( 200030) R971 + 14 A 1672-2124(2005) 02-0075 - 06 : Medline Pubmed Ovid Science Direct Proquest : 10 ; ; ; ; ; ; Clinical Evaluation of Atypical Antipsychotics in the Treatment of Schizophrenia HUANGJizhong ZHANG Mingyuan (Shanghai Mental Health Center Shanghai 200030) ABSTRACT OBJ ECTIVE : To systematically review the aspects of clinical usage and research progress of atypical antipsychotics in the treatment of schizophrenia ( SP) and evaluate their clinical efficacy and safety. METHODS : To search medical literatures in resent years at Medline Pubmed Ovid Science Direct and Proquest by internet and some reports published on medical literatures at home and abroad for an analysis. RESULTS & CONCLUSION : Clinical use and research of atypical antipsychotics in the treatment of schizophrenia have been well - performed and the advancements have been swift. Most of new type of atypical antipsychotics such as risperidone olanzapine quetiapine ziprasidone and aripiprazole have already become the first line choice for the treatment of schizophrenia in different level different stage and prevention of recurrence except for clozapine. In particular they have obviously minimized side effects caused by classic antipsychotics and clozapine. Various clinical research results have been confirmed by many clinically systematic researches taking the method of evidence - based psychiatry. KEY WORDS atypical antipsychotics ; classic antipsychotics ; schizophrenia ; clinical trial ; clinical evaluation ; evidence - based psychiatry ; extrapyramidal symptoms ( EPSs) (atypical antipsychotics) D 2 1952 [1 ] 30 (classic antipsychotics) D 2 15 (Risperidone) (Olanzapine) (Quetiapine) ( EPSs) ( Ziprasidone) ( Amisulpiride) EPSs 60 % (Adpiprazolel) 50 % 50 % 1 20 % D 2 D 2 D 2 EPSs - EPSs D 2 - D 2 (PRL) 5 - (5 - HT) (NE) 2005 5 2 75 1995-2005 Tsinghua Tongfang Optical Disc Co. Ltd. All rights reserved.
D 2 ; 5 - HT 1A 2A 2C 3 6 7 NE 1 2 ( ) 2 5 - HT 2A D 2 ; - ; EPSs 200 250mg/ ml 80 D 2 [1 2 ] (Zotepine) (Sertindole) 212 ( Olanzapine) 30 5 20mg/ d EPSs 10mgΠd [2 3 1 6 ( ] 2 000 ) 10 15mg ( 215mg) / d 2 10mgΠd (15 5) mgπd ( RCTs) (Meta ) 1 Medline Pubmed Ovid Science Direct Proquest 1 [8 10 ] Lindenmayer [11 ] 43 40mg/ d 20 40mgΠ d 1617 % 1 18 211 ( Clozapine) 2015mgΠd 30316mgΠd Conley [12 ] 377 8 1214mg/ d 418mg/ d 7712 % 7118 % [4 5 ] Kane 71 29 8 PANSS / EPSs (35 % vs 67 %) Tran (57 % vs 25 %) [13 ] 2 1 [6 ] 1917 % 28 % ( P = 01034) Perry [14 ] Hagg 2312ngΠml [7 ] ;Cohen EPSs 6 - ; 2 018 % 76 Evaluation and analysis of drug2use in hospitals of China 2005 Vol. 5 No. 2 1995-2005 Tsinghua Tongfang Optical Disc Co. Ltd. All rights reserved.
; PRL Liebzeit 6mg/ d EPSs 60 % [15 ] 83 % EPSs [19 6 ] Kopala [20 ] 2 4mg/ d 5 8mg/ d 1 65 6 PANSS 3 5 20mg/ d 80 % EPSs (3Π65) 2 4mg/ d Lane [21 ] 6mgΠd 60 % 213 ( Quetiapine) 40 % (316 019) mg/ d EPSs - 12mgΠd 5 - HT 2 D 1 D 2 M EPSs Csemansky [22 ] 397 3h 6h 1 150 750mg/ d 800mg/ d (34 %/ 60 %) EPSs Purdon [16 ] 25 6 Markianos [23 ] 6 PRL EPSs Copolov [17 ] PRL PRL 1 6 PRL EPSs PRL Emesley [18 ] 1 8 RCT EPSs (PANSS) (BPRS) ( Path - EPSs PRL analysis) 1 8 4 215 214 ( Risperidone) ( Ziprasidone) 5 - HT 5 - HT 2A - D 2 5 - HT NE DA 5 - HT 2A / D 2 5 - HT 1A 312h 10h 80 160mgΠd 20h 22h( 9 - - ) 1 1 16mg/ d 2 1 8mg/ d 3 EPSs EPSs 10mg/ d 20mg/ d 1 ( ) 2005 5 2 77 1995-2005 Tsinghua Tongfang Optical Disc Co. Ltd. All rights reserved.
[24 25 EPSs ] PRL PRL ; ; [29 Q - Tc 1 ] FDA Q - Tc 200 1 200mg/ d FDA 2013ms 2 988 2 (0106 %) Q - Tc ( > 500ms) 440 1 (0123 %) Q - Tc > 500ms 218 ( Zotepine) Q - Tc 5 - HT DA H1 NE 1 NE (TCAs) 3d 4d Q - Tc 75 450mg/ d Q - Tc 150 300mg/ d 10 20mg/ d (Sotalol) (Sparfloxacin) EPSs ; BPRS EPSs ; 1 6 216 ( Sertindole) 5 - HT 2A / D 2 Hwang [30 ] - 3 6 70 EPSs [31 1 ] 16mg/ d 24mg/ d FDA 10mg/ d 8mg/ d EPSs 1 219 ( Aripiprazole) D 2 D 3 ( - D 2 D 2 5 - HT 1A 2A/ C ) Q - Tc Pezawas 5 - HT 1A 5 - HT 2A [26 ] 34 D 2 Q - Tc 1917ms D 2 - EPSs - DA PRL FDA 44h 70h 15 30mg/ d 2 10mg/ d D 2 [26 28 2002 ] EPSs PRL 217 ( Amisulpiride) Potkin 404 4 20mg/ d(n = 101) 30mgΠd (n = 101) D 2 D 3 (n = 103) 6mg/ d(n = 99) PANSS D 2 (CGI) 20mg/ d DA DA 30mgΠd 6mgΠd EPSs PRL 5 Q - Tc (400 800mg/ d) BPRS 5 40mg/ d P 450 25mg/ d Pigott 310 26 (50 300mg/ d) MeQuade 1 294 52 5 - HT 2A D 2 EPSs EPSs - EPSs 78 Evaluation and analysis of drug2use in hospitals of China 2005 Vol. 5 No. 2 1995-2005 Tsinghua Tongfang Optical Disc Co. Ltd. All rights reserved.
[31 34 ] ; (3) 2110 ; (4) Volavka 14 157 3 ; (5) 14 3014mg/ d 1114 mg/ d EPSs PRL Q - Tc ; (6) [35 ] Davis (2003) 1 124 18 Hedges - Olkin (LOCF) [ 1 ] Kinon BJ Lieberman JA. Mechanisms of action of atypical antipsychotic drugs : a critical analysis [ J ]. Psychopharma2 0149 0129 0125 0121 P 2 10-8 3 10-7 2 10-12 3 10-9 cology 1996 124 :2. [2 ] Andersson C Chakos M Mailman R et al. Emerging roles for novel antipsychotic medications in the treatment of schizo2 6 phreniz[j ]. Psychiatr Clin north Am 1998 21 :151. (Ramoxipride) [3 ] Leysen J E Janssen PMF Schotte A et al. Interaction of an2 tipsychotic drugs with neurotransmitter receptor sites in vitro [36 ] and in vivo in relation to pharmacological and clinical effects : Leucht (1999) role of 5HT 2 receptors [J ]. Psychopharmacology 1993 112 : S40. [ 4 ] Kane JM Honigfeld G Singer J et al. Clozapine for the treatment - resistant schizophrenic. A double - blind compari2 son with chlorpromazine [J ]. Arch Gen Psychiatry 1988 45 : [37 EPSs ] 789. 3 [ 5 ] Meltzer HY McGurk SR. The effect of clozapine risperi2 done and olanzapine on cognitive function in schizophrenia [J ]. Schizophr Bull 1999 25 :233. [6 ] Rosenheck R Cramer J Xu W et al. A comparison of cloz2 apine and haloperidol in hospitalized patients with refractory D 2 schizophrenia[j ]. N Engl J Med 1997 337 :809. [7 ] Hagg S Spigset O Bate A et al. Myocarditis related to clozapine treatment [J ]. J Clin Psychopharmacol 2001 21 : 382. [8 ] Beasley CM Tollefson G Tran P et al. Olanzapine versus placebo and haloperidol[j ]. Neuropsychopharmacology 1996 14 :111. [9 ] Tollefson GD Beasley CM Tran PV et al. Olanzapine ver2 : (1) sus haloperidol in the treatment of schizophrenia and schizoaf2 fective and schizophreniform disorders :results of an internation2 ; (2) al collaborative trial[j ]. Am J Psychiatry 1997 154 :457. 2005 5 2 79 1995-2005 Tsinghua Tongfang Optical Disc Co. Ltd. All rights reserved.
[ 10 ] Purdon SE Jones BDW Stip E et al. Neuropsychological change in earlyphase schizophrenia over twelve months of treat2 ment with olanzapine risperidone or haloperidol. The Cana2 dian collaboration group for research in schizophrenia [ J ]. Arch Gen Psychiatry 2000 57 :249. [11 ] Lindenmayer JP Volavka J Lieberman J et al. Olanzapine for schizophrenia refractory to typical and atypical antipsychot2 ics : an open - label prospective trial[j ]. J Clin Psychophar2 macol 2001 21 :448. [12 ] Conley RR Mahmoud R. A randomized double - blind study of risperidone and olanzapine in the treatment of schizophrenia or schizoaffective disorde [J ]. Am J Psychiatry 2001 158 : 765. [ 13 ] Tran PV Hamilton SH Kuntz AJ et al. Double - blind comparison of olanzapine versus risperidone in the treatment of schizophrenia and other psychotic disorders [J ]. J Clin Psy2 chopharmacol 1997 17 :407. [14 ] Perry PJ Lund BC Sanger T et al. Olanzapine plasma con2 centrations and clinical response : acute phase results of the north American olanzapine trial [J ]. J Clin Psychopharmacol 2001 21 :14. [ 15 ] Liebzeit KA Markowitz JS Calry CF. New onset diabetes and atypical antipsychotics[j ]. Eur Neuropsychopharmacol 2001 11 :25. [ 16 ] Purdon SE Malla A Labelle A et al. Neuropsychological change in patients with schizophrenia after treatment with que2 tiapine or haloperidol [J ]. J Psychiatry Neurosci 2001 26 : 137. [17 ] Copolov Dl Link CG Kowalcyk B. A multicentre double - blind randomized comparison of quetiapine and haloperidol in schizophrenia[j ]. Psychol Med 2000 30 :95. [18 ] Emsley RA Raniwalla J Bailey PJ et al. A comparison of the effects of quetiapine ( seroquel ) and haloperidol in schizophrenic patients with a history of and a demonstrated partial response to conventional antipsychotic treatment [ J ]. Int Clin Psychopharmacol 2000 15 :121. [ 19 ] Emsley RA the Risperidone Working Group. Risperidone in the reatment of first - episode psychotic patients : a double - blind multi - center study[j ]. Schizophr Bull 1999 25 :721. [ 20 ] Kipala LC Good KP Honer WG. Extrapyramidal signs and clinical symptoms in first - episode schizophrenia : response to low - dose risperidone[j ]. J Clin Psychopharmacol 1997 17 : 308. [21 ] Lane HY Chiu WC Chou JCY et al. Risperidone in acute2 ly exacerbated schizophrenia :dosing strategies and plasma lev2 els[j ]. J Clin Psychiatry 2000 61 :209. [ 22 ] Csernansky J G Mahmoud R Brenner R. A comparison of risperidone and haloperidol for the prevention of relapse in pa2 tients with schizophrenia[j ]. N Engl J Med 2002 346 :16. [ 23 ] Markianos M Hatzimanolis J Lykouras L. Neuroendocrine responsivities of the pituitary dopamine system in male schizo2 phrenic patients during treatment with clozapine olanzapine risperidone sulpiride or haloperidol[j ]. Eur Arch Psychiatry Clin Neurosci 2001 251 :141. [24 ] Keck P Jr Buffenstein A Ferguson J et al. Ziprasidone 40 and 20 mgπday in the acute exacerbation of schizophrenia and schizoaffective disorder : a 4 - week placebo controlled trial [J ]. Psychopharmacology 1998 140 :173. [25 ] Goff DC Posever T Herz L et al. An exploratory haloperi2 dol - controlled dose finding study of ziprasidone in hospitalized patients with schizophrenia or schizoaffective disorde [ J ]. J Clin Psychopharmacol 1998 18 :296. [ 26 ] Pezawas L Quiner S Moertl D et al. Efficacy cardiac safety and tolerability of sertindole :a drug surveillance[j ]. Int Clin Psychopharmacol 2000 15 :207. [27 ] Van Kammen DP McEvoy JP Targum SD et al. A random2 ized controlled dose - ranging trial of sertindole in patients with schizophrenia[j ]. Psychopharmacology 1996 124 :168. [ 28 ] Zimbroff DL Kane JM Tamminga CA et al. Controlled dose - response study of sertindole and haloperidol in the treat2 ment of schizophrenia[j ]. Am J Psychiatry 1997 154 :782. [29 ] Peuskens J Bech P Moller HJ et al. Amisulpride vs. ris2 peridone in the treatment of acute exacerbations of schizophre2 nia[j ]. Psychiatry Res 1999 88(2) :107. [30 ] Hwang TJ Lin SK Lin HN. Efficacy and safety of zotepine for the treatment of Taiwanese schizophrenic patients :a double - blind comparison with haloperidol[j ]. J Formos Med Assoc 2001 100 :811. [31 ] Petrie JL Saha AR McEvoy JP. Acute and long - term effi2 cacy and safety of aripiprazole : a new atypical antipsychotic [J ]. Schizophr Res 1998 29 :155. [32 ] Potkin SG Saha AR Kujawa MJ et al. Aripiprazole an an2 tipsychotic with a novel mechanism of action and risperidone vs placebo in patients with schizophrenia and schizoaffective disorder[j ]. Arch Gen Psychiatry 2003 60 :681. [ 33 ] Pigott TA. the Aripiprazole Study Group. Aripiprazle for the prevention of relapse in stabilized patients with chronic schizo2 phrenia :a placebo - controlled 26 - week study [J ]. Psychiatry 2003 64 :1 048. J Clin [34 ] McQuade R Carson W Saha A et al. Aripiprazole for long - term maintenance treatment of schizophrenia[j ]. European Neuropsychopharmacology 2002 12 :S288. [35 ] Volavka J Czobor P Sheitman B et al. Clozapine olanzap2 ine risperidone and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder [ J ]. Am J Psychiatry 2002 159 :255. [36 ] Davis JM Chen N Glick ID. A meta - analysis of the effica2 cy of second - generation antipsychotics[j ]. Arch Gen Psychi2 atry 2003 60 :553. [37 ] Leucht S Pitschel Walz G Abraham D et al. Efficacy and extrapyramidal side - effects of the new antipsychotics olanzap2 ine quetiapine risperidone and sertindole compared to conv2 entional antipsychotics and placebo. A meta - analysis of ran2 domized controlled trials[j ]. Schizophr Res 1999 35 :51. ( :2005-01 - 17 :2005-02 - 15) 80 Evaluation and analysis of drug2use in hospitals of China 2005 Vol. 5 No. 2 1995-2005 Tsinghua Tongfang Optical Disc Co. Ltd. All rights reserved.