A path-analytical approach to differentiate between direct and indirect drug effects on negative symptoms in schizophrenic patients

A re-evaluation of the North American risperidone study
  • Hans-Jürgen Möller
  • Horst Müller
  • Richard L. Borison
  • Nina R. Schooler
  • Guy Chouinard
Original Paper

Abstract

The hypothesis that differences in drug effects of risperidone and haloperidol on negative symptoms in schizophrenia are secondary to effects on positive, extrapyramidal, and depressive symptoms was investigated by means of an analysis of the data from the USA-Canada risperidone double-blind randomized clinical trial of 523 chronic schizophrenic patients. Regression analyses in the total sample and within treatment groups confirmed a strong relationship between changes in negative symptoms and the other variables studied (R2=0.50−0.51,p<0.001). Only depressive symptoms did not contribute significantly to these results (p>0.10). Path analysis showed that the greater mean change (p<0.05) of negative symptoms with risperidone compared to haloperidol could not be fully explained by correlations with favourable effects on positive and extrapyramidal symptoms. The relationship between shift in extrapyramidal symptoms and shift in negative symptoms failed to reach statistical significance; however, there was a clear tendency in the expected direction in both treatment groups.

Key words

Neuroleptics Negative symptoms Risperidone Schizophrenia Haloperidol 

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References

  1. American Psychiatric Association (ed) (1987) Diagnostic and statistical manual of mental disorders. 3rd edition, revised. American Psychiatric Association, WashingtonGoogle Scholar
  2. Andreasen NC (1989) The Scale for the Assessment of Negative Symptoms (SANS): conceptual and theoretical foundations. Br J Psychiatry 155, Suppl 7:49–52Google Scholar
  3. Breier A, Buchanan R, Kirkpatrick B, Davis O, Irish D, Summerfelt A, Carpenter W (1994) Effects of lozapine on positive and negative symptoms in outpatients with schizophrenia. Am J Psychiatry 145:578–583Google Scholar
  4. Carpenter WT, Heinrichs DW, Alphs LD (1985) Treatment of negative symptoms. Schizophr Bull 11:440–452Google Scholar
  5. Carpenter WT, Heinrichs DW, Wagman AMI (1988) Deficit and nondeficit forms of schizophrenia: the concept. Am J Psychiatry 145:578–583Google Scholar
  6. Chouinard G, Ross-Chouinard A, Annable L, Jones BD (1980) The Extrapyramidal Symptom Rating Scale. Can J Neurol Sci 7:233Google Scholar
  7. Chouinard G, Jones BD, Remington G et al. (1993) A Canadian multicenter placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients. J Clin Psychopharmacol 13:25–40Google Scholar
  8. Hoffman WF, Labs SM, Casey DE (1987) Neuroleptic-induced parkinsonism in older schizophrenics. Biol Psychiatry 22:427–439Google Scholar
  9. Janssen Research Foundation (ed) (1991) A randomized, doubleblind, multicenter trial of risperidone in the treatment of chronic schizophrenia. Clinical research report (RIS-Int-3), November 1991. Janssen, Piscataway, New Jersey/USAGoogle Scholar
  10. Kammen DP van, Hommer DW, Malas KL (1987) Effect of pimozide on positive and negative symptoms in schizophrenic patients: Are negative symptoms state dependent? Neuropsychobiology 18:113–117Google Scholar
  11. Kay SR, Opler LA, Fiszbein A (1987) Positive and Negative Syndrome Scale (PANSS). Rating Manual. Social and Behavioral Documents. San Rafael, CAGoogle Scholar
  12. Marder SR, Meibach RC (1994) Risperidone in the treatment of schizophrenia. Am J Psychiatry 13:25–40Google Scholar
  13. Meltzer HY (1985) Dopamine and negative symptoms in schizophrenia: critique of the type I–II hypothesis. In: Alpert M (ed) Controversies in schizophrenia. Guilford, New York, pp 110–136Google Scholar
  14. Miller DD, Perry PJ, Cadoret RJ, Andreasen NC (1994) Clozapine's effect on negative symptoms in treatment-refractory schizophrenics. Compr Psychiatry 35:8–15Google Scholar
  15. Möller H-J (1993) Neuroleptic treatment of negative symptoms in schizophrenic patients. Efficay problems and methodological difficulties. Eur Neuropsychopharmacol 3:1–11Google Scholar
  16. Möller H-J, van Praag HM, Aufdembrinke B et al. (1994) Negative symptoms in schizophrenia: considerations for clinical trials. Working group on negative symptoms in schizophrenia. Psychopharmacology 115:221–228Google Scholar
  17. Overall JE, Gorham DE (1961) Brief Psychiatric Rating Scale. Psychol Rep 10:799–812Google Scholar
  18. Overall J, Klett CJ (1972) Applied multivariate analysis. McGraw-Hill, New YorkGoogle Scholar
  19. Prosser ES, Csernansky JG, Kaplan H, Thiemann S, Becker T, Hollister LE (1987) Depression, parkinsonian symptoms, and negative symptoms in schizophrenics treated with neuroleptics. J Nerv Ment Dis 175:100–105Google Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Hans-Jürgen Möller
    • 1
  • Horst Müller
    • 2
  • Richard L. Borison
    • 4
  • Nina R. Schooler
    • 5
  • Guy Chouinard
    • 3
  1. 1.Department of PsychiatryLudwig Maximilian University of MunichMunichGermany
  2. 2.Department of PsychiatryUniversity of BonnBonnGermany
  3. 3.Louis-H Lafontaine HospitalUniversity of Montreal and McGill UniversityMontrealCanada
  4. 4.Department of Psychiatry and Health BehaviorMedical College of GeorgiaAugustaUSA
  5. 5.School of Medicine, Western Psychiatric Institute and ClinicUniversity of PittsburghPittsburghUSA

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