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PTSD symptoms may be lessened by direct-acting antiviral (DAA) drugs used to treat Hepatitis C virus infection

In their lifetimes, more than 6% of Americans will experience posttraumatic stress disorder (PTSD). 

PTSD is a chronic illness that causes disruption in people’s life and might cause new health problems or make pre-existing ones worse, like despair, anxiety, eating disorders, and suicidal thoughts. Despite the fact that PTSD is very common, the US Food and Drug Administration has only licenced paroxetine and sertraline as treatments for it. Both have had only modest success in easing PTSD symptoms. Veterans of the military frequently develop PTSD symptoms; more than 10% of patients at the US Department of Veterans Affairs (VA) do as well.

With support from the National Institute of Mental Health, researchers at the White River Junction Veterans Affairs Medical Center in Vermont and the Boston University School of Public Health (BUSPH) started looking into whether current drugs could lessen PTSD symptoms two years ago.

The researchers unexpectedly discovered that many novel direct-acting antiviral (DAA) drugs used to treat hepatitis C virus infection were related with a reduction in PTSD symptoms during an initial exploratory analysis among a national cohort of VA patients.

The results were released in the Biological Psychiatry journal.

The researchers have now examined and compared the efficacy of the previously recognised DAAs in the reduction of PTSD symptoms in a new, follow-up study. Their most promising DAA for future research as a potential treatment for PTSD in people who do not have hepatitis C virus infection, according to their recent findings.

Published online ahead of print in the American Journal of Epidemiology, the new study found that the medication combination glecaprevir and pibrentasvir had the strongest association with PTSD symptom improvement among the DAAs most prescribed in the VA.

“Many people have PTSD, but they’re 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. “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 researchers examined the same national cohort of VA patients as the prior study, but narrowed the study group to include only patients diagnosed with hepatitis C.

“There has been a lot of interest in finding new medications for PTSD in the field,” says co-principal investigator Brian Shiner, a psychiatrist and acting associate chief of staff for research at the White River Junction VA Medical Center, as well as associate professor of psychiatry at Dartmouth University’s Geisel School of Medicine. “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 me, and we were fortunate to obtain funding to bring a team together to do this work.”

Gradus, Shiner, and associates from the VA, BUSPH, Geisel, and Harvard Medical School investigated 254 VA patients who were identified as having PTSD and hepatitis C between October 1999 and September 2019. They used patient care data from VA medical records. One of three FDA-approved hepatitis C drug combinations—glecaprevir and pibrentasvir (GLE/PIB), ledipasvir and sofosbuvir (LDV/SOF), or sofosbuvir and velpatasvir (SOF/VEL)—was administered to each participant. The patients underwent two clinical visits over an 8–12 week period, and the researchers kept track of their PTSD and HCV symptoms at each.

The team discovered that the GLE/PIB medications were more strongly associated with PTSD symptom improvement than the LDV/SOF and SOF/VEL treatments after adjusting for variables that could potentially influence results, such as opioid prescription use, liver disease diagnoses, and emergency department care for psychiatric crises. This finding is consistent with their earlier 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 says. He and Gradus will be involved with the project, and Vince Watts of the White River Junction VA Medical Center will serve as the principal investigator. “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.”

PTSD symptoms may be lessened by direct-acting antiviral (DAA) drugs used to treat Hepatitis C virus infection

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