BOSTON, Feb. 12 (UPI) -- An experimental treatment combining two antidepressants was found to help treatment-resistant depression by targeting receptors in the endogenous opioid system, researchers reported in a new study.
Researchers at Massachusetts General Hospital found ALKS-5461, a combination of buprenorphine and samidorphan, in a Phase 2 clinical trial funded by the drug's developer, Alkermes, Inc.
The drug has been the focus of three Phase 3 trials, two of which have been concluded. Although full results of the trials have not yet been published, efficacy of ALKS-5461 has been inconsistent, according to a press release from the company.
Buprenorphine is already approved by the FDA for use treating opioid addiction, while samidorphan is a drug under development by Alkermes. Both have similar effects on the endogenous opioid system -- natural opioids released by the central nervous system -- by blocking specific receptors. Previous research has shown reducing natural opioids in the central nervous system can help ease depression.
"The robust treatment effect seen in this clinical study suggests that many patients with depression may have a dysregulation of the endogenous opioid system, which may be why they do not respond to monoamine-based antidepressants that target the serotonin system," said Dr. Maurizio Fava, executive director of the Clinical Trials Network and Institute at Massachusetts General Hospital.
For the current study, published in the American Journal of Psychiatry, researchers recruited 142 patients at 31 sites, using a two-stage randomized trial method to reduce the impact of the placebo effect on results.
For stage 1, the researchers gave 98 patients placebo doses and 43 patients either a 2 milligram or 8 milligram dose of ALKS-5461 for four weeks. Participants in the placebo group who did not respond to treatment were re-randomized for stage 2 of the study, receiving one of the two drug doses or continuing with a placebo.
The researchers reported that both dosages had an effect on depression symptoms, but the effect of the 2 milligram dose was more significant.
In one of two already completed Phase 3 trials of ALKS-5461, a 2 milligram dose was found to be more effective than a 0.5 milligram dose. The other completed trial found that a larger response to placebo was found than with participants given ALKS-5461. The third Phase 3 trial, which is ongoing, compares the effects of a 2 milligram dose with a 1 milligram dose.
"For the substantial percentage of patients who do not respond to monoamine based medications, this combination may represent an important new approach to the treatment of depression," Fava said.