Efficacy and safety of adjunctive therapy to lamotrigine, lithium, or valproate monotherapy in bipolar depression: a systematic review and meta-analysis of randomized controlled trials

Abstract

Background The efficacy and safety of adjunctive therapy are unclear in bipolar depression. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of second-generation antipsychotic, lamotrigine, lithium, or valproate therapy used in adjunction with lamotrigine, lithium, or valproate monotherapy in bipolar depression. A literature search of major electronic databases was conducted in February 2021, and all articles published until then were eligible. Two researchers independently screened relevant publications, extracted data, and evaluated methodological quality according to the Cochrane criteria. Results Five studies met the inclusion criteria. The meta-analysis revealed significant differences in the following outcomes: (i) remission rates from depressive episodes (risk ratio [RR]: 1.23, 95% confidence interval [CI] 1.01–1.50, p = 0.04), (ii) improvement in depressive symptoms (standardized mean difference [SMD]: 0.21, 95% CI 0.09–0.34, p = 0.001), (iii) improvement in quality of life (SMD: 0.22, 95% CI 0.06–0.37, p = 0.005), and (iv) rate of adverse events during the study period (RR: 1.12, 95% CI 1.03–1.22, p = 0.008). There was no significant difference between adjunctive therapy and monotherapy in the emergence of suicide-related behaviors, dropout rate during the study period, or rate of manic switching. Conclusions Our results suggest that adjunctive second-generation antipsychotics, lamotrigine, lithium, or valproate increase both the benefits and risks in patients with bipolar depression, although there is no significant difference in severe adverse events. Adjunctive therapy should be provided through shared decision-making while considering the patients’ condition in clinical settings.

International Trends in Lithium Use for Pharmacotherapy and Clinical Correlates in Bipolar Disorder: A Scoping Review

“…Those that reported on such variations in lithium use observed a high prevalence of polypharmacy use across sites, which could be attributed to the increase in treatment-resistant BD patients [31], elevated tolerance to lithium [99][100][101], greater illness chronicity [58], or limited efficacy of extant treatments for BD [31]. This is consistent with existing treatment guidelines that support the use of combination therapy for treatment-resistant BD [13,89,102], which was associated with reduced hospitalizations, decreased time to recurrence, and improved quality of life for patients with BD [103,104].…”

Short Overview of Oxidative Stress in Mental Disorders

“…However, supplementing with selenium should be preceded by measuring its levels in the blood, as there are controversies surrounding both under and over-dosage. Both scenarios pose a risk factor in promoting depression (Maruki et al, 2022). However, a recent study by Pereira ME et al supports the beneficial antioxidant and antiinflammatory action of selenium in patients with Alzheimer's disease.…”

Appropriate Macronutrients or Mineral Elements Are Beneficial to Improve Depression and Reduce the Risk of Depression

“…Studies have shown that selenium supplementation may be an effective way to prevent postpartum depression [ 139 , 140 ]. However, a study on US youth found the opposite: higher selenium exposure levels are associated with increased depressive symptoms [ 141 ]. Therefore, selenium supplementation for depression requires the first measurement of selenium levels in depressed people, and further clinical studies are required.…”