Advertisement

Psychopharmacology

, Volume 99, Supplement 1, pp S73–S76 | Cite as

Efficacy and adverse effects of clozapine in the treatment of schizophrenia and tardive dyskinesia — a retrospective study of 387 patients

  • D. Naber
  • M. Leppig
  • R. Grohmann
  • H. Hippius
Article

Abstract

Medical charts of 387 in-patients (schizophrenia n=284, tardive dyskinesia, TD, n=48), were analyzed to evaluate efficacy and adverse effects of clozapine. These patients were previously treated with between two and four other neuroleptics and were either therapy resistant or had severe side effects. Schizophrenic patients were treated with clozapine for 48±35 (TD 49±40) days, dosage was 189±119 (TD 220±176) mg. Four per cent showed worsening, 13% no change, 38% slight improvement, 42% marked improvement and 3% nearly total reduction of symptoms. In TD, 44% showed marked improvement, but only in 17% the drug was superior to previous neuroleptics. Adverse effects occurred in 56% of patients. Most frequent were sedation (17%), EEG alterations (16%), increase of liver enzymes (8%), hypotension (7%), hypersalivation (5%), fever (5%), ECG alterations (4%), tachycardia (3%), gastro-intestinal (3%) and delirious states (2%). A gradual increase in dosage seems to considerably reduce the incidence of some side effects. Clozapine treatment had to be discontinued because of severe side effects in 5.9%. In none of these patients did serious complications such as agranulocytosis occur. Only EEG alterations were significantly related to clozapine dosage (P<0.0005). At dismissal, most patients continued to receive clozapine; only in 22% (TD 20%) was it replaced by another neuroleptic. Thus, the ratio benefit/risk of clozapine treatment seems to be satisfactory in most of the negatively selected patients. Never-theless, a gradual increase in dosage and careful control of hematological and other variables is highly recommended.

Key words

Clozapine Schizophrenia Tardive dyskinesia Efficacy Adverse effects Neuroleptics 

References

  1. Ackenheil M, Hippius H (1977) Clozapine. In: Usdin E, Forrest JS (eds) Psychotherapeutic drugs, Part I+II, Psychopharmacology Series, vol II. Dekker, New York, pp 923–956Google Scholar
  2. Amsler HA, Leerenhovi L, Barth E, Harjula K, Vuopio P (1977) Agranulocytosis in patients treated with clozapine. A study of the Finnish epidemic. Acta Psychiatr Scand 56:241–248Google Scholar
  3. Angst J, Bente D, Berner P, Heiman H, Helmchen H, Hippius H (1971a) Das klinische Wirkungsbild, von Clozapin Untersuchung mit dem AMP-System). Pharmakopsychiatrie 13:201–211Google Scholar
  4. Angst J, Jaenicke U, Padrutt A, Scharfetter C (1971b) Ergebnisse eines Doppelblindversuchs von Clozapin (8-Chlor-11-(4-methyl-1-piperazinyl)-5H-dibenzo(b,e)(1,4) diazepin) im Vergleich zu Levomepromazin, Pharmakopsychiatrie 13:192–200Google Scholar
  5. Bauer D, Gartner HJ (1983) Wirkungen der Neuroleptika auf die Leberfunktion, das blutbildende System, den Blutdruck und die Temperaturregulation. Pharmakopsychiatrie 16:23–29Google Scholar
  6. Blum A, Mauruschat W (1972) Temperaturanstiege und Bluteiweißveränderungen unter der Therapie mit Neuroleptika unter besonderer Berücksichtigung des neuartigen Dibenzodiazepin-Derivates Clozapin. Pharmakopsychiatrie 5:155–169Google Scholar
  7. Caine ED, Polinsky RJ, Kartzinel R, Ebert MH (1979) The trial use of clozapine for abnormal involuntary movement disorders. Am J Psychiatry 136:317–320Google Scholar
  8. Carroll G, Curtis J, Kokmen E (1977) Paradoxical response to dopamine agonists in tardive dyskinesia. Am J Psychiatry 137:785–789Google Scholar
  9. Casey DE (1989) Clozapine: neuroleptic-induced EPS and tardive dyskinesia. Psychopharmacology [Suppl] 99:S47-S53Google Scholar
  10. Claghorn J, Honigfeld G, Abuzzahab FS, Wang R, Steinbock R, Tuason V, Klerman G (1987) The risks and benefits of clozapine versus chlorpromazine. J Clin Psychopharmacol 7:377–384Google Scholar
  11. Ekblom B, Häggström JE (1974) Clozapine (Leponex) compared with chlorpromazine: a double-blind evaluation of pharmacological and clinical properties. Curr Ther Res 16:945–957Google Scholar
  12. Fischer-Cornelssen K, Ferner U, Steiner H (1974) Multifokale Psychopharmakaprüfung (“Multihospital Trial”). Arzneimittelforschung/Drug Res 24:1706–1724Google Scholar
  13. Fink M, Irwin P, Weinhold P (1979) EEG profile studies of clozapine in volunteers and psychiatric patients. Pharmakopsychiatrie 12:184–190Google Scholar
  14. Gelenberg AJ, Doller JC (1979) Clozapine versus chlorpromazine for the treatment of schizophrenia: preliminary results from a double-blind study. J Clin Psychiatry 40:238–240Google Scholar
  15. Gerlach J, Simmelsgaard H (1978) Tardive dyskinesia during and following treatment with haloperidol+biperiden, thioridazine, and clozapine. Psychopharmacology 59:105–112Google Scholar
  16. Gerlach J, Koppelhus E, Helweg E, Monrad A (1974) Clozapine and haloperidol in a single-blind cross-over trial: therapeutic and biochemical aspects in the treatment of schizophrenia. Acta Psychiatr Scand 50:410–424Google Scholar
  17. Gerlach J, Thorsen K, Fog R (1975) Extrapyramidal reactions and amine metabolites in cerebrospinal fluid during haloperidol and clozapine treatment of schizophrenic patients. Psychopharmacologia 40:341–350Google Scholar
  18. Grohmann R, Schmidt LG, Spieß-Kiefer C, Ruether R (1989) Agranulocytosis and significant leucopenia with neuroleptic drugs: results from the AMÜP program. Psychopharmacology [Suppl] 99:S109-S112Google Scholar
  19. Gross H, Langner E, Pfolz H (1974) Clozapin in der Langzeittherapie der chronischen Schizophrenie. Arzneimittelforschung/Drug Res 24:987–989Google Scholar
  20. Guirguis E, Voineskos G, Gray J, Schlieman E (1977) Clozapine (Leponex) versus chlorpromazin (Largactil) in acute schizophrenia (a double-blind controlled study). Curr Ther Res 21:707–719Google Scholar
  21. Hippius H (1989) History of clozapine. Psychopharmacology (in press)Google Scholar
  22. Idäänpään-Heikkilä J, Alhava E, Olkinvora M, Palva I (1977) Agranulocytosis during treatment with clozapine. Eur J Clin Pharmacol 11:193–198Google Scholar
  23. Iseman H, Haupt R (1976) Auffällige EEG-Veränderungen unter Clozapin-Behandlung bei paranoid-hallozinatorischen Psychosen. Nervenarzt 47:268Google Scholar
  24. Kane J, Honigfeld G, Singer J, Meltzer H (1988) Clzapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry 45:789–796Google Scholar
  25. Kirkegaard A, Hammershoj E, Ostergard P (1982) Evaluation of side effects due to clozapine in long-term tratment of psychosis. Arzneimittelforschung/Drug Res 32:465–468Google Scholar
  26. Koukkou M, Angst J, Zimmer D (1979) Paroxysmal EEG activity and psychopathology during the treatment with clozapine. Pharmakopsychiatrie 12:173–183Google Scholar
  27. Kuha S, Miettinen E (1986) Long-term effect of clozapine in schizophrenia. A retrospective study of 108 chronic schizophrenics treated with clozapine for up to 7 years. Nord Psykiatr Tidsskr 40:225–230Google Scholar
  28. Lapierre YD, Ghadirian A, St-Laurent J, Chaudhry RP (1980) Clozapine in acute schizophrenia-efficacy and toxicity. Curr Ther Res 27:391–400Google Scholar
  29. Leppig M, Bosch B, Naber D, Hippius H (1989) Clozapine in the treatment of 121 out-patients. Psychopharmacology [Suppl] 99:S77-S79Google Scholar
  30. Lindström LH (1988) The effect of long-therm treatment with clozapine in schizophrenia: a retrospective study in 96 patients treated with clozapine for up to 13 years. Acta Psychiatr Scand 77:524–529Google Scholar
  31. Meltzer HY, Luchins DJ (1984) Effect of clozapine in severe tardive dyskinesia: a case report. J Clin Psychopharmacol 4:286–287Google Scholar
  32. Povisen UJ, Noring U, Fog R, Gerlach J (1985) Tolerability and therapeutic effect of clozapine for up to 12 years. Acta Psychiatr Scand 71:176–185Google Scholar
  33. Shopsin B, Klein H, Aaronsom M, Collora M (1979) Clozapine, chlorpromazine, and placebo in newly hospitalized, acutely schizophrenic patients. Arch Gen Psychiatry 36:657–664Google Scholar
  34. Simpson GM, Varga E (1978) Clozapine in tardive dyskinesia. Psychopharmacology 56:75–80Google Scholar
  35. Small JG, Milstein V, Marhenke JD, Hall DD, Kellams JJ (1987) Treatment outcome with clozapine in tardive dyskinesia, neuroleptic sensitivity, and treatment-resistant psychosis. J Clin Psychiatry 48:263–267Google Scholar
  36. Spatz R, Lorenzi E, Kugler J, Rüther E (1978) Häufigkeit und Form von EEG-Anomalien bei Clozapintherapie. Arzneimittelforschung 28:1499–1500Google Scholar
  37. Stille G, Hippius H (1971) Kritische Stellungnahme zum Begriff der Neuroleptika. Pharmacopsychiatry 4:182–191Google Scholar

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • D. Naber
    • 1
  • M. Leppig
    • 1
  • R. Grohmann
    • 1
  • H. Hippius
    • 1
  1. 1.Psychiatric Hospital of the University of MunichMunich 2Federal Republic of Germany

Personalised recommendations