Skip to main content
SpringerLink
Log in

Neurological and Psychiatric Adverse Effects of Immunological Therapy

  • Adverse Effects
  • Published:
CNS Drugs Aims and scope Submit manuscript

Summary

Immunological therapy with cytokines can cause acute, subacute, delayed and, occasionally, irreversible toxicity to the CNS. Neurotoxic adverse effects are manifested by changes in cognitive, motor and emotional functioning. Although these changes are sometimes global in nature, most subacute neurotoxic symptoms attributable to interferon-α, interleukin-2 and tumour necrosis factor are specific to frontal-subcortical dysfunction and involve specific neuroanatomical and neurochemical systems.

The symptoms observed typically include memory deficits, difficulties with motivation and flexible thinking (frontal lobe executive function) and motor coordination. Reasoning, language functions and visual perception are generally not affected. Depression and other psychiatric presentations are common and appear to be due to the biochemical changes induced by cytokines rather than psychological reactions to the illness for which the agents are administered.

The mechanism of action of cytokines on brain function may include alterations in neurotransmitter function (mostly involving opioid and dopaminergic systems), induction of the release of neuroendocrine hormones and of other cytokines. Improved understanding of the mechanism of cytokine action in the brain is guiding the development of treatment interventions to reduce or eliminate CNS toxicity without sacrificing therapeutic efficacy. In addition, studies of cytokine neurotoxicity have advanced our knowledge of the normal role of these agents in the CNS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Goldstein D, Laszlo J. The role of interferon in cancer therapy: a current perspective. Cancer J Clin 1988; 38: 258–77

    Article  CAS  Google Scholar 

  2. Fent K, Zbinden G. Toxicity of interferon and interleukin. Trends Pharmacol Res 1987; 8: 100–5

    Article  CAS  Google Scholar 

  3. Denicoff KD, Rubinow DR, Papa MZ, et al. The neuropsychiatric effects of treatment with interleukin-2 and lymphokine-activated killer cells. Ann Intern Med 1987; 107: 293–300

    PubMed  CAS  Google Scholar 

  4. Lenk H, Tanneberger S, Muller U, et al. Phase II clinical trial of high-dose recombinant human tumor necrosis factor. Cancer Chemother Pharmacol 1989; 24: 391–2

    Article  PubMed  CAS  Google Scholar 

  5. Adams F, Quesada JR, Gutterman JU. Neuropsychiatric manifestations of human leukocyte interferon therapy in patients with cancer. JAMA 1984; 252: 938–41

    Article  PubMed  CAS  Google Scholar 

  6. Mattson K, Niiranen A, Iivanainen M, et al. Neurotoxicity of interferon. Cancer Treat Rep 1983; 67: 958–61

    PubMed  CAS  Google Scholar 

  7. Meyers CA, Abbruzzese J. Cognitive functioning in cancer patients: effect of previous treatment. Neurology 1992; 42: 434–6

    Article  PubMed  CAS  Google Scholar 

  8. Waltrip RW, Carrigan DR, Carpenter WT. Immunopathology and viral reactivation. A general theory of schizophrenia. J Nerv Ment Dis 1990; 178: 729–38

    Article  PubMed  Google Scholar 

  9. Preble O, Torrey E. Serum interferon in patients with psychosis. Am J Psychiatry 1985; 142: 1184–6

    PubMed  CAS  Google Scholar 

  10. Piper BF, Rieger PT, Brophy L, et al. Recent advances in the management of biotherapy-related side effects: fatigue. Oncol Nurs Forum 1989; 16(4 Suppl.): 27–34

    PubMed  CAS  Google Scholar 

  11. Smedley H, Katrak M, Sikora K, et al. Neurological effects of recombinant human interferon. BMJ 1983; 286: 262–4

    Article  PubMed  CAS  Google Scholar 

  12. Spiegel RJ. The alpha interferons: clinical overview. Urology 1989; 34Suppl. 4: 75–9

    Article  PubMed  CAS  Google Scholar 

  13. Smith A, Tyrrell D, Coyle K, et al. Effects of interferon alpha on performance in man: a preliminary report. Psychopharmacology 1988; 96: 414–6

    Article  PubMed  CAS  Google Scholar 

  14. Iivanainen M, Laaksonen R, Niemi ML, et al. Memory and psychomotor impairment following high-dose interferon treatment in amyotrophic lateral sclerosis. Acta Neurol Scand 1985; 72: 475–80

    Article  PubMed  CAS  Google Scholar 

  15. McDonald E, Mann A, Thomas H. Interferons as mediators of psychiatric morbidity: an investigation in a trial of recombinant interferon-alfa in hepatitis B carriers. Lancet 1987; 2: 1175–8

    Article  PubMed  CAS  Google Scholar 

  16. Renault PF, Hoofnagle JH, Park Y, et al. Psychiatric complications of long-term interferon alfa therapy. Arch Intern Med 1987; 147: 1577–80

    Article  PubMed  CAS  Google Scholar 

  17. Meyers CA, Obbens EAMT, Scheibel RS, et al. Neurotoxicity of intraventricularly administered alpha interferon for leptomeningeal disease. Cancer 1991; 68: 88–92

    Article  PubMed  CAS  Google Scholar 

  18. Wadler S, Feel S, Haynes H, et al. Treatment of carcinoma of the esophagus with 5-fluorouracil and recombinant alfa-2a-interferon. Cancer 1993; 71: 1726–30

    Article  PubMed  CAS  Google Scholar 

  19. Rohatiner AZS, Prior PF, Burton AC, et al. Central nervous system toxicity of interferon. Br J Cancer 1983; 47: 419–22

    Article  PubMed  CAS  Google Scholar 

  20. Suter CC, Westmoreland BF, Sharbrough FW, et al. Electroencephalographic abnormalities in interferon encephalopathy: a preliminary report. Mayo Clin Proc 1984; 59: 847–50

    PubMed  CAS  Google Scholar 

  21. Farkkila M, Iivanainen M, Roine R, et al. Neurotoxic and other side effects of high-dose interferon in amyotrophic lateral sclerosis. Acta Neurol Scand 1984; 70: 42–6

    Article  PubMed  CAS  Google Scholar 

  22. Honigsberger L, Fielding JW, Priestman TJ. Neurologic effects of recombinant human interferon [letter]. BMJ 1983; 286: 719

    Article  PubMed  CAS  Google Scholar 

  23. Dantzer R, Bluthe RM, Kent S, et al. Behavioral effects of cytokines. In: Rothwell NJ, Dantzer RD, editors. Interleukin-L in the brain. New York: Pergamon Press, 1992: 135–50

    Google Scholar 

  24. Triozzi PL, Kinney P, Rinehart JJ. Central nervous system toxicity of biological response modifiers. Ann NY Acad Sci 1990; 594: 347–54

    Article  PubMed  CAS  Google Scholar 

  25. Meyers CA, Mattis PJ, Pavol MA, et al. Pattern of neuro-behavioral deficits associated with interferon-a neurotoxicity [abstract]. Proc Am Assoc Cancer Res 1993; 34: 218

    Google Scholar 

  26. Cummings JL, editor. Subcortical dementia. New York: Oxford University Press, 1990

    Google Scholar 

  27. Durelli L, Bongioanni MR, Cavallo R, et al. Chronic systemic high-dose recombinant interferon alfa-2a reduces exacerbation rate, MRI signs of disease activity, and lymphocyte interferon gamma production in relapsing-remitting multiple sclerosis. Neurology 1994; 44: 406–13

    Article  PubMed  CAS  Google Scholar 

  28. Bocci V. Central nervous system toxicity of interferons and other cytokines. J Biol Regul Homeost Agents 1988; 3: 107–18

    Google Scholar 

  29. Meyers CA, Scheibel RS, Forman AD. Persistent neurotoxicity of systemically administered interferon-alpha. Neurology 1991; 41: 672–6

    Article  PubMed  CAS  Google Scholar 

  30. Merimsky O, Chaitchik S. Neurotoxicity of interferon-α. Anticancer Drugs 1992; 3: 567–70

    Article  PubMed  CAS  Google Scholar 

  31. Liberati AM, Biscottini B, Fizzotti M, et al. A phase I study of human natural interferon-β in cancer patients. J Interferon 1989; 9: 339–48

    Article  CAS  Google Scholar 

  32. The IFNB Multiple Sclerosis Study Group. Interferon beta-lb in effective in relapsing-remitting multiple sclerosis: I. Clinical results of a multicenter, randomized, double-blind placebo-controlled trial. Neurology 1993; 43: 655–61

    Google Scholar 

  33. von der Maase H, Geertsen P, Thatcher C, et al. Recombinant interleukin-2 in metastatic renal cell carcinoma - a European multicentre phase II study. Eur J Cancer 1991; 27: 1583–9

    Article  PubMed  Google Scholar 

  34. Krigel R, Padavic-Shaller K, Rudolph A, et al. A phase I study of recombinant interleukin-2 plus recombinant beta interferon. Cancer Res 1988; 48: 3875–81

    PubMed  CAS  Google Scholar 

  35. Rosenberg SA, Yang JC, Topalian SL, et al. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA 1994; 271: 907–13

    Article  PubMed  CAS  Google Scholar 

  36. Meyers CA, Yung WKA. Delayed neurotoxicity of intraventricular interleukin-2: a case report. J Neurooncol 1993; 15: 265–7

    Article  PubMed  CAS  Google Scholar 

  37. Spriggs DR, Sherman ML, Michie H, et al. Recombinant human tumor necrosis factor administered as a 24-hour intravenous infusion. A phase I and pharmacologic study. J Natl Cancer Inst 1988; 80: 1039–44

    Article  PubMed  CAS  Google Scholar 

  38. Meyers CA, Valentine AD, Wong FL, et al. Reversible neurotoxicity of IL-2 and TNF: correlation of SPECT with neuropsychological testing. J Neuropsychiatry Clin Neurosci 1994; 6: 285–8

    PubMed  CAS  Google Scholar 

  39. Lipowski Z. Update on delirium. Psychiatr Clin North Am 1992; 15: 335–46

    PubMed  CAS  Google Scholar 

  40. Slaby A, Erie S. Dementia and delirium. In: Stoudemire A, Fogel BS, editors. Psychiatric care of the medical patient. New York: Oxford University Press, 1993: 415–53

    Google Scholar 

  41. Cummings JL, Benson FD. Dementia: a clinical approach. 2nd ed. Boston: Butterworth-Heinemann, 1992: 217–65

    Google Scholar 

  42. Cohen-Cole S, Brown F, McDaniel JS. Assessment of depression and grief reactions in the medically ill. In: Stoudemire A, Fogel BS, editors. Psychiatric care of the medical patient. New York: Oxford University Press, 1993: 53–69

    Google Scholar 

  43. Massie MJ, Holland JC. Depression and the cancer patient. J Clin Psychiatry 1990; 71: 7 (Suppl.): 12–7

    Google Scholar 

  44. Adams F, Fernandez F, Mavligit G. Interferon-induced organic mental disorders associated with unsuspected pre-existing neurologic abnormalities. J Neurooncol 1988; 6: 355–9

    Article  PubMed  CAS  Google Scholar 

  45. Ellison MD, Krieg RJ, Povlishock JT. Differential central nervous system responses following single and multiple recombinant interleukin-2 infusions. J Neuroimmunol 1990; 28: 249–60

    Article  PubMed  CAS  Google Scholar 

  46. Saris SC, Rosenberg SA, Friedman RB, et al. Penetration of recombinant interleukin-2 across the blood-cerebrospinal fluid barrier. J Neurosurg 1988; 69: 29–34

    Article  PubMed  CAS  Google Scholar 

  47. Ellison MD, Povlishock JT, Merchant RE. Blood-brain barrier dysfunction in cats following recombinant interleukin-2 infusion. Cancer Res 1987; 47: 5765–70

    PubMed  CAS  Google Scholar 

  48. Blatteis CM, Hales JRS, McKinley MH, et al. Role of the anteroventral third ventricle region in fever in sheep. Can J Physiol Pharmacol 1986; 65: 1255–60

    Article  Google Scholar 

  49. Shibata M, Blatteis C. Human recombinant tumor necrosis factor and interferon affect the activity of neurons in the organum vasculosum laminae terminalis. Brain Res 1991; 562: 323–6

    Article  PubMed  CAS  Google Scholar 

  50. Calvet M, Gresser I. Interferon enhances the excitability of cultured neurones. Nature 1979; 278: 558–60

    Article  PubMed  CAS  Google Scholar 

  51. Dafny N. Interferon modifies EEG and EEG-like activity recorded from sensory, motor, and limbic system structures in freely behaving rats. Neurotoxicology 1983; 4: 235–40

    PubMed  CAS  Google Scholar 

  52. Dafny N, Prieto-Gomez B, Reyes-Vazquez C. Does the immune system communicate with the central nervous system? Interferon modifies central nervous activity. J Neuroimmunol 1985; 9: 1–12

    Article  PubMed  CAS  Google Scholar 

  53. Prieto-Gomez B, Reyes-Vazquez C, Dafny N. Differential effects of interferon on ventromedial hypothalamus and dorsal hippocampus. J Neurosci Res 1983; 10: 273–8

    Article  PubMed  CAS  Google Scholar 

  54. Bindoni M, Perciavalle V, Berretta S, et al. Interleukin-2 modifies the bioelectric activity of some neurosecretory nuclei in the rat hypothalamus. Brain Res 1988; 462: 10–4

    Article  PubMed  CAS  Google Scholar 

  55. Berk M, Finkelstein J. Efferent connections of the lateral hypothalamic area of the rat: an autoradiographic investigation. Brain Res Bull 1982; 8: 511–26

    Article  PubMed  CAS  Google Scholar 

  56. Carpenter M, Sutin J. Human neuroanatomy. Baltimore: Williams & Wilkins, 1983

    Google Scholar 

  57. Issacson R. The limbic system. New York: Plenum Press, 1982

    Google Scholar 

  58. Villalobos J, Ferssiwi A. The differential ascending projections from the anterior, central, and posterior regions of the lateral hypothalamic area: an autoradiographic study. Neurosci Lett 1987; 81: 89–94

    Article  PubMed  CAS  Google Scholar 

  59. Villalobos J, Ferssiwi A. The differential descending projections from the anterior, central, and posterior regions of the lateral hypothalamic area: an autoradiographic study. Neurosci Lett 1987; 81: 95–9

    Article  PubMed  CAS  Google Scholar 

  60. Cotran RS, Pober JS, Gimbrone MA, et al. Endothelial activation during interleukin 2 immunotherapy: a possible mechanism for a vascular leak syndrome. J Immunol 1987; 137: 1883–8

    Google Scholar 

  61. Saris SC, Patronas N, Rosenberg SA. The effect of intravenous interleukin-2 on brain water content. J Neurosurg 1989; 71: 169–74

    Article  PubMed  CAS  Google Scholar 

  62. Vial T, Descotes J. Clinical toxicity of interleukin-2. Drug Saf 1992; 7: 417–33

    Article  PubMed  CAS  Google Scholar 

  63. Bernard JT, Ameriso S, Kempf RA, et al. Transient focal neurologic deficits complicating interleukin-2 therapy. Neurology 1990; 40: 154–5

    Article  PubMed  CAS  Google Scholar 

  64. Dvorak HF, Gresser I. Microvascular injury in pathogenesis of interferon-induced necrosis of subcutaneous tumors in mice. J Natl Cancer Inst 1989; 81: 497–502

    Article  PubMed  CAS  Google Scholar 

  65. Blalock JE, Smith EM. Human leukocyte interferon: structural and biological relatedness to adrenocorticotropic hormones and endorphins. Proc Nat Acad Sci USA 1980; 77: 5972–4

    Article  PubMed  CAS  Google Scholar 

  66. Blalock JE, Stanton JD. Common pathways of interferon and hormonal action. Nature 1980; 283: 406–8

    Article  PubMed  CAS  Google Scholar 

  67. Tracey K, Lowry S, Fahey T, et al. Cachectin/tumor necrosis factor induces lethal shock and stress hormone responses in the dog. Surg Gynecol Obstet 1987; 164: 415–22

    PubMed  CAS  Google Scholar 

  68. Tsagarakis S, Gillies G, Rees L, et al. Interleukin-1 directly stimulates the release of corticotropin releasing factor from rat hypothalamus. Neuroendocrinology 1989; 9: 98–101

    Article  Google Scholar 

  69. Schultzberg M. Location of interleukin-1 in the nervous system. In: Rothwell NJ, Dantzer RD, editors. Interleukin-1 in the brain. New York: Pergamon Press, 1992: 1–11

    Google Scholar 

  70. Gottschall PE, Komaki G, Arimura A. Interleukin-1β activation of the central nervous system. In: Rothwell NJ, Dantzer RD, editors. Interleukin-1 in the brain. New York: Pergamon Press, 1992: 27–49

    Google Scholar 

  71. McEwen B, Weis J, Schwartz L. Selective retention of corticosterone by limbic structures in rat brain. Nature 1968; 220: 911–2

    Article  PubMed  CAS  Google Scholar 

  72. McEwen B, De Kloet E, Rostene W. Adrenal steroid receptors and actions in the central nervous system. Physiological Rev 1986; 66: 1121–88

    CAS  Google Scholar 

  73. McEwen B, Micco D. Toward an understanding of the multiplicity of glucocorticoid actions on brain function and behavior. In: De Weid D, van Keep P, editors. Hormones and the brain. Baltimore, MD: University Park, 1980: 11–28

    Chapter  Google Scholar 

  74. Gray J. The neuropsychology of anxiety: an inquiry into the functions of the septo-hippocampal system. New York: Oxford University Press, 1982

    Google Scholar 

  75. Lynch G. Synapses, circuits, and the beginnings of memory. Cambridge, MA: MIT Press, 1986

    Google Scholar 

  76. Squire L. Memory and brain. New York: Oxford University Press, 1987

    Google Scholar 

  77. Holsboer F. Implications of altered limbic-hypothalamicpituitary-adrenocortical (LHPA)-function for the neurobiology of depression. Acta Psychiatr Scand 1988; 341(Suppl.): 72–111

    Article  CAS  Google Scholar 

  78. Sapolsky RM. A mechanism of glucocorticoid toxicity in the hippocampus: increased neuronal vulnerability to metabolic insults. J Neurosci 1985; 5: 1228–32

    PubMed  CAS  Google Scholar 

  79. Sapolsky RM, Paean DR, Vale WW. Glucocorticoid toxicity in the hippocampus: in vitro demonstration. Brain Res 1988; 453: 367–71

    Article  PubMed  CAS  Google Scholar 

  80. Masters J, Finch C, Sapolsky R. Glucocorticoid endangerment of hippocampal neurons does not involve deoxyribonucleic acid cleavage. Endocrinology 1989; 124: 3083–8

    Article  PubMed  CAS  Google Scholar 

  81. Johnson M, Stone D, Bush L, et al. Glucocorticoids and 3,4-methylenedioxymethamphetamine (MDMA)-induced neurotoxicity. Eur J Pharmacol 1989; 161: 181–8

    Article  PubMed  CAS  Google Scholar 

  82. Kirkegaard C, Faber J, Hummer L, et al. Increased levels of TRH in cerebrospinal fluid from patients with endogenous depression. Psychoneuroendocrinology 1979; 4: 227–35

    Article  PubMed  CAS  Google Scholar 

  83. Prange AJ, Lara PP, Wilson IC, et al. Effects of thyrotropin-releasing hormone in depression. Lancet 1972; ii: 99–1002

    Google Scholar 

  84. Nemeroff CB, Simon JS, Haggerty JJ, et al. Antithyroid antibodies in depressed patients. Am J Psychiatry 1985; 142: 840–3

    PubMed  CAS  Google Scholar 

  85. Carrol BJ. The dexamethasone suppression test for melancholia. Br J Psychiatry 1982; 140: 292–304

    Article  Google Scholar 

  86. Sachar EJ, Hellman L, Fukushima DK, et al. Cortisol production in depressive illness. Arch Gen Psychiatry 1970; 23: 289–98

    Article  PubMed  CAS  Google Scholar 

  87. Nemeroff CB, Widerlov E, Bissett G, et al. Elevated concentration of CSF corticotropin releasing factor-like immuno-reactivity in depressed patients. Science 1984; 226: 1342–4

    Article  PubMed  CAS  Google Scholar 

  88. Nemeroff CB, Ranga K, Krishnan RR, et al. Adrenal gland enlargement in major depression. Arch Gen Psychiatry 1992; 49: 384–7

    Article  PubMed  CAS  Google Scholar 

  89. Arenzana-Seisdedos F, Virelizer JL. Interferons as macrophage-activating factors: II. Enhanced secretion of interleukin-1 by lipopolysaccharide-stimulated human monocytes. Eur J Immunol 1983; 13: 437–40

    Article  PubMed  CAS  Google Scholar 

  90. Herman J, Kew M, Rabson A. Defective interleukin-1 production by monocytes from patients with malignant disease. Cancer Immunol Immunother 1984; 16: 182–5

    Article  PubMed  CAS  Google Scholar 

  91. Mier JW, Vachino G, Van Der Meer JWM, et al. Induction of circulating tumor necrosis factor (TNF alpha) as the mechanism for the febrile response to interleukin-2 (IL-2) in cancer patients. J Clin Immunol 1988; 8: 426–36

    Article  PubMed  CAS  Google Scholar 

  92. Breder C, Dinarello CA, Saper C. Interleukin-1 immunoreactive innervation of the human hypothalamus. Science 1988; 240: 321–4

    Article  PubMed  CAS  Google Scholar 

  93. Farrar W, Killian P, Ruff M, et al. Visualization and characterization of interleukin-1 receptors in brain. J Immunol 1987; 139: 459–63

    PubMed  CAS  Google Scholar 

  94. Kabiersch A, Del Rey A, Honegger CG, et al. Interleukin-1 produces changes in norepinephrine metabolism in the rat brain. Brain Behav Immun 1988; 2: 267–74

    Article  PubMed  CAS  Google Scholar 

  95. Plata-Salaman CR, Ffrench-Mullen JM. Interleukin-1 beta depresses calcium currents in CA1 hippocampal neurons at pathophysiological concentrations. Brain Res Bull 1992; 29: 221–3

    Article  PubMed  CAS  Google Scholar 

  96. Mier JW, Vachino G, Lempner MS, et al. Inhibition of interleukin-2-induced tumor necrosis factor release by dexamethasone: prevention of an acquired neutrophil chemotaxis defect and differential suppression of interleukin-2-associated side effects. Blood 1990; 76: 1933–40

    PubMed  CAS  Google Scholar 

  97. Ellison MD, Merchant RE. Appearance of cytokine-associated central nervous system myelin damage coincides temporarily with serum tumor necrosis factor induction after recombinant interleukin-2 infusion in rats. J Neuroimmunol 1991; 33: 245–51

    Article  PubMed  CAS  Google Scholar 

  98. Waage A, Espevik T. Interleukin-1 potentiates the lethal effect of tumor necrosis factor alpha/cachectin in mice. J Exp Med 1988; 167: 1987–92

    Article  PubMed  CAS  Google Scholar 

  99. Wollman EE, Kopmels B, Bakalian A, et al. Cytokines and neuronal degeneration. In: Rothwell NJ, Dantzer RD, editors. Interleukin-1 in the brain. New York: Pergamon Press, 1992: 187–203

    Google Scholar 

  100. Cooper JR, Bloom FE, Roth RH. The biochemical basis of neuropharmacology, 6th ed. New York: Oxford University Press, 1991

    Google Scholar 

  101. Blalock JE, Smith EM. Human leukocyte interferon (HuIFN-α): potent endorphin-like opioid activity. Biochem Biophys Res Commun 1981; 101: 472–8

    Article  PubMed  CAS  Google Scholar 

  102. Birmanns B, Saphier D, Abramsky O. α-Interferon modifies cortical EEG activity: dose-dependence and antagonism by naloxone. J Neurol Sci 1990; 100: 22–6

    Article  PubMed  CAS  Google Scholar 

  103. Ho B, Huo Y, Lu J, et al. Opioid-dopaminergic mechanisms in the potentiation of d-amphetamine discrimination by interferon-α. Pharmacol Biochem Behav 1991; 42: 57–60

    Article  Google Scholar 

  104. Ho BT, Lu JG, Huo YY, et al. Neurochemical basis of interleukin-2 modified discrimination behavior. Cytokines. In press

  105. Dafny N, Reyes-Vazquez C. Single injection of three different preparations of α-interferon modifies morphine abstinence for a prolonged period. Int J Neurosci 1987; 32: 953–61

    Article  PubMed  CAS  Google Scholar 

  106. Dafny N, Zielinski M, Reyes-Vazquez C. Alteration of morphine withdrawal to naloxone by interferon. Neuropeptides 1983; 3: 453–63

    Article  PubMed  CAS  Google Scholar 

  107. Nakashima T, Hori T, Kiriyama K. et al. Naloxone blocks the interferon-α induced changes in hypothalamic neuronal activity. Neurosci Lett 1987; 82: 332–6

    Article  PubMed  CAS  Google Scholar 

  108. Levine P, Silberfarb P, Kipowski Z. Mental disorders in cancer patients: a study of 100 psychiatric referrals. Cancer 1978; 43: 1385–91

    Article  Google Scholar 

  109. Folstein M, Folstein S, McHugh P. ‘Mini-mental state’: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189–98

    Article  PubMed  CAS  Google Scholar 

  110. Auerbach V, Faibish G. Mini-mental state examination: diagnostic limitations [abstract]. J Clin Exp Neuropsychol 1989; 11: 75

    Google Scholar 

  111. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th ed. Washington DC: American Psychiatric Association, 1994

  112. Smith M, Khayat D. Residual acute confusional and hallucinatory syndromes induced by interleukin-2/α-interferon treatment. Psycho-oncology 1992; 1: 115–8

    Article  Google Scholar 

  113. Levenson J, Fallon H. Fluoxetine treatment of depression caused by interferon-α. Am J Gastroenterol 1993; 88: 760–1

    PubMed  CAS  Google Scholar 

  114. Goldman LS. Successful treatment of interferon-alfa-induced mood disorder with nortriptyline. Psychosomatics 1994; 35: 412–3

    Article  PubMed  CAS  Google Scholar 

  115. Valentine A, Meyers CA, Talpaz M. Treatment of neurotoxic side effects of interferon-a with naltrexone. Cancer Invest. In press

  116. Fossa SD. Improved subjective tolerability of interferon by combination with prednisolone. Eur J Can Clin Oncol 1987; 23: 875–6

    Article  CAS  Google Scholar 

  117. Abdi EA. Combination of interferon and prednisone in human cancer. Eur J Can Clin Oncol 1988; 24: 723–4

    Article  CAS  Google Scholar 

  118. Fossa SD, Gunderson R, Moe B. Recombinant interferon-alpha combined with prednisone in metastatic renal cell carcinoma. Cancer 1990; 65: 2451–4

    Article  PubMed  CAS  Google Scholar 

  119. Stiefel FC, Breitbart WS, Holland JC. Corticosteroids in cancer: neuropsychiatric complications. Cancer Invest 1989; 7: 479–91

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neuro-Oncology, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd, Box 100, Houston, Texas, 77030, USA

    Christina A. Meyers & Alan D. Valentine

Authors
  1. Christina A. Meyers
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alan D. Valentine
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Meyers, C.A., Valentine, A.D. Neurological and Psychiatric Adverse Effects of Immunological Therapy. CNS Drugs 3, 56–68 (1995). https://doi.org/10.2165/00023210-199503010-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00023210-199503010-00006

Keywords

Search

Navigation