Correspondence

More on the Depressive Effects of Interferon Alfa

N Engl J Med 1999; 341:849-850September 9, 1999

Article

To the Editor:

In a recent letter, Capuron and Ravaud described their use of a depression rating scale as a method of predicting depressive symptoms associated with high doses of interferon alfa (April 29 issue).1 We strongly endorse the authors' recommendation of a routine psychiatric assessment before treatment with interferon alfa. However, we consider their conclusions — that “the effects of interferon alfa on mood depend on the initial affective state of the patients” and that a base-line measurement of mood symptoms constitutes “an easy way to identify patients who are at risk for mood disorders” — to be both premature and potentially deleterious.

We suggest substantially greater caution in interpreting their findings, which are inconsistent with the published data on interferon-induced neuropsychiatric effects. Multiple case reports and reviews have documented the development of depression and suicidal behavior in patients who do not have a history of psychiatric disorders or mood symptoms before treatment with interferon alfa.2-5 We have observed that in patients who have chronic hepatitis C and are treated with interferon alfa, serious depression and suicidal ideation can emerge in those who have no history of psychiatric disorders. Depression associated with interferon alfa also appears to be dependent on both the dose and the duration of treatment.6 The study conducted by Capuron and Ravaud lasted only four weeks and may well have underestimated the incidence and severity of interferon-induced depression.

Donald L. Rosenstein, M.D.
Darin Lerner, M.D.
Jun Cai, M.D.
National Institute of Mental Health, Bethesda, MD 20892

6 References

1. 1

   Capuron L, Ravaud A. Prediction of the depressive effects of interferon alfa therapy by the patient's initial affective state. N Engl J Med 1999;340:1370-1370
   Full Text | Web of Science | Medline

2. 2

   Janssen HL, Brouwer JT, van der Mast RC, Schalm SW. Suicide associated with alfa-interferon therapy for chronic viral hepatitis. J Hepatol 1994;21:241-243
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3. 3

   Rifflet H, Vuillemin E, Oberti F, et al. Suicidal impulses in patients with chronic viral hepatitis C during or after therapy with interferon alpha. Gastroenterol Clin Biol 1998;22:353-357
   Web of Science | Medline

4. 4

   Fukunishi K, Tanaka H, Maruyama J, et al. Burns in a suicide attempt related to psychiatric side effects of interferon. Burns 1998;24:581-583
   CrossRef | Web of Science | Medline

5. 5

   Schalm SW. Eurohep: a European Community sponsored concerted action on viral hepatitis: its rationale and execution. J Hepatol 1992;15:1-3
   CrossRef | Web of Science | Medline

6. 6

   Lindsay KL, Davis GL, Schiff ER, et al. Response to higher doses of interferon alfa-2b in patients with chronic hepatitis C: a randomized multicenter trial. Hepatology 1996;24:1034-1040
   Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: We agree with Rosenstein et al. that depressive symptoms can develop in response to interferon alfa in patients without a history of psychiatric disorders. In our study, we included only patients with no history of psychiatric disorders. Using the Montgomery–Asberg Depression Rating Scale (MADRS), we showed that patients who became depressed after interferon alfa therapy were those who already had a relatively high MADRS score before the initiation of treatment. However, these patients' absolute MADRS scores were in the normal range, and there was no clinical evidence of depression. We proposed that subclinical symptoms may precede the appearance of interferon-induced mood disturbance.

We are fully aware that the likelihood that neuropsychiatric disorders will develop depends on the dose and duration of treatment. We recently confirmed that low doses of interferon alfa, in contrast to high doses, did not induce mood changes for the same duration of therapy.1

Considering the deleterious effects of interferon alfa–induced depression, it now seems important that patients in whom complications are likely to develop be identified early so that preventive treatment can be introduced. A recent report shows that it is possible to reduce drastically the number of psychiatric complications associated with interferon alfa treatment by using an antidepressant.2

Lucile Capuron, M.Psych.
INSERM Unité 394, 33077 Bordeaux CEDEX, France

Alain Ravaud, M.D., Ph.D.
Institut Bergonié, 33076 Bordeaux CEDEX, France

2 References

1. 1

   Capuron L, Goodall G, Dantzer R, Ravaud A. Different mood and cognitive changes induced by alpha-interferon and/or interleukin-2 in treatment of cancer patients. Prog Proc Am Soc Clin Oncol 1999;18:585a-585a abstract.
   

2. 2

   Miller A, Musselman D, Penna S, Su C, Pearce B, Nemeroff C. Pretreatment with the antidepressant paroxetine prevents cytokine-induced depression during interferon-alpha therapy for malignant melanoma. Neuroimmunomodulation 1999;6:237-237
   CrossRef | Web of Science

Citing Articles (7)

Citing Articles

1. 1

   Bernhard Baune. 2011. Depression and Cytokine-Regulated Pathways. , 293-316.
   CrossRef

2. 2

   Debbie G. A. Janssen, Riccardo N. Caniato, Joris C. Verster, Bernhard T. Baune. (2010) A psychoneuroimmunological review on cytokines involved in antidepressant treatment response. Human Psychopharmacology: Clinical and Experimental 25:3, 201-215
   CrossRef

3. 3

   Bernhard T. Baune, Udo Dannlowski, Katharina Domschke, Debbie G.A. Janssen, Margaret A. Jordan, Patricia Ohrmann, Jochen Bauer, Erik Biros, Volker Arolt, Harald Kugel, Alan G. Baxter, Thomas Suslow. (2010) The Interleukin 1 Beta (IL1B) Gene Is Associated with Failure to Achieve Remission and Impaired Emotion Processing in Major Depression. Biological Psychiatry 67:6, 543-549
   CrossRef

4. 4

   S J Bull, P Huezo-Diaz, E B Binder, J F Cubells, G Ranjith, C Maddock, C Miyazaki, N Alexander, M Hotopf, A J Cleare, S Norris, E Cassidy, K J Aitchison, A H Miller, C M Pariante. (2009) Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-α and ribavirin treatment. Molecular Psychiatry 14:12, 1095-1104
   CrossRef

5. 5

   A. F. G. Leentjens, F. R. J. Verhey. (2002) Depression and Parkinson's disease: a conceptual challenge. Acta Neuropsychiatrica 14:3, 147-153
   CrossRef

6. 6

   Stefania Bonaccorso, Herbert Meltzer, Michael Maes. (2000) Psychological and behavioural effects of interferons. Current Opinion in Psychiatry 13:6, 673-677
   CrossRef

7. 7

   (2000) Current Awareness. Pharmacoepidemiology and Drug Safety 9:1, 75-90
   CrossRef