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Haloperidol for psychosis-induced aggression or agitation (rapid tranquillisation)

Haloperidol, used alone is recommended to help calm situations of aggression with people with psychosis. This drug is widely accessible and may be the only antipsychotic medication available in areas where resources are limited. To investigate whether haloperidol alone, administered orally, intramus...

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Published in:Cochrane database of systematic reviews 2012-11, Vol.11, p.CD009377-CD009377
Main Authors: Powney, Melanie J, Adams, Clive E, Jones, Hannah
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Adams, Clive E
Jones, Hannah
description Haloperidol, used alone is recommended to help calm situations of aggression with people with psychosis. This drug is widely accessible and may be the only antipsychotic medication available in areas where resources are limited. To investigate whether haloperidol alone, administered orally, intramuscularly or intravenously, is effective treatment for psychosis-induced agitation or aggression. We searched the Cochrane Schizophrenia Group Trials Register (1st June 2011). Randomised controlled  trials (RCTs) involving people exhibiting agitation or aggression (or both) thought to be due to psychosis, allocated rapid use of haloperidol alone (by any route), compared with any other treatment. Outcomes included tranquillisation or asleep by 30 minutes, repeated need for rapid tranquillisation within 24 hours, specific behaviours (threat or injury to others/self), adverse effects. We independently selected and assessed studies for methodological quality and extracted data. 'Summary of findings' tables were produced for each comparison grading the evidence and calculating, where possible and appropriate, a range of absolute effects. We included 32 studies comparing haloperidol with 18 other treatments. Few studies were undertaken in circumstances that reflect real world practice, and, with notable exceptions, most were small and carried considerable risk of bias.Compared with placebo, more people in the haloperidol group were asleep at two hours (2 RCTs, n = 220, risk ratio (RR) 0.88, 95% confidence interval (CI) 0.82 to 0.95). Dystonia was common (2 RCTs, n = 207, RR 7.49, CI 0.93 to 60.21). Compared with aripiprazole, people in the haloperidol group required fewer injections than those in the aripiprazole group (2 RCTs, n = 473, RR 0.78, CI 0.62 to 0.99). More people in the haloperidol group experienced dystonia (2 RCTs, n = 477, RR 6.63, CI 1.52 to 28.86).Despite three larger trials with ziprasidone (total n = 739), data remain patchy, largely because of poor design and reporting. Compared with zuclopenthixol acetate, more people who received haloperidol required more than three injections (1 RCT, n = 70, RR 2.54, CI 1.19 to 5.46).Three trials (n = 205) compared haloperidol with lorazepam. There were no significant differences between the groups with regard to the number of participants asleep at one hour (1 RCT, n = 60, RR 1.05, CI 0.76 to 1.44). However, by three hours, significantly more people were asleep in the lorazepam group compared with the haloperidol
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This drug is widely accessible and may be the only antipsychotic medication available in areas where resources are limited. To investigate whether haloperidol alone, administered orally, intramuscularly or intravenously, is effective treatment for psychosis-induced agitation or aggression. We searched the Cochrane Schizophrenia Group Trials Register (1st June 2011). Randomised controlled  trials (RCTs) involving people exhibiting agitation or aggression (or both) thought to be due to psychosis, allocated rapid use of haloperidol alone (by any route), compared with any other treatment. Outcomes included tranquillisation or asleep by 30 minutes, repeated need for rapid tranquillisation within 24 hours, specific behaviours (threat or injury to others/self), adverse effects. We independently selected and assessed studies for methodological quality and extracted data. 'Summary of findings' tables were produced for each comparison grading the evidence and calculating, where possible and appropriate, a range of absolute effects. We included 32 studies comparing haloperidol with 18 other treatments. Few studies were undertaken in circumstances that reflect real world practice, and, with notable exceptions, most were small and carried considerable risk of bias.Compared with placebo, more people in the haloperidol group were asleep at two hours (2 RCTs, n = 220, risk ratio (RR) 0.88, 95% confidence interval (CI) 0.82 to 0.95). Dystonia was common (2 RCTs, n = 207, RR 7.49, CI 0.93 to 60.21). Compared with aripiprazole, people in the haloperidol group required fewer injections than those in the aripiprazole group (2 RCTs, n = 473, RR 0.78, CI 0.62 to 0.99). More people in the haloperidol group experienced dystonia (2 RCTs, n = 477, RR 6.63, CI 1.52 to 28.86).Despite three larger trials with ziprasidone (total n = 739), data remain patchy, largely because of poor design and reporting. Compared with zuclopenthixol acetate, more people who received haloperidol required more than three injections (1 RCT, n = 70, RR 2.54, CI 1.19 to 5.46).Three trials (n = 205) compared haloperidol with lorazepam. There were no significant differences between the groups with regard to the number of participants asleep at one hour (1 RCT, n = 60, RR 1.05, CI 0.76 to 1.44). However, by three hours, significantly more people were asleep in the lorazepam group compared with the haloperidol group (1 RCT, n = 66, RR 1.93, CI 1.14 to 3.27). There were no differences in numbers requiring more than one injection (1 RCT, n = 66, RR 1.14, CI 0.91 to 1.43).Haloperidol's adverse effects were not offset by addition of lorazepam (e.g. dystonia 1 RCT, n = 67, RR 8.25, CI 0.46 to 147.45; required antiparkinson medication RR 2.74, CI 0.81 to 9.25). Addition of promethazine was investigated in one larger and better graded trial (n = 316). More people in the haloperidol group were not tranquil or asleep by 20 minutes (RR 1.60, CI 1.18 to 2.16). Significantly more people in the haloperidol alone group experienced one or more adverse effects (RR 11.28, CI 1.47 to 86.35). Acute dystonia for those allocated haloperidol alone was too common for the trial to continue beyond the interim analysis (RR 19.48, CI 1.14 to 331.92). If no other alternative exists, sole use of intramuscular haloperidol could be life-saving. Where additional drugs to offset the adverse effects are available, sole use of haloperidol for the extreme emergency, in situations of coercion, could be considered unethical. Addition of the sedating promethazine has support from better-grade evidence from within randomised trials. Use of an alternative antipsychotic drug is only partially supported by fragmented and poor-grade evidence. Evidence for use of newer generation antipsychotic alternatives is no stronger than that for older drugs. Adding a benzodiazepine to haloperidol does not have strong evidence of benefit and carries a risk of additional harm.After six decades of use for emergency rapid tranquillisation, this is still an area in need of good independent trials relevant to real world practice.</description><identifier>EISSN: 1469-493X</identifier><identifier>DOI: 10.1002/14651858.CD009377.pub2</identifier><identifier>PMID: 23152276</identifier><language>eng</language><publisher>England</publisher><subject><![CDATA[Aggression - drug effects ; Aggression - psychology ; Antipsychotic Agents - administration & dosage ; Antipsychotic Agents - adverse effects ; Aripiprazole ; Clopenthixol - administration & dosage ; Dystonia - chemically induced ; Haloperidol - administration & dosage ; Haloperidol - adverse effects ; Humans ; Lorazepam - administration & dosage ; Piperazines - administration & dosage ; Psychomotor Agitation - drug therapy ; Psychotic Disorders - drug therapy ; Psychotic Disorders - psychology ; Quinolones - administration & dosage ; Randomized Controlled Trials as Topic ; Sleep ; Thiazoles - administration & dosage]]></subject><ispartof>Cochrane database of systematic reviews, 2012-11, Vol.11, p.CD009377-CD009377</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c264t-59712d5ae4729959d9c260677ac111ce2beee74e00b0b60af7ffea6a5e8b0f353</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23152276$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Powney, Melanie J</creatorcontrib><creatorcontrib>Adams, Clive E</creatorcontrib><creatorcontrib>Jones, Hannah</creatorcontrib><title>Haloperidol for psychosis-induced aggression or agitation (rapid tranquillisation)</title><title>Cochrane database of systematic reviews</title><addtitle>Cochrane Database Syst Rev</addtitle><description>Haloperidol, used alone is recommended to help calm situations of aggression with people with psychosis. This drug is widely accessible and may be the only antipsychotic medication available in areas where resources are limited. To investigate whether haloperidol alone, administered orally, intramuscularly or intravenously, is effective treatment for psychosis-induced agitation or aggression. We searched the Cochrane Schizophrenia Group Trials Register (1st June 2011). Randomised controlled  trials (RCTs) involving people exhibiting agitation or aggression (or both) thought to be due to psychosis, allocated rapid use of haloperidol alone (by any route), compared with any other treatment. Outcomes included tranquillisation or asleep by 30 minutes, repeated need for rapid tranquillisation within 24 hours, specific behaviours (threat or injury to others/self), adverse effects. We independently selected and assessed studies for methodological quality and extracted data. 'Summary of findings' tables were produced for each comparison grading the evidence and calculating, where possible and appropriate, a range of absolute effects. We included 32 studies comparing haloperidol with 18 other treatments. Few studies were undertaken in circumstances that reflect real world practice, and, with notable exceptions, most were small and carried considerable risk of bias.Compared with placebo, more people in the haloperidol group were asleep at two hours (2 RCTs, n = 220, risk ratio (RR) 0.88, 95% confidence interval (CI) 0.82 to 0.95). Dystonia was common (2 RCTs, n = 207, RR 7.49, CI 0.93 to 60.21). Compared with aripiprazole, people in the haloperidol group required fewer injections than those in the aripiprazole group (2 RCTs, n = 473, RR 0.78, CI 0.62 to 0.99). More people in the haloperidol group experienced dystonia (2 RCTs, n = 477, RR 6.63, CI 1.52 to 28.86).Despite three larger trials with ziprasidone (total n = 739), data remain patchy, largely because of poor design and reporting. Compared with zuclopenthixol acetate, more people who received haloperidol required more than three injections (1 RCT, n = 70, RR 2.54, CI 1.19 to 5.46).Three trials (n = 205) compared haloperidol with lorazepam. There were no significant differences between the groups with regard to the number of participants asleep at one hour (1 RCT, n = 60, RR 1.05, CI 0.76 to 1.44). However, by three hours, significantly more people were asleep in the lorazepam group compared with the haloperidol group (1 RCT, n = 66, RR 1.93, CI 1.14 to 3.27). There were no differences in numbers requiring more than one injection (1 RCT, n = 66, RR 1.14, CI 0.91 to 1.43).Haloperidol's adverse effects were not offset by addition of lorazepam (e.g. dystonia 1 RCT, n = 67, RR 8.25, CI 0.46 to 147.45; required antiparkinson medication RR 2.74, CI 0.81 to 9.25). Addition of promethazine was investigated in one larger and better graded trial (n = 316). More people in the haloperidol group were not tranquil or asleep by 20 minutes (RR 1.60, CI 1.18 to 2.16). Significantly more people in the haloperidol alone group experienced one or more adverse effects (RR 11.28, CI 1.47 to 86.35). Acute dystonia for those allocated haloperidol alone was too common for the trial to continue beyond the interim analysis (RR 19.48, CI 1.14 to 331.92). If no other alternative exists, sole use of intramuscular haloperidol could be life-saving. Where additional drugs to offset the adverse effects are available, sole use of haloperidol for the extreme emergency, in situations of coercion, could be considered unethical. Addition of the sedating promethazine has support from better-grade evidence from within randomised trials. Use of an alternative antipsychotic drug is only partially supported by fragmented and poor-grade evidence. Evidence for use of newer generation antipsychotic alternatives is no stronger than that for older drugs. Adding a benzodiazepine to haloperidol does not have strong evidence of benefit and carries a risk of additional harm.After six decades of use for emergency rapid tranquillisation, this is still an area in need of good independent trials relevant to real world practice.</description><subject>Aggression - drug effects</subject><subject>Aggression - psychology</subject><subject>Antipsychotic Agents - administration &amp; dosage</subject><subject>Antipsychotic Agents - adverse effects</subject><subject>Aripiprazole</subject><subject>Clopenthixol - administration &amp; dosage</subject><subject>Dystonia - chemically induced</subject><subject>Haloperidol - administration &amp; dosage</subject><subject>Haloperidol - adverse effects</subject><subject>Humans</subject><subject>Lorazepam - administration &amp; dosage</subject><subject>Piperazines - administration &amp; dosage</subject><subject>Psychomotor Agitation - drug therapy</subject><subject>Psychotic Disorders - drug therapy</subject><subject>Psychotic Disorders - psychology</subject><subject>Quinolones - administration &amp; dosage</subject><subject>Randomized Controlled Trials as Topic</subject><subject>Sleep</subject><subject>Thiazoles - administration &amp; dosage</subject><issn>1469-493X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNo1kD1PwzAYhC0kREvhL1QZy5Di147teETho0iVkBBIbJETvylGaZzaydB_T4Ayne6e0w1HyBLoGihlt5BJAbnI18U9pZorte7Hip2R-QR0mmn-MSOXMX5RyjVAfkFmjINgTMk5ed2Y1vcYnPVt0viQ9PFYf_roYuo6O9ZoE7PbBYzR-S6ZuNm5wQw_ZhVM72wyBNMdRte2Lv7mN1fkvDFtxOuTLsj748NbsUm3L0_Pxd02rZnMhlRoBcwKg5liWgtt9ZRTqZSpAaBGViGiypDSilaSmkY1DRppBOYVbbjgC7L62-2DP4wYh3LvYo1tazr0YywBFORS5dMBC7I8Vcdqj7bsg9ubcCz_f-DfvsBg4Q</recordid><startdate>20121114</startdate><enddate>20121114</enddate><creator>Powney, Melanie J</creator><creator>Adams, Clive E</creator><creator>Jones, Hannah</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20121114</creationdate><title>Haloperidol for psychosis-induced aggression or agitation (rapid tranquillisation)</title><author>Powney, Melanie J ; Adams, Clive E ; Jones, Hannah</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c264t-59712d5ae4729959d9c260677ac111ce2beee74e00b0b60af7ffea6a5e8b0f353</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Aggression - drug effects</topic><topic>Aggression - psychology</topic><topic>Antipsychotic Agents - administration &amp; dosage</topic><topic>Antipsychotic Agents - adverse effects</topic><topic>Aripiprazole</topic><topic>Clopenthixol - administration &amp; dosage</topic><topic>Dystonia - chemically induced</topic><topic>Haloperidol - administration &amp; dosage</topic><topic>Haloperidol - adverse effects</topic><topic>Humans</topic><topic>Lorazepam - administration &amp; dosage</topic><topic>Piperazines - administration &amp; dosage</topic><topic>Psychomotor Agitation - drug therapy</topic><topic>Psychotic Disorders - drug therapy</topic><topic>Psychotic Disorders - psychology</topic><topic>Quinolones - administration &amp; dosage</topic><topic>Randomized Controlled Trials as Topic</topic><topic>Sleep</topic><topic>Thiazoles - administration &amp; dosage</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Powney, Melanie J</creatorcontrib><creatorcontrib>Adams, Clive E</creatorcontrib><creatorcontrib>Jones, Hannah</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Cochrane database of systematic reviews</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Powney, Melanie J</au><au>Adams, Clive E</au><au>Jones, Hannah</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Haloperidol for psychosis-induced aggression or agitation (rapid tranquillisation)</atitle><jtitle>Cochrane database of systematic reviews</jtitle><addtitle>Cochrane Database Syst Rev</addtitle><date>2012-11-14</date><risdate>2012</risdate><volume>11</volume><spage>CD009377</spage><epage>CD009377</epage><pages>CD009377-CD009377</pages><eissn>1469-493X</eissn><abstract>Haloperidol, used alone is recommended to help calm situations of aggression with people with psychosis. This drug is widely accessible and may be the only antipsychotic medication available in areas where resources are limited. To investigate whether haloperidol alone, administered orally, intramuscularly or intravenously, is effective treatment for psychosis-induced agitation or aggression. We searched the Cochrane Schizophrenia Group Trials Register (1st June 2011). Randomised controlled  trials (RCTs) involving people exhibiting agitation or aggression (or both) thought to be due to psychosis, allocated rapid use of haloperidol alone (by any route), compared with any other treatment. Outcomes included tranquillisation or asleep by 30 minutes, repeated need for rapid tranquillisation within 24 hours, specific behaviours (threat or injury to others/self), adverse effects. We independently selected and assessed studies for methodological quality and extracted data. 'Summary of findings' tables were produced for each comparison grading the evidence and calculating, where possible and appropriate, a range of absolute effects. We included 32 studies comparing haloperidol with 18 other treatments. Few studies were undertaken in circumstances that reflect real world practice, and, with notable exceptions, most were small and carried considerable risk of bias.Compared with placebo, more people in the haloperidol group were asleep at two hours (2 RCTs, n = 220, risk ratio (RR) 0.88, 95% confidence interval (CI) 0.82 to 0.95). Dystonia was common (2 RCTs, n = 207, RR 7.49, CI 0.93 to 60.21). Compared with aripiprazole, people in the haloperidol group required fewer injections than those in the aripiprazole group (2 RCTs, n = 473, RR 0.78, CI 0.62 to 0.99). More people in the haloperidol group experienced dystonia (2 RCTs, n = 477, RR 6.63, CI 1.52 to 28.86).Despite three larger trials with ziprasidone (total n = 739), data remain patchy, largely because of poor design and reporting. Compared with zuclopenthixol acetate, more people who received haloperidol required more than three injections (1 RCT, n = 70, RR 2.54, CI 1.19 to 5.46).Three trials (n = 205) compared haloperidol with lorazepam. There were no significant differences between the groups with regard to the number of participants asleep at one hour (1 RCT, n = 60, RR 1.05, CI 0.76 to 1.44). However, by three hours, significantly more people were asleep in the lorazepam group compared with the haloperidol group (1 RCT, n = 66, RR 1.93, CI 1.14 to 3.27). There were no differences in numbers requiring more than one injection (1 RCT, n = 66, RR 1.14, CI 0.91 to 1.43).Haloperidol's adverse effects were not offset by addition of lorazepam (e.g. dystonia 1 RCT, n = 67, RR 8.25, CI 0.46 to 147.45; required antiparkinson medication RR 2.74, CI 0.81 to 9.25). Addition of promethazine was investigated in one larger and better graded trial (n = 316). More people in the haloperidol group were not tranquil or asleep by 20 minutes (RR 1.60, CI 1.18 to 2.16). Significantly more people in the haloperidol alone group experienced one or more adverse effects (RR 11.28, CI 1.47 to 86.35). Acute dystonia for those allocated haloperidol alone was too common for the trial to continue beyond the interim analysis (RR 19.48, CI 1.14 to 331.92). If no other alternative exists, sole use of intramuscular haloperidol could be life-saving. Where additional drugs to offset the adverse effects are available, sole use of haloperidol for the extreme emergency, in situations of coercion, could be considered unethical. Addition of the sedating promethazine has support from better-grade evidence from within randomised trials. Use of an alternative antipsychotic drug is only partially supported by fragmented and poor-grade evidence. Evidence for use of newer generation antipsychotic alternatives is no stronger than that for older drugs. Adding a benzodiazepine to haloperidol does not have strong evidence of benefit and carries a risk of additional harm.After six decades of use for emergency rapid tranquillisation, this is still an area in need of good independent trials relevant to real world practice.</abstract><cop>England</cop><pmid>23152276</pmid><doi>10.1002/14651858.CD009377.pub2</doi></addata></record>
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subjects Aggression - drug effects
Aggression - psychology
Antipsychotic Agents - administration & dosage
Antipsychotic Agents - adverse effects
Aripiprazole
Clopenthixol - administration & dosage
Dystonia - chemically induced
Haloperidol - administration & dosage
Haloperidol - adverse effects
Humans
Lorazepam - administration & dosage
Piperazines - administration & dosage
Psychomotor Agitation - drug therapy
Psychotic Disorders - drug therapy
Psychotic Disorders - psychology
Quinolones - administration & dosage
Randomized Controlled Trials as Topic
Sleep
Thiazoles - administration & dosage
title Haloperidol for psychosis-induced aggression or agitation (rapid tranquillisation)
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