Evaluation of depression as a risk factor for treatment failure in chronic hepatitis C†

Abstract

The Major Depression Inventory (MDI) was used to estimate the value of routine medical interviews in diagnosing major depression among patients receiving peginterferon alfa‐2a and ribavirin therapy for chronic hepatitis C virus (HCV) infection (n = 325). According to criteria from the MDI and Diagnostic and Statistical Manual of Mental Disorders (DSM‐IV), 19 patients (6%) had major depression at baseline. An additional 114 (37%) developed depression while on HCV combination therapy, with baseline MDI score and female sex independently predicting the emergence of major depression during treatment in a multivariate analysis. Only 36 (32%) of the 114 patients developing major depression according to MDI/DSM‐IV criteria were correctly diagnosed during routine medical interviews. The emergence of major depression frequently led to premature discontinuation of peginterferon/ribavirin therapy, and an on‐treatment MDI score increment exceeding 30 points (i.e., a validated marker of idiopathic DSM‐IV major depression) was correlated with impaired outcome of HCV therapy (P = 0.02). This difference was even more pronounced among patients with an on‐treatment increase in MDI score greater than 35 points (P = 0.003). Conclusion: We conclude that (1) depressive symptoms among patients undergoing HCV therapy are commonly overlooked by routine clinical interviews, (2) the emergence of depression compromises the outcome of HCV therapy, and (3) the MDI scale may be useful in identifying patients at risk for treatment‐induced depression. (HEPATOLOGY 2010;)

Role of inflammatory cytokines in depression: Focus on interleukin-1β

“…Depressive symptoms have been frequently reported in patients undergoing chemotherapy, which often leads to treatment failure (63). Increased levels of pro-inflammatory cytokines have been implicated in the depressive, as well as cachectic symptoms undergoing such treatment (64).…”

Review article: depression and the use of antidepressants in patients with chronic liver disease or liver transplantation

“…27,[32][33][34][35] The type of interferon used (pegylated or standard interferon) does not appear to have any differential impact on the prevalence of IFN-a-related depression; however, it does appear to be sensitive to dosage and duration of treatment as well as pre-morbid patient-related risk factors, including a previous history of psychiatric disorders and female sex. 33,36 This phenomenon has an increasingly well-characterised biological basis, with activation of a pro-inflammatory cytokine network and alterations in serotonin and dopamine neurotransmitter metabolism being postulated to exert the mood changes associated with IFN-a. 27,33 Specifically, IFN-a induces expression of indoleamine (2,3)-dioxygenase (IDO), which causes increased catabolism of the serotonin precursor, tryptophan, resulting in reduced peripheral serotonin levels.…”

“…38 Development of depression is the commonest reason for HCV treatment discontinuation. 36 A recent study found that up to 10% of patients treated for HCV with pegylated interferon and ribavirin had to prematurely withdraw from treatment, and the majority (65%) of these patients had developed features of major depression [as defined by total score >35 points on the Major Depression Inventory (MDI)]. 36 15% of the patients who did not achieve a sustained virological response (SVR) had an on-treatment increase in their MDI score from baseline by 35 points, as compared to the 2% who did achieve SVR.…”

Interferon α bei Patienten mit chronischer Hepatitis C

“…So wird die Therapietreue bzw. die Adhärenz erhöht und oft unnötige Therapieabbrüche verhindert [10,18,24]. Über die Möglichkeit der Entwicklung psychiatrischer Symptome sollten die Patienten schon vor dem Beginn einer Therapie mit INF-α ausreichend aufgeklärt werden.…”

“…Interferon alpha (IFN-α), ein Zytokin mit starken antiviralen und antiproliferativen Eigenschaften, ist ein wichtiges Medikament zur Behandlung der chronischen Hepatitis C. Eine häufige und unter Umständen sogar therapielimitierende IFN-α-Nebenwirkung sind depressive Episoden, die meist innerhalb von 3 Monaten nach Therapiebeginn auftreten und die Adhärenz und die Lebensqualität der Betroffenen beeinträchtigen und den häu-figsten Abbruchgrund der Interferontherapie darstellen [10,18,24].…”