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Patients with hepatitis C should be carefully evaluated for symptoms of depression before and during pegylated interferon-based therapy, investigators write in the International Journal of Interferon, Cytokine and Mediator Research. The authors also highlighted evidence showing that SSRI antidepressants are an effective and safe therapy for depressive disorders during interferon treatment. However, they note that the effectiveness of the prophylactic use of antidepressants has yet to be established.

“Depression is a relatively frequent and potentially serious complication of IFN [interferon] therapy for HCV [hepatitis C virus] infection,” emphasise the authors. “Since depressed patients can suffer from longer disability period, lower quality of life, have potentially more inpatient and outpatients visits, and increased suicide risk, early detection and treatment of depression is very important.”

Despite recent advances in the treatment of hepatitis C, pegylated interferon is likely to remain a mainstay of therapy for the foreseeable future. The drug can cause significant side-effects, including disturbances in mood and depression. These side-effects not only have a major impact on patient quality of life, but also lead some patients to discontinue therapy.

A team of investigators lead by Haris Papafragkakis of the University of Miami conducted a review of published studies to establish a clearer understanding of the prevalence of depression among hepatitis C-infected patients treated with interferon. They also reviewed research looking at screening strategies; the effectiveness of antidepressant therapy for the prevention and treatment of depression caused by interferon; and the management of suicidal thoughts or intent.

Estimates of the prevalence of depression among hepatitis C-infected patients treated with pegylated interferon were found to vary between 10 to 40%. However, research suggests that a number of standard screening tools can successfully identify patients with depression before they start interferon-based therapy. The use of the same screening techniques during treatment was also able to identify incident cases of depression.

The authors highlighted the results of one study which showed the value of a multidisciplinary approach, commenting: “monthly evaluation of patients by a psychiatrist was associated with less depression, psychosis, and delirium compared to an ‘as needed’ approach.”

However, they stress that patients with hepatitis C often have multiple risk factors for depression. Therefore interferon therapy may be just one of many causes.

There was some evidence that a more robust immune response during hepatitis C therapy might be associated with higher rates of depression. The IL-28B gene – which is associated with an improved response to hepatitis C therapy – has also been associated with sleep disturbances. “More studies are needed to elucidate this association further,” write the authors.

It is uncertain if pegylated interferon therapy increases the risk of suicidal thoughts. One small study showed that 17% of patients had suicidal ideation before starting treatment with standard interferon and that this increased to 26% during therapy. However, a study of 400 hepatitis C-infected patients on pegylated interferon treatment showed that only 4% had thoughts of suicide.

Despite the inconsistency in the research findings, the investigators emphasise that the risk of suicide should always be taken seriously “and should be discussed with patients and their families prior to commencement of therapy.” They also recommend that patients with a history of serious mood disorders, depression, suicidal thoughts or attempts as well as those with drug and alcohol problems “should be carefully interviewed and referred to a specialist for assessment of suicide risk and treatment of the underlying disorder before treatment with IFN can be considered.”

Therapy with SSRI antidepressants has been shown to be a safe and effective treatment of depression for patients taking interferon. A study involving 15 people treated with citalopram showed that 87% experienced an improvement in their symptoms and none had changes in their liver function. A recent placebo-controlled trial similarly indicated the effectiveness of this drug.

The authors make specific recommendations for the use of antidepressants. These take into account the severity of the symptoms.

  • Mild: Low-dose SSRI; continued monitoring with dose increase if needed.
  • Moderate: Moderate-dose SSRI; consider psychiatric evaluation; cessation of hepatitis C therapy may be needed.
  • Severe/suicidal: Stop hepatitis C treatment; psychiatric evaluation; consider hospitalisation.

Conflicting data about the prophylactic use of antidepressants are highlighted and discussed by the authors. They also stress that interferon therapy can disturb thyroid function and that this should therefore be monitored during therapy.


Papafragkakis H et al. Depression and pegylated interferon-based hepatitis C treatment. International Journal of Interferon, Cytokine and Mediator Research, 4: 25-35, 2012.

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