BackgroundTreatment of Hepatitis C virus (HCV) infection has evolved from interferon (IFN)-based treatments to direct-acting antivirals (DAAs). Patients with HCV have an elevated psychiatric morbidity (including substance abuse) and patients with such comorbidity have often been excluded from treatment with IFN. To date, little is known about psychiatric adverse effects of DAA-based regimens. We therefore aimed to study the psychiatric side effects of new IFN-free treatment for HCV (including depressive symptoms and sleep) in real world patients also including those with a history of psychiatric diagnosis, substance abuse or drug dependence.MethodsConsecutive patients were monitored during treatment with three of the latest DAA agents (sofosbuvir, simeprevir and daclatasvir). Repeated expert psychiatric assessments from baseline to 12 weeks post-treatment were performed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) clinical version and the self-report versions of the Montgomery Åsberg Depression Rating Scale (MADRS-S) and the Pittsburgh Sleep Quality Index (PSQI). Friedman’s test was performed to calculate differences in the MADRS-S and PSQI over time. In a post-hoc analysis Wilcoxon’s test was used to compare baseline depressive symptoms with those at post-treatment. Spearman’s rank correlation test was conducted in another post-hoc analysis to evaluate the correlation between symptoms of depression and HCV viral load at baseline.ResultsAt baseline, 15/17 patients (88%) had a history of any psychiatric diagnosis; 11 (65%) had a history of substance abuse or dependence; and 11 (65%) had previously been treated with IFN and six of those had experienced psychiatric side effects. There was no correlation between depressive symptoms and HCV viral load at baseline. Symptoms of depression did not increase during DAA treatment and were lower 12 weeks post-treatment compared with baseline: MADRS-S 10.7 vs. 8.3 (p = 0.01). This observation held when excluding patients taking antidepressant medication. Sleep quality did not significantly change during treatment. Adherence to treatment was estimated to 95% and sustained virological response was 88%.ConclusionsDespite high psychiatric morbidity, including previous substance abuse, patients successfully completed DAA treatment without increasing depressive symptoms or sleep disturbance. Symptoms of depression were significantly reduced 12 weeks after DAA treatment.

Reduced levels of melatonin have been associated with severe depression. The aim was to investigate the correlation between salivary melatonin and dimensional measures of depressive symptom severity in young adult psychiatric patients. Levels of melatonin were analyzed in six saliva samples during waking hours from 119 young adult patients under outpatient psychiatric care. Melatonin levels were tested for association with the severity of depressive symptoms using the self-rating version of the Montgomery Åsberg Depression Rating Scale (MADRS-S). Where possible, depressive symptoms were assessed again after 6±2 months of treatment. Response was defined as decrease in MADRS-S by ≥50% between baseline and follow-up. Patients with levels of melatonin in the lowest quartile at bedtime had an increased probability of a high MADRS-S score compared to those with the highest levels of melatonin (odds ratio 1.39, 95% CI 1.15–1.69, p<0.01). A post hoc regression analysis found that bedtime melatonin levels predicted response (odds ratio 4.4, 95% CI 1.06–18.43, p<0.05). A negative relationship between salivary melatonin and dimensional measures of depressive symptom severity was found in young patients under outpatient psychiatric care. Bedtime salivary melatonin levels may have prognostic implications.

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