Summary: Researchers report that several direct-acting antiviral drugs, originally developed to treat hepatitis C, appear to ease symptoms of posttraumatic stress disorder (PTSD).
Source: Boston University
More than six percent of Americans develop posttraumatic stress disorder (PTSD) at some point in their lives. PTSD can become a chronic, disabling condition that affects daily functioning and often coincides with depression, anxiety, disordered eating, and suicidal thoughts.
Despite its prevalence, pharmacologic options for PTSD remain limited. The U.S. Food and Drug Administration has approved only two medications for PTSD—sertraline and paroxetine—and both produce modest benefits for many patients.
PTSD rates are higher among military veterans, with over 10 percent of patients treated through the U.S. Department of Veterans Affairs (VA) reporting PTSD symptoms. Two years ago, investigators from the Boston University School of Public Health (BUSPH) and the White River Junction VA Medical Center began exploring whether existing, FDA-approved medications might reduce PTSD symptoms. This work received funding from the National Institute of Mental Health.
An early exploratory analysis of national VA clinical data produced an unexpected finding: several newer direct-acting antivirals (DAAs) used to cure hepatitis C virus (HCV) infection were linked with improvements in PTSD symptoms. The initial observations were published in Biological Psychiatry.
Building on that signal, the research team conducted a more rigorous, follow-up analysis to compare specific DAAs and determine which agents showed the strongest association with PTSD symptom change. Their updated results, published online ahead of print in the American Journal of Epidemiology, identified the combination of glecaprevir and pibrentasvir (GLE/PIB) as having the most robust association with symptom improvement among the DAAs commonly prescribed in the VA system.
“There are many people living with PTSD but relatively few effective drug treatments and limited active drug development,” says Jaimie Gradus, associate professor of epidemiology at BUSPH and co-principal investigator on the study. “Psychotherapy remains the most effective option for many patients, but access, time commitment, and dropout are ongoing barriers. Broadening treatment choices is therefore an important goal.”
For this analysis, the investigators revisited the same national VA cohort used in their earlier work but restricted the sample to patients diagnosed with both PTSD and hepatitis C. The research team included clinicians and methodologists from the VA, BUSPH, Dartmouth’s Geisel School of Medicine, and Harvard Medical School.
Co-principal investigator Brian Shiner, a psychiatrist and acting associate chief of staff for research at the White River Junction VA Medical Center, describes how the project developed. “Interest in new PTSD medications has grown across the field,” he says. “This line of inquiry emerged from conversations among the VA PTSD Psychopharmacology Working Group and the National Institutes of Mental Health. With collaboration and funding, we were able to examine VA patient records to explore potential repurposing of existing drugs.”
The study used VA clinical records to identify 254 patients diagnosed with PTSD and HCV between October 1999 and September 2019 who had both baseline and follow-up PTSD symptom measurements recorded on the PTSD Checklist (PCL). Patients received one of three commonly prescribed DAA regimens: glecaprevir/pibrentasvir (GLE/PIB), ledipasvir/sofosbuvir (LDV/SOF), or sofosbuvir/velpatasvir (SOF/VEL). The investigators tracked changes in PTSD symptoms across 8 to 12 weeks of antiviral treatment while also monitoring HCV cure rates.
Using propensity score weighting to account for potential confounding factors—such as opioid prescriptions, liver disease diagnosis, and emergency psychiatric care—the team compared symptom changes between the medication groups. GLE/PIB demonstrated a stronger association with PTSD symptom improvement than LDV/SOF, with an average difference of 7.3 points on the PCL score (95% confidence interval: 1.1 to 13.6). Differences between GLE/PIB and SOF/VEL, and between SOF/VEL and LDV/SOF, were smaller and less precise.
Nearly all patients in the study achieved virologic cure of hepatitis C—about 92.5%—regardless of which antiviral they received. The fact that PTSD outcomes varied by DAA suggests the effect may not be solely tied to viral cure, and supports further investigation of GLE/PIB’s potential neuropsychiatric effects.
“The magnitude of PTSD symptom reduction associated with GLE/PIB is notable and exceeds the typical improvements seen with paroxetine and sertraline in routine care,” Gradus notes. “While observational electronic health record data have limitations, they provide valuable real-world signals. The logical next step is a controlled prospective trial in patients without hepatitis C.”
Shiner adds that the team recently secured Department of Defense funding to conduct a randomized, placebo-controlled trial testing GLE/PIB for PTSD. The study will be led by investigators at the White River Junction VA Medical Center, with Gradus and Shiner participating. “It will take several years to complete, but this is an encouraging example of how VA patient data can inform development of new treatments for veteran health priorities,” he says.
About this psychopharmacology and PTSD research news
Author: Press Office, Boston University
Source: Boston University
Contact: Press Office – Boston University
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Original Research: Closed access. “Comparative Effectiveness of Direct-Acting Antivirals for Posttraumatic Stress Disorder in Veterans Affairs Patients With Hepatitis C Virus Infection” by Brian Shiner et al., American Journal of Epidemiology. DOI: 10.1093/aje/kwac104
Abstract
Comparative Effectiveness of Direct-Acting Antivirals for Posttraumatic Stress Disorder in Veterans Affairs Patients With Hepatitis C Virus Infection
In a prior exploratory analysis of VA patients treated for hepatitis C, several direct-acting antivirals (DAAs) were linked with PTSD symptom improvement. In the present study, limiting the cohort to patients with both PTSD and HCV, investigators compared individual DAAs using propensity score methods to estimate differential associations with PTSD symptom change measured by the PTSD Checklist (PCL) over an 8–12 week course of therapy.
Among patients with available baseline and endpoint PCL scores, the most commonly prescribed DAAs were glecaprevir/pibrentasvir (GLE/PIB; n = 54), sofosbuvir/velpatasvir (SOF/VEL; n = 54), and ledipasvir/sofosbuvir (LDV/SOF; n = 145). GLE/PIB showed superior PTSD symptom improvement compared with LDV/SOF, with a mean PCL difference of 7.3 points (95% CI: 1.1, 13.6). Differences between the other regimens were smaller and did not reach the same level of precision. Although HCV cure rates were high across all groups, the differential PTSD outcomes suggest GLE/PIB merits further investigation as a potential treatment for PTSD independent of its antiviral effects.