Refractory depression: a review with particular reference to the use of lithium augmentation

The literature on pharmacological treatments of refractory depression is reviewed, with particular reference to problems in definition of treatment resistance, criteria for adequacy of treatment and the lack of controlled trial evidence for many putative treatment approaches. The results of a placebo-controlled trial of lithium augmentation of patients failing to respond to fluoxetine or lofepramine are presented. The data from this trial (particularly when analysed in combination with that in earlier, smaller published studies) establish the efficacy of lithium augmentation but illustrate the difficulty of achieving adequate plasma lithium levels and the high rate of partial response to continued antidepressant alone.