Abstract
Treatment resistance constitutes a significant dilemma in schizophrenia since it affects a substantial number of patients, their families and the health care professionals involved in their care. Nonresponsiveness needs to be approached as a multidimensional syndrome by specifying which symptoms in the spectrum of positive symptoms, negative symptoms, excitement/hostility, cognitive symptoms, and anxiety/depression are failing to respond to treatment. This review presents some of the clinical, demographic and biological correlates of nonresponse, in addition to compliance issues, psychosocial factors or side effects and as-yet-untreated comorbidities as a source for nonresponse. The effects of the atypicals clozapine, olanzapine, risperidone and quetiapine as compared to typicals are reviewed using available double-blind studies in this treatment refractory group of schizophrenia patients. The limited number of reports on the comparison of atypical compounds amongst each other are critically presented. Given that a subset of patients still do not respond to these agents, clinicians are using various augmentation strategies. We review studies with augmentation strategies which remain difficult to interpret given the open label and uncontrolled nature of most of these studies.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
Beuzen J-N, Birkett MA, Kiesler GM, Tollefson GD, Wood AJ, Beasley CW (1998): Olanzapine vs. clozapine: an international double-blind study in the treatment of resistant schizophrenia. 37th ACNP Annual Meeting, December 14-18, 1998, Puerto Rico (Abstract).
Birkett M, Dossenbach M, Shoshani D, Tran P and Rampey V (1996): Treatment failure with clozapine: can olanzapine be the alternative therapy? 35th Annual Meeting of the American College of Neuropsychopharmacology, December 9-13: 253 (Abstract).
Bondolfi G, Dufour H, Patris M, et al.: Risperidone versus clozapine in treatment-resistant chronic schizophrenia: a randomized double-blind study. Am J Psychiatry. 155:499–504, 1998.
Breier A, Hamilton SH. Comparative efficacy of olanzapine and haloperidol for patients with treatment-resistant schizophrenia. Biol Psychiatry 45:403–411, 1999.
Breier A, Buchanan RW, Kirkpatrick B, et al.: Effects of clozapine on positive and negative symptoms in outpatients with schizophrenia. Am J Psychiatry 151:20–26, 1994.
Conley RR, Buchanan RW: Evaluation of treatment-resistant schizophrenia. Schizophr Bull. 23:663–674, 1997.
Conley RR, Tamminga CA, Bartko JJ, et al.: Olanzapine compared with chlorpromazine in treatment resistant schizophrenia. Am J Psychiatry 155: 914–920, 1998.
Crow TJ et al.: Br J Psychiatry 148:120–127, 1986.
Davis JM, Schaffer CB, Killian GA, Kinard C, Chan C: Important issues in the drug treatment of schizophrenia. Schizophr Bull 6:70–87, 1980.
Emsley R: Partial Response to Antipsychotic Treatment: The Patient with Enduring Symptoms. J. of Clin Psychiatry 60(suppl 23):10–13, 1999.
Huber G et al.: Longitudinal studies of schizophrenic patients. Schizophr Bull 6:592–605, 1980.
Kane JA, Lieberman JA: Maintenance pharmacotherapy in schizophrenia. In: Meltzer HY, ed. Psychopharmacology: The Third Generation of Progress. New York, NY: Raven Press 1103–1109, 1987.
Kane J, Honigfeld G, Singer J, Meltzer H, Group at CCS: Clozapine for the treatment-resistant schizophrenic: a double-blind comparison with chlorpromazine. Arch Gen Psychiatry 45:789–796, 1998.
Kaplan MJ, Lazoff M, Kelly K, Lukin R, Garver DL: Enlargement of cerebral third ventricle in psychotic patients with delayed response to neuroleptics. Biol Psychiatry 27:205–214, 1990.
Lieberman JA: Understanding the mechanism of action of atypical antipsychotic drugs. A review of compounds in use and development [published erratum appears in Br J Psychiatry 1994; 164:709]. Br J Psychiatry. 163(suppl 22):7–18, 1993.
Lieberman J, Jody D, Geisler S, et al.: Time course and biologic correlates of 384 PSYCHIATRIC QUARTERLY treatment response in first-episode schizophrenia. Arch Gen Psychiatry 50:369–376, 1993.
Lieberman J et al.: Time course and biologic correlates of treatment response in first-episode schizophrenia. Arch Gen Psychiatry 50:369–376, 1993.
Lieberman JA et al.: Factors influencing treatment response and outcome of first-episode schizophrenia. J Clin Psychiatry. 57(suppl 9):5–9, 1996.
Lieberman JA, Koreen AR, Chakos M et al.: Factors influencing treatment response an doutcome of first-episode schizohrenia: implications for understanding the pathophysiology of schizophrenia. J Clin Psychiatry 57(suppl 9): 5–9, 1996.
Lindenmayer JP, Volavka J, Lieberman J, Sheitman B, Chakos M, Czobor P, Parker BJ, Iskander A: Olanzapine in schizphrenia refractory to typical and atypical antipsychotics: An opne lable, prospective trial. American Psychiatric Annual Meeting May 1999, New Research Poster Lindenmayer et al. (unpublished/personal communication) OMH Pharmacy and Therapeutics subcommittee on Algorithm for treatment refractory schizophrenia, 1999.
Meltzer HY, Okayli G: Reduction of suicidality during clozapine treatment of neuroleptic-resistant schizophrenia: impact on risk-benefit assessment. Am J Psychiatry 152:183–190, 1995.
Meltzer HY et al.: Growth hormone and prolactin response to apomorphine in schizophrenia and the major affective disorders. Arch Gen Psychiatry 41:512–519 1984.
Rosenheck R, Cramer J, Xu W, et al.: A comparison of clozapine and haloperidol in hospitalized patients with refractory schizophrenia. N Engl J Med 337:809–815, 1997.
van Kammen DP et al.: d-Amphetamine-induced heterogeneous changes in psychotic behavior in schizophrenia. Am J Psychiatry 139:991–997, 1982.
Wahlbeck K, Cheine M, Essali A, and Adams C: Evidence of clozapine's effectiveness in schizophrenia: A systematic review and meta-analysis of randomized trials. Am J of Psychiatry 156:990–999, 1999.
Weinberger DR, Bigelow LB, Kleinman JE, Klein ST, Rosenblatt JE, Wyatt RJ: Cerebral ventricular enlargement in chronic schizophrenia: an association with poor response to treatment. Arch Gen Psychiatry 37:11–13, 1980.
Wirshing D, Marshall B, Green M, Mintz J, Marder S Wirshing W: Risperidone in treatment-refractory schizophrenia. Am J Psych 156:1374–1379, 1999.
Wolkin A: PET in the study of neuroleptic response, in The Neuroleptic-Nonresponsive Patient: Characterization and Treatment (Angrist &; Schulz, eds.) Am Psychiatric Press Inc. 1990.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lindenmayer, JP. Treatment Refractory Schizophrenia. Psychiatr Q 71, 373–384 (2000). https://doi.org/10.1023/A:1004640408501
Issue Date:
DOI: https://doi.org/10.1023/A:1004640408501