Posttraumatic stress disorder affects a lot of people (PTSD). This possibly chronic illness causes disruption in people's lives and might cause new health problems or make pre-existing ones worse, like despair, anxiety, eating disorders, and suicidal thoughts.
Despite the significant frequency of PTSD, only two medications--sertraline and paroxetine--have been approved by the US Food and Drug Administration to treat it, and both have demonstrated relatively little efficacy in easing PTSD symptoms.
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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 surprisingly discovered that several novel direct-acting antiviral (DAA) drugs used to treat hepatitis C virus infection were related to 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 recognized DAAs in the reduction of PTSD symptoms in a new, follow-up study. Their most promising DAA for future research is a potential treatment for PTSD in people who do not have hepatitis C virus infection, according to their recent findings.
The most often prescribed DAAs in the VA, according to a recent study published online ahead of print in the American Journal of Epidemiology, were glecaprevir and pibrentasvir. This medicine combination showed the strongest association with PTSD symptom improvement.
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"Many people have PTSD, yet there are few effective pharmacologic therapies and limited pharmacological development for PTSD," says Jaimie Gradus, associate professor of epidemiology at BUSPH and the study's senior author. The majority of currently available effective treatments are forms of psychotherapy, and while they are effective, they also have drawbacks, such as high rates of treatment drop-out and time commitment. Therefore, expanding the range of available treatment options for individuals is of utmost importance.
The same nationwide cohort of VA patients from the earlier study was evaluated by the researchers, but they limited the study population to only those with a hepatitis C diagnosis.
According to co-principal investigator Brian Shiner, a psychiatrist who serves as acting associate chief of staff for research at the White River Junction VA Medical Center and an associate professor of psychiatry at Dartmouth University's Geisel School of Medicine, "there really has been a lot of interest in finding new medications for PTSD in the field." The VA PTSD Psychopharmacology Working Group and the National Institutes of Mental Health had a discussion in the scientific literature that gave rise to the notion to analyze VA data in this manner. Jaimie and I were introduced by Paula Schnurr from the National Center for PTSD, and we had great luck in getting funds to put a team together to work on this project.
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.
Gradus explains that for some years, "at BUSPH, we have been collaborating with our VA colleagues to look at PTSD symptom improvement in normal care utilizing medical data." "The level of improvement we observe for GLE/PIB is remarkable and more than twice as much as what we observed for paroxetine and sertraline. An important next step in this line of research will be a prospective placebo-controlled study in individuals without hepatitis C virus infection. I believe we have done the best we can give the data from medical records.
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