, Volume 114, Issue 4, pp 529–538 | Cite as

Pharmacologic treatment of schizoaffective disorder

  • Paul E. KeckJr.
  • Susan L. McElroy
  • Stephen M. Strakowski
  • Scott A. West


In contrast to the considerable systematic study of the pharmacologic treatment of schizophrenia and mood disorders, the pharmacologic treatment of schizoaffective disorder has been relatively ignored. The authors reviewed the available literature regarding the pharmacologic treatment of schizoaffective disorder. The total number of controlled studies of the acute and prophylactic treatment of schizoaffective disorder was small and few used modern criteria to define the disorder. In studies of schizoaffective disorder, bipolar type (manic), lithium and antipsychotics produced comparable albeit incomplete responses, except in highly agitated patients when antipsychotics exerted superior efficacy. The combination of lithium and antipsychotics appeared to be superior to antipsychotics alone for schizoaffective, bipolar type patients. In the only controlled study of schizoaffective disorder, depressed type, the presumed superiority of combined antidepressant and antipsychotic treatment to antipsychotic alone was not found. Although combined antipsychotic and thymoleptic treatment represents common prophylactic management of schizoaffective disorder in clinical practice, the efficacy of this strategy has not been studied in controlled trials. Advances in the nosology of schizoaffective disorder, emerging epidemiologic data demonstrating large numbers of patients with this disorder in clinical populations, and preliminary evidence that clozapine may have combined antipsychotic and thymoleptic properties as well as efficacy in both the psychotic and affective components of schizoaffective disorder, suggest that renewed interest in the diagnosis and treatment of this disorder may lead to improved delivery of care for this understudied but seriously ill group of patients.

Key words

Schizoaffective disorder Mood Antipsychotics Lithium 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abrams R, Taylor MA (1976) Mania and schizoaffective disorder, manic type: a comparison. Am J Psychiatry 133:1445–1447Google Scholar
  2. Abrams R, Taylor MA (1981) Importance of schizophrenic symptoms in the diagnosis of mania. Am J Psychiatry 138:658–661Google Scholar
  3. Alexander PE, Van Kammen DP, Bunney WE (1979) Antipsychotic effects of lithium in schizophrenia. Am J Psychiatry 136:282–287Google Scholar
  4. American Psychiatric Association (1952) Diagnostic and statistical manual of mental disorders. American Psychiatric Association, Washington DCGoogle Scholar
  5. American Psychiatric Association (1968) Diagnostic and statistical manual of mental disorders, 2nd edn. American Psychiatric Association, Washington DCGoogle Scholar
  6. American Psychiatric Association (1987) Diagnostic and statistical manual of mental disorders, 3rd edn, Revised. American Psychiatric Press, Washington DCGoogle Scholar
  7. Angst J, Dittrich A, Grof P (1969) The course of endogenous affective psychosis and its modification by prophylactic treatment. Int Pharmacopsychiatry 2:1–11Google Scholar
  8. Angst J, Weis P, Grof P Baastrup PC, Shou M (1970) Lithium prophylaxis in recurrent affective disorders. Br J Psychiatry 125:604–614Google Scholar
  9. Aprison MH, Takahashi R, Tachiki K (1978) Hypersensitive serotonergic receptors involved in clinical depression — a theory. In: Haber B, Aprison MH (eds) Neuropharmacology and behavior. Plenum, New York, pp 23–48Google Scholar
  10. Arora RC, Meltzer HY (1989a) Increased serotonin2 (5-HT2) receptor binding as measured by3H-lysergic acid diethylamide (3H-LSD) in the blood platelets of depressed patients. Life Sci 44:725–734Google Scholar
  11. Arora RC, Meltzer HY (1989b) Serotonergic measures in the brains of suicide victims: 5-HT2 binding sites in the frontal cortex of suicide victims and control subjects. Am J Psychiatry 146:730–736Google Scholar
  12. Baldessarini RJ, Huston-Lyons D, Campbell A, Marsh E, Cohen BM (1992) Do central antiadrenergic actions contribute to the atypical properties of clozapine? Br J Psychiatry 160 [Suppl 17]:12–16Google Scholar
  13. Banov MD, Zarate CA, Scialabba BA, Tohen M, Wines J (1993) Clozapine therapy in refractory affective disorders: polarity predicts response in long-term follow-up. American Psychiatric Association Annual Meeting Abstract 163, San FranciscoGoogle Scholar
  14. Biederman J, Lerner Y, Belmaker RH (1979) Combination of lithium carbonate and haloperidol in schizoaffective disorder. Arch Gen Psychiatry 36:327–333Google Scholar
  15. Bigelow LB, Weinberger DR, Wyatt RJ (1981) Synergism of combined lithium-neuroleptic therapy: a double-blind, placebo-controlled case study. Am J Psychiatry 138:81–83Google Scholar
  16. Bigeon A, Weizman A, Karp L, Ram A, Tiano S, Wolff M (1987) Serotonin 5-HT2 receptor binding on blood platelets — a peripheral marker for depression? Life Sci 41:2485–2492Google Scholar
  17. Blackshear MA, Sanders-Bush E (1982) Serotonin receptor sensitivity after acute and chronic treatment with mianserin. J Pharmacol Exp Ther 221:303–308Google Scholar
  18. Braden W, Fink EB, Qualls CB, Ho CK, Samuels WO (1982) Lithium and chlorpromazine in psychotic inpatients. Psychiatry Res 7:69–81Google Scholar
  19. Brockington IF, Leff JP (1979) Schizoaffective psychosis: definitions and incidence. Psychol Med 9:91–99Google Scholar
  20. Brockington IF, Kendall RE, Kellett JM, Curry SH, Wainwright S (1978) Trials of lithium, chlorpromazine and amitriptyline in schizoaffective patients. Br J Psychiatry 133:162–168Google Scholar
  21. Brockington IF, Wainwright S, Kendall RE (1980) Manic patients with schizophrenic or paranoid symptoms. Psychol Med 10:73–83Google Scholar
  22. Brockington IF, Roper A, Copas J, Buckley M, Andrade CE, Wigg P, Farmer A, Kaufman C, Hawley R (1991) Schizophrenia, bipolar disorder and depression. A discriminant analysis, using „lifetime“ psychopathology ratings. Br J Psychiatry 159:485–494Google Scholar
  23. Calabrese JR, Meltzer HY, Markovitz PJ (1991) Clozapine prophylaxis in rapid cycling bipolar disorder. J Clin Psychopharmacol 11:396–397Google Scholar
  24. Carman JS, Bigelow LB, Wyatt RJ (1981) Lithium combined with neuroleptics in chronic schizophrenic and schizoaffective patients. J Clin Psychiatry 42:124–128Google Scholar
  25. Casey DE (1992) What makes a neuroleptic atypical? In: Meltzer HY (ed) Novel antipsychotic drugs. Raven, New York, pp 241–251Google Scholar
  26. Chalmers TL (1992) The potential impact of meta-analysis on medical care. In: Fava M, Rosenbaum JF (eds) Research designs and methods in psychiatry. Elsevier, Amsterdam, pp 85–89Google Scholar
  27. Cheetham SC, Crompton MR, Katona CLE, Horton RW (1988) Brain 5-HT2 receptor binding sites in depressed suicide victims. Brain Res 443:272–280Google Scholar
  28. Cole JO, Banov MD, Green A, Tohen M, Patel J (1993) Clozapine in the treatment of refractory acute bipolar mania. American Psychiatric Association Annual Meeting Abstract 455, San FranciscoGoogle Scholar
  29. Cowen PJ, Charig EM, Fraser S, Elliott JM (1987) Platelet 5-HT receptor binding during depressive illness and tricyclic antidepressant treatment. J Affective Disord 13:45–50Google Scholar
  30. Croughan JL, Welner A, Robins E (1974) The group of schizoaffective and related psychoses — critique, record, follow-up, and family studies. Arch Gen Psychiatry 31:632–637Google Scholar
  31. Crow TJ, Cross AJ, Cooper SJ, Deakin JFW, Ferrier IN, Johnson JA, Joseph MH, Own F, Poulter M, Lofthouse R, Corsellis JAN, Chambers DR, Blessed G, Perry EK, Perry RH, Tomlinson BE (1984) Neurotransmitter receptors and monoamine metabolites in the brains of patients with Alzheimer-type dementia and depression, and suicides. Neuropharmacology 23:1561–1569Google Scholar
  32. Engleman EA, Murphy JM, Zhou FE, Hingtgen JN (1992) Response suppression induced with selective 5-HT agonists can be differentially blocked with LY53857 in an animal model of depression. Neurochem Res 17:483–488Google Scholar
  33. Feighner JP, Robins E, Guze SB, Woodruff RD, Winokur G, Munoz R (1972) Diagnostic criteria for use in psychiatric research. Arch Gen Psychiatry 26:57–63Google Scholar
  34. Frankenburg FR (1993) Clozapine and bipolar disorder. J Clin Psychopharmacol 13:289–290Google Scholar
  35. Gandolfi O, Barbaccia ML, Costa E (1984) Different effects of serotonin antagonists on3H-kitanserin recognition sites. Life Sci 36:713–721Google Scholar
  36. Goodnick PJ, Meltzer HY (1984) Treatment of schizoaffective disorders. Schizophr Bull 10:30–48Google Scholar
  37. Growe GA, Crayton JW, Klass DB, Evans H, Strizich M (1979) Lithium in chronic schizophrenia. Am J Psychiatry 136:454–455Google Scholar
  38. Himmelhoch JA, Fuchs CZ, May SJ (1981) When schizoaffective diagnosis has meaning. J Nerv Ment Dis 169:277–282Google Scholar
  39. Hingtgen JN, Hendrie HC, Aprison MH (1983) Postsynaptic serotonergic blockade following chronic antidepressive treatment with trazodone in an animal model of depression. Pharmacol Biochem Behav 20:425–428Google Scholar
  40. Hingtgen JN, Fuller RW, Mason NR (1985) Blockade of a 5-hydroxytryptophan-induced animal model of depression with a potent and selective 5-HT2 receptor antagonist (LY53857). Biol Psychiatry 20:592–597Google Scholar
  41. Johnson G, Gershon S, Hekiman LJ (1968) Controlled evaluation of lithium and chlorpromazine in the treatment of manic states: an interim report. Compr Psychiatry 9:563–573Google Scholar
  42. Johnson G, Gershon S, Burdock EI, Floyd A, Hekiman L (1971) Comparative effects of lithium and chlorpromazine in the treatment of acute manic states. Br J Psychiatry 119:267–276Google Scholar
  43. Kasanin J (1933) The acute schizoaffective psychoses. Am J Psychiatry 13:97–126Google Scholar
  44. Keck PE, McElroy SL, Nemeroff CB (1992) Anticonvulsants in the treatment of bipolar disorder. J Neuropsychiatry Clin Neurosci 4:395–405Google Scholar
  45. Keck PE, McElroy SL, Strakowski SM, Tugrul KC, Hawkins JM, Huber TJ, Newman RM (1993) Comorbidity in first-compared with multiple-episode mania. American Academy of Clinical Psychiatrists Annual Meeting Abstracts, ChicagoGoogle Scholar
  46. Kendler KS, Gruenberg AM, Tsuang MT (1986) A DSM-III family study of nonschizophrenic psychotic disorders. Am J Psychiatry 143:1098–1106Google Scholar
  47. Lapenseé MA (1992) A review of schizoaffective disorder: II. Somatic treatment. Can J Psychiatry 37:347–349Google Scholar
  48. Lee CK, Kwak YS, Rhee H, Kim YS, Han JH, Choi JO, Lee YH (1987) The nationwide epidemiological study of mental disorders in Korea. J Korean Med Sci 2:19–34Google Scholar
  49. Levenson DF, Levitt MEM (1987) Schizoaffective mania reconsidered. Am J Psychiatry 144:415–425Google Scholar
  50. Levitt JJ, Tsuang MT (1988) The heterogeneity of schizoaffective disorder: implications for treatment. Am J Psychiatry 145:926–936Google Scholar
  51. Lindström LH (1989) A retrospective study of the long-term efficacy and safety of clozapine in 96 schizophrenic and schizoaffective patients during a 13-year period. Psychopharmacology 99[Suppl]:84–86Google Scholar
  52. Maes M, De Ruyter M, Claes R, Bosma G, Suy E (1989) The cortisol response to 5-hydroxytryptophan, orally, in depressive inpatients. J Affective Disord 13:23–30Google Scholar
  53. Maier W, Lichterman D, Minges J, Heun R, Hallmayer J, Benkert O (1992) Schizoaffective disorder and affective disorders with mood-incongruent psychotic features: keep separate or combine? Evidence from a family study. Am J Psychiatry 149:1666–1673Google Scholar
  54. Maj M (1984) Evolution of the American concept of schizoaffective psychosis. Neuropsychobiology 11:7–13Google Scholar
  55. Malhotra A, Litman RE, Su TP, Smyser CH, Pickar D (1993) Clozapine response in schizoaffective disorder. American Psychiatric Association Annual Meeting Abstract 53, San FranciscoGoogle Scholar
  56. Mann JJ, Stanley M, McBride PA, McEwen BS (1986) Increased serotonin2 and beta-adrenergic receptor binding in the frontal cortices of suicide victims. Arch Gen Psychiatry 43:954–959Google Scholar
  57. Marneros A, Rohde A, Diester A (1989) Unipolar and bipolar schizoaffective disorders: a comparative study. Eur Arch Psychiatr Neurol Sci 239:164–170Google Scholar
  58. Marneros A, Diester A, Rohde A (1991) Stability of diagnoses in affective, schizoaffective and schizophrenic disorders. Eur Arch Psychiatr Clin Neurosci 241:187–192Google Scholar
  59. Mattes JA, Nayak D (1984) Lithium versus fluphenazine for prophylaxis in mainly schizophrenic schizoaffectives. Biol Psychiatry 19:445–449Google Scholar
  60. McElroy SL, Keck PE (1993) Treatment guidelines for valproate in bipolar and schizoaffective disorders. Can J Psychiatry 38[Suppl 2]:62–66Google Scholar
  61. McElroy SL, Dessain EC, Pope HG, Cole JO, Keck PE, Frankenburg FR, Aizley HG, O'Brien S (1991) Clozapine in the treatment of psychotic mood disorders, schizoaffective disorder, and schizophrenia. J Clin Psychiatry 52:411–414Google Scholar
  62. McKeith IG, Marshall EF, Ferrier IN, Armstrong MM, Kennedy WN, Perry RH, Perry EK, Eccleston D (1987) 5-HT receptor binding in post-mortem brain from patients with affective disorder. J Affective Disord 13:67–74Google Scholar
  63. Meltzer HY (1989) Clinical studies on the mechanism of action of clozapine: The dopamine-serotonin hypothesis of schizophrenia. Psychopharmacology 99:S18-S27Google Scholar
  64. Meltzer HY (1992) The mechanism of action of clozapine in relation to its clinical advantages. In: Meltzer HY (ed) Novel antipsychotic drugs. Raven Press, New York, pp 1–13Google Scholar
  65. Meltzer HY, Umberkoman-Wiita B, Robertson A, Tricou BJ, Lowy M, Perline R (1984) Effect of 5-hydroxytryptophan on serum cortisol levels in major affective disorders. Arch Gen Psychiatry 41:366–374Google Scholar
  66. Müller-Oerlinghausen B, Ahrens B, Grof E, Grof P, Lenz G, Sihou M, Simhandl C, Thau K, Volk J, Wolf R, Wolf T (1992) The effect of long-term lithium treatment on the mortality of patients with manic-depressive and schizoaffective illness. Acta Psychiatr Scand 86:218–272Google Scholar
  67. Naber D, Hippius H (1990) The European experience with use of clozapine. Hosp Commun Psychiatry 41:886–890Google Scholar
  68. Okuma T, Yamashita I, Takahashi R, Itoh H, Otsuki S, Watanabe S, Sarai K, Hazama H, Inanga K (1989) A double-blind study of adjunctive carbamazepine versus placebo on excited states of schizophrenic and schizoaffective disorders. Acta Psychiatr Scand 80:250–259Google Scholar
  69. Owen F, Chambers DR, Cooper SJ, Crow TJ, Johnson JA, Lofthouse R, Poulter M (1986) Serotonergic mechanisms in brains of suicide victims. Brain Res 362:185–188Google Scholar
  70. Pandey GN, Pandey SC, Janicak PG, Marks RC, Davis JM (1990) Platelet serotonin-2 receptor binding sites in depression and suicide. Biol Psychiatry 28:215–222Google Scholar
  71. Parsa MA, Ramirez LF, Loula EC, Meltzer HY (1991) Effect of clozapine on psychotic depression and Parkinsonism. J Clin Psychopharmacol 11:330–331Google Scholar
  72. Peroutka SJ, Snyder SH (1980) Regulation of serotonin2 (5-HT2) receptors labeled with [3H] spiroperidol by chronic treatment with the antidepressant amitriptyline. J Pharmacol Exp Ther 215:582–587Google Scholar
  73. 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 47:490–494Google Scholar
  74. Pope HG, Lipinski JF, Cohen BM, Axelrod DT (1980) “Schizoaffective disorder”: An invalid diagnosis? A comparison of schizoaffective disorder, schizophrenia, and affective disorder. Am J Psychiatry 137:921–927Google Scholar
  75. Prien RF, Point P, Caffey EM, Klett CJ (1972) A comparison of lithium carbonate and chlorpromazine in the treatment of excited schizoaffectives. Arch Gen Psychiatry 27:182–189Google Scholar
  76. Prien RF, Caffey EM, Klett CJ (1974) Factors associated with treatment success in lithium carbonate prophylaxis. Arch Gen Psychiatry 31:189–192Google Scholar
  77. Privitera MR, Lamberti JS, Maharaj K (1993) Clozapine in a bioplar depressed patient. Am J Psychiatry 150:986Google Scholar
  78. Reyntjens A, Gelders YG, Hoppenbrouwers M-LJA, Bussche GV (1986) Thymosthenic effects of ritanserin, a centrally acting serotonin-S2 receptor blocker. Drug Dev Res 8:205–211Google Scholar
  79. Robins LN, Helzer JE, Weissman MM, Orvaschel H, Gruenberg E, Burke JD, Regier DA (1984) Lifetime prevalence of specific psychiatric disorders in three sites. Arch Gen Psychiatry 41:949–958Google Scholar
  80. Rosenthal NE, Rosenthal LN, Stallone F, Dunner DL, Fieve RR (1980) Toward the validation of RDC schizoaffective disorder. Arch Gen Psychiatry 37:804–810Google Scholar
  81. Shopsin B, Kim SS, Gershon S (1971) A controlled study of lithium vs. chlorpromazine in acute schizophrenics. Br J Psychiatry 119:435–440Google Scholar
  82. Simhandl C, Meszaros K (1992) The use of carbamazepine in the treatment of schizophrenic and schizoaffective psychoses: a review. J Psychiatr Neurosci 17:1–14Google Scholar
  83. Skodol AE (1987) Problems in differential diagnosis: from DSM-III to DSM-III-R in clinical practice. American Psychiatric Press, Washington DCGoogle Scholar
  84. Skodol AE, Spitzer RL (1987) An annotated bibliography of DSM-III. American Psychiatric Press, Washington DCGoogle Scholar
  85. Small JG, Kellams JJ, Milstein V, Moore J (1975) A placebo-controlled study of lithium combined with neuroleptics in chronic schizophrenic patients. Am J Psychiatry 132:1315–1317Google Scholar
  86. Spitzer RL, Endicott J, Robins E (1978) Research diagnostic criteria. Rationale and reliability. Arch Gen Psychiatry 35:773–782Google Scholar
  87. Stanley M, Mann JJ (1983) Increased serotonin-2 binding sties in frontal cortex of suicide victims. Lancet i:214–216Google Scholar
  88. Stefanowicz P (1990) Initial results of clozapine and lithium carbonate treatment of manic syndromes in the course of schizoaffective psychosis. Psychiatr Pol 24:27–30Google Scholar
  89. Suppes T, McElroy SL, Gilbert J, Dessain EC, Cole JO (1992) Clozapine in the treatment of dysphoric mania. Biol Psychiatry 32:270–280Google Scholar
  90. Tsuang MT (1991) Morbidity risks of schizophrenia and affective disorders among first-degree relatives of patients with schizoaffective disorders. Br J Psychiatry 158:165–170Google Scholar
  91. Tsuang D, Coryell W (1993) An 8-year follow-up of patients with DSM-III-R psychotic depression, schizoaffective disorder, and schizophrenia. Am J Psychiatry 150:1182–1188Google Scholar
  92. Williams PV, McGlashan TH (1987) Schizoaffective psychosis I. Comparative long-term outcome. Arch Gen Psychiatry 44:130–137Google Scholar
  93. Williams JBW, Gibbon M, First MB, Spitzer RL, Davies M, Borus J, Howes MJ, Kane J, Pope HG, Rounsaville B, Wittchen HAU (1992) The structured clinical interview for DSM-III-R (SCID) II. Multisite test-retest reliability. Arch Gen Psychiatry 49:630–636Google Scholar
  94. Wilmot CA, Szczepanik AM (1989) Effects of acute and chronic treatments with clozapine and haloperidol on serotonin (5-HT2) and dopamine (D2) receptors in the rat brain. Brain Res 487:288–298Google Scholar
  95. Winokur G (1984) Psychosis in bipolar and unipolar affective illness with special reference to schizo-affective disorder. Br J Psychiatry 145:236–242Google Scholar
  96. World Health Organization (1992) The ICD-10 classification of mental and behavioral disorders. World Health Organization, GenevaGoogle Scholar
  97. Yates M, Leake A, Candy JM, Fairbairn AF, McKeith IG, Ferrier IN (1990) 5HT2 receptor changes in major depression. Biol Psychiatry 27:489–496Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Paul E. KeckJr.
    • 1
  • Susan L. McElroy
    • 1
  • Stephen M. Strakowski
    • 1
  • Scott A. West
    • 1
  1. 1.Biological Psychiatry Program, Departments of Psychiatry, Pharmacology and Cell BiophysicsUniversity of Cincinnati College of MedicineCincinnatiUSA

Personalised recommendations