Psychopharmacology

, Volume 91, Issue 4, pp 415–433

Provocative tests with psychostimulant drugs in schizophrenia

  • J. A. Lieberman
  • J. M. Kane
  • J. Alvir
Original Investigations

Abstract

The psychotogenic effects of psychostimulant drugs have provided a major line of evidence in support of the DA hypothesis of schizophrenia. To evaluate the effects of psychostimulant (PS) drugs inschizophrenia and the clinical variables which may influence their expression, we reviewed 36 studies of PS drugs in patients with schizophrenia. Approximately 40% evidence a psychotogenic response to PS administration in doses that are subpsychotogenic in normals. Specific clinical variables appear to modify this response, including diagnosis, degree and type of psychopathology, stage of illness and pharmacologic status at the time of testing. Non-amphetamine-like PS drugs, e.g., methylphenidate, appear to have greater psychotogenic potency than amphetamine-like PS drugs. These results suggest the presence of a subgroup of schizophrenic patients who exhibit psychotic symptom activation with PS in a state dependent or independent fashion. This biologic phenomenon may be clinically exploitable and should be investigated further.

Key words

Psychostimulant drugs Schizophrenia Methylphenidate Amphetamine Provocative test Behavioral effects 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Anderson EW (1938) Further observations on benzedrine. Br Med J [Clin Res] 2:60–64Google Scholar
  2. Andreasen NC (1982) Negative symptoms in schizophrenia. Arch Gen Psychiatry 39:784–788Google Scholar
  3. Angrist BM, Gershon S (1970) The phenomenology of experimentally induced amphetamine psychosis-Preliminary observations. Biol Psychiatry 2:95–107Google Scholar
  4. Angrist B, vanKammen DP (1984) CNS stimulants as tools in the study of schizophrenia. Trends NeuroSci 7:388–390Google Scholar
  5. Angrist B, Sathananthan G, Wilk S, Gershon S (1974) Amphetamine psychosis: behavioral and biochemical aspects. J Psychiatr Res 11:13–23Google Scholar
  6. Angrist B, Rotrosen J, Gershon S (1980a) Differential effects of amphetamine and neuroleptics on positive vs. negative symptoms in schizophrenia. Psychopharmacology 72:17–19Google Scholar
  7. Angrist B, Rotrosen J, Gershon S (1980b) Responses to apomorphine, amphetamine, and neuroleptics. Psychpharmacology 67:31–38Google Scholar
  8. Angrist B, Peselow E, Rubinstein M, Wolkin A, Rotrosen J (1985) Amphetamine response and relapse risk after depot neuroleptic discontinuation. Psychopharmacology 85:277–283Google Scholar
  9. Askar AM, Rakhawy YT, Shaheen O (1970) The quantitative assessment of therapeutic effect of methamphetamine on psychiatric patients. J Egypt Med Assoc 53:563–577Google Scholar
  10. Belart VW (1942) Pathogenetisches und therapeutisches aus Pervitinversuchen bei Schizophrenie. Schweiz Med Wochenschr 2:41–43Google Scholar
  11. Bell DS (1973) The experimental reproduction of amphetamine psychosis. Arch Gen Psychiatry 29:35–40Google Scholar
  12. Bischoff A (1951) Über eine therapeutische Verwendung der sogenannten “week-amine” an der Behandlung schizophrener Erregungszustände, Monatsschr Psychiatr Neurol 121:329–344Google Scholar
  13. Brown WA, Corrieveau DP, Ebert MH (1978) Acute psychologic and neuroendocrine effects of dextroamphetamine and methylphenidate. Psychopharmacology 58:189–195Google Scholar
  14. Buchsbaum MC, Rieder RO (1979) Biologic heterogenety and psychiatric research. Arch Gen Psychiatry 36:1163–1169Google Scholar
  15. Connell PH (1958) Amphetamine psychosis. Maudsley Monograph No. 5. Chapman Hall, LondonGoogle Scholar
  16. Creese I, Burt DR, Snyder SH (1976) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192:481–483Google Scholar
  17. Crow TJ (1980) Molecular pathology of schizophrenia: More than one disease process? Br Med J 6207:66–68Google Scholar
  18. Davidoff E, Reifenstein EC (1939) Treatment of schizophrenia with sympathomimetic drugs: Benzedrine sulfate. Am J Psychiatry 95:127–143Google Scholar
  19. Delay J (1949) Section of psychiatry, pharmacological explorations of the personality: narco-analysis and methedrine shock. Proc R Soc Med 62:491–496Google Scholar
  20. Dommisse CS, Schulz C, Narasimhachari N, Blackard WG, Hamer RN (1984) The neuroendocrine and behavioral response to dextroamphetamine in normal individuals. Biol Psychiatry 19:1305–1315Google Scholar
  21. Fawcett J, Siomopoulos V (1971) Dextroamphetamine response as a possible predictor of improvement with tricyclic therapy in depression. Arch Gen Psychiatry 25:247–255Google Scholar
  22. Ferris R, Tang F, Maxwell R (1972) A comparison of the capacities of isomers of amphetamine, deoxypiradrol and methylphenidate to inhibit the uptake of tritiated catecholamines into rat cerebral cortex slices, synaptosomal preparations of rat cerebral cortex, hypothalamus and striatum and into adrenergic nerves of rabbit aorta. J Pharmacol Exp Ther 181:407–416Google Scholar
  23. Flugel FE (1938) Medikamentöse Beeinflussung psychischer Hemmungszustaende. Klin Wochenschr 17. Jahrgang Nr 37:1286–1288Google Scholar
  24. Fung YK, Uretsky J (1982) The differential effects of amphetamine and methylphenidate eon the biosynthesis of [3H] dopa from [3H]tyrosine in mouse striata in vivo. J Pharm Pharmacol 531–532Google Scholar
  25. Gottlieb JS, Coburn FE (1944) Psychopharmacologic study of schizophrenia and depressions. Arch Neurol Psychiatry 51:260–263Google Scholar
  26. Gottliewb JS, Krause H, Friedinger AW (1945) Psychopharmacologic study of schizophrenia and depressions. II. Comparison of tolerance to sodium amytal and amphetamine sulfate. Arch Neurol Psychiatry 54:372–377Google Scholar
  27. Griffith JD, Cavanaugh J, Held J, Oates JA (1972) Dextroamphetamine: Evaluation of psychotomimmetic properties in man. Arch Gen Psychiatry 26:97–100Google Scholar
  28. Groves PM, Rebec GV (1976) Biochemistry and behavior: Some central actions of amphetamine and antipsychotic drugs. Annu Rev Psychol 27:91–127Google Scholar
  29. Guile LA (1963) Intravenous methylphenidate — a pilot study. Med J Aust 2:93–97Google Scholar
  30. Gutman E, Sargant W (1937) Observations on benzedrine. Br Med J 1:1013–1015Google Scholar
  31. Halbreich U, Asnis G, Ross D, Endicott J (1981) Amphetamine-induced dysphoria in postmenopausal women. Br J Psychiatry 138:470–473Google Scholar
  32. Haracz JL (1982) The dopamine hypothesis: An overview of studies with schizophrenic patients. Schizophr Bull 8:438–469Google Scholar
  33. Hauger RL, Hulihan-Giblin B, Janowsky A, Angel I, Berger P, Luu MD, Schweri MM, Vocci F, Skolnick P, Paul SM (1986) CNS recognition sites for psychomotor stimulants: methylphenidate and amphetamine (in press)Google Scholar
  34. Hope JM, Callaway E, Sands SL (1951) Intravenous pervitin and the psychopathology of schizophrenia. Dis Nerv Syst 12:67–72Google Scholar
  35. Hornykiewicz O (1982) Brain catecholamines in schizophrenia — a good case for noradrenaline. Nature 299:484–486Google Scholar
  36. Janowsky DS, El-Yousef MK, Davis JM, Sekerke J (1973) Provocation of schizophrenic symptoms by intravenous administration of methylphenidate. Arch Gen Psychiatry 28:185–191Google Scholar
  37. Janowsky DS, Davis JM (1976) Methylphenidate, dextroamphetamine, and levamphetamine. Effects on schizophrenic symptoms. Arch Gen Psychiatry 33:304–308Google Scholar
  38. Janowsky DS, Huey L, Storms L, Judd L (1977) Methylphenidate hydrochloride effects on psychological tests in acute schizophrenic and non-psychotic patients. Arch Gen Psychiatry 34:189–194Google Scholar
  39. Janowsky DS, Leichner P, Clopton P, Parka D, Judd L, Huey L (1978) Comparison of oral and intravenous methylphenidate. Psychopharmacology 59:75–78Google Scholar
  40. Johnstone EC, Crow TJ, Frith CD, Carney MWP, Price JS (1978) Mechanism of the antipsychotic effect in the treatment of acute schizophrenia. Lancet 2:848–851Google Scholar
  41. Jonas AD (1954) The adjunctive use of an intravenous amphetamine derivative in psychotherapy. J Nerv Ment Dis 119:135–147Google Scholar
  42. Jonsson LE (1972) Pharmacological blockade of amphetamine effects in amphetamine dependent subjects. Eur J Clin Pharmacol 4:206–211Google Scholar
  43. Kiloh LG, Neilson M, Andrews G (1974) Response of depressed patients to methylamphetamine. Br J Psychiatry 125:496–499Google Scholar
  44. Kornetsky C (1976) Hyporesponsivity of chronic schizophrenic patients to dextroamphetamine. Arch Gen Psychiatry 33:1425–1428Google Scholar
  45. Lehmann HE, Ban TA (1964) Notes from the log-book of a psychopharmacological research unit II. Can Psychiatr Assoc J 9:111–113Google Scholar
  46. Levine J, Rinkel M, Greenblatt M (1978) Psychological and physiological effects of intravenous pervitin. Am J Psychiatry 105:429–434Google Scholar
  47. Liddell DW, Weil-Malherbe H (1953) The effects of methedrine and of lysergic acid diethylamine on mental processes and on the blood adrenaline level. J Neurol Neurosurg Psychiatry 16:713Google Scholar
  48. Lieberman JA, Kane JM, Gadaleta D, Brenner R, Lesser MS, Kinon B (1984) Methylphenidate challenge as a predictor of relapse in schizophrenia. Am J Psychiatry 141:633–638Google Scholar
  49. Lieberman JA, Cooper T, Kinon B, Novacenko H, Harris P, Kane J (1985) Biochemical and clinical responses of schizophrenic patients to pharmacologic challenge tests on and off neuroleptic treatment. Presented at the Annual Meeting of the American College of Neuropsychopharmacology, Hawaii, December 9–13Google Scholar
  50. Mackay A, Crow TJ (1980) Positive and negative schizophrenic symptoms and the role of dopamine. Br J Psychiatry 137:379–386Google Scholar
  51. Martin WR, Sloan JW, Sapira JD, Janinski DR (1971) Psychologic, subjective, and behavioral effects of amphetamine, methamphetamine, ephedrine, phennetrazine, and methylphenidate in man. Clin Pharmacol Ther 12:245–258PubMedGoogle Scholar
  52. McMillen BA (1983) CNS stimulants: two distinct mechanisms of action for amphetamine-like drugs. TIPS 429–432Google Scholar
  53. Meltzer HY, Stahl SM (1976) The dopamine hypothesis of schizophrenia: A review. Schizophr Bull 2:19–76Google Scholar
  54. Merali Z, Toth G (1982) Effects of fluphenazine decanoate (a long-acting phenothiazine) on serum prolactin and amphetamine-induced behavioural changes. Pharmacol Biochem Behav 17:25–30Google Scholar
  55. Modell W, Hussar AE (1965) Failure of dextroamphetamine sulfate to influence eating and sleeping patterns in obese schizophrenic patients. JAMA 194:95–98Google Scholar
  56. Moore KE (1978) The actions of amphetamine on neurotransmitters: A brief review. Biol Psychiatry 12:451–462Google Scholar
  57. Nielsen JA, Chapin DS, Moore KE (1983) Differential effects of d-amphetamine, d-phenylethylamine, cocaine and methylphenidate on the rate of dopamine synthesis in terminals of nigrostriatal and mesolimbic neurons and on the efflux of dopamine metabolites into cerbroventricular perfusates of rats. Life Sci 33:1899–1907Google Scholar
  58. Pennes HH (1954) Clinical reactions of schizophrenics to sodium amytal, pervitin hydrochloride, mescaline sulfate, and d-lysergic acid diethylamide (LSD25). J Nerv Ment Dis 119:95–111Google Scholar
  59. Rall TW (1980) Central Nervous System Stimulants. In: Goodman LS, Gilman A (eds) The pharmacological basis of therapeutics. Macmillan, New York, pp 592–607Google Scholar
  60. Scheel-Krüger J (1971) Comparative studies of various amphetamine analogue demonstrating different interactions with the metabolism of the catecholamines in the brain. Eur J Pharmacol 14:47–59Google Scholar
  61. Schube PG, McManamy MC, Trapp CE (1937) The effect of benzedrine sulphate on certain abnormal mental states. Am J Psychiatry 94:27–32Google Scholar
  62. Seeman P, Lee T, Chau-Wong M, Wong K (1976) Antipsychotic drug doses and neuroleptic-dopamine receptors. Nature 261:717–719Google Scholar
  63. Shore PA, McMillen BA, Miller HH, Sanghera MK, Kiser RS, German DC (1979) The dopamine neuronal storage system and non-amphetamine psychotogenic stimulants: A model for psychosis. In: Usdin E, Kopin IJ, Barchas J (eds) Catecholamines: basic and clinical frontiers. Pergamon, New York, pp 722–727Google Scholar
  64. Simon JL, Taube H (1946) A preliminary study on the use of methedrine on psychiatric diagnosis. J Nerv Ment Dis 104:593–596Google Scholar
  65. Snyder SH (1973) Amphetamine psychosis: A “model” schizophrenia mediated by catecholamines. Am J Psychiatry 130:61–67Google Scholar
  66. Snyder SH (1976) The dopamine hypothesis of schizophrenia: Focus on the dopamine receptor. Am J Psychiatry 133:197–202Google Scholar
  67. Snyder SJ, Banerjee SP, Yamamura HI, Greenberg D (1974) Drugs, neurotransmitters and schizophrenia. Science 184:1243–1253Google Scholar
  68. Strube MJ, Hartmann DP (1983) Meta-analysis: techniques, applications, and functions. J Consult Clin Psychol 51:14–27Google Scholar
  69. Tecce JJ, Cole JO (1974) Amphetamine effects in man: paradoxical drowsiness and lowered electrical brain activity. Science 185:451–453Google Scholar
  70. Tune LE, Creese I, Coyle JT, Pearlson G, Snyder SH (1980) Low neuroleptic serum levels in patients receiving fluphenazine decanoate. Am J Psychiatry 137:80–82Google Scholar
  71. vanKammen D (1984) Amphetamine response in schizophrenia: An episode marker.: American Psychiatric Association 137th Annual Meeting, Los Angeles, California, pp 98–99Google Scholar
  72. vanKammen DP, Bunney WE, Docherty JP, Jimerson DC, Post RM, Siris S, Ebert M, Gillin JC (1977) Amphetamine-induced catecholamine activation in schizophrenia and depression: behavioral and physiological effects. In: Costa E, Gessa GL (eds) Advances in biochemical psychopharmacology Vol. 16. Raven, New York, pp 655–659Google Scholar
  73. vanKammen D, Docherty J, Marder SR, Schulz SC, Bunnery WE (1980) Lack of behavioral supersensitivity to d-amphetamine after pimozide withdrawal. Arch Gen Psychiatry 37:287–290Google Scholar
  74. vanKammen D, Docherty J, Bunney W (1982a) Prediction of early relapse after pimozide discontinuation by response to d-amphetamine during pimozide treatment. Biol Psychiatry 17:233–242Google Scholar
  75. vanKammen D, Docherty J, Marder S, Rayner JN, Bunney WE (1982b) Long-term pimozide pretreatment differentially affects behavioral responses to dextroamphetamine in schizophrenia. Arch Gen Psychiatry 39:275–281Google Scholar
  76. vanKammen D, Docherty J, Marder S, Schulz SC, Dalton L (1982c) Antipsychotic effects of pimozide in schizophrenia. Arch Gen Psychiatry 39:261–266Google Scholar
  77. Wald D, Ebstein RP, Belmaker RH (1978) Haloperidol and lithium blocking of the mood response in intravenous methylphenidate. Psychopharmacology 57:93–97Google Scholar
  78. Weiner N (1980) Norepinephrine, epinephrine, and the sympathomimetic amines. In: Goodman LS, Gilman A (eds) The pharmacological basis of therapeutics. Macmillan, New York, pp 138–175Google Scholar
  79. Witton K (1960a) Directive psychotherapy with parenteral Ritalin in advanced schizophrenia. Dis Nerv Syst 21:681–685Google Scholar
  80. Witton K (1960b) Clinical observations on Ritlin HCL (methylphenidylacetate) injectable multiple dose vial. Am J Psychiatry 7:117–156Google Scholar
  81. Woolley LF (1938) The clinical effects of benzedrine sulfate in mental patients with retarded activity. Psychiatr Q 12:66–83Google Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • J. A. Lieberman
    • 1
    • 2
  • J. M. Kane
    • 1
    • 2
  • J. Alvir
    • 1
  1. 1.Hillside Hospital Division of Long Island Jewish Medical CenterGlen OaksUSA
  2. 2.SUNYStony BrookUSA

Personalised recommendations