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GERI-BD: A Randomized Double-Blind Controlled Trial of Lithium and Divalproex in the Treatment of Mania in Older Patients With Bipolar Disorder.

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 ?g/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.

SUBMITTER: Young RC

PROVIDER: S-EPMC6214451 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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GERI-BD: A Randomized Double-Blind Controlled Trial of Lithium and Divalproex in the Treatment of Mania in Older Patients With Bipolar Disorder.

Young Robert C RC Mulsant Benoit H BH Sajatovic Martha M Gildengers Ariel G AG Gyulai Laszlo L Al Jurdi Rayan K RK Beyer John J Evans Jovier J Banerjee Samprit S Greenberg Rebecca R Marino Patricia P Kunik Mark E ME Chen Peijun P Barrett Marna M Schulberg Herbert C HC Bruce Martha L ML Reynolds Charles F CF Alexopoulos George S GS

The American journal of psychiatry 20170804 11

<h4>Objective</h4>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.<h4>Method</h4>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 ...[more]

PMID: 29088928

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Project description:Metabolic risk factors, termed metabolic syndrome, which include obesity, diabetes, dyslipidemia, and hypertension, are more common in patients with bipolar disorder than in the general population. Moreover, medications used to treat bipolar disorder carry some risk of worsening metabolic parameters.The study was conducted at 46 study centers in the United States, although only 31 study centers enrolled patients in the 40-week extension phase. Patients with acute bipolar I mania, manic or mixed (DSM-IV-TR criteria; Young Mania Rating Scale score ? 20), who required hospitalization were randomly assigned to double-blind aripiprazole (15-30 mg/d), lithium (900-1500 mg/d), or placebo for 3 weeks. Patients treated with aripiprazole or lithium continued treatment to week 12, after which they could enter a double-blind 40-week extension phase. Patients were enrolled in the 12-week acute treatment phase between April 2004 and July 2006; the first patient entered extension treatment in October 2004, and the last patient completed treatment in May 2007. Changes in metabolic parameters were compared between patients treated with aripiprazole or lithium for up to 52 weeks using last observation carried forward and analysis of covariance. Analysis stratified by baseline body mass index (BMI) was also conducted.Modest increases in body weight were observed in both groups: +0.97 kg (2.1 lb) for aripiprazole (n = 127) and + 0.74 (1.6 lb) for lithium (n = 136), P = .60. A significant difference in body weight increase was observed only among patients with a BMI < 25: + 2.66 kg (5.9 lb) for aripiprazole (n = 35) and + 0.40 kg (0.9 lb) for lithium (n = 37), P = .02. Mean changes from baseline to week 52 in fasting levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, plasma glucose, triglycerides, or insulin (last observation carried forward) were small in both aripiprazole and lithium treatment groups; no significant differences were observed. Mean laboratory values were within the normal or borderline range for both treatment groups across all BMI categories.Comparably modest and similar changes in metabolic parameters were observed in patients with bipolar disorder treated for up to 1 year with either lithium or aripiprazole.clinicaltrials.gov Identifier: NCT00095511.

Project description:A systematic review and random-effects model network meta-analysis was conducted to compare the efficacy, acceptability, tolerability, and safety of pharmacological interventions for adults with acute bipolar mania. We searched PubMed, the Cochrane Library, and Embase databases for eligible studies published before March 14, 2021. Randomized controlled trials (RCTs) of oral medication monotherapy lasting ≥10 days in adults with mania were included, and studies that allowed the use of antipsychotics as a rescue medication during a trial were excluded. The primary outcomes were response to treatment (efficacy) and all-cause discontinuation (acceptability). The secondary outcomes were the improvement of mania symptoms and discontinuation due to inefficacy. Of the 79 eligible RCTs, 72 double-blind RCTs of 23 drugs and a placebo were included in the meta-analysis (mean study duration = 3.96 ± 2.39 weeks, n = 16442, mean age = 39.55 years, with 50.93% males). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed response to treatment (N = 56, n = 14503); aripiprazole, olanzapine, quetiapine, and risperidone had lower all-cause discontinuation; however, topiramate had higher all-cause discontinuation (N = 70, n = 16324). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed the improvement of mania symptoms (N = 61, n = 15466), and aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, valproate, and ziprasidone had lower discontinuation due to inefficacy (N = 50, n = 14284). In conclusions, these antipsychotics, carbamazepine, lithium, tamoxifen, and valproate were effective for acute mania. However, only aripiprazole, olanzapine, quetiapine, and risperidone had better acceptability than the placebo.

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

GERI-BD: A Randomized Double-Blind Controlled Trial of Lithium and Divalproex in the Treatment of Mania in Older Patients With Bipolar Disorder.

Publications

GERI-BD: A Randomized Double-Blind Controlled Trial of Lithium and Divalproex in the Treatment of Mania in Older Patients With Bipolar Disorder.

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