Dataset Information

Lithium in the Acute Treatment of Bipolar I Disorder: A Double-Blind, Placebo-Controlled Study.

ABSTRACT: Lithium is a benchmark treatment for bipolar disorder in adults. Definitive studies of lithium in pediatric bipolar I disorder (BP-I) are lacking.This multicenter, randomized, double-blind, placebo-controlled study of pediatric participants (ages 7-17 years) with BP-I/manic or mixed episodes compared lithium (n = 53) versus placebo (n = 28) for up to 8 weeks. The a priori primary efficacy measure was change from baseline to the end of study (week 8/ET) in the Young Mania Rating Scale (YMRS) score, based on last-observation-carried-forward analysis.The change in YMRS score was significantly larger in lithium-treated participants (5.51 [95% confidence interval: 0.51 to 10.50]) after adjustment for baseline YMRS score, age group, weight group, gender, and study site (P = .03). Overall Clinical Global Impression-Improvement scores favored lithium (n = 25; 47% very much/much improved) compared with placebo (n = 6; 21% very much/much improved) at week 8/ET (P = .03). A statistically significant increase in thyrotropin concentration was seen with lithium (3.0 ± 3.1 mIU/L) compared with placebo (-0.1 ± 0.9 mIU/L; P < .001). There was no statistically significant between-group difference with respect to weight gain.Lithium was superior to placebo in reducing manic symptoms in pediatric patients treated for BP-I in this clinical trial. Lithium was generally well tolerated in this patient population and was not associated with weight gain, distinguishing it from other agents commonly used to treat youth with bipolar disorder.

SUBMITTER: Findling RL

PROVIDER: S-EPMC4621794 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Lithium in the Acute Treatment of Bipolar I Disorder: A Double-Blind, Placebo-Controlled Study.

Findling Robert L RL Robb Adelaide A McNamara Nora K NK Pavuluri Mani N MN Kafantaris Vivian V Scheffer Russell R Frazier Jean A JA Rynn Moira M DelBello Melissa M Kowatch Robert A RA Rowles Brieana M BM Lingler Jacqui J Martz Karen K Anand Ravinder R Clemons Traci E TE Taylor-Zapata Perdita P

Pediatrics 20151012 5

<h4>Background</h4>Lithium is a benchmark treatment for bipolar disorder in adults. Definitive studies of lithium in pediatric bipolar I disorder (BP-I) are lacking.<h4>Methods</h4>This multicenter, randomized, double-blind, placebo-controlled study of pediatric participants (ages 7-17 years) with BP-I/manic or mixed episodes compared lithium (n = 53) versus placebo (n = 28) for up to 8 weeks. The a priori primary efficacy measure was change from baseline to the end of study (week 8/ET) in the Y ...[more]

PMID: 26459650

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Project description:ObjectiveThe therapeutics for bipolar disorders are still far from adequate, and new options with improved effectiveness, safety, and tolerability in a wide range of patients are necessary. Preliminary data have suggested a role for dysfunctions targeting the purinergic system in mood disorders. This study aimed to evaluate the efficacy and tolerability of the purinergic agents allopurinol and dipyridamole combined with lithium in bipolar mania.MethodA randomized, placebo-controlled, double-blind study was performed in adult inpatients (N = 180) with a DSM-IV-TR diagnosis of bipolar I disorder, current episode manic with or without psychotic features (rapid cyclers and mixed episodes were not included). No antipsychotic agent was used during the study. Subjects were given fixed oral doses of either allopurinol 600 mg/day (N = 60), dipyridamole 200 mg/day (N = 60), or placebo (N = 60) added to lithium for 4 weeks. Subjects were rated at baseline and days 7, 14, 21, and 28 using the Young Mania Rating Scale (YMRS) as the primary efficacy measure. The study was conducted between September 2003 and September 2006.ResultsAllopurinol resulted in greater mean reductions in YMRS scores from baseline to day 21 (p < .001) and day 28 (p = .003) compared with placebo using a linear model analysis (d = 0.32, 95% CI = 0.07 to 0.57). Remission rates were significantly higher for allopurinol compared with dipyridamole and placebo (p = .008). Lithium showed a significant antimanic efficacy even in the placebo group. Decrease in plasma uric acid levels showed a significant positive association with antimanic effects in the allopurinol group (p < .001).ConclusionAllopurinol is clinically effective and well-tolerated adjunctively with lithium in manic episodes and may represent an alternative approach in the treatment of acute mania, especially for those presenting tolerability and safety issues with antipsychotics. The present results strongly support the involvement of the purinergic system in the pathophysiology and therapeutics of bipolar disorder. Further placebo-controlled studies with allo-purinol compared with standard mood stabilizers in mania and maintenance are warranted.Trial registrationclinicaltrials.gov Identifier: NCT00560079.

Dataset Information

Lithium in the Acute Treatment of Bipolar I Disorder: A Double-Blind, Placebo-Controlled Study.

Publications

Lithium in the Acute Treatment of Bipolar I Disorder: A Double-Blind, Placebo-Controlled Study.

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