In This Article
- Less than 40% of patients with major depression are achieving symptoms remission from currently available first-line antidepressants
- The endogenous opioid system is thought to have a role in several factors affected by major depression, such as mood, motivation and social functions
- Two trials examining a drug that combines buprenorphine and samidorphan to target the opioid system has shown to be safe and effective in reducing symptoms of major depression when added to the standard antidepressant treatment
Treating major depression continues to pose a challenge to clinicians, as fewer than 40% of patients with major depression are achieving symptoms remission from first-line antidepressant treatments that target monoamine-based signaling. Two clinical trials examining an investigational drug that combines buprenorphine and samidorphan to target the opioid system has shown to be safe and effective in reducing symptoms of major depression when added to standard antidepressant treatment.
One challenge of using buprenorphine to treat depression, which is also used for pain relief and treatment of opioid use disorder, is the risk of abuse and dependence. Because of this risk, samidorphan was added to the formulation to block one of the opioid receptors activated by buprenorphine.
The results of FORWARD-4 and FORWARD-5, the Phase 3 trial of the drug combination led by Maurizio Fava, MD, executive director of the Clinical Trials Network & Institute in the Department of Psychiatry, were published in Molecular Psychiatry.
This new combination drug is predicated on evidence that the endogenous opioid system may have a role in several factors affected by major depression, such as mood, motivation and social functions.
The FORWARD-5 trial was conducted at over 100 sites in several countries and included almost 800 adults who have not responded adequately to traditional antidepressant treatment. Two dosage levels—1.0 mg and 2.0 mg—were compared with a placebo. Because placebo effect is known to commonly occur in trials of depression drugs, the trial was specifically designed to reduce that risk. Participants who did not show symptom improvement by week 5 were re-randomized to either continue with the placebo or to receive a test dosage, while all others remained in their original grouping.
At the end of the trial, participants at both dosage levels had a reduction in depression symptoms, and those receiving the 2.0 mg dose had the greatest reduction. These results suggest that this new drug combination could prove to be a promising new pharmacological tool for patients who have not responded to traditional therapies.