Serotonergic function during lithium augmentation of refractory depression

Serotonergic mechanisms have been implicated in the pathophysiology of depression and in the neuropharmacology of antidepressant treatment. One measure of central serotonergic function is the prolactin (PRL) response to IV l-tryptophan (l-TRP). We used the l-TRP test to assess the role of serotonin in the mechanism of action of lithium augmentation in refractory major depression. Twenty-six patients with antidepressant-refractory major depression each received three l-TRP tests (after 2 weeks of placebo, after 4 weeks of active primary antidepressant, and after 1 week of lithium augmentation). Primary antidepressant treatment did not increase the PRL response, but lithium augmentation resulted in a statistically significant increase in PRL response as compared to both placebo pretreatment (P<0.04) and antidepressant treatment alone (P<0.025). This study supports a role for serotonergic mechanisms in the action of lithium augmentation.