Evid Based Mental Health-2014-Pharmacological Interventions-9

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  Review: 15 antipsychotic drugsare more effective than placebofor the treatment of schizophrenia,but vary in their tolerability doi:10.1136/eb-2013-101612 QUESTION Question  What is the comparative ef  󿬁 cacy, risk of all-causediscontinuation and major side effects of antipsychotics usedfor the treatment of schizophrenia ? Outcomes  The mean overall change in symptoms (primary outcome), all-cause discontinuation, weight gain, extrapyr-amidal side effects, prolactin increase, prolonged QT intervaland sedation. METHODS Design  Systematic review and multiple-treatment meta-analysis. Datasources Cochrane Schizophrenia Group ’ s specialised regis-ter, MEDLINE, EMBASE, PsycINFO, CENTRAL were searched up to September 2012, supple-mented by review of Food and Drug Administration andpharmaceutical company websites and reference lists of reviews. Study selection and analysis  Randomised controlled trials(single-blind at minimum) of 15 orally administered anti-psychotic drugs used as monotherapy for the acute treat-ment of schizophrenia or related disorders (schizoaffective,schizophreniform or delusional disorder). Trials in stablepatients, those with predominant negative symptoms, con-comitant medical illnesses or treatment resistance wereexcluded. A multiple-treatment meta-analysis was per-formed. The standardised mean differences were calculatedfor continuous outcomes and ORs for binary outcomes. MAIN RESULTS  A total of 212 studies, with 43 049 participants were included(mean age 38.4 years, mean duration of illness 12.4 years). Alldrugs were more effective than placebo, and clozapine was sig-ni 󿬁 cantly more effective than all other drugs. The standardisedmean differences with 95% credible intervals (CrI), in the orderof effectiveness of 15 antipsychotics, were clozapine, amisul-pride, olanzapine, risperidone, paliperidone, zotepine, haloperi-dol, quetiapine, aripiprazole, sertindole, ziprasidone,chlorpromazine, asenapine, lurasidone and iloperidone. Theodds of all-cause discontinuation were signi 󿬁 cantly lower withall drugs compared with placebo (ORs ranging from 0.43 foramisulpride to 0.80 for haloperidol), with the exception of zotepine. Apart from haloperidol, ziprasidone and lurasidone,all drugs produced more weight gain than placebo. Examiningthe frequency of extrapyramidal side effects, compared withplacebo, it was signi 󿬁 cantly fewer with clozapine; there wereno signi 󿬁 cant differences with sertindole, olanzapine, quetia-pine, aripiprazole, iloperidone, amisulpride and asenapine; andall other drugs caused signi 󿬁 cantly more extrapyramidal sideeffects than placebo. Aripiprazole, quetiapine, asenapine, chlor-promazine and iloperidone did not cause signi 󿬁 cantly increasedprolactin concentrations compared with placebo; all otherdrugs caused signi 󿬁 cantly more prolactin (amisulpride, cloza-pine and zotepine not analysed). QT interval was not signi 󿬁 -cantly prolonged with lurasidone, aripiprazole, paliperidoneand asenapine compared with placebo, but it was signi 󿬁 cantly prolonged with all other drugs (clozapine, chlorpromazine andzotepine not analysed). Amisulpride, paliperidone, sertindoleand iloperidone were not signi 󿬁 cantly more sedating thanplacebo; all other drugs were more sedating than placebo. Foreffect sizes, 95% CrI and rankings of all 15 antipsychotic drugscompared with placebo for all outcomes see Webextra table. CONCLUSIONS This multiple-treatment meta-analysis provides evidence-based hierarchies for the ef  󿬁 cacy and tolerability of anti-psychotic drugs. ABSTRACTED FROM Leucht S,  Cipriani A, Spineli L,  et al  . Comparative ef   󿬁 cacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis.  Lancet  2013; 382 :951 – 62. Correspondence to:  Professor Stefan Leucht, Department of Psychiatry andPsychotherapy, Technische Universität München, Klinikum rechts der Isar,81675 Munich, Germany ( ▸  Additional material is published online only. To view please visit the journal online(  C   O  MME  N T  A R  Y   T he analysis by Leucht and colleagues is animpressive work, and the authors are to becommended on describing their sophisticatedanalyses in such a cogent manner. It is evident that  󿬁 rst-generation and second-generation antipsycho-tics overlap substantially. 1 However, in evidence-based practice we need to take into account thevalues and preferences that individual patients mayhave, and should also consider the penalty imposedon patients when benztropine or other anticholiner-gic medicine is required. 2 In addition, rank-orderingmedications based on data gathered from groupcomparisons can be problematic as there can besubstantial heterogeneity that prevents the reliableprediction of effects on individual persons, exceptwhen there are large differences in the outcomein question such as, for example, effects on prolac-tin increase with aripiprazole vs. risperidone/ paliperidone. 1 Of particular concern is how the Leucht study isreported in the professional media (  󿬁 nds.html), with statements such as “ The researchers found that  …  respectively, thegreatest ef   󿬁 cacy, while  …  showed the least, ”  whichif taken in isolation may lead clinicians to avoid medi-cations at the bottom of the list without fully consid-ering other relevant outcomes such as weight gain,extrapyramidal side effects and sedation that arewell-described and quanti  󿬁 ed elsewhere in thepaper. Matching up the right medication to the rightpatient will require careful consideration of the toler-ability and safety pro  󿬁 le of the medication which willimpact on the patient ’ s adherence to treatment andon the clinician ’ s willingness to prescribe. This studyhas the potential to positively impact clinicaldecision-making, provided that appropriate attentionis paid to both ef   󿬁 cacy and tolerability. Leslie Citrome, 1 Jan Volavka 2 1 New York Medical College, Valhalla, New York,USA; 2 New York University School of Medicine,New York, New York, USA Competing interests  LC in the past 36 months wasengaged in collaborative research with, or receivedconsulting or speaking fees from Alexza, Alkermes,AstraZeneca, Avanir, Bristol-Myers Squibb, Eli Lilly,Envivo, Forest, Genentech, Janssen, Lundbeck, Merck,Mylan, Novartis, Noven, Otsuka, P  󿬁 zer, ReckittBenckiser, Reviva, Shire, Sunovion, Takeda and Valeant. REFERENCES 1.  Volavka J,  Citrome L. Oral antipsychotics for thetreatment of schizophrenia: heterogeneity in ef   󿬁 cacyand tolerability should drive decision-making.  Expert Opin Pharmacother   2009; 10 :1917 – 28.2.  Vinogradov S,  Fisher M, Warm H,  et al  . Thecognitive cost of anticholinergic burden: decreasedresponse to cognitive training in schizophrenia.  Am J  Psychiatry   2009; 166 :1055 – 62.  Evid Based Mental Health  February 2014 Vol 17 No 1 9 Pharmacological interventions  group.bmj.comon October 10, 2014 - Published by ebmh.bmj.comDownloaded from   doi: 10.1136/eb-2013-101612 December 16, 2013 2014 17: 9 srcinally published online Evid Based Mental Health    schizophrenia, but vary in their tolerabilityeffective than placebo for the treatment of Review: 15 antipsychotic drugs are more Updated information and services can be found at: These include:  Data Supplement Supplementary Data   References This article cites 3 articles serviceEmail alerting the box at the top right corner of the online article.Receive free email alerts when new articles cite this article. Sign up in CollectionsTopic  (1471 articles)Epidemiology (947 articles)Clinical trials (epidemiology)  (399 articles)Schizophrenia spectrum  (312 articles)Drugs: psychiatry  Articles on similar topics can be found in the following collections Notes To request permissions go to: To order reprints go to: To subscribe to BMJ go to:  group.bmj.comon October 10, 2014 - Published by ebmh.bmj.comDownloaded from 
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