Differential Efficacy of Lithium and Carbamazepine in the Prophylaxis of Bipolar Disorder: Results of the MAP Study

Abstract

In a randomized clinical trial with an observation period of 2.5 years, the differential efficacy of lithium versus carbamazepine was compared in 171 bipolar patients (DSM-IV). In order to investigate the efficacy of the two drugs in clearly defined subsamples, a series of subgroup analyses was carried out. First, patients with a bipolar I disorder (n = 114) were analyzed separately. In these patients, lithium was superior to carbamazepine. In contrast, carbamazepine was at least equally as efficacious as lithium in the subsample of patients with bipolar II disorder or bipolar disorder not otherwise specified (n = 57). In a second analysis on differential efficacy, the whole sample was subdivided into a classical subgroup (bipolar I patients without mood-incongruent delusions and without comorbidity; n = 67) and a nonclassical subgroup including all other patients (n = 104). Classical bipolar patients had a significantly lower hospitalization rate under lithium than under carbamazepine prophylaxis (26 vs. 62%, p = 0.012). For the nonclassical group, a tendency in favor of carbamazepine was found. In a third step, we analyzed the impact of episode sequence on differential efficacy. In a global view, the episode sequence prior to the index episode was not correlated to differential efficacy. Our results might, however, indicate that patients with an episode sequence of mania-depression-free interval responded better to lithium. Besides differential efficacy, suicidal behavior and patients’ satisfaction with treatment were investigated. Regarding suicidal behavior, a trend in favor of lithium was found. The data on patients’ satisfaction were significantly in favor of carbamazepine. In conclusion, lithium appears to be superior to carbamazepine in classical bipolar cases and might have additional impact on proneness to suicide. The distinctly larger group of patients with nonclassical features might profit more from carbamazepine which seems to be well accepted by the patients. Hence, treatment alternatives to lithium are desirable for the majority of bipolar patients.

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

“…Available data come mostly from naturalistic/cohort studies and few randomized trials 405. Nevertheless, several tentative predictors are emerging from the available data.…”

“…It also remains common for trials to enrol patients with both BDII and BDI without reporting results separately, making it difficult to determine if there are clinically meaningful differences in treatment response between the two illnesses. This is important because, while clinical experience and the results of many studies suggest that response to mood stabilizers and antipsychotics is similar in BDII and BDI, there are enough exceptions to suggest this should not be taken for granted 248, 405, 431. This is also the case for antidepressants, which may have a more favourable risk‐benefit ratio in BDII (reviewed below).…”

“…The authors noted that findings were similar for BDII and BDI, but results were otherwise not reported separately for BDII. In a 2.5‐year study in BDII + BD NOS, lithium and carbamazepine were equally effective on most outcomes, although a numerical advantage favoured carbamazepine for reducing clinical plus subclinical recurrence 405. In contrast, head‐to‐head comparisons with antidepressants (reviewed below) found that lithium was not as effective in preventing depressive relapse as fluoxetine or venlafaxine 469, 497.…”

“…Divalproex (level 4),504 carbamazepine (level 3),405 escitalopram (level 3),505 other antidepressants (level 3),454 and risperidone (mainly for prevention of hypomania) (level 4)436 may be considered as third‐line options.…”

A systematic review and economic model of the clinical effectiveness and cost-effectiveness of interventions for preventing relapse in people with bipolar disorder

“…36,39,40,42,43,[47][48][49][50][52][53][54][55][56][57]60,61,[64][65][66][67]69,72,74,77 Two of these studies compared only different doses of lithium and are not considered in the analyses. 52,61 Trial details are summarised in Table 2 and presented in the data extraction tables (Appendix 6).…”