Biotherapy

, Volume 7, Issue 1, pp 27–37

Treatment of schizophrenic disorder, paranoid type, with intramuscular recombinant alpha-2b interferon

  • J. A. Cabrera Gómez
  • J. R. Cordero Gutierrez
  • O. Fernández López
  • B. Reyes Gutiérrez
  • K. Romero Garcia
  • J. Simón Consuegra
  • R. Feas Cruz
  • A. González Quevedo
  • I. Alfaro Capdegille
  • M. Del Pino Falcón
  • S. Williams Serrano
  • M. Vega Galindo
  • P. López Saura
  • Y. Bello Rivero
Article

Abstract

Twenty patients meeting DSM-III criteria for Schizophrenic Disorder, Paranoid Type were studied. After a 30 day drug-free period the patients were randomized in two groups. During a year, patients in Group 1 received intramuscular injections of a placebo while Group 2 received recombinant IFN alpha-2b. Both groups took anti-psychotic medication (APM) as needed on an individual basis, depending on their psychiatric symptomatology. Double blind evaluations, were performed at the beginning and at the end of the trial, using the Brief Psychiatric Rating Scale (BPRS) and the Reyes Scale for Social Evolution (RSSE). Information about relapses was gathered such as months without relapse, number and duration of the relapses and maximum dosages of APM given for relapse control. The statistical analysis of the results was performed with a matched pairs sign or Student's t tests for comparisons of each group before and after treatment. Groups were compared between them using the Fisher's exact test for frequencies and Student's t test for continuous variables. In Group 1: only one patient improved on the BPRS score; two had improved ratings on the RSSE; 2 patients got worse; and there were no changes in the rest of the group; three patients had no relapses and one increased in relapse frequency. These changes were not significant. The rate of relapses per year and their duration were not significantly modified in Group 1. The maximum dose of APM required for their relapse control was larger than before treatment although not significantly. All these patients required continuous APM. In Group 2 (IFN treated): 6 patients had improved BPRS scores (N=6, K=6, p<0.01) and 5 improved their RSSE scores (n=5, K=5, p<0.05). In 5 patients there were no relapses on their frequency decreased. There was significant reduction in the duration of the relapses (37.8±14.6 to 20.7±12.5 days; t=4.83; d.f.=9; p=0.0009) after treatment. Only 3 patients in Group 2 needed continuous APM after a relapse and the maximum dose required for control was significantly less (1281±527 to 687±552 chlorpromazine-equivalent mg. per day; t=5.56, p < 0.001). Comparisons between groups showed advantage for the IFN treated group in the BPRS change, proportion of patients needing continuous APM and integral evaluation. These results indicate that alpha IFN may be useful in the treatment of Schizophrenic Disorder, Paranoid Type.

Key words

Interferon alpha Schizophrenia intramuscular 

Abbreviations

IFN

Interferon

CSF

cerebrospinal fluid

RSSE

Reyes Scale for Social Evolution

APM

antipsychotic medication

BBB

blood-brain barrier

mRNA

ribonucleic acid messenger

DSM-III

Diagnostic and Statistical Manual of Mental Disorders

JCG

Juan Cordero Gutierrez

OFL

Odalys Fernandez Lopez

BPRS

Brief Psychiatric Rating Scale

ECT

Electroconvulsive treatment

IgG

immunoglobulin G

EEG

Electroencephalogram

SD

standard deviation

CNS

Central Nervous System

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References

  1. 1.
    Stiehm ER, Kronenberg HL, Rosenblatt MH, Bryson I, Merigan T. Interferon: immunobiology and clinical significance. Ann Intern Med 1982; 96: 80–93.PubMedGoogle Scholar
  2. 2.
    Hare HE. Season of birth in schizophrenia and neurosis. Am. J. Psychiatry 1975; 132: 1168–1171.PubMedGoogle Scholar
  3. 3.
    Torrey FE. Functional psychoses and viral encephalitis. Integr. Psychiatry 1986; 4: 224–236.Google Scholar
  4. 4.
    Libíkova H. Schizophrenia and viruses: principles of etiologic studies. Adv. Biol. Psychiat. 1983; 12: 20–51.Google Scholar
  5. 5.
    Mesa S, Cabrera AJ. Estudio de las partículas semejantes a virus observadas en la esquizofrenia. Rev. Hosp. Psiq. Habana. 1979; 20: 725–736.Google Scholar
  6. 6.
    Mesa S, González E, Pérez JL, Domínguez C, Ancheta O, de la Rosa M, Ramos M, Gómez H, Pujada M, Aguilera A, Zacarías E, Hernández M. Análisis digital de las imágenes obtenidas por immunoelectromicroscopía en cerebros de pacientes psicóticos, en su descendencia y en animales experimentalmente inoculados. Primeros resultados. Rev. Hosp. Psiq. Habana, 1989; 30: 343–348.Google Scholar
  7. 7.
    Ahokas A, Rimon R, Koskiniemi M, Vaheri A, Julkunen I, Sarna S. Viral antibodies and interferon in acute psychiatric disorders. J. Clin. Psychiatry 1987; 48: 194–196.PubMedGoogle Scholar
  8. 8.
    Baker HF, Bloxham CA, Crow TJ et al. The viral hypothesis: some experimental approaches. Adv. Biol. Psychiat. 1983; 12: 1–19.Google Scholar
  9. 9.
    Crow TJ. A reevaluation of the viral hypothesis: is psychosis the result of retroviral integration at a site close to the cerebral dominance gene?. British Psychiatry 1984; 145: 243–253.Google Scholar
  10. 10.
    Preble TO, Torrey FE. Serum interferon in patients with psychosis. Am. J. Psychiatry 1985; 142: 1184–1186.PubMedGoogle Scholar
  11. 11.
    Rimon R, Ahokas A: Interferon in schizophrenia. In: Kurstak E, Lipowski ZJ, Morozov PV eds. Viruses, immunity and mental disorders. Plenum Publishing Corporation 1987: 379–382.Google Scholar
  12. 12.
    Roy A, Pickar D, Ninam P, Hooks J, Paul SA. A search for interferon in the CSF of chronic schizophrenic patients. Am. J. Psychiatry 1985; 142: 2.Google Scholar
  13. 13.
    Mesa S, Aguilera A, Sánchez J, González, E. Estudio de las concentraciones de Interferón en pacientes esquizofrénicos. Rev. Hosp. Psiq. Habana, 1986; 27: 329–336.Google Scholar
  14. 14.
    Cabrera AJ, Reyes RB, Fernández O, Pérez I, Molina M, Rojas M. Concentraciones de Interferón y alteraciones celulares en el LCR de pacientes esquizofrénicos. Rev. Hosp. Psiq. Habana, 1989; 30: 77–87.Google Scholar
  15. 15.
    Calvet MO, Gresser I. Interferon enhances the excitability of cultured neurons. Nature 1979; 278: 558–560.PubMedGoogle Scholar
  16. 16.
    Williams S, Santana R, Vives J, De Armas C, Cabrera JA. Alpha IFN versus chloropromazine in the treatment of rat stereotypy. Abstract Second International Conference of Pathophysiology of Nervous System. November 25–30, 1990, Havana, Cuba.Google Scholar
  17. 17.
    Dafny N. Interferon: A candidate as the endogenous substance preventing tolerance and dependence to brain opioids. Prog. Neuro-Psychopharmacol. and Biol. Psychiat. 1984; 8: 351–357.Google Scholar
  18. 18.
    Moises HW, Schindler L, Lerous M, Kirchner H. Decreased production of interferon alpha and interferon gamma in leukocyte cultures of schizophrenic patients. Acta Psychiatr. Scand., 1985; 72: 45–50.PubMedGoogle Scholar
  19. 19.
    Katila H, Cantell K, Hirvonen S, Rimón R. Production of interferon-alpha and gamma by leukocytes from patients with schizophrenia. Schizophrenia Research, 1989, 2: 361–365.PubMedGoogle Scholar
  20. 20.
    Cantell K, Pulkkinen E, Elosuo R, Suominen J. Effect of interferon on severe psychiatric diseases. Ann. Clin. Res. 1980; 12: 131–132.PubMedGoogle Scholar
  21. 21.
    Cabrera AJ, Reyes RB, Fernández O. Interferon: su utilization en el tratamiento de la esquizofrenia. Rev. Hosp. Psiq. Habana, 1989: 30: 349–355.Google Scholar
  22. 22.
    Cabrera AJ, Reyes RB, Fernández O, Pérez I, Molina M, Rojas M. Interferon. Su utilización en nueve pacientes esquizofrénicos. Rev. Hosp. Psiq. Habana, 1990; 31: 81–87.Google Scholar
  23. 23.
    Mesa S, Marquez E, González E, Guerra V, Torres E, Torres P, Ortega M, Anido A, Dominquez W, Estivi J, Robinson D, Cesar I, Aguilera A, López Saura P, Limonta M.: Algunos aspectos relacionados con et tratamiento con IFN intratecal e intramuscular en esquizofrénicos. Rev. Hosp. Psiquiat. Habana 1989; 30: 69–76.Google Scholar
  24. 24.
    Cabrera J, Reyes B, Fernández O, Rojas M, Molina M, Perez I, González M, López-Saura P, Apezteguía I, Aguilera A. Treatment of Schizophrenia with Interferon. A Double Blind Study. Annual Meeting of the International Society for Interferon Research. San Francisco, J. Interferon Res. 1990; 10: s116.Google Scholar
  25. 25.
    Habif DV, Lipton R, Cantell K. Interferon crosses blood cerebrospinal fluid barrier in monkeys. Proc. Soc. Exp. Biol. Med. 1975; 149: 287–289.PubMedGoogle Scholar
  26. 26.
    Smith AR, Norris F, Palmer D, Bernhardt L, Wills JR. Distribution of alpha interferon in serum and cerebrospinal fluid after systemic administration. Clin. Pharmacol. Ther. 1985; 37: 85–88.PubMedGoogle Scholar
  27. 27.
    Billiau A. Interferon Therapy: Pharmacokinetic and pharmacological aspects. Arch. Virol. 1981; 67: 121–133.PubMedGoogle Scholar
  28. 28.
    Smith RA, Landel C, Cornelius CE, Revel M. Mapping the action of interferon on primate brain. J. Interferon Res. 1986; 6 (suppl. 1), 140.Google Scholar
  29. 29.
    Marcovistz R, Germano PML, Riviere Y, Tsiang H, Hovanessian AG. The effect of Interferon treatment in rabies prophylaxis in immunocompetent, immunosuppressed, and immunodeficient mice. J. Interferon Res. 1987; 7: 17–27.PubMedGoogle Scholar
  30. 30.
    Steiniger B, Van Der Meide P. Rat Ependyoma and microglia cell Express Class II-MHC antigens after Intravenous infusion of recombinant gamma Interferon. J. Neuroimmunol. 1988; 19: 111–118.PubMedGoogle Scholar
  31. 31.
    Torrey EF, Albrecht P, Behr DE. Permeability of the blood brain barrier in psychiatric patients. Am. J. Psychiatry. 1985; 142: 657–658.PubMedGoogle Scholar
  32. 32.
    Trastornos esquizofrénicos. In: Diagnostic and Statistical Manual of Mental Disorders. Masson SA, Barcelona 1984: 191–213.Google Scholar
  33. 33.
    Overall JE, Gorham AE. The BPRS. Phychol Res. 1961; 10: 799–812.Google Scholar
  34. 34.
    Reyes GR. La rehabilitación del paciente defectual. Trabajo científico para optar por el título de Especialista en Psiquiatría. Villa Clara, 1977.Google Scholar
  35. 35.
    Tibbling G, Link H, Ohman S. Principles of albumin and IgG analysis in neurological disorders. I. Establishment of reference values. Scand. J. Clin. Invert. 1977; 37: 385–390.Google Scholar
  36. 36.
    McDonald ME, Mann HA, Thomas CH. Interferon as mediators of psychiatric morbility. Lancet 1987; 11: 1175–1177.Google Scholar
  37. 37.
    Knobler RL, Greenstein JI, Johnson KP, Lublin FD, Panitch HS, Bedell L, Marcus SG, Grant-Gorsen S, De Ryk-Maurer T, Limbardi J, Katz E. Systemic Recombinant Human Beta Interferon treatment of relapsing remitting Multiple Sclerosis. Annual Meeting of the International Society for Interferon Research. San Francisco, J. Interferon Res. 1990; 10: s115.Google Scholar
  38. 38.
    FÄrkkilÄ M, Iivanainen M. Interferon in Multiple Sclerosis Clinical Neuropharmacology, 1988 Vol. 11, 2: 120–129, Raven Press, New York.Google Scholar
  39. 39.
    Knobler RL. Systemic interferon therapy of multiple sclerosis: The Pros. Neurology, 1988; 38 (suppl 2): 58–61.PubMedGoogle Scholar
  40. 40.
    Johnson KP, Knobler RL, Greenstein JI et al. Recombinant human beta interferon treatment of relapsing remitting Multiple Sclerosis: A pilot study. Neurology 1990; 40 (suppl 1): 261.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1994

Authors and Affiliations

  • J. A. Cabrera Gómez
    • 4
  • J. R. Cordero Gutierrez
    • 4
  • O. Fernández López
    • 4
  • B. Reyes Gutiérrez
    • 4
  • K. Romero Garcia
    • 4
  • J. Simón Consuegra
    • 4
  • R. Feas Cruz
    • 4
  • A. González Quevedo
    • 1
    • 4
  • I. Alfaro Capdegille
    • 1
    • 4
  • M. Del Pino Falcón
    • 1
    • 4
  • S. Williams Serrano
    • 2
    • 4
  • M. Vega Galindo
    • 2
    • 4
  • P. López Saura
    • 3
    • 4
  • Y. Bello Rivero
    • 3
    • 4
  1. 1.Instituto de Neurología y NeurocirugíaLa HabanaCuba
  2. 2.Facultad de Ciencias Médicas de CienfuegosCuba
  3. 3.Centro de Investigaciónes BiológicasLa HabanaCuba
  4. 4.Hosp. Provincial “Dr. Gustavo Aldereguía”CienfuegosCuba

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