Depression with interferon therapy

In adepressed patientwith a new diagnosis of MS, it iscontro-versial whether to start interferon therapy because depression is a side effect of the interferon therapies, and the incidence of suicide is higher in this population. Practitioners generally will start patients on an antidepressant along with the interferon and watch them closely. Never should interferon be started in a severely depressed patient. 

Yang W, Wang Q, Kanes SJ, Murray JM, Nishikura K. Altered RNA editing of serotonin 5-HT2C receptor induced by interferon implications for depression associated with cytokine therapy. Brain Res Mol Brain Res 2004 124 70-78. 

Psychiatric symptoms have been prospectively examined in 104 patients with chronic hepatitis C, of whom 84 received interferon alfa-2b 15 MU/week and 20 were not treated (338). The incidence of clinically relevant scores for depression, anxiety, or anger/hostility increased from 23% of patients before interferon alfa to 58% of patients during treatment, and returned to 30% and 19% of patients 4 weeks and 6 months after withdrawal respectively. In contrast, there were no significant changes in the reference group. There were also significantly higher scores in the 40 patients who took concomitant ribavirin. Six patients successfully received antidepressant therapy, but withdrawal because of untreatable psychiatric symptoms was needed in 8.3% of patients, i.e. about half of the patients who had interferon-induced major depressive disorders. 

According to a study in 32 patients with cancers, the presence of emotional symptoms and sleep disturbance before treatment can predict the early development of severe depressive symptoms after subsequent therapy with IL-2 and/or interferon alfa (412). Although the number of patients was small, the authors suggested that this potentially high-risk population might benefit from prophylactic antidepressant treatment. 

Horikawa N, Yamazaki T, Izumi N, Uchihara M. Incidence and clinical course of major depression in patients with chronic hepatitis type C undergoing interferon-alpha therapy a prospective study. Gen Hosp Psychiatry 2003 25(l) 34-8. 

Loftis JM, Wall JM, Linardatos E, Benvenga S, Hauser P. A quantitative assessment of depression and thyroid dysfunction secondary to interferon-alpha therapy in patients with hepatitis C. J Endocrinol Invest 2004 27 RC16-20. 

Patten SB, Francis G, Metz LM, Lopez-Bresnahan M, Chang P, Curtin F. The relationship between depression and interferon beta-la therapy in patients with multiple sclerosis. Mult Scler 2005 11 175-81. 

This topic is covered in depth in another chapter. However, briefly, therapy with interferon has been shown to induce many symptoms of depression, including fatigue, depressed mood, psychomotor retardation, social withdrawal, and impaired... 

In a study of 67 patients with chronic viral hepatitis, the self-administered Minnesota Multiphasic Personality Inventory (MMPI), which determines the patient s psychological profile, significantly correlated with the clinical evaluation and was a sensitive and reliable tool for identifying patients at risk of depressive symptoms before the start of interferon alfa therapy (112). It was also successfully used to monitor patients during treatment. 

The FDA has expanded the indications for a combination product to include patients with chronic hepatitis C who have not been treated with interferon alfa. This product, Rebetron Combination Therapy (Schering), contains recombinant interferon alfa-2b for injection (Intron A) plus ribavirin (Rebetol) in capsules, and was previously only approved for patients who had relapsed after treatment with interferon alone (401). Serious adverse effects, such as depression, suicidal ideation, and suicide, have occurred with this regimen and patients should be closely monitored. 

---