Back HCV Treatment Pre-emptive Escitalopram Can Prevent Depression during Hepatitis C Treatment

Pre-emptive Escitalopram Can Prevent Depression during Hepatitis C Treatment

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Taking the antidepressant escitalopram (Lexapro) prior to starting hepatitis C treatment with pegylated interferon reduced the likelihood of depression as well as its severity if it did occur, according to a study described in the July 17, 2012, Annals of Internal Medicine.

Standard therapy for chronic hepatitis C virus (HCV) infection consists of pegylated interferon alfa-2a (Pegasys) or alfa-2b (PegIntron) plus ribavirin, with the HCV protease inhibitors boceprevir (Victrelis) or telaprevir (Incivek) added for appropriate patients.

Depression is a common side effect of interferon-based therapy, occurring in up to 40% of people with no history of psychiatric problems and up to 70% of patients with pre-existing psychiatric conditions. This causes many patients to refuse therapy or stop treatment prematurely, and leads some providers to avoid prescribing treatment for people with pre-existing depression or other psychiatric conditions.

Martin Schaefer from Charité-Universitätsmedizin in Berlin and colleaguesconducted a study to evaluate whether a pre-emptive antidepressant could prevent interferon-induced depression in patients without psychiatric risk factors.

This multicenter clinical trial enrolled 181 hepatitis C patients with no history of psychiatric disorders at 21 academic medical hospitals in Germany between August 2004 and December 2008.

Participants were randomly assigned (1:1) to receive 10 mg/day escitalopram or placebo, administered 2 weeks before starting hepatitis C treatment and continuing for 24 to 48 weeks, depending on HCV genotype, during therapy. Escitalopram is a selective-serotonin reuptake inhibitor (SSRI); interferon-associated depression has been linked to serotonin deficiency and changes in serotonin signaling.

The primary end point was incidence of depression, defined as a Montgomery-Asberg Depression Rating Scale (MADRS) score of 13 or higher. Secondary endpoints were time to depression, incidence of major depression according to the Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition, quality of life, sustained virological response (SVR), tolerability, and safety.

Results

  • 32% of the patients in the escitalopram group developed depression with a MADRS score > 13, compared with 59% in the placebo group, a statistically significant difference (P < 0.001).
  • 8% of the patients in the escitalopram group and 19% in the placebo group developed major depression, also a significant difference(P = 0.031).
  • 56% of patients taking escitalopram achieved SVR compared with 46% in the placebo group, a difference that did not reach statistical significance (P = 0.21).
  • Tolerability and safety measures also did not differ significantly between the 2 groups.

Based on these findings, the study authors concluded, "Prophylactic antidepressant treatment with escitalopram was effective in reducing the incidence and severity of interferon-associated depression in HCV-infected patients without previous psychiatric disease."

"To our knowledge, this is the first trial that demonstrates that preemptive and concomitant therapy with escitalopram significantly decreases the incidence and severity of [pegylated interferon alfa]-associated depression in patients without preexisting psychiatric risk factors," they elaborated in their discussion. "Escitalopram treatment was safe and did not negatively influence sustained virologic response to antiviral therapy, which corroborates the findings of trials showing good safety and tolerability of antidepressants in patients with HCV infection during antiviral therapy."

The researchers emphasized, however, that these results might not be generalizable to people with previous psychiatric conditions.

"Considering our trial's high efficacy in preventing depressive symptoms, as well as the good tolerability of escitalopram, our findings show good reasons to favor a preventive strategy for interferon-associated depression," they wrote. "The diagnosis of major depressive episodes is often missed, because patients with HCV infection are not regularly seen by a psychiatric specialist...Thus, the treat-as-needed strategy might lead to a significant delay in antidepressant therapy with an increased risk for worsening depressive symptoms, nonresponse, treatment discontinuation, or suicide attempts."

"Future trials should evaluate different antidepressants and possible additional effects on other psychiatric symptoms (such as fatigue and sleep disturbances) and on sustained virologic response," they recommended. "Moreover, more information is needed about new antivirals used in combination with [interferon-alfa] and ribavirin and about possible drug-drug interactions between the new antivirals and antidepressants and benzodiazepines."

8/21/12

Reference

M Schaefer, R Sarkar, V Knop, et al. Escitalopram for the Prevention of Peginterferon-alfa2a-Associated Depression in Hepatitis C Virus-Infected Patients Without Previous Psychiatric Disease: A Randomized Trial. Annals of Internal Medicine 157(2):94-103. July 17, 2012.