Correspondence
Prediction of the Depressive Effects of Interferon Alfa Therapy by the Patient's Initial Affective State
N Engl J Med 1999; 340:1370April 29, 1999
- Article
To the Editor:
The antiviral, immunomodulatory, and antiproliferative properties of interferon alfa give this cytokine potential therapeutic effects in chronic viral infections and cancers.1 A major limitation of interferon alfa therapy is its serious side effects, which include fever, headache, myalgias, sleep disturbances, fatigue, anorexia, and in some cases, mood disorders.1-4 Usually observed during late states of treatment, depressive symptoms are detrimental to the patient's quality of life and may justify adjustment or interruption of the treatment.3 Identifying patients at risk for these mood disturbances early in the treatment would permit the adoption of corrective measures.
We investigated whether the patient's mood at the start of treatment could be used to predict the intensity of depressive symptoms induced by high doses of interferon alfa in patients with cancer. Ten patients (four men and six women; mean [±SE] age, 37.6±3.9 years) with high-risk metastatic melanoma were given high doses of interferon alfa as adjuvant immunotherapy according to the protocol of Kirkwood et al.2 The study was performed during the first four weeks of treatment, when interferon alfa was injected intravenously at a dose of 20×106 IU per square meter of body-surface area per day for five consecutive days per week. We evaluated the mood of patients before the initiation of the treatment (day 1) and at the end of the fourth week of treatment, using the Montgomery–Asberg Depression Rating Scale (MADRS).5 Patients who had psychiatric problems before the treatment were excluded.
The patients' MADRS scores were significantly higher at week 4 of interferon alfa immunotherapy than on day 1 (P<0.01), with 3 of the 10 patients having intense depressive symptoms. The magnitude of the scores on the MADRS before interferon alfa treatment significantly predicted the intensity of the patients' depressive symptoms at week 4 (Figure 1Figure 1
Relation between Depression Scores Measured on the Montgomery–Asberg Depression Rating Scale (MADRS) before (Day 1) and Four Weeks after the Initiation of Immunotherapy with Interferon Alfa (Week 4).).These results clearly demonstrate that the effects of interferon alfa on mood depend on the initial affective state of the patients. Even if they did not initially have depression, patients whose MADRS scores were higher on day 1 had more intense depressive symptoms during immunotherapy with interferon alfa than patients with low initial MADRS scores. These preliminary findings provide an easy way to identify patients who are at risk for mood disorders when treated with high doses of interferon alfa and demonstrate the usefulness of introducing a routine psychiatric assessment before initiating interferon alfa treatment.
5 ReferencesLucile Capuron, M.Psych.
INSERM Unité 394, 33077 Bordeaux CEDEX, FranceAlain Ravaud, M.D., Ph.D.
Institut Bergonié, 33076 Bordeaux CEDEX, France1
Borden EC ,Parkinson D . A perspective on the clinical effectiveness and tolerance of interferon-α. Semin Oncol 1998;25:Suppl 1:3-8
Web of Science | Medline2
Kirkwood JM ,Strawderman MH ,Ernstoff MS ,Smith TJ ,Borden EC ,Blum RH . Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma. J Clin Oncol 1996;14:7-17
Web of Science | Medline3
Cole BF ,Gelber RD ,Kirkwood JM ,Goldhirsch A ,Barylak E ,Borden E . Quality-of-life-adjusted survival analysis of interferon alfa-2b adjuvant treatment of high-risk resected cutaneous melanoma: an Eastern Cooperative Oncology Group study. J Clin Oncol 1996;14:2666-2673
Web of Science | Medline4
Ravaud A, Bedane C, Geoffrois L, Lesimple T, Delaunay M. Toxicity and feasibility of adjuvant high dose interferon alfa-2b in patients with melanoma in clinical oncology practice. Br J Cancer (in press).
5
Montgomery SA ,Asberg M . A new depression scale designed to be sensitive to change. Br J Psychiatry 1979;134:382-389
CrossRef | Web of Science | Medline
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CrossRef31
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CrossRef32
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CrossRef35
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CrossRef36
L. A. Mistler. (2006) Hepatitis C Treatment for People With Severe Mental Illness. Psychosomatics 47:2, 93-107
CrossRef37
2006. Interferon alfa. , 1793-1831.
CrossRef38
Abraham Reichenberg, Jack M Gorman, Douglas T Dieterich. (2005) Interferon-induced depression and cognitive impairment in hepatitis C virus patients: a 72 week prospective study. AIDS 19:Suppl 3, S174-S178
CrossRef39
Lisa I Backus, Derek Boothroyd, Lawrence R Deyton. (2005) HIV, hepatitis C and HIV/hepatitis C virus co-infection in vulnerable populations. AIDS 19:Suppl 3, S13-S19
CrossRef40
M. Germana Orrù, Antonella Baita, Rossella Sitzia, Alessandra Costa, Elisabetta Muntoni, Sabine Landau, Luchino Chessa, M. Giulia Farci, Bernardo Carpiniello, Carmine M. Pariante. (2005) Interferon-alpha-induced psychiatric side effects in patients with chronic viral hepatitis: a prospective, observational, controlled study. Epidemiologia e Psichiatria Sociale 14:03, 145-153
CrossRef41
Alan D. Valentine, Christina A. Meyers. (2005) Neurobehavioral effects of interferon therapy. Current Psychiatry Reports 7:5, 391-395
CrossRef42
Donn A. Simmons, Patricia A. Broderick. (2005) Cytokines, stressors, and clinical depression: Augmented adaptation responses underlie depression pathogenesis. Progress in Neuro-Psychopharmacology and Biological Psychiatry 29:5, 793-807
CrossRef43
Gregory M. Asnis, Richard De La Garza. (2005) Interferon-induced depression: Strategies in treatment. Progress in Neuro-Psychopharmacology and Biological Psychiatry 29:5, 808-818
CrossRef44
A. Scalori, M. Pozzi, V. Bellia, P. Apale, G. Santamaria, T. Bordoni, A. Redaelli, A. Avolio, P. Parravicini, P. Pioltelli, L. Roffi. (2005) Interferon-induced depression: prevalence and management. Digestive and Liver Disease 37:2, 102-107
CrossRef45
Cai Song, Brian E. Leonard. (2005) The olfactory bulbectomised rat as a model of depression. Neuroscience & Biobehavioral Reviews 29:4-5, 627-647
CrossRef46
Charles L Raison, Marina Demetrashvili, Lucile Capuron, Andrew H Miller. (2005) Neuropsychiatric Adverse Effects of Interferon-??. CNS Drugs 19:2, 105-123
CrossRef47
Piero Amodio, Enrico N. De Toni, Luisa Cavalletto, Daniela Mapelli, Elisabetta Bernardinello, Franco Del Piccolo, Cristina Bergamelli, Raffaella Costanzo, Federica Bergamaschi, Stefano Zanone Poma, Liliana Chemello, Angelo Gatta, Giulia Perini. (2005) Mood, cognition and EEG changes during interferon α (alpha-IFN) treatment for chronic hepatitis C. Journal of Affective Disorders 84:1, 93-98
CrossRef48
Jennifer M. Loftis, Peter Hauser. (2004) The phenomenology and treatment of interferon-induced depression. Journal of Affective Disorders 82:2, 175-190
CrossRef49
Martin Schaefer, Andreas Heinz, Markus Backmund. (2004) Treatment of chronic hepatitis C in patients with drug dependence: time to change the rules?. Addiction 99:9, 1167-1175
CrossRef50
Lucile Capuron, Alain Ravaud, Andrew H Miller, Robert Dantzer. (2004) Baseline mood and psychosocial characteristics of patients developing depressive symptoms during interleukin-2 and/or interferon-alpha cancer therapy. Brain, Behavior, and Immunity 18:3, 205-213
CrossRef51
Richard De La Garza, Gregory M. Asnis. (2003) The non-steroidal anti-inflammatory drug diclofenac sodium attenuates IFN-α induced alterations to monoamine turnover in prefrontal cortex and hippocampus. Brain Research 977:1, 70-79
CrossRef52
Lucile Capuron, Robert Dantzer. (2003) Cytokines and depression: The need for a new paradigm. Brain, Behavior, and Immunity 17:1, 119-124
CrossRef53
Naoshi Horikawa, Tomoko Yamazaki, Namiki Izumi, Masakatsu Uchihara. (2003) Incidence and clinical course of major depression in patients with chronic hepatitis type C undergoing interferon-alpha therapy: a prospective study. General Hospital Psychiatry 25:1, 34-38
CrossRef54
Bénédicte Gohier, Jean-Louis Goeb, Karine Rannou-Dubas, Isabelle Fouchard, Paul Calès, Jean-Bernard Garré. (2003) Hepatitis C, alpha interferon, anxiety and depression disorders: A prospective study of 71 patients. World Journal of Biological Psychiatry 4:3, 115-118
CrossRef55
N Combalbert, J.-L Bret-Dibat, A.-M Favard. (2002) Intérêts et limites de l’approche biologique pour l’étude des comportements agressifs. Annales Médico-psychologiques, revue psychiatrique 160:9, 640-648
CrossRef56
G. Garcia-Pares. (2002) Psychosis Induced by Interferon-alpha. Psychosomatics 43:5, 428-429
CrossRef57
Pariante, Carmine M., Landau, Sabine, , Carpiniello, Bernardo, . (2002) Interferon Alfa–Induced Adverse Effects in Patients with a Psychiatric Diagnosis. New England Journal of Medicine 347:2, 148-149
Full Text58
O. I. Okereke. (2002) Neuropsychiatric Complications Associated With Interferon-Alpha-2b Treatment of Malignant Melanoma. Psychosomatics 43:3, 237-240
CrossRef59
Stephen Sammut, Ingrid Bethus, Glyn Goodall, Richard Muscat. (2002) Antidepressant reversal of interferon-α-induced anhedonia. Physiology & Behavior 75:5, 765-772
CrossRef60
O Guilbaud, M Corcos, L Hjalmarsson, G Loas, P Jeammet. (2002) Modèles psycho-neuro-immunologiques de la dépression : une revue critique. Annales Médico-psychologiques, revue psychiatrique 160:2, 179-185
CrossRef61
K. Ademmer. (2001) Suicidal Ideation With IFN-alpha and Ribavirin in a Patient With Hepatitis C. Psychosomatics 42:4, 365-367
CrossRef62
Paul L. Kimmel. (2001) Psychosocial factors in dialysis patients. Kidney International 59:4, 1599-1613
CrossRef63
Musselman, Dominique L., Lawson, David H., Gumnick, Jane F., Manatunga, Amita K., Penna, Suzanne, Goodkin, Rebecca S., Greiner, Kristen, Nemeroff, Charles B., Miller, Andrew H., . (2001) Paroxetine for the Prevention of Depression Induced by High-Dose Interferon Alfa. New England Journal of Medicine 344:13, 961-966
Full Text64
Robert Dantzer. (2001) Cytokine-Induced Sickness Behavior: Mechanisms and Implications. Annals of the New York Academy of Sciences 933:1, 222-234
CrossRef65
Stefania Bonaccorso, Herbert Meltzer, Michael Maes. (2000) Psychological and behavioural effects of interferons. Current Opinion in Psychiatry 13:6, 673-677
CrossRef66
Michael Maes. (1999) Psychological stress, cytokines and the inflammatory response system. Current Opinion in Psychiatry 12:6, 695-700
CrossRef67
(1999) More on the Depressive Effects of Interferon Alfa. New England Journal of Medicine 341:11, 849-850
Full Text68
&NA;. (1999) Interferon-?? therapy ??? which patients will develop depression?. Reactions Weekly &NA;:750, 4
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