Comparative Effectiveness of Direct-Acting Antiviral Treatment for Hepatitis C Virus Infection on Depressive Symptoms in Patients With Posttraumatic Stress Disorder.

Purpose: Newer medications for Hepatitis C Virus Infection (HCV), called direct acting antivirals (DAAs), are less likely to cause depression than older interferon-containing treatments. However, the risk of exacerbating depression has not been examined in subgroups of patients with pre-existing mental illness. We investigated whether several DAAs for HCV, including glecaprevir/pibrentasvir (GLE/PIB), ledipasvir/sofosbuvir (LDV/SOF), and sofosbuvir/velpatasvir (SOF/VEL), impact depressive symptoms in a population of patients with post-traumatic stress disorder (PTSD).

Methods: We developed a retrospective cohort of United States Department of Veterans Affairs (VA) patients with PTSD receiving DAAs for HCV. We measured depressive symptoms before and after DAA treatment using the Patient Health Questionare-9 (PHQ-9), a patient-reported outcome measure with a range of 0-27, a screening threshold of 10 or higher, and a minimal clinically important difference of 5 points. We measured pre/post changes in PHQ-9 score and compared adjusted differences between treatment groups.

Findings: Our cohort included 873 patients (GLE/PIB n = 357, LDV/SOF n = 308, SOF/VEL n = 208). Adjusted baseline PHQ-9 scores were consistent with mild depression and similar across groups (10.5 ± 7.2 for GLE/PIB, 10.6 ± 7.2 for LDV/SOF, 10.9 ± 7.2 for SOF/VEL). Adjusted change in PHQ-9 score was minimal and did not differ across groups (-2.0 ± 5.8 for GLE/PIB, -1.1 ± 6.5 for LDV/SOF, -2.2 ± 6.1 for SOF/VEL). The adjusted frequency of 5-pont change was low and did not differ meaningfully across groups (Improvement: 22.4% for GLE/PIB, 18.9% for LDV/SOF, 26.6% for SOF/VEL; Worsening: 9.1% for GLE/PIB, 14.3% for LDV/SOF, 10.1% for SOF/VEL).

Implications: DAAs had very little impact on depressive symptoms for VA patients with PTSD and HCV infection.