Prophylactic efficacy of lithium, valproic acid, and carbamazepine in the maintenance phase of bipolar disorder

Abstract

Mood stabilizers are used clinically for the management of bipolar disorder. Prophylactic therapy with mood stabilizers is the primary treatment for preventing depressive and manic relapses in bipolar patients once they are stabilized. In this study, we examined the relative efficacy of the three most commonly used mood-stabilizing agents: lithium (Li), valproic acid (VPA), and carbamazepine (CBZ), in preventing relapse episodes. A total of 225 patients with bipolar disorder were included in the present analysis. Patients taking Li, VPA, or CBZ were followed up for up to 124 months, until suffering a manic, mixed, or depressive episode (relapse), or until the end of the study/study termination (no relapse), whichever came first. The median unadjusted survival time was 36 months for patients taking VPA, 42 months for patients taking CBZ, and 81 months for patients taking Li. These results indicate that patients stayed longer on Li, suggesting that it might have been better tolerated than either CBZ or VPA. χ-Analysis showed that patients taking Li were significantly less likely to experience relapse during the observational period than patients taking either VPA or CBZ (P<0.05). A Cox regression model showed that the hazard of experiencing relapse was significantly predicted by the total number of depressive (P=0.007) and manic symptoms (P=0.02) assessed before the observation period. In addition, after controlling for symptom covariates, the hazard of experiencing relapse was 1.66 times (95% confidence interval 1.03-2.67) or 66% higher for patients taking VPA compared with patients taking Li (P=0.037). Although the hazard of experiencing relapse was higher for patients taking CBZ compared with those taking Li, the risk was not elevated by a significant amount. Notwithstanding the limitations of the naturalistic design of this study, the differences in relapse prevention and survival time observed in these medications show Li fairing relatively better in prophylactic therapy.

Lithium, valproate, and carbamazepine prescribing patterns for long‐term treatment of bipolar I and II disorders: A prospective study

“…The need to treat comorbid anxiety disorders could explain the high rate of antidepressant prescription in this group. The use of VA or CBZ monotherapy in patients with anxiety disorder comorbidity is in agreement with Malhi and colleagues opinion (Malhi et al, ), who highlighted that anticonvulsant monotherapy is the most common therapeutic choice for BD with anxious comorbidities, but in contrast with Peselow and colleagues opinion (Peselow, Clevenger, & IsHak, ) who stated that Li is the most effective prophylactic drug, regardless of concomitant psychiatric comorbidities.…”

Genetics of Lithium Response in Bipolar Disorder

“…For example, higher success rate for lithium with respect to valproate, lamotrigine, and carbamazepine has been reported [22]. Likewise, another study reported a longer median unadjusted survival time before relapse for patients taking lithium compared to valproate or carbamazepine [23]. These studies, together with other population-based studies and data from specialty clinics, add to the evidence [5,[24][25][26].…”

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

“…Their main advantage usually is the length of observation, in some instances reaching several decades 363, 364, 365. This comes at the cost of generalizability, in terms of both patient selection and non‐random treatment allocation.…”