A rational approach to the non-responding depressed patient.

At least 30% of patients with major depression fail to respond to conventional antidepressant medication, even when given adequate doses. Numerous factors have been implicated in treatment resistance including subclinical hypothyroidism, alcohol abuse, occult carcinoma, minor head injuries and the use of calcium channel blockers such as nifedipine. Lithium augmentation of traditional tricyclic antidepressants and selective serotonin re-uptake inhibitors such as fluoxetine are the most extensively investigated combinations used to treat non-responsive depression. Other strategies are also briefly discussed.