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Direct-acting antiviral treatment in real world patients with hepatitis C not associated with psychiatric side effects: a prospective observational study
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.ORCID-id: 0000-0003-3271-0456
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.ORCID-id: 0000-0001-7876-7779
2018 (Engelska)Ingår i: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, Vol. 18, artikel-id 157Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: Treatment 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. Methods: Consecutive 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 Asberg 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. Results: At 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%. Conclusions: Despite 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.

Ort, förlag, år, upplaga, sidor
2018. Vol. 18, artikel-id 157
Nyckelord [en]
Hepatitis C virus, Direct-acting antiviral, Depression, Sleep, Side effects
Nationell ämneskategori
Psykiatri
Identifikatorer
URN: urn:nbn:se:uu:diva-357557DOI: 10.1186/s12888-018-1735-6ISI: 000433388700005PubMedID: 29843679OAI: oai:DiVA.org:uu-357557DiVA, id: diva2:1240011
Forskningsfinansiär
Svenska läkaresällskapetFredrik och Ingrid Thurings StiftelseErik, Karin och Gösta Selanders stiftelseTillgänglig från: 2018-08-20 Skapad: 2018-08-20 Senast uppdaterad: 2018-12-12Bibliografiskt granskad
Ingår i avhandling
1. Exploring Links between Melatonin, Inflammation and Depression
Öppna denna publikation i ny flik eller fönster >>Exploring Links between Melatonin, Inflammation and Depression
2019 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Major depressive disorder (MDD) is one of the leading global causes of disease burden. Worse yet, about one third of the patients with MDD do not experience a remission with current treatments. The symptoms of MDD likely represent a variety of underlying pathologic processes and more knowledge about these processes is needed to optimize treatment for MDD. The focus of this thesis was to study the relationship between inflammation, melatonin and symptoms of depression. 

In papers I-III a population of young adults seeking psychiatric care was examined for depressive symptoms, melatonin levels in saliva, gastrointestinal (GI) symptoms and inflammatory markers in blood. In paper IV a cohort of patients with hepatitis C receiving treatment with new direct-acting agents (DAAs) were prospectively followed during treatment for depressive symptoms and sleep.

All patients were diagnosed by means of structured or semi-structured interviews and depressive symptoms were assessed with the self-rating version of the Montgomery Åsberg Depression Rating Scale. Sleep quality was measured by the Pittsburgh Sleep Quality Index, and GI symptoms were assessed with the Gastrointestinal Symptom Rating Scale-IBS. Melatonin in saliva was measured using enzyme-linked immunosorbent assay, and inflammatory markers in blood were analysed by proximity extension assay.

In young adults seeking psychiatric care melatonin levels at bedtime were inversely correlated with depressive symptoms. In those patients with a current depressive episode low melatonin values at bedtime were a negative prognostic factor for response after 6 months (paper I). Postprandial melatonin levels were positively associated with GI symptoms of bloating and pain (paper II). Postprandial melatonin levels were also associated with the inflammatory markers vascular endothelial growth factor A (VEGF-A), monocyte chemoattractant protein-1 (MCP-1) and monocyte inflammatory protein-1α (MIP-1α). Evening levels of melatonin did not correlate with the inflammatory markers. VEGF-A and MCP-1 as well as postprandial levels of melatonin correlated with a diagnosis of anxiety disorder, whereas MIP-1α correlated with MDD (paper III). Patients with hepatitis C underwent treatment with DAAs without experiencing pronounced psychiatric side effects in terms of depressive symptoms or sleep disturbances (paper IV).

In summary, the findings confirm a relationship between bedtime melatonin levels and depressive symptoms. The findings also show a connection between daytime melatonin and GI-symptoms. In addition, the findings indicate an association between inflammation and daytime melatonin. Together these results demonstrate links between melatonin, inflammation and depression. Lastly, interferon-free treatment against hepatitis C did not induce depressive symptoms.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2019. s. 70
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1526
Nyckelord
melatonin, inflammation, depression, biomarkers, cytokines, anxiety, hepatitis C
Nationell ämneskategori
Psykiatri
Forskningsämne
Psykiatri
Identifikatorer
urn:nbn:se:uu:diva-369411 (URN)978-91-513-0535-6 (ISBN)
Disputation
2019-02-15, Sal IV, Universitetshuset, Biskopsgatan 3, Uppsala, 09:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2019-01-25 Skapad: 2018-12-12 Senast uppdaterad: 2019-02-18

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