Source: American Journal of Psychiatry
Date: 156:2017, December 1999

Treatment Augmentation With Opiates in Severe and Refractory Major Depression
Belmont, Mass.

Letter to the Editor

To the Editor: Substantial evidence supports the antidepressant efficacy of opiates (1). This report summarizes our open-label experience using the µ-opiate agonists oxycodone or oxymorphone in patients with highly refractory and chronic 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.

This report describes three patients with chronic and refractory major depression who were treated with the µ-opiate agonists oxycodone or oxymorphone. All three patients experienced a sustained moderate to marked antidepressant effect from the opiates. The patients described a reduction in psychic pain and distress, much as they would describe the analgesic effects of opiates in treating nocioceptive pain.

Two of the three patients described in this report were previous abusers of opiates. Although the clinical use of opiates in patients with a history of opiate addiction is usually contraindicated, in these cases there was a strong indication that they were self-medicating their mood disorders (2) with illicit opiates. None of the patients abused the opiates, developed tolerance, or started using other illicit substances.

We used oxycodone in three additional patients without histories of opiate abuse. In two of these three patients, oxycodone produced a similar sustained antidepressant effect. Two of these patients experienced mild-to-moderate constipation, and one experienced daytime drowsiness from the opiates. Opiates should be considered a reasonable option in carefully selected patients who are desperately ill with major depression that is refractory to standard therapies.


Bodkin JA, Zornberg GL, Lukas SE, Cole JO: Buprenorphine treatment of refractory depression. J Clin Psychopharmacol 1994; 15:49–57

Khantzian EJ: Self-regulation and self-medication factors in alcoholism and the addictions: similarities and differences. Recent Dev Alcohol 1990; 8:255–271

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