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Practitioner Review: Pharmacological treatment of attention‐deficit/hyperactivity disorder symptoms in children and youth with autism spectrum disorder: a systematic review and meta‐analysis
Background Clinically significant attention‐deficit/hyperactivity disorder (ADHD) symptoms are common and impairing in children and youth with autism spectrum disorder(ASD). The aim of this systematic review and meta‐analysis was to (a) evaluate the efficacy and safety of pharmacotherapy for the tre...
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| Published in: | Journal of child psychology and psychiatry 2021-06, Vol.62 (6), p.680-700 |
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| container_title | Journal of child psychology and psychiatry |
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| creator | Rodrigues, Rebecca Lai, Meng‐Chuan Beswick, Adam Gorman, Daniel A. Anagnostou, Evdokia Szatmari, Peter Anderson, Kelly K. Ameis, Stephanie H. |
| description | Background
Clinically significant attention‐deficit/hyperactivity disorder (ADHD) symptoms are common and impairing in children and youth with autism spectrum disorder(ASD). The aim of this systematic review and meta‐analysis was to (a) evaluate the efficacy and safety of pharmacotherapy for the treatment of ADHD symptoms in ASD and (b) distil findings for clinical translation.
Methods
We searched electronic databases and clinical trial registries (1992 onwards). We selected randomized controlled trials conducted in participants |
| doi_str_mv | 10.1111/jcpp.13305 |
| format | article |
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Clinically significant attention‐deficit/hyperactivity disorder (ADHD) symptoms are common and impairing in children and youth with autism spectrum disorder(ASD). The aim of this systematic review and meta‐analysis was to (a) evaluate the efficacy and safety of pharmacotherapy for the treatment of ADHD symptoms in ASD and (b) distil findings for clinical translation.
Methods
We searched electronic databases and clinical trial registries (1992 onwards). We selected randomized controlled trials conducted in participants <25 years of age, diagnosed with ASD that evaluated ADHD outcomes (hyperactivity/impulsivity and inattention) following treatment with stimulants (methylphenidate or amphetamines), atomoxetine, alpha‐2 adrenergic receptor agonists, antipsychotics, tricyclic antidepressants, bupropion, modafinil, venlafaxine, or a combination, in comparison with placebo, any of the listed medications, or behavioral therapies. Data were pooled using a random‐effects model.
Results
Twenty‐five studies (4 methylphenidate, 4 atomoxetine, 1 guanfacine, 14 antipsychotic, 1 venlafaxine, and 1 tianeptine) were included. Methylphenidate reduced hyperactivity (parent‐rated: standardized mean difference [SMD] = −.63, 95%CI = −.95,−.30; teacher‐rated: SMD = −.81, 95%CI = −1.43,−.19) and inattention (parent‐rated: SMD = −.36, 95%CI = −.64,−.07; teacher‐rated: SMD = −.30, 95%CI = −.49,−.11). Atomoxetine reduced inattention (parent‐rated: SMD = −.54, 95%CI = −.98,−.09; teacher/investigator‐rated: SMD = −0.38, 95%CI = −0.75, −0.01) and parent‐rated hyperactivity (parent‐rated: SMD = −.49, 95%CI = −.76,−.23; teacher‐rated: SMD = −.43, 95%CI = −.92, .06). Indirect evidence for significant reductions in hyperactivity with second‐generation antipsychotics was also found. Quality of evidence for all interventions was low/very low. Methylphenidate was associated with a nonsignificant elevated risk of dropout due to adverse events.
Conclusions
Direct pooled evidence supports the efficacy and tolerability of methylphenidate or atomoxetine for treatment of ADHD symptoms in children and youth with ASD. The current review highlights the efficacy of standard ADHD pharmacotherapy for treatment of ADHD symptoms in children and youth with ASD. Consideration of the benefits weighed against the limitations of safety/efficacy data and lack of data evaluating long‐term continuation is undertaken to help guide clinical decision‐making regarding treatment of co‐occurring ADHD symptoms in children and youth with ASD.</description><identifier>ISSN: 0021-9630</identifier><identifier>EISSN: 1469-7610</identifier><identifier>DOI: 10.1111/jcpp.13305</identifier><identifier>PMID: 32845025</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>ADHD ; alpha‐2 agonists ; Amphetamines ; Antidepressants ; antipsychotics ; Atomoxetine ; Attention Deficit Disorders ; Attention deficit hyperactivity disorder ; Autism ; autism spectrum disorder ; Autism Spectrum Disorders ; Autistic children ; Bupropion ; Child & adolescent psychiatry ; Children & youth ; Clinical decision making ; Clinical research ; Clinical significance ; Clinical trials ; Critical incidents ; Dropping out ; Drug therapy ; Drugs ; Efficacy ; Evidence ; Hyperactivity ; Impulsivity ; inattention ; Meta-analysis ; Methylphenidate ; Modafinil ; Parents ; pervasive developmental disorder ; Pharmacology ; pharmacotherapy ; Psychotropic drugs ; Randomized Controlled Trials ; Stimulants ; Systematic review ; Teachers ; Translation ; Treatment methods ; tricyclic antidepressants ; venlafaxine ; Youth</subject><ispartof>Journal of child psychology and psychiatry, 2021-06, Vol.62 (6), p.680-700</ispartof><rights>2020 Association for Child and Adolescent Mental Health</rights><rights>2020 Association for Child and Adolescent Mental Health.</rights><rights>Copyright © 2021 Association for Child and Adolescent Mental Health</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3575-1497c7084c73e55bd87b069a8f27d7e0379bde523230d3a8337d0167a8b6fd953</citedby><cites>FETCH-LOGICAL-c3575-1497c7084c73e55bd87b069a8f27d7e0379bde523230d3a8337d0167a8b6fd953</cites><orcidid>0000-0002-9593-5508 ; 0000-0002-7282-6077</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925,30999</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32845025$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rodrigues, Rebecca</creatorcontrib><creatorcontrib>Lai, Meng‐Chuan</creatorcontrib><creatorcontrib>Beswick, Adam</creatorcontrib><creatorcontrib>Gorman, Daniel A.</creatorcontrib><creatorcontrib>Anagnostou, Evdokia</creatorcontrib><creatorcontrib>Szatmari, Peter</creatorcontrib><creatorcontrib>Anderson, Kelly K.</creatorcontrib><creatorcontrib>Ameis, Stephanie H.</creatorcontrib><title>Practitioner Review: Pharmacological treatment of attention‐deficit/hyperactivity disorder symptoms in children and youth with autism spectrum disorder: a systematic review and meta‐analysis</title><title>Journal of child psychology and psychiatry</title><addtitle>J Child Psychol Psychiatry</addtitle><description>Background
Clinically significant attention‐deficit/hyperactivity disorder (ADHD) symptoms are common and impairing in children and youth with autism spectrum disorder(ASD). The aim of this systematic review and meta‐analysis was to (a) evaluate the efficacy and safety of pharmacotherapy for the treatment of ADHD symptoms in ASD and (b) distil findings for clinical translation.
Methods
We searched electronic databases and clinical trial registries (1992 onwards). We selected randomized controlled trials conducted in participants <25 years of age, diagnosed with ASD that evaluated ADHD outcomes (hyperactivity/impulsivity and inattention) following treatment with stimulants (methylphenidate or amphetamines), atomoxetine, alpha‐2 adrenergic receptor agonists, antipsychotics, tricyclic antidepressants, bupropion, modafinil, venlafaxine, or a combination, in comparison with placebo, any of the listed medications, or behavioral therapies. Data were pooled using a random‐effects model.
Results
Twenty‐five studies (4 methylphenidate, 4 atomoxetine, 1 guanfacine, 14 antipsychotic, 1 venlafaxine, and 1 tianeptine) were included. Methylphenidate reduced hyperactivity (parent‐rated: standardized mean difference [SMD] = −.63, 95%CI = −.95,−.30; teacher‐rated: SMD = −.81, 95%CI = −1.43,−.19) and inattention (parent‐rated: SMD = −.36, 95%CI = −.64,−.07; teacher‐rated: SMD = −.30, 95%CI = −.49,−.11). Atomoxetine reduced inattention (parent‐rated: SMD = −.54, 95%CI = −.98,−.09; teacher/investigator‐rated: SMD = −0.38, 95%CI = −0.75, −0.01) and parent‐rated hyperactivity (parent‐rated: SMD = −.49, 95%CI = −.76,−.23; teacher‐rated: SMD = −.43, 95%CI = −.92, .06). Indirect evidence for significant reductions in hyperactivity with second‐generation antipsychotics was also found. Quality of evidence for all interventions was low/very low. Methylphenidate was associated with a nonsignificant elevated risk of dropout due to adverse events.
Conclusions
Direct pooled evidence supports the efficacy and tolerability of methylphenidate or atomoxetine for treatment of ADHD symptoms in children and youth with ASD. The current review highlights the efficacy of standard ADHD pharmacotherapy for treatment of ADHD symptoms in children and youth with ASD. Consideration of the benefits weighed against the limitations of safety/efficacy data and lack of data evaluating long‐term continuation is undertaken to help guide clinical decision‐making regarding treatment of co‐occurring ADHD symptoms in children and youth with ASD.</description><subject>ADHD</subject><subject>alpha‐2 agonists</subject><subject>Amphetamines</subject><subject>Antidepressants</subject><subject>antipsychotics</subject><subject>Atomoxetine</subject><subject>Attention Deficit Disorders</subject><subject>Attention deficit hyperactivity disorder</subject><subject>Autism</subject><subject>autism spectrum disorder</subject><subject>Autism Spectrum Disorders</subject><subject>Autistic children</subject><subject>Bupropion</subject><subject>Child & adolescent psychiatry</subject><subject>Children & youth</subject><subject>Clinical decision making</subject><subject>Clinical research</subject><subject>Clinical significance</subject><subject>Clinical trials</subject><subject>Critical incidents</subject><subject>Dropping out</subject><subject>Drug therapy</subject><subject>Drugs</subject><subject>Efficacy</subject><subject>Evidence</subject><subject>Hyperactivity</subject><subject>Impulsivity</subject><subject>inattention</subject><subject>Meta-analysis</subject><subject>Methylphenidate</subject><subject>Modafinil</subject><subject>Parents</subject><subject>pervasive developmental disorder</subject><subject>Pharmacology</subject><subject>pharmacotherapy</subject><subject>Psychotropic drugs</subject><subject>Randomized Controlled Trials</subject><subject>Stimulants</subject><subject>Systematic review</subject><subject>Teachers</subject><subject>Translation</subject><subject>Treatment methods</subject><subject>tricyclic antidepressants</subject><subject>venlafaxine</subject><subject>Youth</subject><issn>0021-9630</issn><issn>1469-7610</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>7QJ</sourceid><recordid>eNp9kU1u1DAYhi1ERYeBDQdAltigSmntOI6T7qoR5UeVOkKwjhz7C-NRHAfb6Sg7jsCZOAonwTPTdsGiXthePO_jT34RekPJOU3rYqvG8ZwyRvgztKBFWWeipOQ5WhCS06wuGTlFL0PYEkJKxqsX6JTlVcFJzhfoz9pLFU00bgCPv8Kdgd0lXm-kt1K53v0wSvY4epDRwhCx67CMMd1S4O-v3xo6o0y82MwjHER3Js5Ym-C8Tr4w2zE6G7AZsNqYXnsYsBw0nt0UN3hn0ianaILFYQQV_WQfw5dYpnyIYGU0CvvDaIewhSjT23KQ_RxMeIVOOtkHeH1_LtH36w_fVp-ym9uPn1dXN5liXPCMFrVQglSFEgw4b3UlWlLWsupyoQUQJupWA89ZzohmsmJMaEJLIau27HTN2RK9P3pH735OEGJjTVDQ93IAN4UmL5hgdVmnD1-id_-hWzf5NG-ieF6VNHW1p86OlPIuBA9dM3pjpZ8bSpp9s82-2ebQbILf3iun1oJ-RB-qTAA9AjvTw_yEqvmyWq-P0n80BbVF</recordid><startdate>202106</startdate><enddate>202106</enddate><creator>Rodrigues, Rebecca</creator><creator>Lai, Meng‐Chuan</creator><creator>Beswick, Adam</creator><creator>Gorman, Daniel A.</creator><creator>Anagnostou, Evdokia</creator><creator>Szatmari, Peter</creator><creator>Anderson, Kelly K.</creator><creator>Ameis, Stephanie H.</creator><general>Blackwell Publishing Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QJ</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9593-5508</orcidid><orcidid>https://orcid.org/0000-0002-7282-6077</orcidid></search><sort><creationdate>202106</creationdate><title>Practitioner Review: Pharmacological treatment of attention‐deficit/hyperactivity disorder symptoms in children and youth with autism spectrum disorder: a systematic review and meta‐analysis</title><author>Rodrigues, Rebecca ; Lai, Meng‐Chuan ; Beswick, Adam ; Gorman, Daniel A. ; Anagnostou, Evdokia ; Szatmari, Peter ; Anderson, Kelly K. ; Ameis, Stephanie H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3575-1497c7084c73e55bd87b069a8f27d7e0379bde523230d3a8337d0167a8b6fd953</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>ADHD</topic><topic>alpha‐2 agonists</topic><topic>Amphetamines</topic><topic>Antidepressants</topic><topic>antipsychotics</topic><topic>Atomoxetine</topic><topic>Attention Deficit Disorders</topic><topic>Attention deficit hyperactivity disorder</topic><topic>Autism</topic><topic>autism spectrum disorder</topic><topic>Autism Spectrum Disorders</topic><topic>Autistic children</topic><topic>Bupropion</topic><topic>Child & adolescent psychiatry</topic><topic>Children & youth</topic><topic>Clinical decision making</topic><topic>Clinical research</topic><topic>Clinical significance</topic><topic>Clinical trials</topic><topic>Critical incidents</topic><topic>Dropping out</topic><topic>Drug therapy</topic><topic>Drugs</topic><topic>Efficacy</topic><topic>Evidence</topic><topic>Hyperactivity</topic><topic>Impulsivity</topic><topic>inattention</topic><topic>Meta-analysis</topic><topic>Methylphenidate</topic><topic>Modafinil</topic><topic>Parents</topic><topic>pervasive developmental disorder</topic><topic>Pharmacology</topic><topic>pharmacotherapy</topic><topic>Psychotropic drugs</topic><topic>Randomized Controlled Trials</topic><topic>Stimulants</topic><topic>Systematic review</topic><topic>Teachers</topic><topic>Translation</topic><topic>Treatment methods</topic><topic>tricyclic antidepressants</topic><topic>venlafaxine</topic><topic>Youth</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rodrigues, Rebecca</creatorcontrib><creatorcontrib>Lai, Meng‐Chuan</creatorcontrib><creatorcontrib>Beswick, Adam</creatorcontrib><creatorcontrib>Gorman, Daniel A.</creatorcontrib><creatorcontrib>Anagnostou, Evdokia</creatorcontrib><creatorcontrib>Szatmari, Peter</creatorcontrib><creatorcontrib>Anderson, Kelly K.</creatorcontrib><creatorcontrib>Ameis, Stephanie H.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Applied Social Sciences Index & Abstracts (ASSIA)</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of child psychology and psychiatry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rodrigues, Rebecca</au><au>Lai, Meng‐Chuan</au><au>Beswick, Adam</au><au>Gorman, Daniel A.</au><au>Anagnostou, Evdokia</au><au>Szatmari, Peter</au><au>Anderson, Kelly K.</au><au>Ameis, Stephanie H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Practitioner Review: Pharmacological treatment of attention‐deficit/hyperactivity disorder symptoms in children and youth with autism spectrum disorder: a systematic review and meta‐analysis</atitle><jtitle>Journal of child psychology and psychiatry</jtitle><addtitle>J Child Psychol Psychiatry</addtitle><date>2021-06</date><risdate>2021</risdate><volume>62</volume><issue>6</issue><spage>680</spage><epage>700</epage><pages>680-700</pages><issn>0021-9630</issn><eissn>1469-7610</eissn><abstract>Background
Clinically significant attention‐deficit/hyperactivity disorder (ADHD) symptoms are common and impairing in children and youth with autism spectrum disorder(ASD). The aim of this systematic review and meta‐analysis was to (a) evaluate the efficacy and safety of pharmacotherapy for the treatment of ADHD symptoms in ASD and (b) distil findings for clinical translation.
Methods
We searched electronic databases and clinical trial registries (1992 onwards). We selected randomized controlled trials conducted in participants <25 years of age, diagnosed with ASD that evaluated ADHD outcomes (hyperactivity/impulsivity and inattention) following treatment with stimulants (methylphenidate or amphetamines), atomoxetine, alpha‐2 adrenergic receptor agonists, antipsychotics, tricyclic antidepressants, bupropion, modafinil, venlafaxine, or a combination, in comparison with placebo, any of the listed medications, or behavioral therapies. Data were pooled using a random‐effects model.
Results
Twenty‐five studies (4 methylphenidate, 4 atomoxetine, 1 guanfacine, 14 antipsychotic, 1 venlafaxine, and 1 tianeptine) were included. Methylphenidate reduced hyperactivity (parent‐rated: standardized mean difference [SMD] = −.63, 95%CI = −.95,−.30; teacher‐rated: SMD = −.81, 95%CI = −1.43,−.19) and inattention (parent‐rated: SMD = −.36, 95%CI = −.64,−.07; teacher‐rated: SMD = −.30, 95%CI = −.49,−.11). Atomoxetine reduced inattention (parent‐rated: SMD = −.54, 95%CI = −.98,−.09; teacher/investigator‐rated: SMD = −0.38, 95%CI = −0.75, −0.01) and parent‐rated hyperactivity (parent‐rated: SMD = −.49, 95%CI = −.76,−.23; teacher‐rated: SMD = −.43, 95%CI = −.92, .06). Indirect evidence for significant reductions in hyperactivity with second‐generation antipsychotics was also found. Quality of evidence for all interventions was low/very low. Methylphenidate was associated with a nonsignificant elevated risk of dropout due to adverse events.
Conclusions
Direct pooled evidence supports the efficacy and tolerability of methylphenidate or atomoxetine for treatment of ADHD symptoms in children and youth with ASD. The current review highlights the efficacy of standard ADHD pharmacotherapy for treatment of ADHD symptoms in children and youth with ASD. Consideration of the benefits weighed against the limitations of safety/efficacy data and lack of data evaluating long‐term continuation is undertaken to help guide clinical decision‐making regarding treatment of co‐occurring ADHD symptoms in children and youth with ASD.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>32845025</pmid><doi>10.1111/jcpp.13305</doi><tpages>21</tpages><orcidid>https://orcid.org/0000-0002-9593-5508</orcidid><orcidid>https://orcid.org/0000-0002-7282-6077</orcidid></addata></record> |
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| source | Applied Social Sciences Index & Abstracts (ASSIA); Wiley-Blackwell Read & Publish Collection |
| subjects | ADHD alpha‐2 agonists Amphetamines Antidepressants antipsychotics Atomoxetine Attention Deficit Disorders Attention deficit hyperactivity disorder Autism autism spectrum disorder Autism Spectrum Disorders Autistic children Bupropion Child & adolescent psychiatry Children & youth Clinical decision making Clinical research Clinical significance Clinical trials Critical incidents Dropping out Drug therapy Drugs Efficacy Evidence Hyperactivity Impulsivity inattention Meta-analysis Methylphenidate Modafinil Parents pervasive developmental disorder Pharmacology pharmacotherapy Psychotropic drugs Randomized Controlled Trials Stimulants Systematic review Teachers Translation Treatment methods tricyclic antidepressants venlafaxine Youth |
| title | Practitioner Review: Pharmacological treatment of attention‐deficit/hyperactivity disorder symptoms in children and youth with autism spectrum disorder: a systematic review and meta‐analysis |
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