PLACEBO-CONTROLLED TRIAL OF LITHIUM AUGMENTATION OF FLUOXETINE AND LOFEPRAMINE

Background. This study was designed to establish whether (as suggested in a number of open and relatively small controlled trials) lithium augmentation is more effective than continued antidepressant alone, where response to a standard course of antidepressant treatment has been absent or partial. Method. Lithium or placebo was added on a double-blind basis for six weeks to the drug regime of 62 patients with major depressive illness (in both hospital and primary care settings) who had failed to respond to a controlled trial of fluoxetine or lofepramine. Response was defined as a final Hamilton Depression Rating Scale (HDRS) score of <10. Results. Response was seen more frequently in patients taking lithium (15/29) than in those remaining on antidepressant alone (8/32; P<0.05). Rapid response to lithium augmentation (LA) was not consistently observed in this cohort. Mean HDRS scores after six weeks were significantly lower (P<0.01) in the lithium group after excluding those who had not achieved significant exposure to lithium (arbitrarily defined as two or more lithium levels greater than or equal to 0.4 mmol/l). No differences in the efficacy of LA were apparent between fluoxetine and lofepramine. Conclusions. Our results confirm that LA is a useful strategy in the treatment of antidepressant-resistant depression. Partial response was, however, frequently observed with continued antidepressant treatment alone, and the superiority of LA appears to depend on achieving adequate serum lithium levels.