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

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Web of Science, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov, for published and unpublished studies from database inception to Nov 19, 2021.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 participants (mean age 11·8 [SD 4·5] years; 3676 [80·8%] male participants) and evaluated 23 individual medications distributed across six medication categories. When considering medication categories, first-generation (standardised mean difference [SMD] –0·65 [95% CI –0·79 to –0·51]; low certainty of evidence) and second-generation (–0·71 [–0·88 to –0·54]; moderate certainty of evidence) antipsychotic drugs, as well as α-2 agonists (–0·21 [–0·39 to –0·03]; moderate certainty of evidence), were more efficacious than placebo. First-generation and second-generation antipsychotic drugs did not differ from each other (SMD 0·06 [95% CI –0·14 to 0·25]; low certainty of evidence). However, both first-generation (SMD 0·44 [95% CI 0·21 to 0·66]) and second-generation (0·49 [0·25 to 0·74]) antipsychotic drugs outperformed α-2 agonists, with moderate certainty of evidence. Similar findings were observed when individual medications were considered: aripiprazole (SMD –0·60 [95% CI –0·83 to –0·38]), haloperidol (–0·51 [–0·88 to –0·14]), olanzapine (–0·83 [–1·49 to –0·18]), pimozide (–0·48 [–0·84 to –0·12]), risperidone (–0·66 [–0·98 to –0·34]), and clonidine (–0·20 [–0·37 to –0·02]) 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 –0·40 [95% CI –0·69 to –0·12]) and risperidone (–0·46 [–0·82 to –0·11]) 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 α-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 α-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.

Author/s:

Farhat, L. C., Behling, E., Landeros-Weisenberger, A., Levine, J. L. S., Ferreira de Barros, P. M., Wang, Z., Bloch, M. H.

Therapeutic use of cannabis and cannabinoids: an evidence mapping and appraisal of systematic reviews

John Bayhi — Mon, 03 Feb 2020 19:39:52 +0000

Date Added:

February 3, 2020

Journal/Publication:

BMC Complementary Medicine and Therapies

Publisher:

Springer Nature

Publication Date:

January 15, 2020

Issue:

Volume:

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1186/s12906-019-2803-2

Keywords

Another summary of what we know about the therapeutic effects of cannabinoids. The figures appear to be useful. James W. Mold, MD, MPH

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Background

Although cannabis and cannabinoids are widely used with therapeutic purposes, their claimed efficacy is highly controversial. For this reason, medical cannabis use is a broad field of research that is rapidly expanding. Our objectives are to identify, characterize, appraise, and organize the current available evidence surrounding therapeutic use of cannabis and cannabinoids, using evidence maps.

Methods

We searched PubMed, EMBASE, The Cochrane Library and CINAHL, to identify systematic reviews (SRs) published from their inception up to December 2017. Two authors assessed eligibility and extracted data independently. We assessed methodological quality of the included SRs using the AMSTAR tool. To illustrate the extent of use of medical cannabis, we organized the results according to identified PICO questions using bubble plots corresponding to different clinical scenarios.

Results

A total of 44 SRs published between 2001 and 2017 were included in this evidence mapping with data from 158 individual studies. We extracted 96 PICO questions in the following medical conditions: multiple sclerosis, movement disorders (e.g. Tourette Syndrome, Parkinson Disease), psychiatry conditions, Alzheimer disease, epilepsy, acute and chronic pain, cancer, neuropathic pain, symptoms related to cancer (e.g. emesis and anorexia related with chemotherapy), rheumatic disorders, HIV-related symptoms, glaucoma, and COPD. The evidence about these conditions is heterogeneous regarding the conclusions and the quality of the individual primary studies. The quality of the SRs was moderate to high according to AMSTAR scores.

Conclusions

Evidence on medical uses of cannabis is broad. However, due to methodological limitations, conclusions were weak in most of the assessed comparisons. Evidence mapping methodology is useful to perform an overview of available research, since it is possible to systematically describe the extent and distribution of evidence, and to organize scattered data.

Author/s:

Montero-Oleas, N, Arevalo-Rodriguez, I, Nunez-Gonzalez, S, Viteri-Garcia, A, Simancas-Racines, D