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.