Fatigue may be misdiagnosed as depression during anti-HCV therapy in HIV coinfected

Fatigue is more than twice as prevalent as depression during anti-hepatitis C (HCV) treatment in HIV-positive individuals, according to a study presented to the Second International Workshop on HIV and Hepatitis Coinfection, held in Amsterdam earlier this month. Lead author, Dr Kristina Jones of Weill Cornell Medical Center, New York, suggests that fatigue is being misdiagnosed as depression in these individuals and recommends using standardised questionnaires so that the coinfected patient can be correctly assessed and treated. Her findings also suggest that coinfected individuals can be treated safely with anti-HCV therapy despite the development of depression, provided psychiatric care is integrated with medical care.

The psychological side-effects of current anti-HCV treatments are a frequent reason for discontinuation, although there are few data regarding the prevalence of depression and fatigue during anti-HCV therapy.

Consequently, Dr Kristina Jones of the Department of Psychiatry, The New York-Presbyterian Hospital, Weill Cornell Medical Center, set up a substudy of 93 HIV/HCV coinfected patients who were enrolled in a prospective trial of the optimal management of anaemia and neutropenia (comparing dose reduction versus growth factor supplementation) in individuals receiving pegylated interferon alfa-2b (Viraferon-Peg / Peg-Intron) and ribavirin (Copegus / Rebetol / Virazole).

A total of 72 (77%) men and 21 (23%) women were included in the study, 43% of whom were African American, 30% of whom were Caucasian, and 22% of whom were Hispanic. Patients with a history of severe depression (defined as a history of hospitalisation, electro-convulsive therapy or history of serious suicide attempt) were excluded, as were those who were active substance abusers.

At baseline, 18 individuals (19%) reported a history of depression, six (6%) reported a history of attempting suicide and one (1%) reported a history of suicidal ideation. HIV viral load was below 400 copies/ml in 68 (73%) and HCV viral load was over one million copies in 46 (49%) patients.

Fatigue and anaemia

A total of 65 (70%) experienced fatigue during the study, and this developed very early (during week 1) for the majority of participants, and peaked at week 4. Prevalence of fatigue was strongly associated with anaemia: of the 44 individuals diagnosed with anaemia, 34 (77%) experienced fatigue during the study. Only 20% of non-anaemic individuals complained of fatigue, resulting in a 3.8-fold increase in the prevalence of fatigue amongst anaemic participants compared with non-anaemic participants.

No association was found between depression and fatigue, and although one person discontinued anti-HCV treatment early due to fatigue, fatigue was not statistically significantly associated with early discontinuation. In addition, there was no association between depression and anaemia: 27% of anaemic patients were depressed, whereas 77% of anaemic patients were fatigued.

Depression

A total of 31 (33%) were diagnosed with depression using a standardised questionnaire based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Of these 31, 25 (81%) experienced both depression and fatigue. The 33% prevalence of depression found in this study is similar to the 35% prevalence of depression in monoinfected individuals on anti-HCV therapy (Kraus, 2003).

Depression was slower to develop in comparison to fatigue, but in the majority of cases occurred by week 12. Of the 31 patients who became depressed, seven of these had a history of depression and 24 did not. These observations suggest that 77% were de novo depression.

Despite the 19% pre-existing prevalence of depression and although there was one episode of suicidal ideation, there were no suicide attempts or completed suicides, and the person who experienced suicidal ideation did not discontinue the study early.

In total, there were two early discontinuations due to depression. However, depression was not found to be a statistically significant predictor of early discontinuation. In fact, early discontinuation was found to be associated with anaemia and neutropenia, but not with psychiatric side-effects.

"A bit of a shock"

Dr Jones told the conference that she suggests all patients ought to be "checked for depression at baseline and by week 4 using standardised questionnaires to detect depression," adding that "nurses could do these questionnaires, saving the doctor's time. Using standardised questionnaires would enable us to detect those one-third of patients who are going to suffer from depression during treatment and who are going to need treatment."

She added that "my data don't support the idea of prophylactic treatment of depression. Since only a third develop depression", this would result in over-treatment.

She also concluded that her findings suggest that HIV/HCV coinfected individuals can be treated safely with anti-HCV therapy despite the development of depression, "provided that psychiatric care is integrated with medical care."

Dr Marion Peters, from the University of California in San Francisco, and a member of the on-stage panel that discussed Dr Jones' data added that she thought this were "very important data" and questioned Dr Jones further about the differences between fatigue and depression. "We say 69% of patients on [anti-HCV therapy] need antidepressants," Dr Peters said, before asking: "Is it just that we're terrible psychiatrists? Are we calling fatigue depression?"

Dr Jones replied that "the critical point of the study is that's it's hard to tell the difference between fatigue and depression unless you ask the nine questions necessary for the diagnosis of depression using DSM-IV. In the present moment of fatigue a patient will report being depressed. The fascinating thing for me was that I thought it was going to be the depressed patients who got depressed again, but it wasn't. And that was a bit of a shock."