Comparative efficacy, tolerability, and acceptability of pharmacological interventions for the treatment of children, adolescents, and young adults with Tourette?s syndrome: a systematic review and network meta-analysis

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6
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article
Data de publicação
2023
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Scopus
Web of Science
PubMed
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ELSEVIER SCI LTD
Autores
BEHLING, Emily
LANDEROS-WEISENBERGER, Angeli
LEVINE, Jessica L. S.
WANG, Ziyu
BLOCH, Michael H.
Citação
LANCET CHILD & ADOLESCENT HEALTH, v.7, n.2, p.112-126, 2023
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Background In clinical practice guidelines there is no consensus about the medications that should be initially offered to children and young people with Tourette's syndrome. To provide a rigorous evidence base that could help guide decision making and guideline development, we aimed to compare the efficacy, tolerability, and acceptability of pharmacological interventions for Tourette's syndrome. Methods For this systematic review and network meta-analysis, we searched the Cochrane Central Register of Controlled Trials, Embase, PsycINFO, PubMed, Web of Science, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov, for published and unpublished studies from database inception to Nov 19, 2021. We included double-blind randomised controlled trials of any medication administered as a monotherapy for at least 1 week against another medication or placebo in children and adolescents (aged =4 years and =18 years), adults (>18 years), or both, diagnosed with Tourette's syndrome according to standardised criteria. We excluded studies that exclusively recruited participants with comorbid attention-deficit hyperactivity disorder or obsessive-compulsive disorder. The primary outcome was change in severity of tic symptoms (efficacy). Secondary outcomes were treatment discontinuations due to adverse events (tolerability) and for any reason (acceptability). Pharmacological interventions were examined considering medication categories and medications individually in separate analyses. Summary data were extracted and pooled with a random-effects network meta-analysis to calculate standardised mean differences for efficacy and odds ratios for tolerability and acceptability, with 95% CIs. The Confidence in Network Meta-Analysis (CINeMA) framework was used to assess the certainty of evidence. The protocol was pre-registered in PROSPERO (CRD42022296975). Findings Of the 12 088 records identified through the database search, 88 records representing 39 randomised controlled trials were included in the network meta-analysis; these 39 randomised controlled trials comprised 4578 partici-pants (mean age 11 center dot 8 [SD 4 center dot 5] years; 3676 [80 center dot 8%] male participants) and evaluated 23 individual medications distributed across six medication categories. When considering medication categories, first-generation (standardised mean difference [SMD] -0 center dot 65 [95% CI -0 center dot 79 to -0 center dot 51]; low certainty of evidence) and second-generation (-0 center dot 71 [-0 center dot 88 to -0 center dot 54]; moderate certainty of evidence) antipsychotic drugs, as well as a-2 agonists (-0 center dot 21 [-0 center dot 39 to -0 center dot 03]; moderate certainty of evidence), were more efficacious than placebo. First-generation and second-generation antipsychotic drugs did not differ from each other (SMD 0 center dot 06 [95% CI -0 center dot 14 to 0 center dot 25]; low certainty of evidence). However, both first-generation (SMD 0 center dot 44 [95% CI 0 center dot 21 to 0 center dot 66]) and second-generation (0 center dot 49 [0 center dot 25 to 0 center dot 74]) antipsychotic drugs outperformed a-2 agonists, with moderate certainty of evidence. Similar findings were observed when individual medications were considered: aripiprazole (SMD -0 center dot 60 [95% CI -0 center dot 83 to -0 center dot 38]), haloperidol (-0 center dot 51 [-0 center dot 88 to -0 center dot 14]), olanzapine (-0 center dot 83 [-1 center dot 49 to -0 center dot 18]), pimozide (-0 center dot 48 [-0 center dot 84 to -0 center dot 12]), risperidone (-0 center dot 66 [-0 center dot 98 to -0 center dot 34]), and clonidine (-0 center dot 20 [-0 center dot 37 to -0 center dot 02]) all outperformed placebo, with moderate certainty of evidence. Antipsychotic medications did not differ from each other, but there was low to very low certainty of evidence for these comparisons. However, aripiprazole (SMD -0 center dot 40 [95% CI -0 center dot 69 to -0 center dot 12]) and risperidone (-0 center dot 46 [-0 center dot 82 to -0 center dot 11]) outperformed clonidine, with moderate certainty of evidence. Heterogeneity or inconsistency only emerged for a few comparisons. In terms of tolerability and acceptability, there were no relevant findings for any of the efficacious medication categories or individual medications against each other or placebo, but there was low to very low certainty of evidence associated with these comparisons. Interpretation Our analyses show that antipsychotic drugs are the most efficacious intervention for Tourette's syndrome, while a-2 agonists are also more efficacious than placebo and could be chosen by those who elect not to take antipsychotic drugs. Shared decision making about the degree of tic-related severity and distress or impairment, the trade-offs of efficacy and safety between antipsychotic drugs and a-2 agonists, and other highly relevant individual factors that could not be addressed in the present analysis, should guide the choice of medication for children and young people with Tourette's syndrome.
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https://observatorio.fm.usp.br/handle/OPI/54819
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Artigos e Materiais de Revistas Científicas - FM/Outros
Artigos e Materiais de Revistas Científicas - LIM/23