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Allergan’s failed depression drug shows promise in opioid withdrawal

In rats, Allergan’s rapastinel reversed signs of opioid withdrawal in three days, according to a new study presented during the 2019 Experimental Biology meeting. (Getty/BackyardProduction)

Last month, Allergan said that rapastinel—the centerpiece of its $560 million acquisition of Naurex—had failed in three pivotal trials in major depressive disorder. But not all is lost. Scientists at Duke University and Villanova University may have found a use for the drug in treating opioid withdrawal.

People who become dependent on opioids can experience excruciating withdrawal symptoms, such as anxiety, vomiting, diarrhea and insomnia. These symptoms often prevent them from seeking help, or they cause relapse in patients who do seek out treatment for addiction.

Rapastinel might help manage those symptoms, according to a new study by Julia Ferrante at Villanova University and Cynthia Kuhn at Duke University. The experimental drug substantially reversed acute withdraw signs in rats in three days, the researchers said in a release. The study was presented at the American Society for Pharmacology and Experimental Therapeutics annual meeting in Orlando.

There are FDA-approved drugs to treat opioid use disorder. Buprenorphine and methadone are commonly used to help eliminate the opioid cravings. But they are also opioids that can be abused, they can cause side effects, and patients sometimes need to use them over the long term to avoid relapse.

Two other drugs, naloxone and naltrexone, are not opioids. But patients need to detox before they can use naltrexone, and naloxone is more appropriate for use in emergency settings to reverse opioid overdoses.

Rapastinel, in comparison, binds to the same NMDA receptor that the “party drug” ketamine uses, but at a different site. In their study, Ferrante and Kuhn gave rat models of opioid dependence either rapastinel, ketamine or a saline solution. On the third day, rats given rapastinel showed significantly fewer signs of withdrawal than the other animals did, the researchers reported.

Opioid overdose has become a public health crisis in the U.S., with an estimated 130 people dying each day from opioid-related drug overdoses, according to the U.S. Department of Health and Human Services. While health regulators are pursuing tactics for cutting down on opioid use, scientists are stepping up their research efforts, looking for new ways to fight addiction.

Last May, the FDA greenlighted US WorldMeds’ Lucemyra as the first approved drug specifically for opioid withdrawal, even though the drug had been used for more than two decades in the U.S.

Scientists at the Walter Reed Army Institute of Research previously found a heroin vaccine could block the euphoric effects of opioids in the brain by blocking heroin from crossing the blood-brain barrier.

Although rapastinel’s use in depression turned out to be a dead end, clinical trials have shown it is well-tolerated in people. Before rapastinel can be moved into clinical trials in opioid withdrawal, more studies are needed to investigate its molecular effects and to determine whether it can reduce the possibility of relapse, according to the researchers.