Bupropion and sertraline combination treatment in refractory depression.

A sizeable minority of depressed patients, estimated at 15-20%, suffer chronic symptoms which often persist despite appropriate treatment. The search for new, more efficacious pharmacotherapies has included testing existing medications for additional therapeutic effects, such as in combination treatment. Four treatment- refractory patients who presented to the authors for clinical care are described, in which the combination of bupropion and sertraline was effective for a major depressive episode. None of the patients experienced adverse effects. Two carried the diagnosis of unipolar depression, and two, bipolar disorder. All had prior adequate, but ineffective, separate trials of buproprion and a selective serotonin re-uptake inhibitor (SSRI), including sertraline. All had chronic depression with multiple failed medication treatments, arguing against the alternative explanation that their improvement represented a placebo response or spontaneous remission. The efficacious combination of sertraline and bupropion may be due to synergism of its two distinct antidepressant mechanisms involving serotonergic, dopaminergic and noradrenergic systems.