Changes in Depressive Symptoms and Impact on Treatment Course Among Hepatitis C Patients Undergoing Interferon-α and Ribavirin Therapy: A Prospective Evaluation

Veterans Affairs Palo Alto Health Care System, Psychology Service, Palo Alto, California, USA.
The American Journal of Gastroenterology (Impact Factor: 10.76). 08/2011; 106(12):2123-32. DOI: 10.1038/ajg.2011.252
Source: PubMed


Accounting for severity of depressive symptoms at baseline (pretreatment), this study describes (i) depressive symptom change over the course of antiviral treatment among patients with hepatitis C virus (HCV), and (ii) the relationship of such symptom change to treatment duration and response.
Depressive symptoms, measured with the Beck Depression Inventory (BDI), were examined prospectively among 129 HCV patients (95% male) who endorsed minimal (n=91), mild (n=28), or moderate depressive symptoms (n=10) prior to commencement of antiviral therapy. Assessments were obtained at baseline, 2 weeks, 4 weeks, and thereafter at 4-week intervals until treatment was discontinued or completed.
The average depression score of the participants prior to commencing treatment was 7.4 (minimal depression). Depressive symptoms increased over the course of treatment, with average scores of 12.6 (mild depression) at the final assessment at the end of treatment. Patients with mild depressive symptoms at baseline demonstrated the greatest increase (M(increase)=12.7) and the greatest change (M(Δ)=5.8) in depressive symptoms from baseline to treatment completion. Patients who were minimally depressed at baseline completed the least amount of treatment (74%). Likewise, minimally depressed patients were less likely than mildly and moderately depressed patients to attain an antiviral treatment response.
Depressive symptoms may worsen during antiviral therapy among patients with HCV. Notable changes in patients with subclinical depressive symptoms at baseline may be of significant concern, as the present work suggests that their depressive symptom changes are the most unstable. Thus, findings suggest that the degree of within treatment symptom change may be a more useful predictor (compared with baseline depression status) of ability to tolerate treatment. As the findings of the present study are preliminary, we urge further research and replication before drawing firm conclusions.

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    • "This study demonstrated a high prevalence of depression and anxiety symptoms as detected by the HADS score in patients with CHC infection and an association of depressive symptoms with apoE deficiency. The prevalence of depression and anxiety as detected by HADS scores ≥8 in this non-responder cohort is similar to that previously reported in CHC (Golub et al. 2004; Nelligan et al. 2008; Chapman et al. 2011). Although approximately 1 in 5 subjects were already on anti-depressant therapy at the start of the trial, the HADS score suggested that >20 % still had depressive symptoms, while almost half the patients had significant anxiety symptoms. "
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    ABSTRACT: Neuro-psychiatric and cognitive disorders are frequent in patients with chronic hepatitis C (CHC) virus (HCV) infection which adversely impact quality of life, antiviral treatment adherence and outcome. HCV has neurotrophic properties and affects lipid metabolism, essential for cognitive function. We evaluated the relationship of lipid profiles with depression and anxiety symptoms and the effects of 12-weeks of therapy with fluvastatin and omega-3 ethyl esters (n-3 PUFA) in a randomised pilot study of CHC prior non-responders. Participants (n = 60) had fasting lipid profiles and assessment of depression and anxiety symptoms using the Hospital Anxiety and Depression Scale (HADS) questionnaire at each study visit. At screening 26/60 (43 %) had HADS-A score ≥8 and 13/60 (22 %) had HADS-D scores ≥8. Depressed patients had significantly lower apolipoprotein-E concentrations (30 mg/l vs 39 mg/l, P = 0.029) than those without depression and a tendency toward lower total cholesterol (3.8 vs 4.4 mmol/l, P = 0.053). 3 patients discontinued lipid-modifying treatment because of worsening depression. However, there was a small but significant improvement in anxiety symptoms after 12-weeks of high-dose (2-4 g daily) n-3 PUFA. In conclusion, depression in CHC is associated with plasma apoE deficiency. We postulate that apoE deficiency disrupts blood brain barrier integrity to promote HCV infection of the CNS. High-dose n-PUFAs may alleviate anxiety in some CHC patients but the use of lipid lowering therapy must be balanced against risks of worsening depression.
    No preview · Article · Mar 2014 · Metabolic Brain Disease
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    • "The HPSS-D was administered for 7 consecutive days at three time points: baseline, week 4 and week 12. (Although patients completed the HPSS-D for seven consecutive days at each time point, for comparability with the second study where it was only collected for one day, data from only day 1 of the HPSS-D were used). Additional measures administered in the EMERGE trial included the Beck Depression Inventory II (BDI-II) [22–24], the Fatigue Severity Scale (FSS) [25, 26], and investigator reports of flu-like symptoms and musculoskeletal symptoms. The BDI-II and FSS were administered at baseline, while reporting of treatment side effects was obtained at each time point. "
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    ABSTRACT: Chronic Hepatitis C (CHC) Virus infection is a serious health issue in the US. Standard treatment involves peginterferon alpha and ribavirin, often associated with adverse side effects including flu-like symptoms. These adverse effects are common reasons for the discontinuation of treatment and therefore represent a major obstacle in the effective treatment of CHC. The Hepatitis Physical Symptom Severity Diary, a newly developed patient-reported outcome measure for assessing physical symptoms in CHC patients, was recently developed. It contains four questions addressing flu-like symptoms [the Flu-Like Symptom Index (FLSI)]. Measurement properties of the FLSI in CHC patients were assessed using data from two randomized clinical trials. Exploratory factor analysis using data from baseline and the last visit while on treatment supported a single-factor solution for the FLSI. Internal reliability and test-retest reliability are acceptable (Cronbach's alpha range 0.73-0.81; intraclass correlation coefficient range 0.85-0.97), and correspondence to several similar constructs was acceptable. The FLSI score was higher among those with investigator-reported flu-like symptoms (mean = 4.1) versus those without (1.4), although not statistically significant (p = 0.12). Responsiveness of the FLSI was moderate, as measured by standardized effect sizes and response means, and the minimum important difference (MID) was estimated at 2.5-3.0 points. While additional research should be conducted to evaluate validity with more closely related constructs and to utilize anchor-based methods for estimating the MID, data suggest that the FLSI has acceptable measurement properties and can be an effective tool in assessing flu-like symptoms in CHC patients.
    Full-text · Article · Dec 2013 · Quality of Life Research
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    ABSTRACT: Eine Analyse der aktuellen Literatur ergab gesicherte Hinweise, dass Patienten mit Hepatitis C nicht nur unter den internistischen Auswirkungen dieser Erkrankung leiden, sondern nach Einleitung einer virostatischen Therapie unter Einschluss von Interferon α und Ribavirin insbesondere Depressionen, jedoch auch anderweitige psychische Auffälligkeiten entwickeln, welche nach Beendigung der antiviralen Therapie nicht regelmäßig abzuklingen pflegen. Bei etwa 1/3 der betroffenen Patienten verbleiben neuropsychiatrische Auffälligkeiten mit den Leitsymptomen der Antriebsschwäche, Depressivität sowie auch kognitiven Leistungsstörungen. Als Ursache für diese Entwicklung fanden sich Hinweise auf eine Einwanderung des Hepatitis-C-Virus ins Gehirn während der Virämiephase sowie einen Neurotropismus des Virus. Darüber hinaus ergaben sich Hinweise auf Einwirkungen der Virostatika auf das Neurotransmittersystem. Diese Befunde sollten Konsequenzen für die Steuerung des Heilverfahrens bei Hepatitis-C-Patienten haben.
    No preview · Article · Sep 2012 · Trauma und Berufskrankheit
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