Hepatitis C drugs show promise as PTSD treatment

BOSTON — Help may soon be on the way for post-traumatic stress disorder patients from an unlikely source. Researchers at the Boston University School of Public Health (BUSPH) and the White River Junction Veterans Affairs Medical Center in Vermont report several new direct acting antiviral (DAA) medications intended to treat hepatitis C infections also appear to alleviate symptoms of PTSD.

That initial discovery, published in the scientific journal Biological Psychiatry following an analysis of VA patients nationwide, set the stage for further follow-up research comparing the effectiveness of those identified DAAs. The follow-up study identified a specific DAA pairing that shows the most promise as a potential PTSD treatment: glecaprevir and pibrentasvir. This medicinal combination displayed the strongest association with PTSD symptom improvement among the DAAs most prescribed in the VA.

Estimates show that about six percent of Americans develop PTSD over the course of their lives, and over 10 percent of U.S. Department of Veterans Affairs (VA) patients experience PTSD-related symptoms. Unfortunately, the FDA currently only has two approved medications (sertraline and paroxetine) to treat PTSD, and neither display robust effectiveness in curbing symptoms.

What exactly is PTSD?

Post-traumatic stress disorder (PTSD) develops following an especially traumatic, scary, or dangerous event, and is more common among military veterans. First coined in the 1970s due to the influx of Vietnam veterans returning home and struggling to transition back to civilian life, studies have linked PTSD to a plethora of health problems, including depression, intense anxiety, nervousness, eating disorders, and suicidal thoughts.

“Many people have PTSD, but there’s few effective pharmacologic treatments and limited drug development for PTSD,” says co-principal investigator and study senior author Jaimie Gradus, associate professor of epidemiology at BUSPH, in a university release. “Existing effective treatments are mostly psychotherapy, and while they work well, there are also issues with them, including a lot of treatment drop-out and they’re time-intensive, so adding to the suite of treatment options for people is a high priority.”

The same national sampling of VA patients from the first study also took part in the follow-up project. This time, however, researchers only included patients specifically diagnosed with hepatitis C.

“There really has been a lot of interest in finding new medications for PTSD in the field,” explains co-principal investigator Brian Shiner, a psychiatrist and acting associate chief of staff for research at the White River Junction VA Medical Center. “The idea to look at VA data in this way grew out of a conversation in the scientific literature between the VA PTSD Psychopharmacology Working Group and the National Institutes of Mental Health. Paula Schnurr from the National Center for PTSD connected Jaimie and I, and we were really fortunate to obtain funding to bring a team together to do this work.”

Glecaprevir and pibrentasvir twice as effective as other treatments

Via patient care data provided by VA medical records, researchers analyzed 254 VA patients diagnosed with both PTSD and hepatitis C between October 1999 and September 2019. Each veteran received a combination of FDA-approved hepatitis C medications, such glecaprevir and pibrentasvir (GLE/PIB); ledipasvir and sofosbuvir (LDV/SOF); or sofosbuvir and velpatasvir (SOF/VEL). Then, study authors closely monitored each patient for any signs of either PTSD or HCV between two clinical visits over the course of eight to 12 weeks.

Researchers were also sure to account for numerous potentially influential variables, such as opioid prescription use, liver disease diagnoses, or emergency department care for psychiatric crises. They found that the GLE/PIB medications had the strongest association with PTSD symptom improvement than either the LDV/SOF or the SOF/VEL treatments — which was consistent with their previous findings.

“At BUSPH, we have been working with our VA colleagues to look at PTSD symptom improvement in routine care using medical records for several years,” Gradus says. “The level of improvement we see for GLE/PIB is impressive and over twice what we have seen for paroxetine and sertraline. I think we have done the best we can with medical records data, an important next step in this line of work will be a prospective placebo-controlled study in patients without hepatitis C virus infection.”

“We recently received funding from the Department of Defense to study GLE/PIB as a potential treatment for PTSD in a prospective randomized placebo-controlled trial,” Shiner concludes. “It will be several years until we see the results, but this is a very exciting case where we used VA patient data to identify a potential treatment for PTSD, which is a very important problem for veterans’ health. In this way, veterans have informed PTSD treatment development.”

The study is published in the American Journal of Epidemiology.

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