Lithium augmentation of antidepressants in treatment-refractory depression

The use of lithium to convert antidepressant nonresponders to responders is reviewed. Although there is little doubt that lithium is effective in a sizable percentage of patients who do not respond to tricyclic antidepressants (TCAs) and serotonin selective reuptake inhibitors (SSRIs), much remains obscure about this effect. Does it work preferentially on antidepressants that act primarily on serotonergic neurons, or is it equally effective with agents that act upon other neurotransmitter systems? When should lithium, compared with other strategies, be utilized in antidepressant nonresponders? Are certain subtypes of depression more likely than others to respond to lithium augmentation? The available literature highlights the efficacy of lithium as an augmenting agent in refractory depression and serves as an impetus for additional neurobiological and clinical studies of this phenomenon.