Opioids, which are currently creating a mayhem in the United States, was historically used for treating mood disorders. However, the addictive nature of the drugs has given rise to a slew of problems and doctors need to be careful while prescribing them.
However, a new study by the Massachusetts General Hospital (MGH) has found that ALKS-5461, a combination of two antidepressants can help in treatment-resistant major depression by targeting receptors in the endogenous opioid system.
ALKS-5461 is a combination of buprenorphine and samidorphan and is currently undergoing a phase-2 clinical trial, funded by the developer of the drug Alkermes, Inc.
The clinical trial of ALKS-5461 found that modulation of the endogenous opioid system may improve the effectiveness of drugs that target the action of serotonin and related monoamine neurotransmitters.
Maurizio Fava, MD, executive director of the Clinical Trials Network & Institute in the MGH Department of Psychiatry and lead author of the study, said that there are more than half of patients with major depression whose first antidepressant may fail to have any effect. Around 40 percent of patients who switches or adds other drugs will continue to have depressive symptoms.
ALKS-5461 is a combination of buprenorphine and samidorphan. Buprenorphine is approved by the U.S. Food and Drugs Administration, while samidorphan is a drug under development by Alkermes. Both the drugs have similar effects on the endogenous opioid system. The endogenous opioids are natural opioids released by the central nervous system which have shown to ease depression, states studies.
Regarding the findings, Dr. Fava said, “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.”
The study, published in the American Journal of Psychiatry in February 2016, made 142 patients with treatment-resistant depression undergo trial at 31 sites in the U.S. However, they used a design developed in 2003 by Fava and David Schoenfeld, PhD, MGH, biostatician, to lessen the effects of placebo, since depression treatment trials are always likely to have a large placebo response. This was a two-staged randomized trial method to reduce the impact of the placebo effect on results.
In the first stage, the researchers gave placebo to 98 patients and either a 2 milligram or 8 milligram dose of ALKS-5461 for four weeks to 43 patients. However, the participants who were non-responsive to treatment in the placebo group were again randomized in the second stage. These participants received one of the two drug doses or were continued with a placebo.
However, it was seen that both the dosage levels of ALKS-5461 had shown a decrease in depression symptoms compared to the placebo. In fact, the lower dosage of 2 milligrams of each drug proved to have a stronger effect.
Dr. Fava added that higher doses can have side effects which are seemingly low in lower doses. Though the participants reported nausea, vomiting, and dizziness during the first few days of treatment, there was no evidence, however, of any kind of withdrawal symptoms after the trial, from the abuse of ALKS-5461.
The researchers were of the view that the combination of antidepressants can work for patients who did not respond to conventional depression therapy and medications. This drug can provide a novel approach to treating depression. Alkermes Inc, which funded the trial, is conducting a three-stage study of ALKS-5461, out of which two stages are complete.
If you or your loved one is suffering from depression and is heavily dependent on opioids treating depression, you can seek help. The Prescription Drug Addiction Helpline can provide access to effective treatment programs and facilities. Please chat online or call 866-623-3847.