Opioids for Treatment Resistant Depression?
My colleague, Mark Rose, recently submitted this post about the potential use of buprenorphine as an antidepressant treatment for treatment resistant depression. To our knowledge, no further studies of this have been done. Perhaps it's time?
MW
Buprenorphine may be effective in treatment-refractory depression
Mark E. Rose, MA
Licensed Psychologist
Persons with major depressive disorder (MDD) are considered treatment-refractory (TRD) when they fail to respond to multiple trials of antidepressant medication from different classes (Keller 2005). TRD is a devastating condition that results in substantial health care and economic cost, and untold suffering to the patient and family members (Nierenberg et al. 2007). Most FDA-approved antidepressant drugs act through monoamine reuptake inhibition, and medications that act through alternate mechanisms need to be available to patients with unrelenting depression that is untreatable with conventional antidepressants. The results of a study published 15 years ago hint that a currently available drug may provide greater benefit to patients with TRD than any other known pharmaceutical agent.
Although opioids were used to treat MDD until the late 1950s, research evaluating their antidepressant potential has been very rare in the past 60 years (Berrocoso et al. 2009). The synthetic opioid buprenorphine is a partial mu receptor agonist and kappa receptor antagonist, is exceptionally safe in overdose, and produces substantially less euphoria than pure mu receptor agonists such as morphine and oxycodone. A small study (Bodkin et al. 1995) evaluated the therapeutic potential of buprenorphine in the treatment of TRD. The 10 study participants averaged a 20.7–year duration of unipolar major depression, 7.6 previous unsuccessful antidepressant trials, and a HAM-D score of 28.1. Buprenorphine was initiated in open-label manner at 0.15 mg/d with maximum upward titration to 1.80 mg/d over the 4-6 week trial (final mean dose 1.26 mg/d). Three subjects dropped out due to malaise, nausea, and dysphoria. Of the remaining 7 subjects, 6 achieved marked clinical improvement. The mean endpoint HAM-D score was 10.7, a 60.7% reduction from baseline, and 4 patients achieved complete remission (HAM-D ≤ 6). The mean overall level of functioning increased 45.5% and mean subjective depression rating decreased 50%. Significant improvement became apparent at the end of week 1.
The authors conclude that the results are remarkable, with the number of previous treatment failures, the level of disease severity, and the duration of improvement arguing against placebo effect as the basis of treatment response. Patients did not report euphoria or intoxication but instead felt ‘more normal’, which together with the 33% drop-out suggest limited abuse liability in persons with TRD. These results are literally begging for replication, but sadly, despite awareness of this data for 15 years, researchers have not conducted follow-up studies due to the stigma surrounding opioid drugs and their association with addiction.
Keller MB. Issues in treatment-resistant depression. J Clin Psychiatry. 2005;66(Suppl 8):5-12.
Nierenberg AA, Katz J, Fava M. A critical overview of the pharmacologic
management of treatment-resistant depression. Psychiatr Clin North Am. 2007;30(1):13-29.
Berrocoso E, et al. Opiates as antidepressants. Current Pharmaceutical Design. 2009;15:1612-1622.
Bodkin JA, Zornberg GL, Lukas SE, Cole JO. Buprenorphine treatment of refractory depression. J Clin Psychopharmacol. 1995;15:49-57.
MW
Buprenorphine may be effective in treatment-refractory depression
Mark E. Rose, MA
Licensed Psychologist
Persons with major depressive disorder (MDD) are considered treatment-refractory (TRD) when they fail to respond to multiple trials of antidepressant medication from different classes (Keller 2005). TRD is a devastating condition that results in substantial health care and economic cost, and untold suffering to the patient and family members (Nierenberg et al. 2007). Most FDA-approved antidepressant drugs act through monoamine reuptake inhibition, and medications that act through alternate mechanisms need to be available to patients with unrelenting depression that is untreatable with conventional antidepressants. The results of a study published 15 years ago hint that a currently available drug may provide greater benefit to patients with TRD than any other known pharmaceutical agent.
Although opioids were used to treat MDD until the late 1950s, research evaluating their antidepressant potential has been very rare in the past 60 years (Berrocoso et al. 2009). The synthetic opioid buprenorphine is a partial mu receptor agonist and kappa receptor antagonist, is exceptionally safe in overdose, and produces substantially less euphoria than pure mu receptor agonists such as morphine and oxycodone. A small study (Bodkin et al. 1995) evaluated the therapeutic potential of buprenorphine in the treatment of TRD. The 10 study participants averaged a 20.7–year duration of unipolar major depression, 7.6 previous unsuccessful antidepressant trials, and a HAM-D score of 28.1. Buprenorphine was initiated in open-label manner at 0.15 mg/d with maximum upward titration to 1.80 mg/d over the 4-6 week trial (final mean dose 1.26 mg/d). Three subjects dropped out due to malaise, nausea, and dysphoria. Of the remaining 7 subjects, 6 achieved marked clinical improvement. The mean endpoint HAM-D score was 10.7, a 60.7% reduction from baseline, and 4 patients achieved complete remission (HAM-D ≤ 6). The mean overall level of functioning increased 45.5% and mean subjective depression rating decreased 50%. Significant improvement became apparent at the end of week 1.
The authors conclude that the results are remarkable, with the number of previous treatment failures, the level of disease severity, and the duration of improvement arguing against placebo effect as the basis of treatment response. Patients did not report euphoria or intoxication but instead felt ‘more normal’, which together with the 33% drop-out suggest limited abuse liability in persons with TRD. These results are literally begging for replication, but sadly, despite awareness of this data for 15 years, researchers have not conducted follow-up studies due to the stigma surrounding opioid drugs and their association with addiction.
Keller MB. Issues in treatment-resistant depression. J Clin Psychiatry. 2005;66(Suppl 8):5-12.
Nierenberg AA, Katz J, Fava M. A critical overview of the pharmacologic
management of treatment-resistant depression. Psychiatr Clin North Am. 2007;30(1):13-29.
Berrocoso E, et al. Opiates as antidepressants. Current Pharmaceutical Design. 2009;15:1612-1622.
Bodkin JA, Zornberg GL, Lukas SE, Cole JO. Buprenorphine treatment of refractory depression. J Clin Psychopharmacol. 1995;15:49-57.
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