Effect of bupropion on nocturnal urinary free cortisol and its association with antidepressant response.

The study examined the relationship between pre-treatment nocturnal hypothalamic-pituitary-adrenal (HPA) activity, as reflected by nocturnal urinary free cortisol (NUFC) response to a single-dose of sustained-release bupropion, and the antidepressant effect of the drug. NUFC changes in response to treatment with bupropion also were assessed. NUFC was measured in 20 patients with unipolar major depressive disorder before and after initiating treatment with sustained-release bupropion. Prior to treatment, subjects were studied on two separate sessions, one week apart. On the morning of each session, the participants received bupropion (150 mg, PO) or placebo using a randomized, double-blind procedure. Following the second session, subjects then received open-label treatment with bupropion for 8 weeks. NUFC sampling was repeated at the end of treatment. There was a significant interaction between NUFC concentration in response to single-dose bupropion and its antidepressant effect. Treatment non-responders showed a significant increase in NUFC in response to a single-dose of bupropion, whereas responders showed no such change. In addition, the NUFC response to bupropion challenge correlated significantly with the change in depression ratings as a result of treatment. In contrast to many other antidepressants, treatment with bupropion for 8 weeks did not reduce HPA activity in either responders or non-responders. These findings suggest that the NUFC response to a test-dose of bupropion might be helpful in predicting its antidepressant effect. One possible mechanism for the association between the NUFC response to acute bupropion challenge and antidepressant efficacy might be linked through dopaminergic and/or noradrenergic mechanisms.