Archiv für Psychiatrie und Nervenkrankheiten

, Volume 229, Issue 4, pp 315–329 | Cite as

Outcome and risks of ultra-long-term treatment with an oral neuroleptic drug

Relationship between perazine serum levels and clinical variables in schizophrenic outpatients
  • A. Pietzcker
  • A. Poppenberg
  • J. Schley
  • B. Müller-Oerlinghausen
Article

Summary

In 33 schizophrenic patients treated continuously as outpatients with perazine over two decades, the rehospitalization rate decreased from 0.58 before treatment to 0.07 during treatment. The intensity of psychopathologic symptoms and the side effects were found to be remarkably low. The high intraindividual constancy of perazine plasma levels and the tight correlation between dose and plasma levels indicated satisfactory patient compliance. Plasma levels amounted to only 25% of those under acute treatment and correlated positively with the severity of the disease. Higher plasma levels coincided with more frequent side effects such as slightly pathologic liver function and moderate impairment of oral glucose tolerance. The results suggest that low-dose maintenance treatment of schizophrenic patients with oral neuroleptics is effective and relatively safe.

Key words

Long-term treatment Schizophrenic outpatients Perazine plasma level Outcome AMP system 

Zusammenfassung

Bei 33 schizophrenen Patienten, die seit durchschnittlich 18 Jahren kontinuierlich ambulant mit Perazin behandelt wurden, sank die Rehospitalisierungsrate pro Jahr von 0,58 vor auf 0,07 während der Behandlung. Die Intensität der psychopathologischen Symptomatik sowie der Nebenwirkungen waren bemerkenswert gering. Die hohe intraindividuelle Konstanz der Perazin-Plasmaspiegels und die enge Korrelation zwischen Dosis und Plasmaspiegel sprach für eine befriedigende Compliance (Behandlungstreue) der Patienten. Die Höhe der Plasmaspiegel betrug nur etwa ein Viertel der Spiegel, die während einer Akutbehandlung gemessen werden, und sie korrelierte positiv mit der Schwere der Erkrankung. Je höher die Plasmaspiegel waren, desto häufiger waren Nebenwirkungen wie geringfügig pathologische Leberfunktion und eine mäßige Verschlechterung der oralen Glucosetoleranz.

Die Ergebnisse legen den Schluß nahe, daß eine niedrig dosierte Langzeitbehandlung schizophrener Patienten mit oralen Neuroleptika effektiv und relativ sicher ist.

Schlüsselwörter

Ambulante Langzeitbehandlung Schizophrene Patienten Perazin-Plasmaspiegel Erfolgsstudie AMP-System 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Affleck JW, Burns J, Forrest AD (1976) Long-term follow-up of schizophrenic patients in Edinburgh. Acta Psychiat Scand 53:227–237PubMedGoogle Scholar
  2. Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie (1979) Das AMDP- System; Manual zur Dokumentation psychiatrischer Befunde, 3. Auflage. Springer, Heidelberg Berlin New YorkGoogle Scholar
  3. Axelsson R (1975) On the pharmacokinetics of thioridazine in psychiatric patients. In: Sedvall G et al. (eds) Antipsychotic drugs: Pharmacodynamics and pharmaco kinetics. Pergamon Press, Oxford, pp 353–358Google Scholar
  4. Baumann U, Angst J (1975) Methodological development of the AMP-system. Neuropsychopharmacology Proc. IX. Cong CINP Paris 1974. Excerpta Medica, Amsterdam; American Elsevier Publishing Co, New YorkGoogle Scholar
  5. Beard JH, Malamud TJ, Rossmann E (1978) Psychiatric rehabilitation and long-term rehospitalization rates: The findings of two research studies. Schizophr Bull 4:622–635PubMedGoogle Scholar
  6. Bland RC, Parker JH, Orn H (1976) Prognosis in schizophrenia. A ten-year follow-up of first admissions. Arch Gen Psychiatry 33:949–954PubMedGoogle Scholar
  7. Bland RC, Parker JH, Orn H (1978) Prognosis in schizophrenia. Prognostic predictors and outcome. Arch Gen Psychiatry 35:72–77PubMedGoogle Scholar
  8. Bleuler M (1972) Die schizophrenen Geistesstörungen im Lichte langjähriger Kranken- und Familiengeschichten. Thieme, StuttgartGoogle Scholar
  9. Bosch G, Pietzcker A (1975) Nachbehandlung krankenhausentlassener schizophrener Patienten — Ergebnisse einer empirischen Untersuchung. Anhang zum Bericht der Lage der Psychiatrie in der Bundesrepublik Deutschland, S 344–360Google Scholar
  10. Breyer U, Müller-Oerlinghausen B, Mauruschat W (1977) Phenothiazines with piperazine side chain. In: Forrest IS, Usdin E (eds) Psychotherapeutic drugs. Marcel Dekker, New YorkGoogle Scholar
  11. Davis JM (1975) Overview: Maintenance therapy in psychiatry: I. Schizophrenia. Am J Psychiatry 132:1237–1245PubMedGoogle Scholar
  12. Degkwitz R, Consbruch U, Haddenbrock S, Neusch B, Oehlert W, Unsöld R (1976) Therapeutische Risiken bei der Langzeitbehandlung mit Neuroleptika und Lithium. Nervenarzt 47:81–87PubMedGoogle Scholar
  13. Dimroth G, Gebhardt R, Langer C, Müller-Oerlinghausen B, Renfordt E, Schley J (1980) The influence of anticholinergic medication on the state of well-being, psychomotoric performance, EPMS, and psychopathology of acute psychotic patients under neuroleptic treatment. Arzneim Forsch (Drug Res) 30:1202–1203Google Scholar
  14. EDESG (1970) Report of the European Diabetes Epidemiology Study Group. Diabetologia 6:646–647Google Scholar
  15. Giel R, Duk S, van Weerden-Dukstra JR (1978) Mortality in the long-stay population of all Dutch mental hospitals. Acta Psychiat Scand 57:361–368PubMedGoogle Scholar
  16. Gonçalves N (1978) „Schwund“ bei ambulant behandelten Schizophrenen. Nervenarzt 49:58–64PubMedGoogle Scholar
  17. Goncalves N, Grüneberg F (1975) Einseitige orale Glukosebelastung bei langfristig neuroleptisch behandelten Schizophrenen. Pharmakopsychiatrie 8:289–295Google Scholar
  18. Hansen LB, Larsen NE (1977) Plasma concentrations of perphenazine and its sulphoxide metabolite during continuous oral treatment. Psychopharmacology 53:127–130PubMedGoogle Scholar
  19. Helmchen H (1978) Forschungsaufgaben bei psychiatrischer Langzeitmedikation. Nervenarzt 49:534–538PubMedGoogle Scholar
  20. Helmchen H, Hippius H, Tiling P (1967) Die Zusammenarbeit von Klinik und Praxis bei der langfristigen medikamentösen Behandlung von Psychose-Kranken. Internist 9:328–331Google Scholar
  21. Hippius H, Selbach H (1961) Zur medikamentösen Dauertherapie bei Psychosen. Neuropsychopharmakologie, 2. Symposium, Nürnberg 1961. Med Exp 5:298–305PubMedGoogle Scholar
  22. Hippius H, Tiling P (1967) Möglichkeiten einer Zusammenarbeit von Klinik und Praxis bei medikamentöser Dauertherapie klinikentlassener psychotischer Kranken. In: Heinrich K (ed) Der entlassene Anstaltspatient in der psychiatrischen Rehabilitation. Alma-Mater, KonstanzGoogle Scholar
  23. Hogarty GE, Goldberg SC, Schooler NR, Ulrich RF (1974) Drug and sociotherapy in the aftercare of schizophrenic patients: Two-year relapse rates. Arch Gen Psychiatry 31:603–608PubMedGoogle Scholar
  24. Hogarty GE, Ulrich RF, Mussare F, Arishgueta N (1976) Drug discontinuation among long term, successfully maintained schizophrenic outpatient. Dis Nerv Syst 37:494–500PubMedGoogle Scholar
  25. Köbberling J, Creutzfeldt W (1970) Comparison of different methods for the evaluation of the oral glucose tolerance test. Diabetes 19:870–877PubMedGoogle Scholar
  26. Levine J, Schooler NR, Cassano GB (1979) The role of depot neuroleptics in the treatment of schizophrenic patients. Psychol Med 9:383–386PubMedGoogle Scholar
  27. Linden M (in press) Definition of compliance. Int J Clin Pharmacol BiopharmGoogle Scholar
  28. Lonowski DJ, Sterling FE, Kennedy JC (1978) Gradual reduction of neuroleptic drugs among chronic schizophrenics. A double-blind controlled study. Acta Psychiat Scand 57:97–102PubMedGoogle Scholar
  29. March JE, Donato D, Turano P, Turner WJ (1972) Interpatient variation and significance of plasma levels of chlorpromazine in psychotic patients. J Med 3:146–162PubMedGoogle Scholar
  30. Müller P, Kind J, Lohrengel S, Steuber H, Hartmann W, Jung F, Pudel V (1977) Die neuroleptische Rezidivprophylaxe schizophrener Psychosen. Vorläufige Mitteilung. Nervenarzt 48:560–561Google Scholar
  31. Müller-Oerlinghausen B (1980a) Antipsychotics. (Clinical pharmacology—pharmacokinetics) In: Hoffmeister F, Stille G (eds) Handbook of experimental pharmacology. Vol: Psychotropic agents; Part: Antipsychotics and antidepressants. Springer, Berlin Heidelberg New York, pp 267–285Google Scholar
  32. Müller-Oerlinghausen B (1980b) Schäden nach langfristiger Behandlung mit Psychopharmaka. AMI-Bericht I/1980, BerlinGoogle Scholar
  33. Müller-Oerlinghausen B, Passoth PM, Poser W, Pudel V (1979) Impaired glucose tolerance in long-term lithium-treated patients. Int Pharmacopsychiatry 14:350–362PubMedGoogle Scholar
  34. Müller-Oerlinghausen B, Passoth PM, Poser W, Schlecht W (1978 Zum Einfluß langfristiger Behandlung mit Neuroleptika oder Lithiumsalzen auf den Kohlenhydratstoffwechsel. Arzneim Forsch (Drug Res) 28:1522–1524Google Scholar
  35. Müller-Oerlinghausen B, Riedel R, Schley J (1977) TLC and GLC procedures for the determination of perazine and its metabolites in human body fluids. Int J Clin Pharmacol 15: 366–372Google Scholar
  36. Muusze RG, Vanderheeren FA (1977) Plasma levels and half lives of thioridazine and some of its metabolites. II. Low doses in older psychiatric patients. Eur J Clin Pharmacol 11:141–147PubMedGoogle Scholar
  37. Pietzcker A, Gebhardt R, Freudenthal K (1977) Ein vergleich nosologisch-diagnostischer mit cluster-analytisch gefundenen Gruppen anhand AMP-dokumentierter psychopathologischer Befunde. Nervenarzt 48:276–282PubMedGoogle Scholar
  38. Pietzcker A (1978) Langzeitmedikation bei schizophrenen Kranken. Nervenarzt 49:518–533PubMedGoogle Scholar
  39. Rifkin A, Quitkin F, Rabiner CJ, Klein DF (1977) Fluphenazine decanoate, fluphenazine hydrochloride given orally and placebo in remitted schizophrenics. I. Relapse rates after one year. Arch Gen Psychiatry 34:43–47PubMedGoogle Scholar
  40. Scharfetter Ch (1971) Das AMP-System. Manual zur Dokumentation psychiatrischer Befunde. Springer, Berlin Heidelberg New YorkGoogle Scholar
  41. Schley J, Riedel F, Müller-Oerlinghausen B (1978) Determination of perazine (Taxilan®) serum levels by GLC under clinical routine conditions. J Chem Clin Biochem 16:307–311Google Scholar
  42. Schwalb H, Hanika R, Meier G, Gruber E, Reinhold H (1974) Kardiologische Risikofaktoren bei Patienten eines Psychiatrischen Krankenhauses. Nervenarzt 45:544–547PubMedGoogle Scholar
  43. Serban G, Thomas A (1974) Attitudes and behaviors of acute and chronic schizophrenic patients regarding ambulatory treatment. Am J Psychiatry 131:991–995PubMedGoogle Scholar
  44. Stephens JH, Astrup Ch (1963) Prognosis in “Process” and “Non-Process” schizophrenia. Am J Psychiatry 119:945–953Google Scholar
  45. Stephens JH (1978) Long-term prognosis and follow-up in schizophrenia. Schizophr Bull 4: 25–47PubMedGoogle Scholar
  46. Strauss JS, Carpenter WT Jr (1974) The prediction of outcome in schizophrenia. II. Relationship between predictor and outcome variables: A report from the WHO international pilot study of schizophrenia. Arch Gen Psychiatry 31:37–42PubMedGoogle Scholar
  47. Strauss JS, Carpenter WT (1977) Prediction of outcome in schizophrenia. III. Five-year out-come and its predictors. Arch Gen Psychiatry 34:159–163PubMedGoogle Scholar
  48. Studer E, Cikes M, Widmer LK (1969) Blutzucker und Alter. Beobachtungen an 1060 Männern in der Basler Studie II. Dtsch Med Wochenschr 94:1179–1182PubMedGoogle Scholar
  49. Wiles DH, Kolakowska T, McNeilly AS, Mandelbrote BM, Gelder MG (1976) Clinical significance of plasma chlorpromazine levels. I. Plasma levels of the drug, some of its metabolites and prolactin during acute treatment. Psychol Med 6:407–415PubMedGoogle Scholar
  50. Woggon B, Angst J, Margoses N (1975) Gegenwärtiger Stand der neuroleptischen Langzeit-behandlung der Schizophrenie. Nervenarzt 46:611–616PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • A. Pietzcker
    • 1
  • A. Poppenberg
    • 1
  • J. Schley
    • 1
  • B. Müller-Oerlinghausen
    • 1
  1. 1.Department of PsychiatryFree University of BerlinBerlin 19

Personalised recommendations