, Volume 99, Supplement 1, pp S80–S83 | Cite as

Clinical experience with clozapine in Germany

  • H. Helmchen


The so-far successful development of the atypical neuroleptic clozapine had been interrupted by the Finnish epidemic of agranulocytosis in 1975. However, though the strong regulatory control of prescribing clozapine, since then its clinical use has increased steadily, particularly recently. This may be due mainly to the considerable number of patients whose psychotic states or at least whose negative symptoms do not respond to other neuroleptics, or who have problems with extrapyramidal side effects. Due to its significant antipsychotic, and to its probable even if mild antidepressive efficacy as well as to its possible efficacy against some negative symptoms of schizophrenia, clozapine is currently a real and indispensable alternative to other existing neuroleptics. Further research should be directed both to the clinical validation of the latter mentioned therapeutically desired effects and to the causes and predictability of agranulocytosis, as yet the main risk of clozapine therapy. Theoretically profitable would be the clarification of the causes of hyperthermia and particularly of those of the mutual independency of extrapyramidal motor disturbances and antipsychotic efficacy.

Key words

Clozapine Clinical experience Therapeutical efficacy Adverse drug reactions 


  1. 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
  2. Anden NE, Stock G (1973) Effect of clozapine on the turnover of dopamine in the corpus striatum and in the limbic system. J Pharm Pharmacol 25:346–348Google Scholar
  3. Angst J, Bente D, Heimann H, Helmchen H, Hippius H (1971a) Das klinische Wirkungsbild von Clozapin (Untersuchung mit dem AMP-System). Pharmacopsychiatry 4:201–211Google Scholar
  4. Angst J, Jaenicke U, Padrutt A, Scharfetter C (1971b) Ergebnisse eines Doppelblindversuchs von Clozapin (8-Chlor-II-(4-methyl-1-piperazinyl)-5H-dibenzo-(b,e) (1,4) diazepin) im Vergleich zu Levomepromazin. Pharmacopsychiatry 4:192–200Google Scholar
  5. Aschauer HN, Schönbeck G, Langer G, Koinig G, Resch F, Hatzinger R, Chaudry HR, Sieghart W (1988) Plasma concentrations of haloperidol and prolactin and clinical outcome in acutely psychotic patients. Pharmacopsychiatry 21:246–251Google Scholar
  6. Bauer D, Gärtner HJ (1983) Wirkungen der Neuroleptica auf die Leberfunktion, das blutbildende System, den Blutdruck und die Temperaturregulation. Ein Vergleich zwischen Clozapin, Perazin und Haloperidol anhand von Krankenblattauswertungen. Pharmacopsychiatry 16:23–29Google Scholar
  7. Berner P, Saletu B (1975) Clozapin. Second Symposium, Wien, June 7Google Scholar
  8. Berzewski H, Helmchen H, Hippius, H, Hoffmann H, Kanowski S (1969) Das klinische Wirkungsspektrum eines neuen Dibenzodiazepin-Derivates (W 108/HF 1854: 8-Chlor-11-(4-methyl)-piperazino-5-dibenzo-(b,e) (1,4) diazepin). Arzneimittelforschung 19:495–496Google Scholar
  9. Blum A, Mauruschat W (1972) Temperaturanstiege und Bluteiweißveränderungen unter der Therapie mit Neuroleptikaunter besonderer Berücksichtigung des neuartigen Dibenzodiazepin-Derivates Clozapin. Pharmacopsychiatry 5:155–169Google Scholar
  10. Delini-Stula A (1986) Neuromatomical, neuropharmacological and neurobiochemical target systems for antipsychotic activity of neuroleptics. Pharmacopsychiatry 19:134–139Google Scholar
  11. Fink M, Irwin P, Weinhold P (1979) EEG profile studies of clozapine in volunteers and psychotic patients. Pharmacopsychiatry 12:184–190Google Scholar
  12. Gebhardt R (1972) Veränderungen der subjecktiven Befindlichkeit psychotischer Patienten unter neuroleptischer Therapie. Pharmacopsychiatry 5:295–300Google Scholar
  13. Giovannetti A, Trombetta N (1974) Pretreatment of problem youths with clozapin in preparation for group psychotherapy. Pharmacopsychiatry 7:230–236Google Scholar
  14. Goncalves N, Grüneberg F (1977) Laborklinische Untersuchungen unter besonderer Berücksichtigung des Leberstoffwechsels bei Schizophrenen unter ambulanter neuroleptischer Langzeitmedikation. Pharmacopsychiatry 10:36–40Google Scholar
  15. Gross H, Hackl H, Kaltenbaeck E (1970) Results of double-blind study of clozapine and thioridazine. Seventh CINP Congress, Prag, August 11–15Google Scholar
  16. Gross H, Langner E (1966) Das Wirkungsprofil eines chemisch neuartigen Breitbandneuroleptikums der Dibenzodiazepingruppe. Wien Med Wochenschr 116:814–816Google Scholar
  17. Helmchen H, Hippius H, Matussek, N, Müller-Oerlinghausen B (1975) Über Blutzellschädigungen durch trizyklische Psychopharmaka. Dtsch Ärztebl 43:2961–2964Google Scholar
  18. Idänpään-Heikkilä J, Alhava E, Olkinuora M, Palva IP (1977) Agranulocytosis during treatment with clozapine. Eur J Clin Pharmacol 11:194–198Google Scholar
  19. Isermann H, Haupt R (1976) Auffällige EEG-Veränderungen unter Clozapine-Behandlung bei paranoid-halluzinatorischen Psychosen. Nervenarzt 47:268–271Google Scholar
  20. Jungi W, Fischer J, Seen HJ, Hartlapp J, Pöldinger W, Kunz H, Krupp P (1977) Gehäufte durch Clozapin (Leponex) induzierte Agranulocytosen in der Ostschweiz? Schweiz Med Wochenschr 107:1861–1864Google Scholar
  21. Klik J, Krausova J, Krizova A, Maresova H, Vencovsky E (1976) Experience with clozapine in psyychiatric home practice. Cesk Psychiatr 72:197–201Google Scholar
  22. Kogan W, Nikolaenko N (1974) New drug in the treatment of nervous and mental diseases. Rept Leningrad Bechterev Psychoneurol Res Inst, pp 40–41Google Scholar
  23. Koukkou M, Angst J, Zimmer D (1979) Paroxysmal EEG activity and psychopathology during the treatment with clozapine. Pharmacopsychiatry 12:173–183Google Scholar
  24. Kugler J, Lorenzi E, Spatz R, Zimmermann H (1979) Drug-induced paroxysmal EEG-activities. Pharmacopsychiatry 12:165–172Google Scholar
  25. Nahunek K, Svestka J, Misurec J, Rodova A (1975) Experiences with clozapine. Cesk Psychiatr 71:11–15Google Scholar
  26. Pietzcker A, Stahl HP (1988) Rezidivprophylaxe Behandlungsstrategie und Katamnestische Erhebungen bei Perazin-Langzeitpatienten. In: Helmchen H, Hippius H, Tölle R (eds) Therapie mit Neuroleptika-Perazin. Thieme, Stuttgart, pp 149–158Google Scholar
  27. Roubicek J, Major J (1977) EEG profile and behavioral changes after a single dose of clozapine in normals and schizophrenics. Biol Psychiatry 12:613–633Google Scholar
  28. Saletu B, Grünberger J, Linzmayer L, Anderer P (1987) Comparative placebo-controlled pharmacodynamic studies with zotepine and clozapine utilizing pharmaco-EEG and psychometry. Pharmacopsychiatry 20:12–27Google Scholar
  29. Schäfer M-L (1977) Veränderungen des weißen Blutbildes unter dem Einfluß von Psychopharmaka unter besonderer Berücksichtigung der Agranulocytose. Dissertation. Freie Universität BerlinGoogle Scholar
  30. Schmidt LG, Siemetzki H (1988) Differentielle Wirkprofile der neuroleptischen Therapie akut Schizophrener. Ergebnisse einer Klinisch-naturalistischen Studie. Nervenarzt 59:721–726Google Scholar
  31. Spatz E, Rüther E, Lorenzi E, Kugler J (1977) Zur Frage der Häufung abnormer EEG-Befunde unter Clozapin-Therapie. AGNP Symposium, NürnbergGoogle Scholar
  32. Stahl HP, Pietzcker A (1988) Nebenwirkungen einer langfristigen Perazin- und Clozapin-Therapie. In: Helmchen H, Hippius H, Tölle R (eds) Therapie mit Neuroleptika — Perazin. Thieme, Stuttgart, pp 91–93Google Scholar
  33. Stille G, Hippius H (1971) Kritische Stellungnahme zum Begriff der Neuroleptika (anhand von pharmakologischen und klinischen Befunden mit Clozapin). Pharmacopsychiatry 4:182–191Google Scholar
  34. Sulser F, Robinson SE (1978) Clinical implications of pharmacological differences among antipsychotic drugs (with particular emphasis on biochemical central synaptic adrenergic mechanisms). In: Lipton MA, Dimascio A, Killam KF (eds) Psychopharmacology: a generation of progress Raven, New York, pp 943–954Google Scholar
  35. Vyncke J (1974) The treatment of behavior disorders in idiocy and imbecility with clozapine. Pharmacopsychiatry 7:225–229Google Scholar

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • H. Helmchen
    • 1
  1. 1.Psychiatrische Klinik und Poliklinik der Freien Universität BerlinBerlin 19

Personalised recommendations