Time is ticking for TikTok tics: A retrospective follow-up study in the post-COVID-19 isolation era.

INTRODUCTION: During the COVID-19 pandemic, an influx of adolescents presented worldwide with acute onset of functional tic-like behaviors (FTLBs). Our goal was to evaluate psychosocial factors around onset, to elucidate outcomes after pandemic isolation protocols were lifted, and to examine therapy and medication management. METHODS: A retrospective review was performed of 56 patients ages 10-18 years with new-onset FTLBs seen at Boston Children's Hospital beginning in March 2020. Demographic factors, medical history, and treatment were evaluated. Patient outcomes were determined retrospectively based on the Clinical Global Impression Improvement (CGI-I) and Severity (CGI-S) scales from follow-up visits. CGI-I scores assessed the progression of FTLBs; CGI-S assessed overall function. RESULTS: Ninety-six percent of patients were female-assigned at birth with high rates of comorbid anxiety (93%) and depression (71%). Forty-five percent were gender-diverse. Based on scales that assessed FTLBs (CGI-I) and overall functioning (CGI-S), up to 79% of patients improved independent of comorbid diagnosis or treatment. Evidence-based tic-specific treatments were not more effective than other treatments. A subset of patients had improvement in their FTLBs but not in their general functioning and continued to have other psychosomatic presentations. CONCLUSION: While many patients' FTLBs improved, it is critical to remain alert to patients' overall function and to assess for other functional neurological disorders and mental health concerns. The tendency of FTLBs to improve in this population, independent of treatment, highlights the unique pathophysiology of FTLBs. Future research on contributing psychosocial factors and specific treatment protocols will allow optimal support for these patients.

Pharmacological treatment of Tourette's syndrome: from the past to the future.

Tourette's syndrome (TS) is a neuropsychiatric disease featuring tics and vocal tics, with a prevalence of approximately 1%, including 75% of the total number of male patients. TS seriously disturbs the patients' career, education, and life and brings a serious and unbearable psychological burden to the patients themselves and their families. At present, there are no specific clinical medications recommended for treating TS. Therefore, it is necessary to select the appropriate medication for symptomatic treatment based on the doctor's personal experience and the patient's symptoms, with the main goal of relieving symptoms, thus improving the patient's social skills and psychological problems. Here we conducted a comprehensive search on PubMed to review and organize the history and current status of the development of drug therapy for TS through a timeline format. We also systematically evaluated the effects of each drug for TS treatment to summarize the current problems and new research directions and to provide some ideas for clinical treatment.

Efficacy and Safety of Acupuncture Combined with Herbal Medicine for Children and Adolescents with Tourette Syndrome: A Systematic Review and Meta-Analysis.

BACKGROUND: With the increasing prevalence of Tourette syndrome (TS), the search for alternative therapy for TS is a growing public concern. In recent years, a growing number of randomized controlled trials (RCTs) have revealed the value of acupuncture combined with herbal medicine for the treatment of TS; however, its holistic efficacy and safety remains unclear. This study aimed to evaluate the efficacy and safety of acupuncture combined with herbal medicine and to provide preliminary evidence for clinical practice. METHODS: Eight databases were searched from their establishment to November 27, 2022, to collect RCTs of acupuncture combined with herbal medicine for TS treatment. Two researchers independently completed the study screening, data extraction, and risk of bias assessment by using NoteExpress, Excel, and Cochrane Risk of Bias Tool 2.0 (RoB 2.0). Stata 15.0 software was applied to conduct meta-analysis. RESULTS: A total of 1,400 participants in 18 RCTs were included. Compared with the Western medicine, acupuncture combined with herbal medicine had better curative effect in the field of effective rate (risk ratio [RR] = 1.18, 95% CI: [1.12, 1.23], p < 0.05, I2 = 0%), Yale Global Tic Severity Scale (YGTSS) total score (mean difference [MD] = -3.91, 95% CI: [-5.49, -2.33], p < 0.05, I2 = 96.4%), TCM syndrome total score (MD = -2.42, 95% CI: [-3.71, -1.13], p < 0.05, I2 = 87.1%), and serum IgE negative rate (RR = 3.41, 95% CI: [1.69, 6.87], p < 0.05, I2 = 0%). Furthermore, acupuncture combined with herbal medicine reduced the adverse reaction rate (RR = 0.20, 95% CI: [0.14, 0.30], p < 0.05, I2 = 0%) and the recurrence rate (RR = 0.27, 95% CI: [0.13, 0.52], p < 0.05, I2 = 0%). CONCLUSION: This study demonstrated the efficacy and safety of acupuncture combined with herbal medicine, which is probably a better alternative therapy for TS. However, the small number, low quality, and potential bias of the included studies caused the limitations of our results. More high-quality RCTs are required to provide supplementary evidence in the future.Mit der steigenden Prävalenz des Tourette-Syndroms (TS) ist die Suche nach alternativen Therapien für TS zunehmend zu einer Angelegenheit von öffentlichem Interesse geworden. In den vergangenen Jahren zeigte eine immer größer werdende Zahl randomisierter, kontrollierter Studien den Nutzen der Akupunktur in Kombination mit Heilkräutern; ihre ganzheitliche Wirksamkeit und Sicherheit ist jedoch weiterhin nicht klar. Mit dieser Studie sollten die Wirksamkeit und Sicherheit von Akupunktur in Kombination mit Heilkräutern beurteilt und erste Belege für die klinische Praxis gewonnen werden.Acht (8) Datenbanken wurden ab ihrer Einrichtung bis zum 27. November 2022 nach randomisierten kontrollierten Studien (RCTs) über Akupunktur in Kombination mit Heilkräutern zur Behandlung von TS durchsucht. Das Screening der Studien, die Datenextraktion und die Bewertung des Verzerrungsrisikos wurden von zwei unabhängigen Forschern mit Hilfe von NoteExpress, Excel und dem Cochrane Risk of Bias Tool 2.0 (RoB 2.0) durchgeführt. Die Metaanalyse erfolgte mit der Software Stata 15.0.Insgesamt wurden 1400 Teilnehmer in 18 RCTs eingeschlossen. Im Vergleich zur westlichen Medizin (WM) hatte Akupunktur in Kombination mit Heilkräutern eine bessere kurative Wirkung in Bezug auf die Wirksamkeitsrate (RR = 1,18, 95%-KI [1,12, 1,23], p < 0,05, I2 = 0%), den Gesamtscore der Yale Global Tic Severity Scale (YGTSS) (MD = -3,91, 95%-KI [-5,49, -2,33], p < 0,05, I2 = 96,4%), den TCM-Syndrom-Gesamtscore (MD = -2,42, 95%-KI [-3,71, -1,13], p < 0,05, I2 = 87,1%) und die Serum-IgE-Negativrate (RR = 3,41, 95%-KI [1,69, 6,87], p <0,05, I2 = 0 %). Darüber hinaus verringerte Akupunktur in Kombination mit Heilkräutern die Nebenwirkungsrate (RR = 0,20, 95%-KI [0,14, 0,30], p < 0,05, I2 = 0%) sowie die Rezidivrate (RR = 0,27, 95%-KI [0,13, 0,52], p < 0,05, I2 = 0%).Diese Studie belegt die Wirksamkeit und Sicherheit der Akupunktur in Kombination mit Heilkräutern, die wahrscheinlich eine bessere alternative Therapie für TS darstellt. Unsere Ergebnisse werden allerdings durch die geringe Zahl, die niedrige Qualität und die potenzielle Verzerrung der eingeschlossenen Studien eingeschränkt. Zukünftig sind weitere hochwertige RCTs erforderlich, die zusätzliche Belege liefern.

[Three oral Chinese patent medicines for children with tic disorder: a rapid health technology assessment].

This study aims to comprehensively evaluate the clinical value of Shaoma Zhijing Granules(SZG), Changma Xifeng Tablets(CXT), and Jiuwei Xifeng Granules(JXG) in the treatment of children with tic disorder with the method of rapid health technology assessment(RHTA), which is expected to serve as a reference for medical and health decision-making and clinical rational use of drugs in children. To be specific, relevant articles were retrieved from eight databases and three clinical trial registry platforms. After the quality evaluation, rapid assessment was carried out from the dimensions of disease burden and unmet needs, technical characteristics, safety, efficacy and economy, and the results were analyzed and presented descriptively. A total of 22 articles(1 in English, 21 in Chinese) were screened out: 18 randomized controlled trials(RCTs) and 4 clinical controlled trials(CCTs). Among them, 5 were about the SZG(all RCTs) and 9 were on CXT(6 RCTs and 3 CCTs). The rest 8 focused on JXG(7 RCTs and 1 CCT). Moreover, the overall risk of bias for 94.40% RCTs was evaluated as "some concerns" and only one(5.60%) had high risk of bias. In terms of quality, the 4 CCTs scored 5-6 points(<7 points), suggesting low quality. SZG alone or in combination with tiapride has obvious advantages in improving traditional Chinese medicine syndromes and tic symptoms compared with tiapride alone, with the average daily cost of CNY 79.44-119.16. Compared with conventional western medicine or placebo, CXT alone or in combination with conventional western medicine can improve the total effective rate and alleviate tic symptoms, and the average daily cost is CNY 22.50-67.50. JXG alone or in combination with conventional western medicine can effectively relieve tic symptoms compared with conventio-nal western medicine or placebo, with the average daily cost of CNY 82.42-164.85. The adverse events related to the three Chinese patent medicines mainly occurred in the digestive, respiratory, and nervous systems, all of which were mild. In general, SZG, CXT, and JXG are effective for children with tic disorder. They have been approved to be used in this field, of which SZG was approved in 2019, with the most up-to-date research evidence and high-quality RCT in Q1 journals. However, the comparative analysis of the three was affected by many factors, which should be further clarified. Based on the large sample data available in multiple dimensions, a comprehensive comparative evaluation of the three Chinese patent medicines should be carried out, thereby highlighting the advantages and disadvantages of them and serving a reference for rational clinical use and drug supervision.

Real-world experience with VMAT2 inhibitors in Tourette syndrome.

OBJECTIVES: We aimed to review our "real-world" experience with the vesicular monoamine transporter 2 (VMAT2) inhibitors tetrabenazine, deutetrabenazine, and valbenazine for treatment of Tourette syndrome, focusing on therapeutic benefits, side effect profile, and accessibility for the off-label use of these drugs. METHODS: We performed a retrospective chart review, supplemented with a telephone survey, of all our patients treated for their tics with VMAT2 inhibitors over a period of 4 years from January 2017 until January 2021. RESULTS: We identified 164 patients treated with the various VMAT2 inhibitors (tetrabenazine, n = 135; deutetrabenazine, n = 71; valbenazine, n = 20). Data on the mean treatment duration and daily dosages were collected. The response to VMAT2 inhibitors was assessed by a Likert scale by comparing the symptom severity before initiation and while on treatment. Side effects were mild and mostly consisted of depression as the major side effect but there was no suicidality reported. CONCLUSION: VMAT2 inhibitors are effective and safe in the treatment of tics associated with Tourette syndrome but are not readily accessible by patients in the United States, partly because of lack of approval by the Food and Drug Administration.

Efficacy of clonidine in the treatment of children with tic disorder co-morbid with attention deficit hyperactivity disorder.

OBJECTIVE: The current research was designed to assess the efficacy of clonidine in the treatment of children with tic disorder co-morbid with attention deficit hyperactivity disorder. PATIENTS AND METHODS: A total of 154 children with tic disorder co-morbid with attention deficit hyperactivity disorder admitted to our hospital from July 2019 to July 2022 were recruited and assigned to receive either methylphenidate hydrochloride plus haloperidol (observation group) or clonidine (experimental group), with 77 cases in each group. Outcome measures included clinical efficacy, Yale Global Tic Severity Scale (YGTSS) scores, Conners Parent Symptom Questionnaire (PSQ) scores, and adverse events. RESULTS: Clonidine was associated with markedly higher clinical efficacy vs. methylphenidate hydrochloride plus haloperidol (p<0.05). Clonidine offered more significant mitigation of the tic disorder vs. methylphenidate hydrochloride plus haloperidol, as evinced by the lower kinetic tic scores, vocal tic scores, and total scores (p<0.05). Children exhibited markedly milder tic symptoms after clonidine monotherapy vs. those with dual therapy of methylphenidate hydrochloride and haloperidol, suggested by the lower scores of character problems, learning problems, psychosomatic disorders, hyperactivity/impulsivity, anxiety index, and hyperactivity index (p<0.05). Clonidine features a higher safety profile than methylphenidate hydrochloride plus haloperidol by reducing the incidence of adverse events (p<0.05). CONCLUSIONS: Clonidine effectively alleviates tic symptoms, reduces attention deficit and hyperactivity/impulsivity in children with tic disorder co-morbid attention deficit hyperactivity disorder, and features a high safety profile.

Ecopipam for Tourette Syndrome: A Randomized Trial.

BACKGROUND AND OBJECTIVES: All US Food and Drug Administration-approved medications for Tourette syndrome are antipsychotics, and their use is limited by the risk of weight gain, metabolic changes, and drug-induced movement disorders. Several small trials suggest that ecopipam, a first-in-class, selective dopamine 1 receptor antagonist, reduces tics with a low risk for these adverse events. This trial sought to further evaluate the efficacy, safety, and tolerability of ecopipam in children and adolescents with moderate to severe Tourette syndrome. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, phase 2b trial. Subjects aged ≥6 to <18 years with a baseline Yale Global Tic Severity Score Total Tic Score of ≥20 were randomly assigned 1:1 to ecopipam (n = 76) or placebo (n = 77). The primary endpoint was mean change over 12 weeks in the Yale Global Tic Severity Score Total Tic Score. The Clinical Global Impression of Tourette Syndrome Severity was the secondary endpoint. Safety and tolerability were evaluated at each study visit. RESULTS: Total tic scores were significantly reduced from baseline to 12 weeks in the ecopipam group compared with placebo (least squares mean differences -3.44, 95% confidence interval -6.09 to -0.79, P = .01). Improvement in Clinical Global Impression of Tourette Syndrome Severity was also greater in the ecopipam group (P = .03). More weight gain was seen in subjects assigned to placebo. No metabolic or electrocardiogram changes were identified. Headache (15.8%), insomnia (14.5%), fatigue (7.9%), and somnolence (7.9%) were the most common adverse events. CONCLUSIONS: Among children and adolescents with TS, ecopipam reduces tics to a greater extent than placebo, without observable evidence of common antipsychotic-associated side effects.

Sertraline-Induced Tics: A Case Report and Narrative Review.

This brief report describes the case of a 16-year-old girl who was commenced on sertraline for anxiety and depression, and subsequently developed severe and debilitating motor tics. Cessation of sertraline was associated with the resolution of tics; after this, paroxetine was trialled and well tolerated with good response of targeted symptoms and without re-emergence of tics. A narrative literature review yielded a retrospective observational study and eight single case reports on selective serotonin receptor inhibitor-induced motor tics (three in adolescents and five in adults). Tics are not commonly considered as a side-effect of SSRIs. This case report is novel is several aspects: the tics emergence was immediate whereas previous cases were delayed; the tics symptoms were measured and quantified by a validated scale; a dose-response relationship was observed; to our knowledge, our case was the first adolescent female reported; and finally, paroxetine was well-tolerated as a substitute, although it is unclear whether the observed tics-sparing effect is co-incidental, ideocratic or can be replicated.

Decision-making under risk and ambiguity in adults with Tourette syndrome.

BACKGROUND: Tourette syndrome (TS) as well as its most common comorbidities are associated with a higher propensity for risky behaviour in everyday life. However, it is unclear whether this increased risk propensity in real-life contexts translates into a generally increased attitude towards risk. We aimed to assess decision-making under risk and ambiguity based on prospect theory by considering the effects of comorbidities and medication. METHODS: Fifty-four individuals with TS and 32 healthy controls performed risk and ambiguity decision-making tasks under both gains and losses conditions. Behavioural and computational parameters were evaluated using (i) univariate analysis to determine parameters difference taking independently; (ii) supervised multivariate analysis to evaluate whether our parameters could jointly account for between-group differences (iii) unsupervised multivariate analysis to explore the potential presence of sub-groups. RESULTS: Except for general 'noisier' (less consistent) decisions in TS, we showed no specific risk-taking behaviour in TS or any relation with tics severity or antipsychotic medication. However, the presence of comorbidities was associated with distortion of decision-making. Specifically, TS with obsessive-compulsive disorder comorbidity was associated with a higher risk-taking profile to increase gain and a higher risk-averse profile to decrease loss. TS with attention-deficit hyperactivity disorder comorbidity was associated with risk-seeking in the ambiguity context to reduce a potential loss. CONCLUSIONS: Impaired valuation of risk and ambiguity was not related to TS per se. Our findings are important for clinical practice: the involvement of individuals with TS in real-life risky situations may actually rather result from other factors such as psychiatric comorbidities.

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.

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 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. FUNDING: None.

A Double-Blind, Randomized, Controlled Crossover Trial of Cannabis in Adults with Tourette Syndrome.

Background: The number of effective evidence-based treatment options for patients with Tourette syndrome (TS) is limited. Emerging evidence shows cannabinoids as promising for the treatment of tics. Objectives: To compare the efficacy and tolerability of single doses of three vaporized medical cannabis products and placebo in reducing tics in adults with TS. Methods: In a randomized, double-blind, crossover design, each participant received a vaporized single 0.25 g dose of Δ9-tetrahydrocannabinol (THC) 10%, THC/cannabidiol (CBD) 9%/9%, CBD 13%, and placebo at 2-week intervals. Our primary outcome was the Modified Rush Video-Based Tic Rating Scale (MRVTRS), taken at baseline and at 0.5, 1, 2, 3, and 5 h after dose administration. Secondary measures included the Premonitory Urge for Tics Scale (PUTS), Subjective Units of Distress Scale (SUDS), and Clinical Global Impression-Improvement (CGI-I). Correlations between outcomes and cannabinoid plasma levels were calculated. Tolerability measures included open-ended and specific questions about adverse events (AEs). Results: Twelve adult patients with TS were randomized, with nine completing the study. There was no statistically significant effect of product on the MRVTRS. However, there was a significant effect of THC 10%, and to a lesser extent THC/CBD 9%9%, versus placebo on the PUTS, SUDS, and CGI-I. As well, there were significant correlations between plasma levels of THC and its metabolites, but not CBD, with MRVTRS, PUTS, and SUDS measures. There were more AEs from all cannabis products relative to placebo, and more AEs from THC 10% versus other cannabis products, particularly cognitive and psychomotor effects. Most participants correctly identified whether they had received cannabis or placebo. Conclusions: In this pilot randomized controlled trial of cannabis for tics in TS, there was no statistically significant difference on the MRVTRS for any of the cannabis products, although the THC 10% product was significantly better than placebo on the secondary outcome measures. Also, THC and metabolite plasma levels correlated with improvement on all measures. The THC 10% product resulted in the most AEs. ClinicalTrials.gov ID: NCT03247244.

Three oral Chinese patent medicines for children with tic disorder: a rapid health technology assessment / 中国中药杂志

This study aims to comprehensively evaluate the clinical value of Shaoma Zhijing Granules(SZG), Changma Xifeng Tablets(CXT), and Jiuwei Xifeng Granules(JXG) in the treatment of children with tic disorder with the method of rapid health technology assessment(RHTA), which is expected to serve as a reference for medical and health decision-making and clinical rational use of drugs in children. To be specific, relevant articles were retrieved from eight databases and three clinical trial registry platforms. After the quality evaluation, rapid assessment was carried out from the dimensions of disease burden and unmet needs, technical characteristics, safety, efficacy and economy, and the results were analyzed and presented descriptively. A total of 22 articles(1 in English, 21 in Chinese) were screened out: 18 randomized controlled trials(RCTs) and 4 clinical controlled trials(CCTs). Among them, 5 were about the SZG(all RCTs) and 9 were on CXT(6 RCTs and 3 CCTs). The rest 8 focused on JXG(7 RCTs and 1 CCT). Moreover, the overall risk of bias for 94.40% RCTs was evaluated as "some concerns" and only one(5.60%) had high risk of bias. In terms of quality, the 4 CCTs scored 5-6 points(<7 points), suggesting low quality. SZG alone or in combination with tiapride has obvious advantages in improving traditional Chinese medicine syndromes and tic symptoms compared with tiapride alone, with the average daily cost of CNY 79.44-119.16. Compared with conventional western medicine or placebo, CXT alone or in combination with conventional western medicine can improve the total effective rate and alleviate tic symptoms, and the average daily cost is CNY 22.50-67.50. JXG alone or in combination with conventional western medicine can effectively relieve tic symptoms compared with conventio-nal western medicine or placebo, with the average daily cost of CNY 82.42-164.85. The adverse events related to the three Chinese patent medicines mainly occurred in the digestive, respiratory, and nervous systems, all of which were mild. In general, SZG, CXT, and JXG are effective for children with tic disorder. They have been approved to be used in this field, of which SZG was approved in 2019, with the most up-to-date research evidence and high-quality RCT in Q1 journals. However, the comparative analysis of the three was affected by many factors, which should be further clarified. Based on the large sample data available in multiple dimensions, a comprehensive comparative evaluation of the three Chinese patent medicines should be carried out, thereby highlighting the advantages and disadvantages of them and serving a reference for rational clinical use and drug supervision.

Pharmacologic Treatment of Comorbid Attention-Deficit/Hyperactivity Disorder and Tourette and Tic Disorders.

A complete and comprehensive medical and psychiatric evaluation is necessary to delineate tic symptoms from attention-deficit/hyperactivity disorder, and to prioritize the most problematic symptoms for intervention. Stimulants are the recommended first-line pharmacotherapy to treat attention-deficit/hyperactivity disorder symptoms in patients with tic disorders. Comprehensive behavioral intervention for tics is an effective behavioral therapy that is generally considered the first-line treatment of persistent tic disorders. α-Agonists can be added to stimulants if tics increase or be used as monotherapy to target attention-deficit/hyperactivity disorder and tics. Atomoxetine is also an excellent option to treat attention-deficit/hyperactivity disorder and tics.

Prognosis of rapid onset functional tic-like behaviors: Prospective follow-up over 6 months.

BACKGROUND AND PURPOSE: The prognosis of rapid onset functional tic-like behaviors (FTLBs) is unknown. This prospective cohort study describes the course and treatment of rapid onset FTLBs in adolescents (n = 20) and adults (n = 9) previously reported in two case series. METHODS: Yale Global Tic Severity Scale (YGTSS) scores were compared between first clinical presentation and 6-month follow-up assessment. All treatments used for FTLBs and any psychiatric comorbidities were recorded. RESULTS: In adolescents with FTLBs, motor tics, vocal tics, total tics, impairment, and global scores on the YGTSS significantly improved at 6 months, with a mean decrease in the YGTSS global score of 31.9 points, 95% confidence interval (CI) 15.4, 48.4, p = .0005. In adults with FTLBs, only impairment and global scores significantly improved, with a mean decrease in the YGTSS global score of 19.6 points, 95% CI -3.2, 42.3, p = .04. Selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT) for anxiety and depression were the most used treatment in both age groups. CONCLUSIONS: This prospective study suggests that adolescents have a better prognosis than adults with FTLBs. Management of comorbidities with SSRIs and CBT seems effective.

Effects of Yi-Gan-san on the psychiatric behavior of children and adolescents with Tourette's Syndrome: A randomized, double-blind, controlled preliminary study.

ETHNOPHARMACOLOGICAL RELEVANCE: Gilles de la Tourette's Syndrome (TS) is a childhood-onset disease with clinical features of motor and phonic tics. Yi-Gan-san (YGS) is a traditional Chinese medicine formula that can reduce aggressiveness and agitation and inhibit dopamine function. This study investigated the effects of YGS on the psychiatric behavior of children and adolescents with TS. METHODS: A double-blind, randomized, controlled preliminary study was conducted. A total of 38 patients with TS were assigned to the control group (CG, 19 patients) who received the oral administration of YGS placebo (90% starch and 10% YGS; 2.5 g thrice daily) or to a treatment group (TG, 19 patients) who received YGS for 4 weeks. The primary outcome measure was the change in Yale Global Tic Severity Scale (YGTSS) overall and subscale scores. RESULTS: The intensity score for phonic tics before oral administration of YGS, and after 2 weeks, 3 weeks and 4 weeks was not significantly different between CG and TG groups (2.94 ± 1.14 vs 2.79 ± 1.08, p = .686; 2.29 ± 1.21 vs 1.95 ± 1.08, p = .370; 2.41 ± 1.18 vs 2.05 ± 1.51, p = .435; and 2.29 ± 1.26 vs 1.84 ± 1.42, p = .323, respectively), while the intensity score for phonic tics after 1-week oral administration of YGS in the TG was 1.89 ± 1.10 lower than 3.06 ± 1.39 in the CG (p = .008). CONCLUSION: Oral administration of YGS for 1 week only reduced the intensity of phonic tics compared with oral administration of YGS placebo, suggesting that YGS can reduce their intensity for a short period, and the compliance of oral administration of YGS for 4 weeks can be accepted in children and adolescents with Tourette's Syndrome. However, because this study was preliminary, the selection of an appropriate placebo and dosage and long-term observations are crucial areas for future studies.

Allopregnanolone: The missing link to explain the effects of stress on tic exacerbation?

The neurosteroid allopregnanolone (3α-hydroxy-5α-pregnan-20-one; AP) elicits pleiotropic effects in the central nervous system, ranging from neuroprotective and anti-inflammatory functions to the regulation of mood and emotional responses. Several lines of research show that the brain rapidly produces AP in response to acute stress to reduce the allostatic load and enhance coping. These effects not only are likely mediated by GABAA receptor activation but also result from the contributions of other mechanisms, such as the stimulation of membrane progesterone receptors. In keeping with this evidence, AP has been shown to exert rapid, potent antidepressant properties and has been recently approved for the therapy of moderate-to-severe postpartum depression. In addition to depression, emerging evidence points to the potential of AP as a therapy for other neuropsychiatric disorders, including anxiety, seizures, post-traumatic stress disorder and cognitive problems. Although this evidence has spurred interest in further therapeutic applications of AP, some investigations suggest that this neurosteroid may also be associated with adverse events in specific disorders. For example, our group has recently documented that AP increases tic-like manifestations in several animal models of tic disorders; furthermore, our results indicate that inhibiting AP synthesis and signalling reduces the exacerbation of tic severity associated with acute stress. Although the specific mechanisms of these effects remain partially elusive, our findings point to the possibility that the GABAergic activation by AP may also lead to disinhibitory effects, which could interfere with the ability of patients to suppress their tics. Future studies will be necessary to verify whether these mechanisms may apply to other externalising manifestations, such as impulse-control problems and manic symptoms.

Endocannabinoid Modulation Using Monoacylglycerol Lipase Inhibition in Tourette Syndrome: A Phase 1 Randomized, Placebo-Controlled Study.

INTRODUCTION: Tourette syndrome (TS) is a complex neurodevelopmental disorder characterized by chronic motor and vocal tics. While consistently effective treatment is lacking, evidence indicates that the modulation of endocannabinoid system is potentially beneficial. Lu AG06466 (previously ABX-1431) is a highly selective inhibitor of monoacylglycerol lipase, the primary enzyme responsible for the degradation of the endocannabinoid ligand 2-arachidonoylglycerol. This exploratory study aimed to determine the effect of Lu AG06466 versus placebo on tics and other symptoms in patients with TS. METHODS: In this phase 1b cross-over study, 20 adult patients with TS on standard-of-care medications were randomized to a single fasted dose of Lu AG06466 (40 mg) or placebo in period 1, followed by the other treatment in period 2. The effects on tics, premonitory urges, and psychiatric comorbidities were evaluated using a variety of scaled approaches at different time points before and after treatment. RESULTS: All scales showed an overall trend of tic reduction, with two out of three tic scales (including the Total Tic Score of the Yale Global Tic Severity Score) showing a significant effect of a single dose of Lu AG06466 versus placebo at various timepoints. Treatment with Lu AG06466 resulted in a significant reduction in premonitory urges versus placebo. Single doses of Lu AG06466 were generally well-tolerated, and the most common adverse events were headache, somnolence, and fatigue. CONCLUSION: In this exploratory trial, a single dose of Lu AG06466 showed statistically significant positive effects on key measures of TS symptoms.

Cannabis-based medicine in treatment of patients with Gilles de la Tourette syndrome.

INTRODUCTION: Gilles de la Tourette syndrome (GTS) is a childhood onset disorder characterised by the presence of motor and vocal tics. The guidelines of both the American Academy of Neurology (AAN) as well as the European Society for the Study of Tourette Syndrome (ESSTS) recommend behavioural therapy and pharmacotherapy, mainly with antipsychotics, as first line treatments for tics. In spite of these well-established therapeutic approaches, a significant number of patients are dissatisfied because of insufficient tic reduction or intolerable side effects. Previous studies have suggested that cannabis-based medicine (CBM) might be an alternative treatment in these patients. MATERIAL AND METHODS: Two reviewers (KS, NS) searched the electronic database of PubMed on 1 July, 2021 for relevant studies using the search terms: ('Tourette syndrome' [MeSH Terms] OR 'Gilles de la Tourette syndrome' [MeSH Terms] OR 'tic disorders' [MeSH Terms] OR 'tics' [MeSH Terms] OR 'tic disorders'[Title/Abstract]) AND ('cannabis-based medicine' [Title/Abstract] OR 'cannabis' [Title/Abstract] OR 'dronabinol' [Title/Abstract] OR 'nabiximols' [Title/Abstract] OR 'tetrahydrocannabinol' [Title/Abstract] OR 'THC' [Title/Abstract] OR 'cannabidiol' [Title/Abstract], limit: 'humans'. These studies were further reviewed for additional relevant citations. The titles and abstracts of the studies obtained through this search were examined by two reviewers (KS, NS) in order to determine article inclusion. Discrepancies were addressed by the reviewers through discussion and eventually conversation with the senior reviewer (KMV). RESULTS: Although the amount of evidence supporting the use of CBM in GTS is growing, the majority of studies are still limited to case reports, case series, and open uncontrolled studies. To date, only two small randomised controlled trials (RCTs) using tetrahydrocannabinol (THC, dronabinol) have been published demonstrating the safety and efficacy of this intervention in the treatment of tics in patients with GTS. On the other hand, another RCT with Lu AG06466 (formerly known as ABX-1431), a modulator of endocannabinoid neurotransmission, has failed to prove effective in the therapy of GTS. Accordingly, under the guidelines of both the ESSTS and the AAN, treatment with CBM is categorised as an experimental intervention that should be applied to patients who are otherwise treatment-resistant. CONCLUSIONS: Increasing evidence suggests that CBM is efficacious in the treatment of tics and psychiatric comorbidities in patients with GTS. The results of ongoing larger RCTs, such as CANNA-TICS (ClinicalTrials.gov Identifier: NCT03087201), will further clarify the role of CBM in the treatment of patients with GTS.

Efficacy and Safety of Fixed-Dose Deutetrabenazine in Children and Adolescents for Tics Associated With Tourette Syndrome: A Randomized Clinical Trial.

Importance: Tourette syndrome is a neurodevelopmental disorder characterized by childhood onset of motor and phonic tics, often accompanied by behavioral and psychiatric comorbidities. Deutetrabenazine is a vesicular monoamine transporter 2 inhibitor approved in the US for the treatment of chorea associated with Huntington disease and tardive dyskinesia. Objective: To report results of the ARTISTS 2 (Alternatives for Reducing Tics in Tourette Syndrome 2) study examining deutetrabenazine for treatment of Tourette syndrome. Design, Setting, and Participants: This phase 3, randomized, double-blind, placebo-controlled, parallel-group, fixed-dose study was conducted over 8 weeks with a 1-week follow-up (June 21, 2018, to December 9, 2019). Children and adolescents aged 6 to 16 years with a diagnosis of Tourette syndrome and active tics causing distress or impairment were enrolled in the study. Children were recruited from 52 sites in 10 countries. Data were analyzed from February 4 to April 22, 2020. Interventions: Participants were randomized (1:1:1) to low-dose deutetrabenazine (up to 36 mg/d), high-dose deutetrabenazine (up to 48 mg/d), or a matching placebo, which were titrated over 4 weeks to the target dose followed by a 4-week maintenance period. Main Outcomes and Measures: The primary efficacy end point was change from baseline to week 8 in the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) for high-dose deutetrabenazine. Key secondary end points included changes in YGTSS-TTS for low-dose deutetrabenazine, Tourette Syndrome Clinical Global Impression score, Tourette Syndrome Patient Global Impression of Impact score, and Child and Adolescent Gilles de la Tourette Syndrome-Quality of Life Activities of Daily Living subscale score. Safety assessments included incidence of treatment-emergent adverse events, laboratory parameters, vital signs, and questionnaires. Results: The study included 158 children and adolescents (mean [SD] age, 11.7 [2.6] years). A total of 119 participants (75%) were boys; 7 (4%), Asian; 1 (1%), Black; 32 (20%), Hispanic; 4 (3%), Native American; 135 (85%), White; 2 (1%), multiracial; 9 (6%), other race; and 1 (0.6%), of unknown ethnic origin. Fifty-two participants were randomized to the high-dose deutetrabenazine group, 54 to the low-dose deutetrabenazine group, and 52 to the placebo group. Baseline characteristics for participants were similar between groups. Of the total 158 participants, 64 (41%) were aged 6 to 11 years, and 94 (59%) were aged 12 to 16 years at baseline. Mean time since Tourette syndrome diagnosis was 3.3 (2.8) years, and mean baseline YGTSS-TTS was 33.8 (6.6) points. At week 8, the difference in YGTSS-TTS was not significant between the high-dose deutetrabenazine and placebo groups (least-squares mean difference, -0.8 points; 95% CI, -3.9 to 2.3 points; P = .60; Cohen d, -0.11). There were no nominally significant differences between groups for key secondary end points. Treatment-emergent adverse events were reported for 34 participants (65%) treated with high-dose deutetrabenazine, 24 (44%) treated with low-dose deutetrabenazine, and 25 (49%) treated with placebo and were generally mild or moderate. Conclusions and Relevance: In this fixed-dose randomized clinical trial of deutetrabenazine in children and adolescents with Tourette syndrome, the primary efficacy end point was not met. No new safety signals were identified. Trial Registration: ClinicalTrials.gov Identifier: NCT03571256.