GERI-BD: A Randomized Double-Blind Controlled Trial of Lithium and Divalproex in the Treatment of Mania in Older Patients With Bipolar Disorder
Publication: American Journal of Psychiatry
Abstract
Objective:
Clinicians treating older patients with bipolar disorder with mood stabilizers need evidence from age-specific randomized controlled trials. The authors describe findings from a first such study of late-life mania.
Method:
The authors compared the tolerability and efficacy of lithium carbonate and divalproex in 224 inpatients and outpatients age 60 or older with bipolar I disorder who presented with a manic, hypomanic, or mixed episode. Participants were randomly assigned, under double-blind conditions, to treatment with lithium (target serum concentration, 0.80–0.99 mEq/L) or divalproex (target serum valproate concentration, 80–99 μg/mL) for 9 weeks. Participants with an inadequate response after 3 weeks received open adjunctive risperidone. The authors hypothesized that divalproex would be better tolerated and more efficacious than lithium. Tolerability was assessed based on a measure of sedation and on the proportions of participants achieving target concentrations. Efficacy was assessed with the Young Mania Rating Scale (YMRS).
Results:
Attrition rates were similar for lithium and divalproex (14% and 18% at week 3 and 51% and 44% at week 9, respectively). The groups did not differ significantly in sedation. Participants in the lithium group tended to experience more tremor. Similar proportions of participants in the lithium and divalproex groups achieved target concentrations (57% and 56%, respectively). A longitudinal mixed model of improvement (change from baseline in YMRS score) favored lithium (change in score, 3.90; 97.5% CI=1.71, 6.09). Nine-week response rates did not differ significantly between the lithium and divalproex groups (79% and 73%, respectively). The need for adjunctive risperidone was low and similar between groups (17% and 14%, respectively).
Conclusions:
Both lithium and divalproex were adequately tolerated and efficacious; lithium was associated with a greater reduction in mania scores over 9 weeks.
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History
Received: 20 May 2015
Revision received: 5 April 2016
Revision received: 7 April 2017
Accepted: 17 April 2017
Published online: 4 August 2017
Published in print: November 01, 2017
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Funding Information
National Institute of Mental Health10.13039/100000025: P30 MH071944, P30 MH085943, P30 MH90333, UL1 RR024996, and UL1 RR024989, U01 MH068846, U01 MH068847, U01 MH074511, R01 MH084921, K02 MH067028, K24 MH069430
Supported by NIH grants U01 MH068846, U01 MH068847, U01 MH074511, R01 MH084921, K02 MH067028, K24 MH069430, P30 MH071944, P30 MH085943, P30 MH90333, UL1 RR024996, and UL1 RR024989. Janssen Scientific Affairs provided risperidone to some sites in the study.Dr. Young has received support from AstraZeneca. Dr. Mulsant has received research support from Brain Canada, the CAMH Foundation, the Canadian Institutes of Health Research, NIH, Bristol-Myers Squibb (medications for an NIH-funded clinical trial), and Pfizer (medications for an NIH-funded clinical trial), and he has received travel support from Roche. Dr. Sajatovic has received research grants from Alkermes, the Centers for Disease Control and Prevention, Merck, NIH, Neurocrine, Ortho-McNeil Janssen, Pfizer, the Reinberger Foundation, the Reuter Foundation, and the Woodruff Foundation; she has served as a consultant for Amgen, Bracket, Health Analytics, Otsuka, Pfizer, Prophase, and Supernus and has received royalties from Lexicomp, Johns Hopkins University Press, Oxford University Press, Springer, and UpToDate. Dr. Gildengers has been funded by NIH and has participated in scientific advisory board meetings for Shire Pharmaceuticals. Dr. Beyer has received research support from AstraZeneca, Elan, Eli Lilly, Forest, NIH, Novartis, Sanofi, and Takeda. Dr. Alexopoulos has received support from NIH and has served on speakers bureaus for AstraZeneca, Forest, Novartis, and Sunovion. The other authors report no financial relationships with commercial interests.Metrics & Citations
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