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Fatigue may be misdiagnosed as depression during anti-HCV therapy in HIV coinfected
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"....a fatigued patient may report being depressed..."
Edwin J. Bernard, Tuesday, January 24, 2006
AIDSmap
Contributions by Jules Levin
Fatigue is more than twice as prevalent (70% vs 35%) 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.
Note from Jules Levin: in speaking with Dr Jones after her discussion, I suggested to her that a number of patients may have a history of undiagnosed depression. That asking patients if they had a history depression may not evoke a correct response because many patients may not know if they have had depression. They may not be capable of self-diagnosis. On interferon therapy patients may confuse whether they have depression or fatigue, they may not be able to distinguish between the two. Also, of note fatigue may cause depression. A patient may be fatigued and this may cause them to be depressed when the patient realizes how much the fatigue debilitates them. This is why activity while on interferon therapy is important. My personal experience on peginterferon/RBV therapy is that although you may feel fatigued and not want to do anything but be a couch potatoe, you must force yourself to be active. Continue work activity even if its at a reduced workload, take breaks as needed. Physical activity is also important. I am a jogger but after several weeks on therapy I had to stop, I no longer had the energy to do it. But, I was very active. You should take every opportunity to remain physically active, go places, go to the supermarket etc. Try to eat foods you like if you lose your appetite as I think loss of appetite & not eating as much as you usually do can contribute to fatigue.
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). Data collected was at weeks1, 4, 8, 12, 16, 24 and 48 regarding patient complaints of fatigue, depression, malaise, irritability and subjective reports of cognitive impairment.
A total of 72 (77%) men and 21 (23%) women were included in the study, 36% of whom were African American, 25% of whom were Caucasian, and 17% 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
70% (n=65) of study patients complained of fatigue on at least one occasion. Only 35% (n=31) complained of depression. The incidence of depression and fatigue were almost equal in the anemic and neutropenic groups. On average depression occurred at week 15 and fatigue at week 11. Time of onset of fatigue was closely correlated with time of onset of anemia. When this group was further broken down into patients with anemia or neutropenia it was observed that fatigued patients had a 50/50 chance of experiencing anemia; and anemic patients had a 3.5 fold increase compared to non-anemic patients of developing fatigue. Despite a 17% baseline rate of depression, no study patients became suicidal or committed suicide during the study.
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 17% 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."
References
Jones K et al. High prevalence of fatigue and depression in HIV/HCV coinfected patients treated with interferon and ribavirin. 2nd Intl Workshop HIV/HCV Coinfection, Amsterdam, abstract 38, 2006.
Kraus MR et al. Psychiatric symptoms in patients with chronic hepatitis C receiving interferon alfa-2b therapy. J Clin Psychiatry 64 (6), 708 - 714, 2003.
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