Studies Investigate Antipsychotics as Adjuncts to Opioid Use Disorder Meds

November 10, 2022

John* grew up in a family severely impacted by substance use disorders. He started using heroin at 15, and he has struggled with addiction, he said, for most of his life. He also experienced homelessness for several years in Kensington, Philadelphia, where he would buy from the open-air drug markets.

When his mother died of an overdose three years ago, “I went off the deep end,” John, now 34, told Filter.

He estimates that he has detoxed from heroin and other drugs, including cocaine, 30 times, and been to rehab 25 times. He is currently in early recovery at a treatment center in Philadelphia. And for the first time in his life, he is on methadone—a medication that reduces mortality among people with opioid use disorder (OUD) by half or more.

John is also participating in research at the University of Pennsylvania’s Center for Studies on Addiction that’s the subject of both hopes and controversy.

The Penn researchers, in two different studies, are using two psychotropic medications as add-ons to methadone or buprenorphine, another well-evidenced medication for opioid use disorder (MOUD). They’re investigating whether they can boost people’s chances of remaining on MOUD by reducing cocaine cravings and/or addressing mood disorders.

The two antipsychotic drugs being studied may “help prevent drop-away from these life-saving [OUD] medications,” Childress told Filter.

One premise of the work, said Dr. Anna Childress, one of the lead researchers, is that cocaine cravings may contribute to people discontinuing MOUD and potentially being exposed to fentanyl and other unregulated opioids—knowingly or not—when they return to the dangerously adulterated illicit drug supply. Mood disorders (which include depression, for example) may separately have the same outcome, she said.

In different ways, the two antipsychotic drugs being studied may “help prevent drop-away from these life-saving [OUD] medications,” Childress told Filter, noting that in an unprecedented overdose crisis, “the taking of these medications is more important than ever.”

The first medication the Penn team is using, cariprazine, acts on the dopamine D3 receptor in the brain, “…a receptor that may be one culprit in the intense ‘pull of cue-triggered drug cravingthe feeling of wanting to ‘GO!’ to the drug,” Childress said. “In our earlier research in human cocaine users, it also reduced the ‘over-excited’ brain response to cocaine cues.”

As a bonus, cariprazine is also FDA-approved for mood swings and thought disorder,” Childress continued. “So it may offer a ‘two-fer’: It could benefit cue-triggered drug use (including cocaine) directly—and it could also offer benefits on mood and thought problems that sometimes drive drug use.”

The other drug Penn researchers are studying is olanzapine, which acts on multiple brain receptors, including dopamine and serotonin receptors. It’s FDA-approved for both schizophrenia and bipolar disorder. Long-term NIH analyses of clinical data showed that OUD patients with mood disorders who took olanzapine were more likely to continue taking MOUD than those taking other antipsychotics, Childress said.

The two studies each aim to enroll 48 participants, who will receive either cariprazine/olanzapine or placebo over an eight-week period, with brief follow-up. If results are encouraging, it should lead to larger studies to determine how much benefit these drugs can offer to MOUD patients, Childress said.

But Jeanette M. Bowles, a postdoctoral fellow at the Centre on Drug Policy Evaluation at St. Michael’s Hospital in Toronto, expressed reservations about the Penn research. She worries about the implications for MOUD patients’ agency of what she terms over-medicalization. And she doesn’t believe one of the premises of the research—that seeking cocaine on the illicit market can cause discontinuation of MOUD.

“In my experience people are kicked off of these medications because of cocaine use,” Bowles said. “This is a systems issue.”

Dr. Bowles “respectfully disagrees” that people discontinue MOUD directly because of cocaine use. Rather, she thinks that any association is due to the punitive policies of MOUD programs that exclude people or deny them take-home doses if they use other drugs. “In my experience people are kicked off of these medications because of cocaine use,” she said. “This is a systems issue.”

“Over-medicalizing drug use can contribute to stigma against people who use drugs,” she continued, “which is dangerous across the board.”

However, Bowles said that despite these worries, she felt that “if adjunctive medications such as the ones used in this study facilitate and honor [the person’s] goals, then perhaps we’ll have another tool in the overdose prevention safety net.”

John said that when he saw a post about the Penn research on Facebook—one of the ways researchers are seeking candidates—he was intrigued because “cocaine was a big part of my addiction.” Methadone cuts his craving for non-prescribed opioids, he said, but it does nothing to stop his ongoing urges to use cocaine.

John started participating in the cariprazine study some weeks ago. Like the other participants, he doesn’t know whether he’s been receiving cariprazine or a placebo. But he said that his cocaine cravings have simmered down. “I think it’s helping me.”

Bowles, however, said there is a better-evidenced path to reducing overdose deaths—one that has already been rolled out in Canada: safe supply.

“Addressing an overdose crisis fueled by an unregulated drug supply—containing, for example, fentanyl, carfentanil, nitazene opioids, benzodiazepines, and xylazine—can be addressed through safe drug supply programs,” she said, “which emerging research is demonstrating the positive effects of already.”  



*Name has been changed to protect privacy, as the source signed an anonymity agreement with the University of Pennsylvania.

Photograph of Dr. Anna Childress courtesy of Childress

Courtenay Harris Bond

Courtenay is a Philadelphia-based freelance journalist. She covers issues around behavioral health and social justice and is a former Rosalynn Carter Fellow for Mental Health Journalism.

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