The combination of the two antiviral medications glecaprevir and pibrentasvir (Mavyret) is linked to improved symptoms in posttraumatic stress disorder, new research suggests.
A national cohort study of U.S. Veterans Affairs patients included more than 250 participants with PTSD and comorbid hepatitis C virus.
Results showed in the study, including ledipasvir/sofosbuvir.
“While there are great treatments available for PTSD, there’s a lot of desire in the field to find a new medication that will be helpful,” lead author Brian Shiner, MD, acting associate chief of staff for research, VA Medical Center, White River Junction, Vt., told this news organization.
“We had a great opportunity to use a novel data mining method to look in a wonderful database for a new treatment and we found something very promising,” said Dr. Shiner, who is also an associate professor of psychiatry at the Geisel School of Medicine at Dartmouth, Hanover, N.H.
The findings were published online in the American Journal of Epidemiology.
Common psychiatric disorder
PTSD is one of the most common psychiatric disorders, with an estimated lifetime prevalence of 6.4% in the United States. Yet only two drugs, the SSRIs sertraline (Zoloft) and paroxetine (Paxil), have been approved by the Food and Drug Administration to treat PTSD.
The VA recommends trauma-based psychotherapy, such as prolonged exposure and cognitive processing therapy, as first-line treatments for PTSD. However, not all patents respond to or have access to these approaches, said Dr. Shiner.
The investigators wanted to examine whether existing medications might reduce PTSD symptoms. Their previous exploratory study used “data mining” of national VA medical records.
Results from that study showed the three hepatitis C antivirals of GLE (an NS3/4A protease inhibitor), PIB (a NS5A protein inhibitor), and velpatasvir (another NS5A protein inhibitor) were associated with more than double the expected number of patients experiencing a clinically meaningful improvement in PTSD symptoms.
Sertraline was associated with only a slightly higher than expected improvement.
“SSRIs are effective, better than placebo, but the effects are not as good as we would hope,” Dr. Shiner said.
He noted that GLE and PIB are always prescribed together (Mavyret), whereas velpatasvir is commonly prescribed with the NS5B polymerase inhibitor sofosbuvir under the brand name Epclusa. Sofosbuvir is also commonly prescribed with the NS5A protein inhibitor ledipasvir under the brand name Harvoni.
Strong association
The new study included 253 VA users with a diagnosis of PTSD and hepatitis C. Of these, 54 were receiving GLE/PIB, 145 were receiving ledipasvir/sofosbuvir, and 54 were receiving sofosbuvir/velpatasvir.
Researchers compared the groups with respect to change over 8-12 weeks on the PTSD Checklist (PCL), a 20-item self-report scale.
In adjusted analyses, the largest mean improvement on the PCL was 14.9 points for the GLE/PIB group and the smallest adjusted mean improvement on the PCL was 7.5 points for the ledipasvir/sofosbuvir group (mean difference, 7.34 points; 95% confidence interval, 1.05-13.63).
The adjusted proportion of patients improving by 15 points or more on the PCL was highest for the GLE/PIB group at 43.6% and lowest for the ledipasvir/sofosbuvir group at 26.3%.
Even when accounting for patients receiving trauma-based therapy or SSRIs, “it still looks like there’s a strong association of the hepatitis C antivirals with PTSD symptom improvement,” said Dr. Shiner.
Researchers also carried out a sensitivity analysis among only patients who were cured of HCV (over 90% of the total sample), defined as having an undetectable HCV viral load up to a year after completion of therapy. The analysis showed PTSD outcomes were still superior for participants receiving GLE/PIB.
“The sensitivity analysis was not that robust because almost everyone was cured, so it included almost everybody, but it didn’t point us away from the possibility of an off-target effect,” Dr. Shiner said.
Why antivirals may improve PTSD symptoms is not clear, but they may affect the immune response in patients with hepatitis C – and there may also be an immune response in PTSD, he noted. “Some of those factors may be shared, and that could explain some of the off-target effect.”
However, he noted the GLE/PIB drug combination is costly and patients with PTSD can probably access it only through enrolling in a study.
“We are not recommending that people go out and purchase this very expensive drug to treat their PTSD at this point,” Dr. Shiner said.
He added that the research team has now received funding from the Department of Defense to conduct a randomized, placebo-controlled trial of GLE/PIB as a potential treatment for PTSD.