These results suggest that olanzapine was significantly more effective than lithium in preventing manic and mixed episode relapse/recurrence in patients acutely stabilized with olanzapine and lithium co-treatment. Both agents were comparable in preventing depression relapse/recurrence.

No abstract

Although a few variables are quite robustly supported as response-predictors in this review, a more in-depth analysis of each potential predictor is needed. As none of the potential predictors had a very strong impact on response, prediction of lithium response should be based on a multitude of variables.

Recent findings have indicated that lithium treatment markedly reduces suicide risk in major affective disorders. To compare the effect of lithium with carbamazepine and amitriptyline, suicidal behavior was analyzed during the randomized prospective long-term MAP study (N = 378; duration 2.5 years). Of the nine suicides and five attempted suicides, none took place during lithium treatment. The findings support the view that lithium has a specific antisuicidal effect over and above its prophylactic benefit.

In a randomized, prospective, multicenter study with an observation period of 2.5 years, the differential prophylactic efficacy of lithium versus carbamazepine was compared in 171 patients fulfilling DSM-IV criteria for bipolar disorder. Serum drug levels were 0.6+/-0.1 mmol/L for lithium and 6.1+/-1.3 microg/mL for carbamazepine. Patients were 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 lower rehospitalization rate with lithium than with carbamazepine prophylaxis (p = 0.005). For the nonclassical group, a trend in favor of carbamazepine was found. In the lithium group, there was a positive association between hospitalization rate and number of nonclassical features (bipolar II/not otherwise specified, mood-incongruent delusions, comorbidity; p = 0.035). For carbamazepine, this association was negative (p = 0.033). Analyses including mixed states as an additional nonclassical feature confirmed the results. In conclusion, lithium seems to be superior to carbamazepine in treating classical bipolar cases. Patients with nonclassical features might profit more from prophylaxis with carbamazepine, which seems to have a broader spectrum of activity.

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.

In a randomised multicentre study, the prophylactic efficacy of lithium and carbamazepine was compared in schizoaffective disorder. A total of 90 ICD-9 schizoaffective patients were included in the maintenance phase (2.5 years). They were also diagnosed according to RDC and DSM-III-R and classified into subgroups. Mean serum levels were 0.58 +/- 0.12 mmol/l for lithium and 6.4 +/- 1.5 micrograms/ml for carbamazepine (mean dose 643 +/- 179 mg/d). Outcome criteria were hospitalisation, recurrence, concomitant psychotropic medication and adverse effects leading to discontinuation. There were more non-completers under carbamazepine than under lithium (p = 0.02). Survival analyses demonstrated no significant differences between lithium and carbamazepine in treatment outcome. Patient's ratings of side effects (p = 0.003) and treatment satisfaction (p = 0.02) favoured carbamazepine. Following the RDC criteria, patients of the schizodepressive and non-classifiable type did better under carbamazepine (p = 0.055 for recurrence), whereas in the schizomanic patients equipotency of both drugs was found. Applying DSM-III-R, carbamazepine demonstrated a superiority in the patient group with more schizophrenia-like or depressive disorders (p = 0.040 for recurrence), but not in patients fulfilling the DSM-III-R criteria of bipolar disorder. Lithium and carbamazepine seem to be equipotent alternatives in the maintenance treatment of broadly defined schizoaffective disorders. However, in subgroups with depressive or schizophrenia-like features and regarding its long-term tolerability carbamazepine seems to be superior.

In the long-term treatment of bipolar disorder clinicians should initially aim for serum lithium levels of 0.6-0.75 mmol/L, while higher levels may benefit patients with predominantly manic symptoms.