The Effects of Clozapine on Negative Symptoms in Patients with Schizophrenia with Minimal Positive Symptoms

Annals of Clinical Psychiatry - Tập 9 - Trang 227-234 - 1997
Jaspreet S. Brar1, K. N. Roy Chengappa1,2, Haranath Parepally1,2, Alan R. Sandman2, Suzanne B. Kreinbrook1,2, Sapna A. Sheth2, Rohan Ganguli1
1Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh
2Mayview State Hospital, Bridgeville

Tóm tắt

The effectiveness of clozapine in the treatment of the negative symptoms of schizophrenia remains controversial, as improvements in negative symptoms are invariably accompanied by improvements in positive symptoms and neurological side effects. We examined the effectiveness of treatment with clozapine on negative symptoms in a cohort of patients with minimal positive symptoms. Improvements in positive and negative symptoms were measured by BPRS ratings in a subgroup of schizophrenic patients (n=17, from a state hospital cohort of 75) with minimal positive symptoms, who had received clozapine for 6 months. In this subgroup, significant improvements were noted by a composite score on the three negative symptom items of emotional withdrawal, blunted affect, and motor retardation. Positive and depressive symptoms remained unchanged. The remaining cohort (n=58) showed improvements in overall psychopathology including positive, negative, and depressive symptoms. Interestingly, nearly 50% of each group were discharged from the hospital. These findings suggest that clozapine may be beneficial in the treatment of core negative symptoms, even in the absence of other improvements in psychopathology. This effect of clozapine may be a function of its unique pharmacological profile.

Tài liệu tham khảo

Meltzer HY: The mechanism of action of novel antipsychotic drugs. Schizophr Bull 1991; 17:263–287

Huttunen M: The evolution of the serotonin-dopamine antagonist concept. J Clin Psychopharmacol 1995; 15(Suppl):4S–10S

Baldessarini RJ, Frankenburg FR: Clozapine. A novel antipsychotic agent. N Engl J Med 1991; 324:746–754

Safferman A, Lieberman JA, Kane JM, Szymanski S, Kinon B: Update on the clinical efficacy and side effects of clozapine. Schizophr Bull 1991; 17:247–261

Kane JM, Marder SR: Psychopharmacologic treatment of schizophrenia. Schizophr Bull 1993; 19:287–302

Carpenter WT: The negative symptom challenge. Arch Gen Psychiatry 1992; 49:236–237

Meltzer HY, Burnett S, Bastani B, Ramirez LF: Effects of 6 months of clozapine treatment on the quality of life of chronic schizophrenic patients. Hosp Community Psychiatry 1990; 41:892–897

Carpenter WT, Heinrichs DW, Wagman AM: Deficit and nondeficit forms of schizophrenia. Am J Psychiatry 1988; 145:578–583

Pogue-Geile MF, Harrow M: Negative symptoms in schizophrenia: Their longitudinal course and prognostic importance. Schizophr Bull 1985; 11:427–439

Simpson GM, Varga E: Clozapine—A new antipsychotic agent. Curr Ther Res 1974; 16:679–686

Ekblom B, Haggstrom JE: Clozapine (Leponex) compared with chlorpromazine: A double-blind evaluation of pharmacological and clinical properties. Curr Ther Res 1974; 16:945–957

Gerlach J, Koppelhus P, Helweg E, Monrad A: Clozapine and haloperidol in a single-blind cross-over trial: Therapeutic and biochemical aspects in the treatment of schizophrenia. Acta Psychiat Scand 1974; 50:410–424

Singer K, Law SK: A double-blind comparison of clozapine (Leponex) and chlorpromazine in schizophrenia of acute symptomatology. J Int Med 1974; 2:433–435

Chiu E, Burrows G, Stevenson J: Double-blind comparison of clozapine with chlorpromazine in acute schizophrenic illness. Aust N Z J Psychiatry 1976; 10:343–347

Fischer-Cornelssen KA, Ferner UJ: An example of European multicenter trials: Multispectral analysis of clozapine. Psychopharmacol Bull 1976; 12:34–39

Guirguis E, Voineskos G, Gary J, Schlieman E: Clozapine (Leponex) vs chlorpromazine (Largactil) in acute schizophrenia (a double-blind controlled study). Curr Therapy Res 1977; 21:707–719

Gelenberg AJ, Doller JC: Clozapine versus chlorpromazine for the treatment of schizophrenia: Preliminary results from a double-blind study. J Clin Psychiatry 1979; 40:238–240

Shopsin B, Klein H, Aaronsom M, Collora M: Clozapine, chlorpromazine, and placebo in newly hospitalized, acutely schizophrenic patients: A controlled, double-blind comparison. Arch Gen Psychiatry 1979; 36:657–664

Claghorn J, Honigfeld G, Abuzzahab FS Sr, Wang R, Steinbook R, Tuason V, Klerman G: The risks and benefits of clozapine versus chlorpromazine. J Clin Psychopharmacol 1987; 7:377–384

Kane JM, Honigfeld G, Singer J, Meltzer H: Clozaril collaborative study group: Clozapine for the treatment resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry 1988; 45:789–796

Leppig M, Bosch B, Naber D, Hippius H: Clozapine in the treatment of 121 out-patients. Psychopharmacology 1989; 99(Suppl):S77–S79

Mattes JA: Clozapine for refractory schizophrenia: An open study of 14 patients treated up to 2 years. J Clin Psychiatry 1989; 50:389–391

Meltzer HY, Bastani B, Young-Kwon K, Ramirez LF, Burnett S, Sharp J: A prospective study of clozapine in treatment resistant schizophrenic patients. Psychopharmacology 1989; 99(Suppl):S68–S72

Pickar D, Owen RR, Litman RE, Konicki PE, Gutierrez L, Rapaport MH: Clinical and biological response to clozapine in patients with schizophrenia. Arch Gen Psychiatry 1992; 49:345–353

Leadbetter R, Shutty M, Pavalonis D, Vieweg V, Higgins P, Downs M: Clozapine-induced weight gain: Prevalence and clinical relevance. Am J Psychiatry 1992; 149:68–72

Clozapine Study Group: The safety and efficacy of clozapine in severe treatment-resistant schizophrenic patients in the UK. Br J Psychiatry 1993; 163:150–154

Kuoppasalmi K, Rimon R, Naukkarinen H, Lang S, Sandqvist A, Leinonen E: The use of clozapine in treatment-refractory schizophrenia. Schizophr Res 1993; 10:29–32

Breier A, Buchanan RW, Irish D, Carpenter WT Jr: Clozapine treatment of outpatients with schizophrenia: Outcome and long-term response patterns. Hosp Community Psychiatry 1993; 44:1145–1149

Breier A, Buchanan RW, Kirkpatrick B, Davis OR, Irish D, Summerfelt A, Carpenter WT Jr: Effects of clozapine on positive and negative symptoms in outpatients with schizophrenia. Am J Psychiatry 1994; 151:20–26

Conley R, Gounaris C, Tamminga C: Clozapine response varies in deficit versus non-deficit schizophrenic subjects. Biol Psychiatry 1994; 35:746

Lindenmayer JP, Grochowski S, Mabugat L: Clozapine effects on positive and negative symptoms: A six-month trial in treatment-refractory schizophrenics. J Clin Psychopharmacol 1994; 14:201–204

Miller DD, Perry PJ, Cadoret RJ, Andreasen NC: Clozapine's effect on negative symptoms in treatment-refractory schizophrenics. Comp Psychiatry 1994; 35:8–15

Lieberman JA, Safferman AZ, Pollack S, Szymanski S, Johns C, Howard A, Kronig M, Bookstein P, Kane JM: Clinical effects of clozapine in chronic schizophrenia: Response to treatment and predictors of outcome. Am J Psychiatry 1994; 151:1744–1752

Jalenques I, Coudert AJ: Clozapine and refractory schizophrenia. Long-term prospective study of 20 patients. Encephale 1994; 20:767–775

Overall JE, Gorham DR: “The brief psychiatric rating scale.” Psychol Rep 1962; 10:799–812

Andreasen NC: Negative symptoms in schizophrenia. Arch Gen Psychiatry 1982; 39:784–788

Andreasen NC: The Scale for the Assessment of Positive Symptoms (SAPS). Iowa City, IA: University of Iowa; 1984

Asberg M, Schalling D: Construction of a new psychiatric rating instrument, the comprehensive psychopathological rating scale (CPRS). Prog Neuro-Psychopharmacol 1979; 3:405–412

Kay SR, Fizbein A, Opler LA: The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987; 2:261–276

Carpenter WT Jr, Conley RR, Buchanan RW, Breier A, Tamminga CA: Patient response and resource management: Another view of clozapine treatment of schizophrenia. Am J Psychiatry 1995; 152:827–832

Meltzer HY: Clozapine: Is another view valid? Am J Psychiatry 1995; 152:821–825

Rao ML, Moller HJ: Biochemical findings of negative symptoms in schizophrenia and their putative relevance to pharmacologic treatment. A review. Neuropsychobiology 1994; 30:160–172

Davis JM, Schaffer CB, Killian GA, Kinard C, Chan C: Important issues in the drug treatment of schizophrenia. Schizophr Bull 1980; 6:70–87

Kane JM, Safferman AZ, Pollack S, John C, Szymanski S, Kronig M, Lieberman JA: Clozapine, negative symptoms and extrapyramidal side-effects. J Clin Psychiatry 1994; 55(Suppl):74–77

Schwartz JT, Brotman AW: A clinical guide to antipsychotic drugs. Drugs 1992; 44:981–992

Singh MM, Kay SR: A comparative study of haloperidol and chlorpromazine in terms of clinical effects and therapeutic reversal with benztropine in schizophrenia. Psychopharmacologia 1975; 43:103–113

Roubicek J, Major I: EEG profile and behavioral changes after a single dose of clozapine in normals and schizophrenics. Biol Psychiatry 1977; 12:613–633

Ranjan R, Meltzer HY: Acute and long-term effectiveness of clozapine in treatment-resistant psychotic depression. Biol Psychiatry 1996; 40:253–258

Weinberger DR, Aloia MS, Goldberg TE, Berman KF: The frontal lobes and schizophrenia. J Neuropsychiatry Clin Neurosci 1994; 6:419–427

Moghaddam B: Preferential activation of cortical dopamine neurotransmission by clozapine: Functional significance. J Clin Psychiatry 1994; 55(Suppl B):27–29

Ereshefsky L, Tran-Johnson TK, Watanabe MD: Pathophysiologic basis for schizophrenia and the efficacy of antipsychotics. Clin Pharmacy 1990; 9:682–707

Meltzer HY, Gudelsky GA: Dopaminergic and serotonergic effects of clozapine. Implications for a unique clinical profile. Arzneimittel-Forschung 1992; 42:268–272

Leysen JE, Janssen PM, Schotte A, Luyten WH, Megens AA: Interaction of antipsychotic drugs with neurotransmitter receptor sites in vitro and in vivo in relation to pharmacological and clinical effects: Role of 5HT2 receptors. Psychopharmacology 1993; 112(Suppl):S40–S54

Lingjaerde O: New perspectives on biological treatment of schizophrenia. Acta Psychiat Scand, 1994; 384(Suppl):102–107

Carpenter WT Jr, Conley RR: Therapeutic approaches to negative symptoms. In: Greden JF, Tandon R, eds. Negative Schizophrenic Symptoms: Pathophysiology and Clinical Implications. Washington, DC, American Psychiatric Press; 1991

Carpenter WT Jr, Heinrichs DW, Wagman AMI: Deficit and non-deficit forms of schizophrenia: The concept. Am J Psychiatry, 1988; 145:578–583

Thông tin
Thông tin xuất bản

Annals of Clinical Psychiatry

Tập 9

227-234

Thông tin tác giả