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Randomized Controlled Trial
. 2012 Feb;22(2):123-31.
doi: 10.1016/j.euroneuro.2011.06.005. Epub 2011 Jul 28.

Ziprasidone with adjunctive mood stabilizer in the maintenance treatment of bipolar I disorder: long-term changes in weight and metabolic profiles

David E Kemp  1 , Onur N Karayal, Joseph R Calabrese, Gary S Sachs, Elizabeth Pappadopulos, Kathleen S Ice, Cynthia O Siu, Eduard Vieta
Affiliations
Randomized Controlled Trial

Ziprasidone with adjunctive mood stabilizer in the maintenance treatment of bipolar I disorder: long-term changes in weight and metabolic profiles

David E Kemp et al. Eur Neuropsychopharmacol. 2012 Feb.

Abstract

This analysis was conducted to compare the effects of adjunctive ziprasidone or placebo on metabolic parameters among patients receiving maintenance treatment with lithium or valproate. We also tested whether metabolic syndrome (MetS) and other risk factors were associated with baseline characteristics and treatment response. In the stabilization phase (Phase 1), 584 bipolar I disorder (DSM-IV) patients received 2.5-4 months of open label ziprasidone (80-160 mg/d) plus lithium or valproic acid (ZIP+MS). Patients who achieved at least 8 weeks of clinical stability were subsequently randomized into Phase 2 to 6-months of double-blind treatment with ZIP+MS (n=127) vs. placebo+MS (n=113). At baseline of Phase 1, MetS was found in 111 participants (23%). Participants with MetS (vs. non-MetS participants) were more likely to be aged 40 years or older, had significantly more severe manic symptoms, higher abdominal obesity, and higher BMI. Increase in abdominal obesity was associated with lower manic symptom improvement (p<0.05, as assessed by MRS change score) during Phase 1, while symptom improvement differed across racial groups. In the Phase 2 double-blind phase, the ZIP+MS group had similar weight and metabolic profiles compared to the placebo+MS group across visits. These results corroborate existing findings on ziprasidone which exhibits a neutral weight and metabolic profile in the treatment of schizophrenia and bipolar patients. Our findings suggest that MetS is highly prevalent in patients with bipolar disorder, may be associated with greater manic symptom severity, and may predict treatment outcomes.

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Figures

Figure 1
Figure 1
Prevalence of Obesity/Overweight and Metabolic Syndrome Risks in Baseline Screening Subjects
Figure 2
Figure 2
Baseline Metabolic Syndrome Status and Associated Risk Factor: Screening Sample (N=482)
Figure 3
Figure 3
MRS Improvement by Race group: 16-Week Open-Label Ziprasidone+Li/VAL Period
Figure 4
Figure 4
Mean Change in Metabolic Variables and Body Weight Over Time in Double-Blind Phase
See this image and copyright information in PMC

References

    1. Allison DB, Loebel AD, Lombardo I, Romano SJ, Siu CO. Understanding the relationship between baseline BMI and subsequent weight change in antipsychotic trials, effect modification or regression to the mean? Psychiatry Res. 2009;170:172–176. - PubMed
    1. Angst F, Stassen HH, Clayto PJ, Angst J. Mortality in patients with mood disorders, follow-up over 34-38 years. J Affect Disord. 2002;68:167–181. - PubMed
    1. Bowden CL, Vieta E, Ice KS, et al. Ziprasidone plus a mood stabilizer in subjects with bipolar I disorder, a 6-month randomized, placebo-controlled, double-blind trial. J Clin Psychiatry. 2010;71:130–137. Epub Jan 26, 2010. - PubMed
    1. Bjorntorp P. Do stress reactions cause abdominal obesity and comorbidities? Obes Rev. 2001;2:73–86. - PubMed
    1. Bronnegard M, Arner P, Hellstrom L, et al. Glucocorticoid receptor messenger ribonucleic acid in different regions of human adipose tissue. Endocrinology. 1990;127:1689–1696. - PubMed

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