Treatment Augmentation With Opiates in Severe and Refractory Major Depression

Mr. A was a 44-year-old man with severe and chronic depression. Numerous trials of antidepressants produced only limited benefit. Mr. A also had an extensive history of opiate abuse, and he noted that the only times he ever felt normal and not depressed was during opiate use. Because of the refractory nature of his depressive symptoms and his apparent self-medication with opiates, Mr. A was given a trial of oxycodone under strict supervision. After 18 months of oxycodone treatment (10 mg/day), Mr. A remained in his longest remission from depression without the emergence of opiate tolerance or abuse.

Ms. B was a 45-year-old woman with bipolar disorder and opiate abuse (in remission for 2 years). A trial with standard mood stabilizers had failed, and she had experienced mania with several standard antidepressant drugs. As with Mr. A, Ms. B reported feeling well only when taking opiates, particularly oxymorphone. Oxymorphone (8 mg/day) was thus cautiously added to ongoing lamotrigine therapy (as a mood stabilizer), and she remained well for a minimum of 20 months without drug tolerance or abuse.

Mr. C was a 43-year-old man with chronic major depression that was unresponsive to numerous antidepressants with and without augmentation. Detailed questioning revealed that he once experienced marked antidepressant effects from opiates that he received after a dental procedure. There was no history of opiate abuse, and a cautious trial of oxycodone was initiated. Mr. C experienced a dramatic and gratifying antidepressant response from oxycodone (10 mg t.i.d. for 9 months) without opiate tolerance or abuse.