Comparison of 2 treatment strategies for depressed inpatients: Imipramine and lithium addition or mirtazapine and lithium addition

Background: The purpose of this study was to compare the overall effectiven ess of 2 treatment strategies for inpatients with severe major depressive e pisode (DSM-III-R): (1) mirtazapine (phase 2) and subsequent lithium additi on (phase 2) or (2) imipramine (phase 1) and subsequent lithium addition (p hase 2). We previously reported the results of phase 1. Method: In phase I, patients were randomly assigned to treatment with eithe r mirtazapine or imipramine, and doses were adjusted to obtain predefined b lood drug levels. Nonresponders had Lithium added to the double-blind mirta zapine or imipramine medication. The dose was adjusted to obtain a blood li thium level of 0.5-1.0 mmol/L. Treatment effects were evaluated weekly by t he Montgomery-Asberg Depression Rating Scale for up to 2 weeks on this bloo d lithium level. Results: Data for 100 patients were available for comparison of the 2 treat ment strategies. 80 patients received no comedication. By the end of phase 2, 24 (48%) of 50 had responded to mirtazapine and 32, (64%) of 50 had resp onded to imipramine (intent-to-treat analysis). A survival analysis of the total patient group intent-to-treat showed a significant difference in favo r of the treatment strategy with imipramine and subsequent lithium addition . Conclusion: Efficacy of imipramine and subsequent lithium addition for nonr esponders is superior to the same treatment strategy with mirtazapine. This applies to the patient sample studied, which consisted of 100 severely dep ressed inpatients, 29 of whom were psychotically depressed. More serious si de effects of imipramine, however, led to discontinuation of imipramine in 5 patients. No serious side effects were observed during the phase of lithi um addition to either imipramine or mirtazapine. We, therefore, prefer to s tart treatment with imipramine and test for fixed blood drug levels, and, i f necessary, add lithium. In the case of prohibitive side effects, patients are switched to a modern antidepressant such as mirtazapine, and, if neces sary, lithium is added to this antidepressant.