Treatment Of Tourette Syndrome Research Articles

Investigation on the status of monotherapy for newly diagnosed tic disorders and its comorbidity in children

Objective: To investigate the status of monotherapy for newly diagnosed tic disorders and its comorbidity in children, so as to provide a reference for clinical medication. Methods: A questionnaire survey was conducted to collect the application experience of monotherapy for newly diagnosed tic disorders and comorbidities in 110 pediatric neurologists and psychiatrists from Chinese Tic Disorders Study Consortium from February to August in 2019. Doctors were asked to rate treatment options based on a rank 5-point scale with "1" least appropriate and "5" most appropriate. The drug evaluation index was based on the comparison of the median score of a single drug with the overall scores of all drugs in this disease (M (Q1, Q3)), single drug M ≥ overall Q3 was recommended as preferred drugs; overall Q1≤ single drug M < overall Q3 was considered as secondary drugs; single drug M < overall Q1 was considered as unsuitable drugs. Results: Among 110 electronic questionnaires, 94 (86%) were availably responded, responding doctors included 37 (39%) males and 57 (61%) females, the age of responding doctors was (48±10) years, and their working year was (17±10) years. In the investigation of the first and second monotherapy for newly diagnosed tic disorders in children without comorbidities, there were no preferred drugs for mild transient tic disorders. The scores of clonidine, aripiprazole and tiapride were 4 (3, 4), 4 (3, 4), 4 (4, 5) scores respectively, and were greater than overall scores (3 (2, 4) scores), so they could be recommended as the preferred drugs for moderate chronic tic disorders, the recommendation for initial mild Tourette syndrome (TS) treatment was the same as preferred drugs for moderate chronic tic disorders. Similarly, clonidine, aripiprazole, tiapride and haloperidol could be recommended as the preferred drugs for other kinds of tic disorders. As for the second monotherapy, the preferred drugs for moderate transient tic disorders, mild chronic tic disorders and severe TS were all aripiprazole, tiapride, haloperidol, sulpiride, clonidine and topiramate. While clonidine, aripiprazole, tiapride could be considered as preferred drugs for severe transient tic disorders, moderate to severe chronic tic disorders and mild to moderate tic disorders. In the investigation of monotherapy for newly diagnosed tic disorders in children with comorbidities, for moderate chronic tic disorders and TS comorbid with obsessive-compulsive disorder, aripiprazole (4 (3, 5) scores) and sertraline (4 (3, 4) scores) were preferred drugs,the median scores of which were all greater than overall scores (3 (3, 4) scores), they were also the preferred treatment for severe transient tic disorders and mild chronic tic disorders. For mild and moderate transient tic disorders, severe chronic tic disorders and TS comorbid with obsessive-compulsive disorder, aripiprazole, fluvoxamine, fluoxetine, haloperidol and sertraline were preferred drugs. When comorbid with attention deficit hyperactivity disorder (ADHD), severe transient tic disorders, moderate chronic tic disorders and TS, tomoxetine and clonidine were recommended as preferred drugs (both 4 (4, 5) scores), and tomoxetine and clonidine were also the preferred treatment for severe TS. For severe chronic tic disorders comorbid with ADHD, clonidine (5(4, 5) scores) was preferred drug, greater than overall scores (4 (3, 5) scores), while for mild and moderate transient tic disorders clonidine, tomoxetine, guanidine and methylphenidate were recommended as preferred drugs. For mild chronic tic disorders and TS comorbid with ADHD tomoxetine was preferred drug. When comorbid with sleep disorders, there were no preferred drugs for mild transient tic disorders; estazolam (3 (2, 3) scores) was the preferred drug for mild chronic tic disorders and TS comorbid with sleep disorders. For othe kind of tic disorders comorbid with sleep disorders, estazolam, melatonin and clonazepam were preferred drugs. When comorbid with anxiety and depressive disorders, for all kinds of tic disorders sertraline was recommended as preferred drugs, the median scores of sertraline were all (4 (3, 5) scores) in severe transient tic disorders, moderate to severe chronic tic disorders and moderate TS, and greater than overall scores (3 (3, 4) scores). While severe chronic tic disorders comorbid with anxiety and depressive disorders, fluvoxamine could also be chosen as preferred drugs. Conclusions: Drug therapy is not recommended for mild transient tic disorders, while tiapride, aripiprazole, clonidine, and haloperidol are mainly preferred drugs for the other kinds of tic disorders. Corresponding drugs should be selected when tic disorders are combined with obsessive-compulsive disorder, ADHD, sleep disorders, anxiety, depression, etc.

Utilizing network pharmacology to explore the underlying mechanism of Qiangzhi decoction in treating Tourette's syndrome.

Tourette's syndrome (TS) is a neurodevelopmental condition characterized by multiple motor and vocal tics. Qiangzhi decoction (QD), a well-known herbal decoction, has been used in treating TS in China for decades. We have found relevance between the indications of QD and the classic symptoms of TS. The pharmacological mechanisms of QD in treating TS are still unclear. The active compounds of QD were extracted from multi-database, including TCMSP (the Traditional Chinese Medicine Systems Pharmacology database), and potential targets of the compounds were compiled by target fishing. The TS target database was established, and then the protein-protein interaction (PPI) network was constructed to analyze the interactions between the potential targets of compounds in QD and targets associated with TS and screened the core targets by topology. The DAVID bioinformatics database was used to conduct the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. 59 active molecules and 585 potential targets of QD were selected. The consequences of the DAVID enrichment analysis show that 36 cellular biological processes (FDR <0.01) and 65 pathways (FDR <0.01) of QD chiefly took part in the convoluted treating effects relevant to the dopamine system, inflammation, and infection, and miRNA pathway. Fourteen core targets of QD were found as potential targets of the treatment of TS. QD could relieve the symptoms of TS through the molecular mechanisms predicted by network pharmacology. This study supplies insight into how network pharmacology can predict traditional Chinese herbal medicine's possible molecular mechanisms (TCHM).

Treatment of Tourette Syndrome With Attention Training Technique-A Case Series.

The existing therapeutic strategies of Tourette syndrome (TS) do not lead to sufficient improvement in a significant number of patients. Recently published studies show that paying attention to tics increases whereas directing attention away decreases tic frequency. The aim of the present case series in three patients with TS was to investigate the effect of attention training technique (ATT) on TS symptoms. ATT is a technique derived from metacognitive therapy that aims on training patients to consciously (re-)focus their attention away from themselves. Friedman’s chi-square test indicated a trend regarding the reduction of tic frequency and tic severity and a significant reduction of positive metacognitions from pre-baseline to follow-up. Reliable Change Indices (RCIs) are given for each measure and patient. Given the small number of patients, further studies including randomized controlled trials appear warranted.

Treatment use among children with Tourette syndrome living in the United States, 2014

Treatment of Tourette syndrome (TS) can be complicated by changes over time in tic expression, severity, and co-occurring disorders. Using the 2014 National Survey of the Diagnosis and Treatment of ADHD and Tourette Syndrome, this study provides descriptive estimates of the use of behavioral interventions and medication among children living with TS. Parent-reported data on 115 children aged 5–17 years ever diagnosed with TS were analyzed to provide descriptive, unweighted results. Overall, 77.4% of children had current or past use of any TS treatment; 59.1% ever used behavioral interventions and 56.1% had ever taken TS medication. Children with "moderate” or “severe” versus “mild” TS, ≥1 co-occurring disorders, and tics that interfered with functioning were significantly more likely to have used one or more TS treatments. Side effects were reported for 84.4% of children who took TS medication. Most parents of children with current TS (87.2%) were satisfied with the management of their child's TS. However, parents of children with “moderate” or “severe” current TS were significantly more dissatisfied compared to parents of children with “mild” TS. Findings from this study could be used to inform efforts to support children living with TS and their families.

Regulatory effects of Ningdong granule on microglia-mediated neuroinflammation in a rat model of Tourette's syndrome.

Tourette's syndrome (TS) is an inherited neurologic disorder characterized by involuntary stereotyped motor and vocal tics. Its pathogenesis is still unclear and its treatment remains limited. Recent research has suggested the involvement of immune mechanisms in the pathophysiology of TS. Microglia are the brain's resident innate immune cells. They can mediate neuroinflammation and regulate brain development and homeostasis. A traditional Chinese medicine (TCM), Ningdong granule (NDG), has been found to be efficacious in the treatment of TS while causing few adverse reactions. In the current study, a rat model of 3,3'-iminodipropionitrile (IDPN)-induced TS was used to explore the regulating effects and mechanisms of NDG on microglia-mediated neuroinflammation. IDNP led to robust pathological changes and neurobehavioral complications, with activation of microglia in the striatum of rats with TS. After activation by IDNP, microglia strongly responded to this specific injury, and TNF-α, IL-6, and MCP-1 were released in the striatum and/or serum of rats with TS. Interestingly, NDG inhibited the activation of microglia and decreased the abnormal expression of TNF-α, IL-6, and MCP-1 in the striatum and/or serum of rats with TS, thus controlling tics. However, there were no significant changes in the striatum and/or serum of rats with TS after treatment with haloperidol. The anti-TS action of haloperidol might occur not through microglial activation and neuroinflammation but through the DAT system, thus controlling tics. In conclusion, microglia might play key roles in mediating neuroinflammatory responses in TS, triggering the release of TNF-α, IL-6, and MCP-1.NDG inhibited tics in rats with TS, and this mechanism may be associated with a reduction in the increased number of activated microglia and a decrease in the expression of pro-inflammatory cytokines and chemokines in the striatum and/or serum.

Why don't children in Uganda have tics? A mixed-methods study of beliefs, knowledge, and attitudes of health professionals.

Tourette syndrome (TS) is reported in all cultures, although is speculated to be rare among those of Sub-Saharan African descent. A lack of research exploring TS in the context of Sub-Saharan Africa has meant that it is not yet established whether this apparent rarity is due to a true low prevalence or if identification of the condition merely is unrecognized. The present study aimed to explore health professionals' knowledge and attitudes of the identification, diagnosis and management of TS in Uganda. A mixed-methods design was used to collect data from 152 Ugandan healthcare professionals by survey. Of these, 6 professionals took part in semi-structured interviews. Data gathered were analyzed with descriptive statistics and qualitatively using thematic analysis. Professionals' views and experiences led to conclusions addressing (a) perceived challenges in diagnosing and treating TS in a Ugandan healthcare setting, (b) the role of cultural factors in help-seeking behaviors, and (c) ways by which efforts can be made to build capacity in awareness and clinical care. The findings suggest that TS is present in Uganda, but a number of factors hinder detection rates causing it to be under-reported in the population. This study highlights the need for more focused and adequate training for all healthcare professionals in Uganda and education campaigns to increase awareness among the general public. Little is currently known about the presentation of or understanding by professionals around Tourette syndrome in Sub-Saharan Africa. This study found health professionals in Uganda indicated a number of factors which interact and negatively impact recognition rates of tic disorders. This included limited training, exposure, and misconceptions, contributing to a lack of clinical awareness and attention. They also reported a lack of help-seeking behaviors due to parental perceptions and Ugandan traditional, cultural and religious beliefs. Professionals perceive that there are likely large numbers of undiagnosed and untreated children with Tourette syndrome in Uganda. This supports existing literature regarding the diagnostic challenges of neurodevelopmental disorders in Africa and provides an alternative explanation for the assumption that tic disorders may be rare and possible absent in Sub-Saharan Africa. There is a need to develop adequate training regarding tic disorders for all healthcare professionals working in Uganda as well as education campaigns for the general public to increase awareness.

Ningdong Granule Upregulates the Striatal DA Transporter and Attenuates Stereotyped Behavior of Tourette Syndrome in Rats.

This study aimed to evaluate the possible mechanism of Ningdong granule (NDG) for the treatment of Tourette syndrome (TS). The rats with stereotyped behavior were established by microinjection with TS patients' sera; then, the model rats were divided into NDG and haloperidol (Hal) group, and the nonmedication model rats were regarded as treatment control (TS group). The stereotyped behavior of the rats was recorded, the level of dopamine (DA) in striatum, and the content of homovanillic acid (HVA) in sera were tested, and dopamine transporter (DAT) expression was measured in the study. The experimental results showed that NDG effectively inhibited the stereotyped behavior (P < 0.01), decreased the levels of DA in the striatum (P < 0.05), increased the content of sera HVA (P < 0.01), and enhanced the protein and mRNA expression of DAT in the striatum (P < 0.01). Additionally, the results also revealed Hal could improve the stereotyped behavior as well but had no remarkable influence on DAT expression and DA metabolism. In conclusion, NDG attenuates stereotyped behavior, and its mechanism of action might be associated with the upregulation of DAT expression to regulate DA metabolism in the brain.

Randomized controlled clinical trial comparing the efficacy and tolerability of aripiprazole and sodium valproate in the treatment of Tourette syndrome

ObjectiveThis study compared the efficacy and tolerability of sodium valproate and aripiprazole in the treatment of Tourette syndrome (TS).Method24 children and adolescents with a diagnosis of TS from the Jiamusi Central Hospital between January 2014 and August 2017 were randomly divided into sodium valproate group and aripiprazole group according to the order of clinic visits and treated for 10 days. Tic severity was rated using the Yale Global Tic Severity Scale (YGTSS) and the Clinical Global Impressions Scale for tics (CGI-Tics) and the adverse reactions were valued using the Treatment Emergent Symptom Scale (TESS) at baseline and at each follow-up visit.ResultsThe TTS score in the YGTSS scale decreased over time in both groups while the aripiprazole group was significantly higher on the 5th day (p < 0.05) and 10th day (p < 0.05) than the sodium valproate group. There was no significant difference in TESS score between the two groups.ConclusionsThe study indicates that the patients treated with sodium valproate injection have a faster onset time than the patients treated with oral aripiprazole in controlling tics.

Professor HUANG Lin-na's experience in treatment of Tourette syndrome with Fang's scalp acupuncture

Professor HUANG Lin-na's experience in treatment of Tourette syndrome with Fang's scalp acupuncture were introduced. Professor HUANG believes that this disease is in category of tremor in TCM. Pathogenic wind is the key in its pathogenesis and liver, spleen and kidney are closely related. Hence, the treatment focuses on eliminating pathogenic wind and regulating the function of liver, spleen and kidney. The cerebrum is the regulation center in human body. The abnormal somatic function can be adjusted by acupuncture at the scalp area where the cerebral cortical function is projected. Fang's scalp acupuncture is suitable in treatment of Tourette syndrome. Such scalp acupuncture was introduced in this paper with the typical case reported so as to provide a new approach to clinical treatment.

Assessment and management of tic disorders and Tourette syndrome by Australian paediatricians.

The diagnosis and management of tic disorders and Tourette syndrome (TS) can be challenging. A better understanding of current approaches by paediatricians is important to inform research and education to improve patient outcomes. We aimed to investigate current assessment and management practices for tics/TS by Australian paediatricians. An online survey was sent to members of the Australian Paediatric Research Network. Primary outcomes of interest included assessment processes, referrals, behavioural interventions and pharmacological management. Four scenarios were presented to elicit information regarding treatment of different types of cases. Of 340 eligible paediatricians, 139 (41%) responded, with 116 (84%) reporting that they diagnose and manage tics/TS as part of their practice. Questionnaires were used more to identify comorbidities (43%) than to quantify tics (12%). Referrals were most likely to be made to psychologists. Medication was considered important in the management of TS by 45% of respondents, with clonidine identified as the first-choice medication by 69%. There was wide variation in both the pharmacological and behavioural management strategies reported. There is substantial practice variation among Australian paediatricians in the assessment and management of patients referred with tics/TS. This may reflect insufficient evidence regarding best practice, as well as limited training in this area. There is a need for improved education of Australian paediatricians in the assessment and management of tics/TS, as well as further research to identify optimal treatments.

Regulatory effects of Ningdong granule on dopaminergic and serotonergic neurotransmission in a rat model of Tourette syndrome assessed by PET.

Dysfunctions in dopamine (DA) and serotonin (5‑HT) metabolism have been widely implicated in Tourette syndrome (TS); however, the exact nature of these dysfunctions remains unclear. The objective of the present study was to investigate the variation in DA and 5‑HT metabolism in a rat model of TS, and to evaluate the therapeutic effect of Ningdong granule (NDG), a traditional Chinese medicine (TCM) preparation used specifically for the treatment of TS. Rats were treated with 3,3'‑iminodipropionitrile for 7days to induce the model of TS, and were then intragastrically administered NDG each day. After 8weeks of treatment, micro‑positron emission tomography was used to measure the binding of DA D2 receptors (D2Rs), DA transporters (DATs), 5‑HT2A receptors (5‑HT2ARs) and 5‑HT transporters (SERTs) in brain regions of interest. The results indicated that NDG could significantly reduce the typical characteristics of TS in the rat model. Decreased D2R binding and increased DAT binding were detected in the striatum compared with the binding activities in untreated rats. The density of 5‑HT2AR was also significantly increased in the striatum following NDG treatment; however, SERT levels were decreased in certain brain regions, including the striatum, cortex, nucleus accumbens and amygdala. Taken together, the current results demonstrated that NDG may be effective in treating patients with TS.

Progress in Pharmacological and Surgical Management of Tourette Syndrome and Other Chronic Tic Disorders.

Tourette syndrome (TS) and other chronic tic disorders are clinically heterogenous and cause physical discomfort, social difficulties, and emotional distress. In addition to tics, TS patients have a variety of behavioral comorbidities, including obsessive-compulsive disorders and attention-deficit hyperactivity disorders. TS treatment is multidisciplinary, involving behavioral therapy, oral medications, and botulinum toxin injections. Relevant studies on pharmacological and surgical treatment options for TS and other chronic tic disorders, their limitations and current recommendations were reviewed using the PubMed search till April 2, 2018. Besides, the reference lists of the retrieved publications were manually searched to explore other relevant studies. This review aims to discuss the progress in pharmacological and surgical treatment options for TS and other chronic tic disorders. Both typical and atypical antipsychotic agents are mainstays of pharmacological treatment of TS and other chronic tic disorder patients; however, their use is limited by serious side effects considering their potential of dopamine blockade. Because of the phenotypic variability, no medication has proven effective for all persons with TS and other chronic tic disorders. Botulinum toxin has emerged as a good therapeutic option, especially for focal and dystonic tics. But, their uses are limited by lack of sufficient evidence and high cost. Surgical treatment is considered in medically refractory and severely disabled tics patients. Deep brain stimulation has replaced lesional surgeries; however, there is uncertainty regarding the selection of patients and target of stimulation.

Deep brain stimulation in Tourette's syndrome: evidence to date.

Tourette’s syndrome (TS) is a neurodevelopmental disorder that comprises vocal and motor tics associated with a high frequency of psychiatric comorbidities, which has an important impact on quality of life. The onset is mainly in childhood and the symptoms can either fade away or require pharmacological therapies associated with cognitive-behavior therapies. In rare cases, patients experience severe and disabling symptoms refractory to conventional treatments. In these cases, deep brain stimulation (DBS) can be considered as an interesting and effective option for symptomatic control. DBS has been studied in numerous trials as a therapy for movement disorders, and currently positive data supports that DBS is partially effective in reducing the motor and non-motor symptoms of TS. The average response, mostly from case series and prospective cohorts and only a few controlled studies, is around 40% improvement on tic severity scales. The ventromedial thalamus has been the preferred target, but more recently the globus pallidus internus has also gained some notoriety. The mechanism by which DBS is effective on tics and other symptoms in TS is not yet understood. As refractory TS is not common, even reference centers have difficulties in performing large controlled trials. However, studies that reproduce the current results in larger and multicenter randomized controlled trials to improve our knowledge so as to support the best target and stimulation settings are still lacking. This article will discuss the selection of the candidates, DBS targets and mechanisms on TS, and clinical evidence to date reviewing current literature about the use of DBS in the treatment of TS.

Repetitive transcranial magnetic stimulation as a treatment for Tourette's syndrome in children: A pilot study

Repetitive transcranial magnetic stimulation as a treatment for Tourette's syndrome in children: A pilot study

Pallidal and thalamic neural oscillatory patterns in tourette's syndrome.

Aberrant oscillatory activity has been hypothesized to play a role in the pathophysiology of Tourette's syndrome (TS). Deep brain stimulation (DBS) has recently been established as an effective treatment for severe TS. Modulation of symptom-specific oscillations may underlie the mechanism of action of DBS and could be used for adaptive neuromodulation to improve therapeutic efficacy. The objective of this study was to demonstrate a pathophysiological association of pallidal and thalamic local field potentials (LFPs) with TS. Nine medication-refractory TS patients were included in the study. Intracerebral LFPs were recorded simultaneously from bilateral pallidal and thalamic DBS electrodes. Spectral and temporal dynamics of pallidal and thalamic oscillations were characterized and correlated with preoperative Yale Global Tic Severity Scale (YGTSS) scores. Peaks of activity in the theta (3-12Hz) and beta (13-35Hz) were present in pallidal and thalamic recordings from all patients (3 women/6 men; mean age, 29.8 years) and coupled through coherence across targets. Presence of prolonged theta bursts in both targets was associated with preoperative motor tic severity. Total preoperative YGTSS scores (mean, 38.1) were correlated with pallidal and thalamic LFP activity using multivariable linear regression (R² = 0.96; p = 0.02). Our findings suggest that pallidothalamic oscillations may be implicated in the pathophysiology of TS. Furthermore, our results highlight the utility of multisite and -spectral oscillatory features in severely affected patients for future identification and clinical use of oscillatory physiomarkers for adaptive stimulation in TS. Ann Neurol 2018;84:505-514.

Antipsychotic-Associated Symptoms of Tourette Syndrome: A Systematic Review.

Although antipsychotics are used to treat Tourette syndrome, there have been reports of paradoxical induction of tics by first- and second-generation antipsychotics. The objective of this systematic review was to better characterize tics as the potential adverse effect of antipsychotics. A literature search was performed, with no language restriction, using the MEDLINE, EMBASE, and PsycINFO databases for all publications up to January 2018. To be included, studies utilizing any study design had to meet the following criteria: (1) a temporal association of tics with antipsychotic use where tics emerged during treatment or after discontinuation and (2) no diagnosis of Tourette syndrome before tic emergence. More stringent criteria were used for individuals under 18years of age that included (1) no personal or family history of primary tic disorder and either (2) tics occurring during antipsychotic treatment improved significantly upon discontinuation or dose reduction or (3) tics emerged after discontinuation of at least 3months of antipsychotic treatment. Data were extracted according to: age, sex, diagnosis, personal history of motor symptoms or family history of tics, antipsychotic type and dose, treatment duration, types of symptoms emerged, treatment strategies, and follow-up. A Fisher's exact test was used to compare the occurrence of symptoms between first- and second-generation antipsychotic users. The search identified 1290 articles, of which 92 full-text articles were assessed leading to the inclusion of 50 articles. Most of the included articles were case reports or series, involving a total of 60 cases. Thirty cases were associated with treatment with first-generation antipsychotics, 27 with second-generation antipsychotics, and three with a combination of first- and second-generation antipsychotics. Antipsychotics were being used to treat schizophrenia in 60% of the cases and other indications included developmental, behavioral, and mood or anxiety disorders. Tics occurred during treatment (n = 44) or following treatment discontinuation (n = 16). The occurrence of vocal tics with or without motor tics was significantly higher in the first- vs. second-generation antipsychotic users (p < 0.0001). Significantly higher occurrences were also noted in the first- vs. second-generation antipsychotic users for specific types of vocal tics (i.e., barking and coprolalia) and other concurrent motor symptoms (i.e., tardive dyskinesia). In the cases identified, antipsychotic-associated tics were treated by (1) discontinuing the offending antipsychotic, reducing its dose, or switching to different antipsychotics for tics occurring during treatment, (2) reinitiating antipsychotic treatment for tics occurring following discontinuation, or (3) using non-antipsychotic agents. It should be noted that symptoms were not always fully reversible and recurred at times. Tics can be a disturbing adverse effect of antipsychotics. Clinicians need to be particularly vigilant when initiating and modifying antipsychotic regimens.

Why does the goalkeeper eschew medication? The challenge of new treatments for tourette syndrome

Why does the <i>goalkeeper</i> eschew medication? The challenge of new treatments for tourette syndrome

Ecopipam, a D1 receptor antagonist, for treatment of tourette syndrome in children: A randomized, placebo-controlled crossover study.

Dopamine D2 receptor antagonists used to treat Tourette syndrome may have inadequate responses or intolerable side effects. We present results of a 4-week randomized, double-blind, placebo-controlled crossover study evaluating the safety, tolerability, and efficacy of the D1 receptor antagonist ecopipam in children and adolescents with Tourette syndrome. Forty youth aged 7 to 17 years with Tourette syndrome and a Yale Global Tic Severity Scale - total tic score of ≥20 were enrolled and randomized to either ecopipam (50 mg/day for weight of <34 kg, 100 mg/day for weight of >34 kg) or placebo for 30 days, followed by a 2-week washout and then crossed to the alternative treatment for 30 days. Stimulants and tic-suppressing medications were excluded. The primary outcome measure was the total tic score. Secondary outcomes included obsessive compulsive and attention deficit/hyperactivity disorder scales. Relative to changes in placebo, reduction in total tic score was greater for ecopipam at 16 days (mean difference, -3.7; 95% CI, -6.5 to -0.9; P = 0.011) and 30 days (mean difference, -3.2; 95% CI, -6.1 to -0.3; P = 0.033). There were no weight gain, drug-induced dyskinesias, or changes in laboratory tests, electrocardiograms, vital signs, or comorbid symptoms. Dropout rate was 5% (2 of 40). Adverse events reported for both treatments were rated predominantly mild to moderate, with only 5 rated severe (2 for ecopipam and 3 for placebo). Ecopipam reduced tics and was well tolerated. This placebo-controlled study of ecopipam supports further clinical trials in children and adolescents with Tourette syndrome. © 2018 International Parkinson and Movement Disorder Society.

Efficacy of repetitive transcranial magnetic stimulation for Tourette syndrome: A systematic review and meta-analysis

BackgroundWhile previous studies have investigated the effect of repetitive transcranial magnetic stimulation (rTMS) in treating Tourette syndrome (TS), the results remain inconclusive. ObjectiveWe aim to systematically review the existing literature related to the efficacy of rTMS in TS and synthesize the results through meta-analysis. MethodsWe searched for PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases without language restriction through January 1, 2018, and included randomized-controlled and open-label trials that assessed the treatment effect of rTMS for tic symptoms. We used a random-effects model to pool effect sizes, which were expressed as Hedges' g and 95% confidence intervals (CIs). The outcomes include symptom improvement of tic, obsessive-compulsive (OC), and attention-deficit hyperactivity disorder. Distribution of sex, age, and differences of rTMS protocol were examined as potential moderators. ResultsEight studies were included in the meta-analysis. rTMS significantly improved tic (g = −0.61; CI: −0.94 to −0.29) and OC (g = −0.48; CI: −0.83 to −0.14) symptoms in TS patients, compared to baseline. However, active rTMS was not effective in tic or OC symptoms among patients with TS when controlled for placebo. Furthermore, stimulation of the bilateral supplementary motor areas was more effective in tic symptoms than that of other areas (g = −0.70; CI: −1.11 to −0.30 vs. g = −0.36; CI: −0.84 to 0.14). Moreover, a younger age was associated with a better treatment effect (coefficient = 0.03, p = 0.027). ConclusionCurrent study indicates that rTMS has a significant effect on tic and OC symptoms in TS patients.

Tourette Syndrome: A Mini-Review.

The purpose of this mini-review is to provide the latest information on epidemiology, pathophysiology, diagnosis, and treatment of Tourette syndrome (TS). The authors conducted a literature search of available sources describing the issue of tic disorders with special focus on TS and made a comparison and evaluation of relevant findings. The results of this mini-review indicate that TS is a complex disorder, which has a significant impact on the quality of life of both the patients and his/her family. Therefore, early and proper diagnosis and treatment are necessary in order to reduce or even eliminate both symptoms and social burden of the patient. This requires a multidisciplinary management approach in order to meet the patients’ special needs. Future research should focus on neuroimaging, new neurotransmitter targets, in functional neurosurgery, as well as the effect of non-pharmacological psychotherapies for these people.