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In older adults with bipolar disorder, what evidence is there to guide treatment?
Despite the increasing number of older adults with bipolar disorder, there is limited evidence to guide its treatment in older patients.
In the past, the treatment of bipolar disorder and mania in older adults was based on uncontrolled studies. As an aggregate, these studies suggested that lithium may be effective in treating bipolar disorder in late life. However, concerns about lithium’s safety in older patients led practitioners to using lower concentrations than what was used in middle aged adults, or to avoid lithium altogether.
Thus, questions remain regarding the optimal lithium level that balances efficacy and adverse effects for patients in this age group.1
The goal of the first double-blind study comparing the safety and efficacy of lithium and divalproex in the treatment of late life mania attempted to answer these questions. The study, conducted at 6 academic centers and funded by the National Institute of Mental Health, was a randomized 9-week double-blind parallel group trial of lithium and divalproex in patients with bipolar I disorder in a current manic, mixed, or hypomanic episode. Patients were aged 60 years or older.2
The average maximum dose of lithium was 780 mg ± 315 mg with a serum concentration of 0.76 ± 0.35 mEq/L. The average maximum dose of divalproex was 1200 mg ± 550 mg with a serum concentration of 74 ± 21 mg/L. Limited use of lorazepam or risperidone was allowed in the first 3 weeks of the study for agitation or insomnia. After 3 weeks of treatment, risperidone up to 4 mg a day was used for an inadequate response to lithium or divalproex.
The attrition rates by study end (51% on lithium and 44% on divalproex) were not significantly different, and they did not depend on age or medical burden. The reasons for attrition were nonadherence, poor tolerance, and lack of efficacy. Patients tolerated both medications equally.
In terms of efficacy, both medications were beneficial in reducing the Young Mania Rating Scale (YMRS) score, but lithium lowered scores slightly more, with moderate effect size. Patients with more severe mania at study entry did better on lithium than on divalproex. Response rates (defined as at least 50% reduction of YMRS from baseline) in the lithium and divalproex groups were 63% and 57%, respectively, at week 3 (nonsignificant) and 79% and 73% at week 9 (also nonsignificant). The cumulative rates of remission (YMRS ≤ to 9) were 46% and 44%, respectively, at week 3 (nonsignificant) and 70% and 63% at week 9 (nonsignificant). Seventeen percent of patients taking lithium and 14% of patients taking divalproex received adjunctive risperidone after the third week of treatment (Figure). The proportion of patients needing adjunctive risperidone was not statistically different between the 2 treatment groups.
The study authors concluded that efficacy and tolerability of lithium and divalproex are comparable in the treatment of mania in older adults. “Treatment with lithium or divalproex with conservative serum concentration targets, combined with limited use of rescue and adjunctive medications, was tolerated by older patients with mania, and it benefited a substantial proportion of them,” the authors reported. “These results suggest that treatment guidelines for older persons with bipolar disorder should emphasize greater use of lithium and less exposure to antipsychotics.”
Dr Gyulai is a psychiatrist in Philadelphia, Pennsylvania and is affiliated with Hospitals of the University of Pennsylvania-Penn Presbyterian.
1. Young RC, Gyulai L, Mulsant BH, et al. Pharmacotherapy of bipolar disorder in old age: review and recommendations. Am J Geriatr Psychiatry. 2004 Jul-Aug;12(4):342-357.
2. Young RC, Mulsant BH, Sajatovic M, et al. GERI-BD: a randomized double-blind controlled trial of lithium and divalproex in the treatment of mania in older patients with bipolar disorder. Am J Psychiatry. 2017;174(11):1086-1093. ❒