Lithium vs carbamazepine in the maintenance treatment of schizoaffective disorder: a randomised study

  • W. Greil
  • W. Ludwig-Mayerhofer
  • N. Erazo
  • R. R. Engel
  • A. Czernik
  • H. Giedke
  • B. Müller-Oerlinghausen
  • M. Osterheider
  • G. A. E. Rudolf
  • H. Sauer
  • J. Tegeler
  • T. Wetterling
Original Paper

Abstract

In a randomised multicentre study, the prophylactic efficacy of lithium and carbamazepine was compared in schizoaffective disorder. A total of 90 ICD-9 schizoaffective patients were included in the maintenance phase (2.5 years). They were also diagnosed according to RDC and DSM-III-R and classified into subgroups. Mean serum levels were 0.58±0.12 mmol/l for lithium and 6.4±1.5 μg/ml for carbamazepine (mean dose 643±179 mg/d). Outcome criteria were hospitalisation, recurrence, concomitant psychotropic medication and adverse effects leading to discontinuation. There were more non-completers under carbamazepine than under lithium (p=0.02). Survival analyses demonstrated no significant differences between lithium and carbamazepine in treatment outcome. Patient’s ratings of side effects (p=0.003) and treatment satisfaction (p=0.02) favoured carbamazepine. Following the RDC criteria, patients of the schizodepressive and non-classifiable type did better under carbamazepine (p=0.055 for recurrence), whereas in the schizomanic patients equipotency of both drugs was found. Applying DSM-III-R, carbamazepine demonstrated a superiority in the patient group with more schizophrenia-like or depressive disorders (p=0.040 for recurrence), but not in patients fulfilling the DSM-III-R criteria of bipolar disorder. Lithium and carbamazepine seem to be equipotent alternatives in the maintenance treatment of broadly defined schizoaffective disorders. However, in subgroups with depressive or schizophrenia-like features and regarding its long-term tolerability carbamazepine seems to be superior.

Key words

Schizoaffective disorder Randomised controlled trial Lithium Carbamazepine Treatment outcome 

References

  1. Aitken, RCB (1969) Measurement of feelings using visual analogue scales. Proc R Soc Med 62: 989–993PubMedGoogle Scholar
  2. American Psychiatric Association (1987) Diagnostic and statistical manual of mental disorders (DSM-III-R), 3-rd edn, revised. American Psychiatric, Washington, DCGoogle Scholar
  3. Angst J, Dittrich A, Grof P (1969) The course of endogenous affective psychoses and its modification by prophylactic administration of imipramine and lithium. Int Pharmacopsychiatry 2: 1–11Google Scholar
  4. Angst J (1981) Ungelöste Probleme bei der Indikationsstellung zur Lithiumprophylaxe affektiver und schizoaffektiver Erkrankungen. Bibl Psychiatr 161: 34–44Google Scholar
  5. Bellaire W, Demisch K, Stoll KD (1990) Carbamazepine versus Lithium. Münch Med Wochenschr 132 [Suppl]: 82–86Google Scholar
  6. Brockington IF, Leff JP (1979) Schizo-affective psychosis: definitions and incidence. Psychol Med 9: 91–99PubMedGoogle Scholar
  7. Brockington IF, Wainwright S, Kendell RE (1980a) Manic patients with schizophrenic or paranoid symptoms. Psychol Med 10: 73–83PubMedGoogle Scholar
  8. Brockington IF, Wainwright S, Kendell RE (1980b) Depressed patients with schizophrenic or paranoid symptoms. Psychol Med 10: 665–675PubMedGoogle Scholar
  9. Coppen A, Montgomery SA, Gupta RK, Bailey JE (1976) A double-blind comparison of lithium carbonate and maprotiline in the prophylaxis of the affective disorders. Br J Psychiatry 128: 479–485PubMedGoogle Scholar
  10. Endicott J, Spitzer RL, Fleiss JL, Cohen J (1976) The global assessment scale. A procedure for measuring overall severity of psychiatric disturbance. Arch Gen Psychiatry 33: 766–771PubMedGoogle Scholar
  11. Greil W, Haag M, Huber D, Schmidt St (1986) Maintenance treatment in affective disorders: overview and design of a collaborative study. Pharmacopsychiatry 19: 167–169Google Scholar
  12. Greil W, Ludwig-Mayerhofer W, Steller B, Czernik A, Giedke H, Müller-Oerlinghausen B, Osterheider M, Rudolf GAE, Sauer H, Tegeler J, Wetterling T (1993) The recruitment process for a multicenter study on the long-term prophylactic treatment of affective disorders. J Affect Disord 28: 257–265PubMedCrossRefGoogle Scholar
  13. Greil W, Ludwig-Mayerhofer W, Erazo N, Engel RR, Czernik A, Giedke H, Müller-Oerlinghausen B, Osterheider M, Rudolf GAE, Sauer H, Tegeler J, Wetterling T (1996) Comparative efficacy of lithium and amitriptyline in the maintenance treatment of recurrent unipolar depression: a randomised study. J Affect Disord 40: 179–190PubMedCrossRefGoogle Scholar
  14. Greil W, Ludwig-Mayerhofer W, Erazo N, Schmidt S, Engel RR. Czernik A, Giedke H, Müller-Oerlinghausen B, Osterheider M, Rudolf GAE, Sauer H, Tegeler J, Wetterling T (1997) Lithium versus carbamazepine in maintenance treatment of bipolar disorders: a randomised study. J Affect Disord (in press)Google Scholar
  15. Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Statistical Assoc 53: 457–481CrossRefGoogle Scholar
  16. Keck PEJ, McElroy SL, Strakowski SM, West SA (1994) Pharmacologic treatment of schizoaffective disorder. Psychopharmacology 114: 529–538PubMedCrossRefGoogle Scholar
  17. Kupfer DJ (1991) Long-term treatment of depression. J Clin Psychiatry 52 (Suppl 5): 28–34PubMedGoogle Scholar
  18. Lenz G, Wolf R (1986) Prophylaxe der schizoaffektiven Psychosen. In: Müller-Oerlinghausen B, Greil W (eds) Die Lithiumprophylaxe: Nutzen, Risiken, Alternativen. Springer, Berlin Heidelberg New York, pp 164–172Google Scholar
  19. Maj M (1984a) Effectiveness of lithium prophylaxis in schizoaffective psychoses: application of a polydiagnostic approach. Acta Psychiatr Scand 70: 228–234PubMedCrossRefGoogle Scholar
  20. Maj M (1984b) Evolution of the American concept of schizoaffective psychosis. Neuropsychobiology 11: 7–13PubMedCrossRefGoogle Scholar
  21. Maj M (1988) Luthium prophylaxis of schizoaffective disorders: a prospective study. J Affect Disord 14: 129–135PubMedCrossRefGoogle Scholar
  22. Mattes JA, Nayak D (1984) Lithium versus fluphenazine for prophylaxis in mainly schizophrenic schizo-affectives. Biol Psychiatry 19: 445–449PubMedGoogle Scholar
  23. Müller-Oerlinghausen B, Thies K, Volk J (1990) Lithium in treatment and prophylaxis of affective and schizoaffective disorders. In: Marneros A, Tsuang MT (eds) Affective and schizo-affective disorders. Springer, Berlin Heidelberg New York, pp 221–261Google Scholar
  24. Nordic Council on Medicines (1985) Nordic drug index with classification and defined daily doses. Nordic Statistics on Medicines 1981–1983. NLN Publication no. 15, Uppsala, SwedenGoogle Scholar
  25. Placidi GF, Lenzi A, Lazzerini F, Cassano GB, Akiskal HS (1986) The comparative efficacy and safety of carbamazepine versus lithium: a randomized, double-blind 3-year trial in 83 patients. J Clin Psychiatry 47: 490–494PubMedGoogle Scholar
  26. Prien RF (1980) Predicting lithium responders and non-responders: psychological indicators. In: Johnson FN (ed) Handbook of lithium therapy. MFP Press, Lancaster, pp 133–136Google Scholar
  27. Prien RF (1989) Lithium in the treatment of schizophrenia and schizoaffective disorders. Arch Gen Psychiatry 36: 852–853Google Scholar
  28. Prien RF, Caffey EM Jr, Klett CJ (1974) Factors associated with treatment success in lithium carbonate prophylaxis. Report of the Veterans Administration and National Institute of Mental Health Collaborative Study Group. Arch Gen Psychiatry 31: 189–192PubMedGoogle Scholar
  29. Spitzer RL, Endicott J, Robins E (1982) Forschungsdiagnosekriterien (RDC) Belz, Weinheim. [Originally Spitzer RL, Endicott J. Robins E (1978). Research Diagnostic Criteria (RDC). Biometrics Research Department, New York State Psychiatric Institute. New York]Google Scholar
  30. Tarone RE, Ware J (1977) On distribution-free tests for equality of survival distributions. Biometrica 64: 156–160CrossRefGoogle Scholar
  31. Thies-Flechtner K, Müller-Oerlinghausen B, Seibert W, Walther A, Greil W (1996) Effect of prophylactic treatment on suicide risk in patients with major affective disorders. Pharmacopsychiatry 29: 103–107PubMedCrossRefGoogle Scholar
  32. Wittchen HU, Zaudig M, Klug J, Horn R (1987) Structuriertes Klinisches Interview für DSM-III-R (SKID) Beltz, Weinheim. [Originally Spitzer RL, Williams JBW, Gibbon M (1984) Structured Clinical Interview for DSM-III-R (SCID) Biometrics Research Department, New York State Psychiatric Institute, New YorkGoogle Scholar
  33. World Health Organisation (1978) Glossary and Guide to the Classification of Mental Disorders in Accordance with the Ninth Revision of the International Classification of Diseases. WHO, GenevaGoogle Scholar

Copyright information

© Springer-Verlag 1997

Authors and Affiliations

  • W. Greil
    • 1
  • W. Ludwig-Mayerhofer
    • 1
  • N. Erazo
    • 1
  • R. R. Engel
    • 1
  • A. Czernik
    • 2
  • H. Giedke
    • 3
  • B. Müller-Oerlinghausen
    • 4
  • M. Osterheider
    • 5
  • G. A. E. Rudolf
    • 6
  • H. Sauer
    • 7
  • J. Tegeler
    • 8
  • T. Wetterling
    • 9
  1. 1.Psychiatric Hospital of the University of MunichMunichGermany
  2. 2.Psychiatric Hospital of the RWTHAachenGermany
  3. 3.Department of PsychiatryUniversity of TübingenTübingenGermany
  4. 4.Department of PsychiatryFreie Universität BerlinBerlinGermany
  5. 5.Psychiatric Hospital of the University of WürzburgWürzburgGermany
  6. 6.Psychiatric Hospital of the University of MünsterMünsterGermany
  7. 7.Psychiatric Hospital of the University of HeidelbergHeidelbergGermany
  8. 8.Psychiatric Hospital of the University of DüsseldorfDüsseldorfGermany
  9. 9.Psychiatric Hospital of the Medical University of LübeckLübeckGermany

Personalised recommendations