3.6%).
Ziprasidone is an effective, safe, and well-tolerated adjunctive treatment with a mood stabilizer for long-term maintenance treatment of bipolar mania.
clinicaltrials.gov Identifier: NCT00280566.
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"Whereas a single mood stabilizer may be effective for less complicated forms of the illness, more complicated symptom pictures (eg, mixtures of depressive and hypomanic symptoms or rapid mood swings) may require combinations of treatments with different actions.42–47 Yet most clinical trials have been of monotherapy, with a few studies of addition of olanzapine, quetiapine, or ziprasidone to lithium or valproate in patients without comorbidity, complexity, or suicidality,48–50 leaving trial and error as the primary method of finding the right combination treatment in more complicated clinical settings. New agents that may be more effective for complex presentations of bipolar disorder, those that have fewer interactions with other medications used for this condition, and agents that can treat bipolar depression without destabilizing the mood disorder are therefore urgently needed. "
[Show abstract][Hide abstract] ABSTRACT: Bipolar disorder is a prevalent disorder that tends to become progressive without treatment and with inadequate treatment. Second generation (atypical) antipsychotic drugs have increasingly been used as adjunctive treatment or monotherapy for mania, but they have the potential for significant adverse effects and their role in maintenance treatment remains unclear. Asenapine is a new atypical antipsychotic medication formulated in a sublingual preparation that has been studied for mania but not maintenance therapy. Evidence indicating efficacy, adverse effects, and potential benefits and drawbacks of using asenapine in the treatment of bipolar disorder based on currently available published data are summarized.
Preview · Article · May 2013 · Neuropsychiatric Disease and Treatment
"For this reason, this guideline does not make a special note or recommendation for specifi c combination treatments as other guidelines , e.g., CANMAT (Yatham et al. 2009) did, unless there is clear evidence for a special synergistic action of medication – which, as far as we can tell, has not been proven for any of the most researched and prescribed combination regimens. Positive placebo-controlled RCTs exist for combination treatments of mood stabilizers, usually valproate or lithium, with all atypical antipsychotics that have a licence for bipolar maintenance treatment – aripiprazole (Marcus et al. 2011), quetiapine (Vieta et al. 2008c; Suppes et al. 2009), risperidone (Yatham et al. 2003) and ziprasidone (Bowden et al. 2010). The 18-month RCT of olanzapine ϩ mood stabiliser vs. placebo ϩ mood stabilizer is the exception as it was underpowered at end point due to a high attrition rate, contributing to olanzapine ' s separation from placebo only on secondary, post-hoc outcomes (Tohen et al. 2004). "
[Show abstract][Hide abstract] 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.
Full-text · Article · Apr 2013 · The World Journal of Biological Psychiatry
"One study by Weisler et al. (2003),  is also cited in guidelines and other papers as supporting evidence but could only be found as an abstract. Bowden et al. (2010),  conducted a 6 month, randomized double-blind trial of ziprasidone or placebo added to either lithium or valproate in patients with continued symptoms of bipolar I disorder (mania or mixed episode). Participants first received ziprasidone and lithium or valproate for an 8 week open label stabilization phase. "
[Show abstract][Hide abstract] ABSTRACT: While indicated for schizophrenia and acute mania, ziprasidone's evidence base and use in clinical practice extends beyond these regulatory approvals. We, an invited panel of experts led by a working group of 3, critically examined the evidence and our collective experience regarding the effectiveness, tolerability and safety of ziprasidone across its clinical uses. There was no opportunity for manufacturer input into the content of the review. As anticipated, ziprasidone was found to be effective for its indicated uses, although its utility in mania and mixed states lacked comparative data. Beyond these uses, the available data were either unimpressive or were lacking. An attractive characteristic is its neutral effect on weight thereby providing patients with a non-obesogenic long-term treatment option. Key challenges in practice include the need for dosing on a full stomach and managing its early onset adverse effect of restlessness. Addressing these issues are critical to its long-term success.
Full-text · Article · Jan 2013 · Annals of General Psychiatry