Efficacy and safety of novel antipsychotics: a critical review

Efficacy and safety of novel antipsychotic (AP) drugs (amisulpride, olanzapine, quetiapine, ziprasidone and zotepine) have been reviewed. Data on their antipsychotic efficacy and side effects profile have been evaluated only on the basis of controlled trials so far published. Overall, all these drugs have shown an antipsychotic efficacy on positive symptoms of schizophrenia similar to that of the conventional AP drugs. On negative symptoms, all novel AP drugs, except quetiapine and ziprasidone, demonstrated a better efficacy than haloperidol. Long‐term efficacy of these AP drugs in the maintenance treatment of schizophrenia needs to be explored by further, better‐designed, epidemiological studies. The safety profile shows that the novel AP drugs are generally well‐tolerated and induce significantly less acute extrapyramidal side effects in comparison with haloperidol. Some methodological flaws in the experimental design of the clinical trials analysed are discussed. Although these novel AP drugs have potential clinical advantages, a number of relevant questions still remain to be addressed, in order to establish the impact of these drugs in the overall treatment of schizophrenia. Copyright © 2000 John Wiley & Sons, Ltd.

[1]  P. Weiden,et al.  Antipsychotic-induced weight gain: a comprehensive research synthesis. , 1999, The American journal of psychiatry.

[2]  C. Coulouvrat,et al.  Safety of amisulpride (Solian): a review of 11 clinical studies. , 1999, International clinical psychopharmacology.

[3]  T. Barnes,et al.  Critical analysis and comparison of the side-effect and safety profiles of the new antipsychotics* , 1999, British Journal of Psychiatry.

[4]  C. Stephenson,et al.  Psychopharmacology of olanzapine , 1999, British Journal of Psychiatry.

[5]  J. Danion,et al.  Improvement of schizophrenic patients with primary negative symptoms treated with amisulpride. Amisulpride Study Group. , 1999, The American journal of psychiatry.

[6]  C. Barbui,et al.  Clinical trials of new antipsychotics: a critical appraisal. , 1999, International clinical psychopharmacology.

[7]  J. Swartz,et al.  Olanzapine treatment after clozapine-induced granulocytopenia in 3 patients. , 1999, The Journal of clinical psychiatry.

[8]  R. Belmaker,et al.  Olanzapine treatment after clozapine induced agranulocytosis , 1998 .

[9]  D. King,et al.  A comparison of bd and tid dose regimens of quetiapine (Seroquel) in the treatment of schizophrenia , 1998, Psychopharmacology.

[10]  J. Gheuens,et al.  Comments on article by Tran and associates, "Double-blind comparison of olanzapine versus risperidone in treatment of schizophrenia and other psychotic disorders". , 1998, Journal of clinical psychopharmacology.

[11]  N. Schooler Comments on article by Tran and colleagues, "Double-blind comparison of olanzapine versus risperidone in treatment of schizophrenia and other psychotic disorders". , 1998, Journal of clinical psychopharmacology.

[12]  A. Hale A review of the safety and tolerability of sertindole , 1998, International clinical psychopharmacology.

[13]  G. Tollefson,et al.  Depressive signs and symptoms in schizophrenia: A prospective blinded trial of olanzapine and haloperidol , 1998, European Neuropsychopharmacology.

[14]  A. Wood Clinical experience with olanzapine, a new atypical antipsychotic , 1998 .

[15]  Masatoshi Tanaka,et al.  A case of meige and neck dystonia appearing following very low dose sulpiride , 1998 .

[16]  T. Barnes,et al.  One-year, low-dose neuroleptic study of in-patients with chronic schizophrenia characterised by persistent negative symptoms , 1997, British Journal of Psychiatry.

[17]  G. Tollefson,et al.  Double-blind comparison of olanzapine versus risperidone in the treatment of schizophrenia and other psychotic disorders. , 1997 .

[18]  L. Arvanitis,et al.  Multiple fixed doses of “Seroquel” (quetiapine) in patients with acute exacerbation of schizophrenia: A comparison with haloperidol and placebo , 1997, Biological Psychiatry.

[19]  R. Kerwin,et al.  Cost-effectiveness of clozapine , 1997, British Journal of Psychiatry.

[20]  S. Cooper,et al.  14-110 Zotepine in the prevention of relapse , 1997, Biological Psychiatry.

[21]  S. Hirsch,et al.  Quetiapine in patients with schizophrenia. A high- and low-dose double-blind comparison with placebo. Seroquel Study Group. , 1997, Archives of general psychiatry.

[22]  G. Tollefson,et al.  Extrapyramidal symptoms and tolerability of olanzapine versus haloperidol in the acute treatment of schizophrenia. , 1997, The Journal of clinical psychiatry.

[23]  H. Freeman Amisulpride compared with standard neuroleptics in acute exacerbations of schizophrenia: three efficacy studies , 1997, International clinical psychopharmacology.

[24]  C. Beasley,et al.  Olanzapine versus haloperidol: acute phase results of the international double-blind olanzapine trial , 1997, European Neuropsychopharmacology.

[25]  R. Tamura,et al.  Olanzapine versus haloperidol in the treatment of schizophrenia and schizoaffective and schizophreniform disorders: results of an international collaborative trial. , 1997, The American journal of psychiatry.

[26]  G. Tollefson,et al.  Negative symptoms: a path analytic approach to a double-blind, placebo- and haloperidol-controlled clinical trial with olanzapine. , 1997, American Journal of Psychiatry.

[27]  G. Tollefson,et al.  Safety of olanzapine. , 1997, The Journal of clinical psychiatry.

[28]  A. Meyer-Lindenberg,et al.  Improvement of Cognitive Function in Schizophrenic Patients Receiving Clozapine or Zotepine: Results from a Double-Blind Study , 1997, Pharmacopsychiatry.

[29]  H. Lôo,et al.  Amisulpride versus placebo in the medium-term treatment of the negative symptoms of schizophrenia , 1997, British Journal of Psychiatry.

[30]  E. Harrigan P-22-8 The efficacy and safety of 28-day treatment with ziprasidone in schizophrenia/schizoaffective disorder , 1996, European Neuropsychopharmacology.

[31]  R. Borison,et al.  ICI 204,636, an atypical antipsychotic: efficacy and safety in a multicenter, placebo-controlled trial in patients with schizophrenia. U.S. SEROQUEL Study Group. , 1996, Journal of clinical psychopharmacology.

[32]  Charles M Beasley,et al.  Olanzapine versus Placebo and Haloperidol , 1996, Neuropsychopharmacology.

[33]  W. Fleischhacker,et al.  ICI 204636 (‘Seroquel’)—A putative new atypical antipsychotic: Results from phase III trials , 1996, Schizophrenia Research.

[34]  D. Heal,et al.  P-4-15 Zotepine: Preclinical tests predict antipsychotic efficacy and an atypical profile , 1995, European Neuropsychopharmacology.

[35]  J Gerlach,et al.  New antipsychotics: the present status , 1995, International clinical psychopharmacology.

[36]  L. Fabre,et al.  ICI 204,636, a novel, atypical antipsychotic: early indication of safety and efficacy in patients with chronic and subchronic schizophrenia. , 1995, Clinical therapeutics.

[37]  E. Lindström,et al.  Efficacy and safety of risperidone in the long-term treatment of patients with schizophrenia. , 1995, Clinical therapeutics.

[38]  J. Goldstein Section Review—Central & Peripheral Nervous Systems: Pre-Clinical Pharmacology of New Atypical Antipsychotics in Late Stage Development , 1995 .

[39]  D. Pickar Prospects for pharmacotherapy of schizophrenia , 1995, The Lancet.

[40]  Y. Lecrubier,et al.  Treatment of Negative Symptoms in Schizophrenia with Amisulpride , 1995, British Journal of Psychiatry.

[41]  D. Javitt,et al.  Serum levels of fluphenazine in schizophrenic outpatients maintained on two reduced doses of fluphenazine decanoate , 1994, European Neuropsychopharmacology.

[42]  B. Miller,et al.  A multicentre, double-blind, controlled comparison of SeroquelTM and chlorpromazine in the treatment of hospitalised patients with acute exacerbation of subchronic and chronic schizophrenia , 1994, European Neuropsychopharmacology.

[43]  J. Leysen,et al.  Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity. , 1994, The Journal of clinical psychiatry.

[44]  G. Sedvall,et al.  Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects. , 1992, Archives of general psychiatry.

[45]  A. Delcker,et al.  Amisulpride Versus Haloperidol in Treatment of Schizophrenic Patients - Results of a Double-Blind Study , 1990, Pharmacopsychiatry.

[46]  Serge Bischoff,et al.  Blockade of hippocampal dopamine (da) receptors: A tool for antipsychotics with low extrapyramidal side effects , 1988, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[47]  O. P. Tandon,et al.  Midbrain cholinergic mechanisms in elicitation of hypothalamic aggressive responses in cats , 1988, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[48]  G Honigfeld,et al.  Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. , 1988, Archives of general psychiatry.

[49]  K. Sarai,et al.  Comparison of Efficacy of Zotepine and Thiothixene in Schizophrenia in a Double-blind Study , 1987, Pharmacopsychiatry.

[50]  R. Ganguli,et al.  Weight gain associated with antipsychotic drugs. , 1999, The Journal of clinical psychiatry.

[51]  D. Casey Drug Evaluations: Drug Evaluation Central & Peripheral Nervous Systems: ‘Seroquel’ (quetiapine): Preclinical and clinical findings of a new atypical antipsychotic , 1996 .

[52]  S. Dollfus,et al.  A comparison of an atypical and typical antipsychotic, zotepine versus haloperidol in patients with acute exacerbation of schizophrenia: a parallel-group double-blind trial. , 1996, Psychopharmacology bulletin.

[53]  G. Ko,et al.  The Relationship between Immunological Function and Stress among Schizophrenic Patients , 1996, European Psychiatry.

[54]  W. Rein,et al.  Amisulpride in the Treatment of Acute Exacerbations of Subchronic Or Chronic Schizophrenia: a Dose Range Finding Study , 1996, European Psychiatry.

[55]  G. Tollefson,et al.  Olanzapine versus placebo and haloperidol: acute phase results of the North American double-blind olanzapine trial. , 1996, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[56]  J. Kane,et al.  Risperidone: efficacy and safety. , 1995, Schizophrenia bulletin.

[57]  Y. Lecrubier,et al.  Improvement of some schizophrenic deficit symptoms with low doses of amisulpride. , 1995, The American journal of psychiatry.

[58]  H. Meltzer Multiple-outcome criteria in schizophrenia: an overview of outcome with clozapine , 1995, European Psychiatry.

[59]  K. Otani,et al.  Correlation between prolactin response and therapeutic effects of zotepine in schizophrenic patients , 1994, International clinical psychopharmacology.

[60]  W. Fleischhacker,et al.  Zotepine in the treatment of schizophrenic patients with prevailingly negative symptoms. A double‐blind trial vs. haloperidol , 1992, International clinical psychopharmacology.