Augmentation of clozapine with a second antipsychotic - a meta-analysis of randomized, placebo-controlled studies
Objective: Inadequate response to clozapine treatment is frequently encountered in practice and augmentation strategies have been developed in an attempt to improve response. Aims of the study were to evaluate the therapeutic effect of adding an antipsychotic drug to clozapine treatment. Method: M...
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| Veröffentlicht in: | Acta Psychiatrica Scandinavica 2009-06, Vol.119 (6), p.419-425 |
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| creator | Taylor, D. M. Smith, L. |
| description | Objective: Inadequate response to clozapine treatment is frequently encountered in practice and augmentation strategies have been developed in an attempt to improve response. Aims of the study were to evaluate the therapeutic effect of adding an antipsychotic drug to clozapine treatment.
Method: Meta‐analysis of randomized, placebo‐controlled studies of antipsychotic augmentation of clozapine treatment.
Results: Ten studies (including 522 subjects) met inclusion criteria. Antipsychotic augmentation showed significant benefit over the addition of placebo on only one outcome measure examined [mean effect size for rating scale score (BPRS/PANSS) −0.180, 95% CI −0.356 to −0.004]. Antipsychotic augmentation showed no advantage on withdrawals from trials (risk ratio 1.261, 95% CI 0.679–2.345) or on CGI scores (effect size −0.661, 95% CI −1.475 to 0.151). Duration of study was not associated with outcome (P = 0.95). There was no evidence of publication bias.
Conclusion: In studies lasting up to 16 weeks, the addition of an antipsychotic to clozapine treatment has marginal therapeutic benefit. Longer and larger trials are necessary to demonstrate the precise therapeutic utility of antipsychotic co‐therapy with clozapine. |
| doi_str_mv | 10.1111/j.1600-0447.2009.01367.x |
| format | Article |
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Method: Meta‐analysis of randomized, placebo‐controlled studies of antipsychotic augmentation of clozapine treatment.
Results: Ten studies (including 522 subjects) met inclusion criteria. Antipsychotic augmentation showed significant benefit over the addition of placebo on only one outcome measure examined [mean effect size for rating scale score (BPRS/PANSS) −0.180, 95% CI −0.356 to −0.004]. Antipsychotic augmentation showed no advantage on withdrawals from trials (risk ratio 1.261, 95% CI 0.679–2.345) or on CGI scores (effect size −0.661, 95% CI −1.475 to 0.151). Duration of study was not associated with outcome (P = 0.95). There was no evidence of publication bias.
Conclusion: In studies lasting up to 16 weeks, the addition of an antipsychotic to clozapine treatment has marginal therapeutic benefit. Longer and larger trials are necessary to demonstrate the precise therapeutic utility of antipsychotic co‐therapy with clozapine.</description><identifier>ISSN: 0001-690X</identifier><identifier>EISSN: 1600-0447</identifier><identifier>EISSN: 0065-1591</identifier><identifier>DOI: 10.1111/j.1600-0447.2009.01367.x</identifier><identifier>PMID: 19245679</identifier><identifier>CODEN: APYSA9</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adult ; Adult and adolescent clinical studies ; Antipsychotic Agents - therapeutic use ; antipsychotics ; Biological and medical sciences ; Brief Psychiatric Rating Scale - statistics & numerical data ; Clinical trials ; Clozapine - therapeutic use ; Drug Therapy, Combination ; Female ; Humans ; Male ; Medical sciences ; Meta-analysis ; Neuropharmacology ; Pharmacology ; Pharmacology. Drug treatments ; Placebos ; Psychiatric Status Rating Scales - statistics & numerical data ; Psychiatry ; Psycholeptics: tranquillizer, neuroleptic ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Psychopharmacology ; Psychoses ; Psychotic Disorders - diagnosis ; Psychotic Disorders - drug therapy ; Psychotic Disorders - psychology ; Randomized Controlled Trials as Topic - statistics & numerical data ; Schizophrenia ; Schizophrenia - diagnosis ; Schizophrenia - drug therapy ; Schizophrenic Psychology ; Treatment Outcome</subject><ispartof>Acta Psychiatrica Scandinavica, 2009-06, Vol.119 (6), p.419-425</ispartof><rights>2009 John Wiley & Sons A/S</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4947-bb48273e85c8242f653201f82ba3475a0500a075f005eebe88546257459d7aa33</citedby><cites>FETCH-LOGICAL-c4947-bb48273e85c8242f653201f82ba3475a0500a075f005eebe88546257459d7aa33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1600-0447.2009.01367.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1600-0447.2009.01367.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21439550$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19245679$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Taylor, D. M.</creatorcontrib><creatorcontrib>Smith, L.</creatorcontrib><title>Augmentation of clozapine with a second antipsychotic - a meta-analysis of randomized, placebo-controlled studies</title><title>Acta Psychiatrica Scandinavica</title><addtitle>Acta Psychiatr Scand</addtitle><description>Objective: Inadequate response to clozapine treatment is frequently encountered in practice and augmentation strategies have been developed in an attempt to improve response. Aims of the study were to evaluate the therapeutic effect of adding an antipsychotic drug to clozapine treatment.
Method: Meta‐analysis of randomized, placebo‐controlled studies of antipsychotic augmentation of clozapine treatment.
Results: Ten studies (including 522 subjects) met inclusion criteria. Antipsychotic augmentation showed significant benefit over the addition of placebo on only one outcome measure examined [mean effect size for rating scale score (BPRS/PANSS) −0.180, 95% CI −0.356 to −0.004]. Antipsychotic augmentation showed no advantage on withdrawals from trials (risk ratio 1.261, 95% CI 0.679–2.345) or on CGI scores (effect size −0.661, 95% CI −1.475 to 0.151). Duration of study was not associated with outcome (P = 0.95). There was no evidence of publication bias.
Conclusion: In studies lasting up to 16 weeks, the addition of an antipsychotic to clozapine treatment has marginal therapeutic benefit. Longer and larger trials are necessary to demonstrate the precise therapeutic utility of antipsychotic co‐therapy with clozapine.</description><subject>Adult</subject><subject>Adult and adolescent clinical studies</subject><subject>Antipsychotic Agents - therapeutic use</subject><subject>antipsychotics</subject><subject>Biological and medical sciences</subject><subject>Brief Psychiatric Rating Scale - statistics & numerical data</subject><subject>Clinical trials</subject><subject>Clozapine - therapeutic use</subject><subject>Drug Therapy, Combination</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Meta-analysis</subject><subject>Neuropharmacology</subject><subject>Pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Placebos</subject><subject>Psychiatric Status Rating Scales - statistics & numerical data</subject><subject>Psychiatry</subject><subject>Psycholeptics: tranquillizer, neuroleptic</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Psychopharmacology</subject><subject>Psychoses</subject><subject>Psychotic Disorders - diagnosis</subject><subject>Psychotic Disorders - drug therapy</subject><subject>Psychotic Disorders - psychology</subject><subject>Randomized Controlled Trials as Topic - statistics & numerical data</subject><subject>Schizophrenia</subject><subject>Schizophrenia - diagnosis</subject><subject>Schizophrenia - drug therapy</subject><subject>Schizophrenic Psychology</subject><subject>Treatment Outcome</subject><issn>0001-690X</issn><issn>1600-0447</issn><issn>0065-1591</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkVtv1DAQhSMEokvhLyALCZ5IGN9i5wVpu0BBWkolrm-W4zjUSxKncaLu9tfjdFeLxAv4xbbmO0czc5IEYchwPK82Gc4BUmBMZASgyADTXGTbe8niWLifLAAAp3kBP06SRyFs4pdjkA-TE1wQxnNRLJLr5fSztd2oR-c75GtkGn-re9dZdOPGK6RRsMZ3FdLd6PqwM1d-dAalsdDaUae6080uuDBLB91VvnW3tnqJ-kYbW_o0asfBN42tUBinytnwOHlQ6ybYJ4f7NPn67u2X1ft0_en8w2q5Tg0rmEjLkkkiqJXcSMJInXNKANeSlJoywTVwAA2C13Eoa0srJWc54YLxohJaU3qavNj79oO_nmwYVeuCsU2jO-unoHJBZM44_BMkkOcMitnx2V_gxk9DXEBQuOCSY4qLCMk9ZAYfwmBr1Q-u1cNOYVBzeGqj5ozUnJGaw1N34altlD49-E9la6s_wkNaEXh-AHQwuqnjwo0LR45gRgt-N9HrPXfjGrv77wbUcnX5eX5Gg3Rv4MJot0cDPfyKa6OCq-8X5-ry4o34-G0t1Rn9DTn8w6c</recordid><startdate>200906</startdate><enddate>200906</enddate><creator>Taylor, D. M.</creator><creator>Smith, L.</creator><general>Blackwell Publishing Ltd</general><general>Blackwell</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>200906</creationdate><title>Augmentation of clozapine with a second antipsychotic - a meta-analysis of randomized, placebo-controlled studies</title><author>Taylor, D. M. ; Smith, L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4947-bb48273e85c8242f653201f82ba3475a0500a075f005eebe88546257459d7aa33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adult</topic><topic>Adult and adolescent clinical studies</topic><topic>Antipsychotic Agents - therapeutic use</topic><topic>antipsychotics</topic><topic>Biological and medical sciences</topic><topic>Brief Psychiatric Rating Scale - statistics & numerical data</topic><topic>Clinical trials</topic><topic>Clozapine - therapeutic use</topic><topic>Drug Therapy, Combination</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Meta-analysis</topic><topic>Neuropharmacology</topic><topic>Pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Placebos</topic><topic>Psychiatric Status Rating Scales - statistics & numerical data</topic><topic>Psychiatry</topic><topic>Psycholeptics: tranquillizer, neuroleptic</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>Psychopharmacology</topic><topic>Psychoses</topic><topic>Psychotic Disorders - diagnosis</topic><topic>Psychotic Disorders - drug therapy</topic><topic>Psychotic Disorders - psychology</topic><topic>Randomized Controlled Trials as Topic - statistics & numerical data</topic><topic>Schizophrenia</topic><topic>Schizophrenia - diagnosis</topic><topic>Schizophrenia - drug therapy</topic><topic>Schizophrenic Psychology</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Taylor, D. M.</creatorcontrib><creatorcontrib>Smith, L.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Acta Psychiatrica Scandinavica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Taylor, D. M.</au><au>Smith, L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Augmentation of clozapine with a second antipsychotic - a meta-analysis of randomized, placebo-controlled studies</atitle><jtitle>Acta Psychiatrica Scandinavica</jtitle><addtitle>Acta Psychiatr Scand</addtitle><date>2009-06</date><risdate>2009</risdate><volume>119</volume><issue>6</issue><spage>419</spage><epage>425</epage><pages>419-425</pages><issn>0001-690X</issn><eissn>1600-0447</eissn><eissn>0065-1591</eissn><coden>APYSA9</coden><abstract>Objective: Inadequate response to clozapine treatment is frequently encountered in practice and augmentation strategies have been developed in an attempt to improve response. Aims of the study were to evaluate the therapeutic effect of adding an antipsychotic drug to clozapine treatment.
Method: Meta‐analysis of randomized, placebo‐controlled studies of antipsychotic augmentation of clozapine treatment.
Results: Ten studies (including 522 subjects) met inclusion criteria. Antipsychotic augmentation showed significant benefit over the addition of placebo on only one outcome measure examined [mean effect size for rating scale score (BPRS/PANSS) −0.180, 95% CI −0.356 to −0.004]. Antipsychotic augmentation showed no advantage on withdrawals from trials (risk ratio 1.261, 95% CI 0.679–2.345) or on CGI scores (effect size −0.661, 95% CI −1.475 to 0.151). Duration of study was not associated with outcome (P = 0.95). There was no evidence of publication bias.
Conclusion: In studies lasting up to 16 weeks, the addition of an antipsychotic to clozapine treatment has marginal therapeutic benefit. Longer and larger trials are necessary to demonstrate the precise therapeutic utility of antipsychotic co‐therapy with clozapine.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>19245679</pmid><doi>10.1111/j.1600-0447.2009.01367.x</doi><tpages>7</tpages></addata></record> |
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| subjects | Adult Adult and adolescent clinical studies Antipsychotic Agents - therapeutic use antipsychotics Biological and medical sciences Brief Psychiatric Rating Scale - statistics & numerical data Clinical trials Clozapine - therapeutic use Drug Therapy, Combination Female Humans Male Medical sciences Meta-analysis Neuropharmacology Pharmacology Pharmacology. Drug treatments Placebos Psychiatric Status Rating Scales - statistics & numerical data Psychiatry Psycholeptics: tranquillizer, neuroleptic Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychopharmacology Psychoses Psychotic Disorders - diagnosis Psychotic Disorders - drug therapy Psychotic Disorders - psychology Randomized Controlled Trials as Topic - statistics & numerical data Schizophrenia Schizophrenia - diagnosis Schizophrenia - drug therapy Schizophrenic Psychology Treatment Outcome |
| title | Augmentation of clozapine with a second antipsychotic - a meta-analysis of randomized, placebo-controlled studies |
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