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The Lancet. Psychiatry Dec 2019Medicinal cannabinoids, including medicinal cannabis and pharmaceutical cannabinoids and their synthetic derivatives, such as tetrahydrocannabinol (THC) and cannabidiol... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Medicinal cannabinoids, including medicinal cannabis and pharmaceutical cannabinoids and their synthetic derivatives, such as tetrahydrocannabinol (THC) and cannabidiol (CBD), have been suggested to have a therapeutic role in certain mental disorders. We analysed the available evidence to ascertain the effectiveness and safety of all types of medicinal cannabinoids in treating symptoms of various mental disorders.
METHODS
For this systematic review and meta-analysis we searched MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Clinical Trials, and the Cochrane Database of Systematic Reviews for studies published between Jan 1, 1980, and April 30, 2018. We also searched for unpublished or ongoing studies on ClinicalTrials.gov, the EU Clinical Trials Register, and the Australian and New Zealand Clinical Trials Registry. We considered all studies examining any type and formulation of a medicinal cannabinoid in adults (≥18 years) for treating depression, anxiety, attention-deficit hyperactivity disorder (ADHD), Tourette syndrome, post-traumatic stress disorder, or psychosis, either as the primary condition or secondary to other medical conditions. We placed no restrictions on language, publication status, or study type (ie, both experimental and observational study designs were included). Primary outcomes were remission from and changes in symptoms of these mental disorders. The safety of medicinal cannabinoids for these mental disorders was also examined. Evidence from randomised controlled trials was synthesised as odds ratios (ORs) for disorder remission, adverse events, and withdrawals and as standardised mean differences (SMDs) for change in symptoms, via random-effects meta-analyses. The quality of the evidence was assessed with the Cochrane risk of bias tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. This study is registered with PROSPERO (CRD42017059372, CRD42017059373, CRD42017059376, CRD42017064996, and CRD42018102977).
FINDINGS
83 eligible studies (40 randomised controlled trials, n=3067) were included: 42 for depression (23 randomised controlled trials; n=2551), 31 for anxiety (17 randomised controlled trials; n=605), eight for Tourette syndrome (two randomised controlled trials; n=36), three for ADHD (one randomised controlled trial; n=30), 12 for post-traumatic stress disorder (one randomised controlled trial; n=10), and 11 for psychosis (six randomised controlled trials; n=281). Pharmaceutical THC (with or without CBD) improved anxiety symptoms among individuals with other medical conditions (primarily chronic non-cancer pain and multiple sclerosis; SMD -0·25 [95% CI -0·49 to -0·01]; seven studies; n=252), although the evidence GRADE was very low. Pharmaceutical THC (with or without CBD) worsened negative symptoms of psychosis in a single study (SMD 0·36 [95% CI 0·10 to 0·62]; n=24). Pharmaceutical THC (with or without CBD) did not significantly affect any other primary outcomes for the mental disorders examined but did increase the number of people who had adverse events (OR 1·99 [95% CI 1·20 to 3·29]; ten studies; n=1495) and withdrawals due to adverse events (2·78 [1·59 to 4·86]; 11 studies; n=1621) compared with placebo across all mental disorders examined. Few randomised controlled trials examined the role of pharmaceutical CBD or medicinal cannabis.
INTERPRETATION
There is scarce evidence to suggest that cannabinoids improve depressive disorders and symptoms, anxiety disorders, attention-deficit hyperactivity disorder, Tourette syndrome, post-traumatic stress disorder, or psychosis. There is very low quality evidence that pharmaceutical THC (with or without CBD) leads to a small improvement in symptoms of anxiety among individuals with other medical conditions. There remains insufficient evidence to provide guidance on the use of cannabinoids for treating mental disorders within a regulatory framework. Further high-quality studies directly examining the effect of cannabinoids on treating mental disorders are needed.
FUNDING
Therapeutic Goods Administration, Australia; Commonwealth Department of Health, Australia; Australian National Health and Medical Research Council; and US National Institutes of Health.
Topics: Anxiety; Attention Deficit Disorder with Hyperactivity; Australia; Cannabinoids; Chronic Pain; Depression; Humans; Stress Disorders, Post-Traumatic; Tourette Syndrome
PubMed: 31672337
DOI: 10.1016/S2215-0366(19)30401-8 -
Neurology and Therapy Dec 2021Comorbid psychiatric conditions in children and adolescents with attention-deficit hyperactivity disorder (ADHD) occur frequently, complicate management, and are... (Review)
Review
INTRODUCTION
Comorbid psychiatric conditions in children and adolescents with attention-deficit hyperactivity disorder (ADHD) occur frequently, complicate management, and are associated with substantial burden on patients and caregivers. Very few systematic reviews have assessed the efficacy and safety of medications for ADHD in children and adolescents with comorbidities. Of those that were conducted, most focused on a particular comorbidity or medication. In this systematic literature review, we summarize the efficacy and safety of treatments for children and adolescents with ADHD and comorbid autism spectrum disorders, oppositional defiant disorder, Tourette's disorder and other tic disorders, generalized anxiety disorder, and major depressive disorder.
METHODS
We searched MEDLINE, Embase, and ClinicalTrials.gov (to October 2019) for studies of patients (aged < 18 years) with an ADHD diagnosis and the specified comorbidities treated with amphetamines, methylphenidate and derivatives, atomoxetine (ATX), and guanfacine extended-release (GXR). For efficacy, placebo-controlled randomized controlled trials (RCTs) or meta-analyses of RCTs were eligible for inclusion; for safety, all study types were eligible. The primary efficacy outcome measure was ADHD Rating Scale IV (ADHD-RS-IV) total score.
RESULTS
Of 2177 publications/trials retrieved, 69 were included in this systematic literature review (5 meta-analyses, 37 placebo-controlled RCTs, 16 cohort studies, 11 case reports). A systematic narrative synthesis is provided because insufficient data were retrieved to combine ADHD-RS-IV total scores or effect sizes. Effect sizes for ADHD-RS-IV total scores were available for ten RCTs and ranged from 0.46 to 1.0 for ATX and from 0.92 to 2.0 for GXR across comorbidities. The numbers and types of adverse events in children with comorbidities were consistent with those in children without comorbidities, but treatment should be individualized to ensure children can tolerate the lowest effective dose.
CONCLUSION
Limited information is available from placebo-controlled RCTs on the efficacy (by ADHD-RS-IV) or safety of medication in children with ADHD and psychiatric comorbidities. Further studies are required to support evidence-based drug selection for these populations.
PubMed: 34089145
DOI: 10.1007/s40120-021-00249-0 -
The Cochrane Database of Systematic... Jun 2018This is an update of the original Cochrane Review published in Issue 4, 2011.Attention deficit hyperactivity disorder (ADHD) is the most prevalent of the comorbid... (Review)
Review
BACKGROUND
This is an update of the original Cochrane Review published in Issue 4, 2011.Attention deficit hyperactivity disorder (ADHD) is the most prevalent of the comorbid psychiatric disorders that complicate tic disorders. Medications commonly used to treat ADHD symptoms include stimulants such as methylphenidate and amphetamine; non-stimulants, such as atomoxetine; tricyclic antidepressants; and alpha agonists. Alpha agonists are also used as a treatment for tics. Due to the impact of ADHD symptoms on the child with tic disorder, treatment of ADHD is often of greater priority than the medical management of tics. However, for many decades, clinicians have been reluctant to use stimulants to treat children with ADHD and tics for fear of worsening their tics. OBJECTIVES: To assess the effects of pharmacological treatments for ADHD in children with comorbid tic disorders on symptoms of ADHD and tics.
SEARCH METHODS
In September 2017, we searched CENTRAL, MEDLINE, Embase, and 12 other databases. We also searched two trial registers and contacted experts in the field for any ongoing or unpublished studies.
SELECTION CRITERIA
We included randomized, double-blind, controlled trials of any pharmacological treatment for ADHD used specifically in children with comorbid tic disorders. We included both parallel-group and cross-over study designs.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures of Cochrane, in that two review authors independently selected studies, extracted data using standardized forms, assessed risk of bias, and graded the overall quality of the evidence by using the GRADE approach.
MAIN RESULTS
We included eight randomized controlled trials (four of which were cross-over trials) with 510 participants (443 boys, 67 girls) in this review. Participants in these studies were children with both ADHD and a chronic tic disorder. All studies took place in the USA and ranged from three to 22 weeks in duration. Five of the eight studies were funded by charitable organizations or government agencies, or both. One study was funded by the drug manufacturer. The other two studies did not specify the source of funding. Risk of bias of included studies was low for blinding; low or unclear for random sequence generation, allocation concealment, and attrition bias; and low or high for selective outcome reporting. We were unable to combine any of the studies in a meta-analysis due to important clinical heterogeneity and unit-of-analysis issues.Several of the trials assessed multiple agents. Medications assessed included methylphenidate, clonidine, desipramine, dextroamphetamine, guanfacine, atomoxetine, and deprenyl. There was low-quality evidence for methylphenidate, atomoxetine, and clonidine, and very low-quality evidence for desipramine, dextroamphetamine, guanfacine and deprenyl in the treatment of ADHD in children with tics. All studies, with the exception of a study using deprenyl, reported improvement in symptoms of ADHD. Tic symptoms also improved in children treated with guanfacine, desipramine, methylphenidate, clonidine, and a combination of methylphenidate and clonidine. In one study, tics limited further dosage increases of methylphenidate. High-dose dextroamphetamine appeared to worsen tics in one study, although the length of this study was limited to three weeks. There was appetite suppression or weight loss in association with methylphenidate, dextroamphetamine, atomoxetine, and desipramine. There was insomnia associated with methylphenidate and dextroamphetamine, and sedation associated with clonidine.
AUTHORS' CONCLUSIONS
Following an updated search of potentially relevant studies, we found no new studies that matched our inclusion criteria and thus our conclusions have not changed.Methylphenidate, clonidine, guanfacine, desipramine, and atomoxetine appear to reduce ADHD symptoms in children with tics though the quality of the available evidence was low to very low. Although stimulants have not been shown to worsen tics in most people with tic disorders, they may, nonetheless, exacerbate tics in individual cases. In these instances, treatment with alpha agonists or atomoxetine may be an alternative. Although there is evidence that desipramine may improve tics and ADHD in children, safety concerns will likely continue to limit its use in this population.
Topics: Adolescent; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Child, Preschool; Clonidine; Desipramine; Dextroamphetamine; Female; Guanfacine; Humans; Male; Methylphenidate; Randomized Controlled Trials as Topic; Selegiline; Tic Disorders
PubMed: 29944175
DOI: 10.1002/14651858.CD007990.pub3 -
Frontiers in Pediatrics 2023Tic disorders (TD) are a common neurodevelopmental disorder, it can be divided into transient tic disorder (TTD), chronic motor or vocal tic disorder (CTD), and Tourette... (Review)
Review
OBJECTIVE
Tic disorders (TD) are a common neurodevelopmental disorder, it can be divided into transient tic disorder (TTD), chronic motor or vocal tic disorder (CTD), and Tourette syndrome (TS). Our research is to evaluate the clinical relationship between tic disorders and vitamin D level in children.
METHODS
Online databases, including CNKI, Wanfang, VIP, Cochrane Library, PubMed and Embase digital knowledge service platform, were checked up to June 2022 for relevant observational studies published in Chinese and English. A random-effects model was incorporated to summarize the study results. The RevMan5.3 software was used for meta-analysis.
RESULTS
Out of 132 retrieved articles, 13 observational studies were eligible for inclusion in the systematic review and meta-analysis, comparing serum Vitamin D levels between children with TD and HC (healthy controls), including different subtypes of TD (TTD, CTD and TS). The results showed that the serum vitamin D levels in the TD group were lower than those in the HC group (MD = -6.64, 95% CI: -9.36 to -3.93, < 0.001, Heterogeneity test: < 0.001, = 94%). There were no statistically significant differences in serum vitamin D levels between the TTD group and the CTD group (MD = 3.84, 95% CI: -0.59 to 8.26, = 0.09, Heterogeneity test: < 0.001, = 90%), or between the CTD group and the TS group (MD = 1.06, 95% CI: -0.04 to 2.16, = 0.0, Heterogeneity test: = 0.54, = 0%). However, there was a statistically significant difference in serum vitamin D levels between the TTD group and the TS group (MD = 5.24, 95% CI: 0.68-9.80, = 0.02, Heterogeneity test: < 0.001, = 92%). The study also found a statistically significant difference in the ratio of male children between the TD group and the HC group (OR = 1.48, 95% CI: 1.07-2.03, = 0.02, Heterogeneity test: < 0.001, = 74%), but no statistically significant difference in the age of children between the TD group and the HC group (OR = 0.46, 95% CI: -0.33 to 1.24, = 0.25, Heterogeneity test: < 0.001, = 96%).
CONCLUSIONS
Our meta-analysis showed that the vitamin D level of children with TD was lower than that of healthy children. However, there was no difference between the subgroup. Due to the limitations of included studies in research design and diagnostic criteria, large samples, multi-center and high-quality studies are still needed for further analysis and confirmation.
PubMed: 37325365
DOI: 10.3389/fped.2023.1173741 -
Neurology May 2019To systematically evaluate the efficacy of treatments for tics and the risks associated with their use.
OBJECTIVE
To systematically evaluate the efficacy of treatments for tics and the risks associated with their use.
METHODS
This project followed the methodologies outlined in the 2011 edition of the American Academy of Neurology's guideline development process manual. We included systematic reviews and randomized controlled trials on the treatment of tics that included at least 20 participants (10 participants if a crossover trial), except for neurostimulation trials, for which no minimum sample size was required. To obtain additional information on drug safety, we included cohort studies or case series that specifically evaluated adverse drug effects in individuals with tics.
RESULTS
There was high confidence that the Comprehensive Behavioral Intervention for Tics was more likely than psychoeducation and supportive therapy to reduce tics. There was moderate confidence that haloperidol, risperidone, aripiprazole, tiapride, clonidine, onabotulinumtoxinA injections, 5-ling granule, Ningdong granule, and deep brain stimulation of the globus pallidus were probably more likely than placebo to reduce tics. There was low confidence that pimozide, ziprasidone, metoclopramide, guanfacine, topiramate, and tetrahydrocannabinol were possibly more likely than placebo to reduce tics. Evidence of harm associated with various treatments was also demonstrated, including weight gain, drug-induced movement disorders, elevated prolactin levels, sedation, and effects on heart rate, blood pressure, and ECGs.
CONCLUSIONS
There is evidence to support the efficacy of various medical, behavioral, and neurostimulation interventions for the treatment of tics. Both the efficacy and harms associated with interventions must be considered in making treatment recommendations.
Topics: Antipsychotic Agents; Behavior Therapy; Deep Brain Stimulation; Humans; Tic Disorders; Tics; Tourette Syndrome
PubMed: 31061209
DOI: 10.1212/WNL.0000000000007467 -
World Psychiatry : Official Journal of... Feb 2023Neurodevelopmental disorders - including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, communication disorders, intellectual disability,...
Neurodevelopmental disorders - including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, communication disorders, intellectual disability, motor disorders, specific learning disorders, and tic disorders - manifest themselves early in development. Valid, reliable and broadly usable biomarkers supporting a timely diagnosis of these disorders would be highly relevant from a clinical and public health standpoint. We conducted the first systematic review of studies on candidate diagnostic biomarkers for these disorders in children and adolescents. We searched Medline and Embase + Embase Classic with terms relating to biomarkers until April 6, 2022, and conducted additional targeted searches for genome-wide association studies (GWAS) and neuroimaging or neurophysiological studies carried out by international consortia. We considered a candidate biomarker as promising if it was reported in at least two independent studies providing evidence of sensitivity and specificity of at least 80%. After screening 10,625 references, we retained 780 studies (374 biochemical, 203 neuroimaging, 133 neurophysiological and 65 neuropsychological studies, and five GWAS), including a total of approximately 120,000 cases and 176,000 controls. While the majority of the studies focused simply on associations, we could not find any biomarker for which there was evidence - from two or more studies from independent research groups, with results going into the same direction - of specificity and sensitivity of at least 80%. Other important metrics to assess the validity of a candidate biomarker, such as positive predictive value and negative predictive value, were infrequently reported. Limitations of the currently available studies include mostly small sample size, heterogeneous approaches and candidate biomarker targets, undue focus on single instead of joint biomarker signatures, and incomplete accounting for potential confounding factors. Future multivariable and multi-level approaches may be best suited to find valid candidate biomarkers, which will then need to be validated in external, independent samples and then, importantly, tested in terms of feasibility and cost-effectiveness, before they can be implemented in daily clinical practice.
PubMed: 36640395
DOI: 10.1002/wps.21037 -
Brain Sciences Sep 2022(1) Introduction: Tourette syndrome (TS) and chronic tic disorder (CTD) are common neurodevelopmental/-psychiatric disorders. The aetiological factors that contribute to... (Review)
Review
(1) Introduction: Tourette syndrome (TS) and chronic tic disorder (CTD) are common neurodevelopmental/-psychiatric disorders. The aetiological factors that contribute to the pathogenesis of TS/CTD are still poorly understood. The possible risk factors for TS/CTD are considered to be a combination of genetic, immunological, psychological and environmental factors. A comprehensive systematic review was conducted to assess the association between aetiological factors and TS/CTD. (2) Methods: Electronic databases, including PubMed, Embase, Web of Science, Wanfang data, and CNKI, were searched to identify the etiological factors of children and adolescents (≤18 years) with TS/CTD based on a case-control study. Quality assessments were performed according to the Newcastle-Ottawa scale (NOS). (3) Results: According to sample sizes and NOS values, recent evidence may support that genetic factors ( and ), immunological factors (streptococcus and mycoplasma pneumoniae infections), environmental factors (conflict, history of perinatal diseases, and family history of neurological and psychiatric diseases and recurrent respiratory infections) and psychological factors (major life events) are associated with the pathogenesis of TS/CTD. (4) Conclusions: Some risk factors in different categories may be the etiological factors of TS/CTD, but there is a lack of studies on the interaction among the factors, which may require more attention in the future.
PubMed: 36138938
DOI: 10.3390/brainsci12091202 -
Neurological Sciences : Official... Apr 2021Movement disorders have been described in the context of different types of encephalitis. Among hyperkinetic manifestations, tics have sporadically been reported in... (Review)
Review
BACKGROUND
Movement disorders have been described in the context of different types of encephalitis. Among hyperkinetic manifestations, tics have sporadically been reported in cases of encephalitis resulting from a range of aetiologies.
OBJECTIVE
This review aimed to assess the prevalence and characteristics of tics in patients with encephalitis.
METHODS
We conducted a systematic literature review of original studies on the major scientific databases, according to the standards outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
In addition to the established association between tics and encephalitis lethargica, our literature search identified reports of tics in patients with immune-mediated pathologies (including autoimmune encephalitides affecting the N-methyl-D-aspartate receptor, voltage-gated potassium channels, and glycine receptors) and infective processes (ranging from relatively common viral pathogens, such as herpes simplex, to prions, as in Creutzfeldt-Jakob disease). Tics were most commonly reported in the post-encephalitic period and involvement of the basal ganglia was frequently observed.
DISCUSSION
The association of new-onset tics and encephalitis, in the background of other neuropsychiatric abnormalities, has practical implications, potentially improving the detection of encephalitis based on clinical features. Future research should focus on the categorisation and treatment of hyperkinetic movement disorders associated with encephalitis.
Topics: Basal Ganglia; Encephalitis; Humans; Tic Disorders; Tics; Tourette Syndrome
PubMed: 33486621
DOI: 10.1007/s10072-021-05065-w -
Neuroscience and Biobehavioral Reviews Jul 2021Persistent tic disorders (PTDs) and attention-deficit hyperactivity disorder (ADHD) are common neurodevelopmental conditions which tend to co-occur. Both diagnoses are... (Meta-Analysis)
Meta-Analysis Review
Overlapping sleep disturbances in persistent tic disorders and attention-deficit hyperactivity disorder: A systematic review and meta-analysis of polysomnographic findings.
INTRODUCTION
Persistent tic disorders (PTDs) and attention-deficit hyperactivity disorder (ADHD) are common neurodevelopmental conditions which tend to co-occur. Both diagnoses are associated with sleep problems. This systematic review and meta-analysis investigates overlaps and distinctions in objective sleep parameters based on diagnosis (PTD-only, PTD + ADHD, and ADHD-only).
METHODS
Databases were searched to identify studies with objective sleep measures in each population. Meta-analyses were conducted using a random effects model.
RESULTS
Polysomnography was the only measure included in all three groups. Twenty studies met final inclusion criteria, combining PTD-only (N = 108), PTD + ADHD (N = 79), and ADHD-only (N = 316). Compared to controls (N = 336), PTD-only and PTD + ADHD groups had significantly lower sleep efficiency and higher sleep onset latency. PTD + ADHD also had significantly increased time in bed and total sleep time. No significant differences were observed between ADHD-only groups and controls.
DISCUSSION
Different sleep profiles appear to characterise each population. PTD + ADHD was associated with more pronounced differences. Further research is required to elucidate disorder-specific sleep problems, ensuring appropriate identification and monitoring of sleep in clinical settings.
Topics: Attention Deficit Disorder with Hyperactivity; Humans; Polysomnography; Sleep; Sleep Wake Disorders; Tic Disorders
PubMed: 33766675
DOI: 10.1016/j.neubiorev.2021.03.018 -
Computational and Mathematical Methods... 2022To evaluate the efficacy of psychotherapy in children with tic disorder and to provide basis for the application of psychotherapy in the treatment of children with tic... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy of psychotherapy in children with tic disorder and to provide basis for the application of psychotherapy in the treatment of children with tic disorder.
METHODS
A detailed search was conducted based on PubMed, Cochrane library database, CNKI, Wanfang Data, and VIP database to determine the randomized controlled trial (RCT) of psychotherapy combined with drugs and oral drugs in the treatment of tic disorder. The search time was from the establishment of the database to August 20, 2021. All kinds of extracted data are meta analyzed, and the statistical software used is Review Manager 5.3 software.
RESULTS
According to the inclusion and exclusion criteria, 14 clinical trials were finally included, including 513 TD children, including 267 in the psychological intervention group and 246 in the control group. All trials were conducted in China and published from 2013 to 2021. In terms of clinical efficacy, compared with the control group, the psychotherapy combined with drugs group had more advantages in improving the effective rate (RR = 3.25, 95% CI: 2.17~4.85, = 5.74, < 0.00001) and improving the clinical symptoms of children with TD (WM = -5.36, 95% CI: -6.41 ~ -4.30, = 9.97, < 0.00000 1).
CONCLUSION
Psychotherapy as an adjuvant therapy for clinical treatment of TD can improve the clinical efficacy, but due to the low methodological quality of the existing trials, the research may have potential bias. In the future, large sample, multicenter, and double-blind randomized controlled trials need to be carried out to provide further support.
Topics: Child; China; Drugs, Chinese Herbal; Humans; Multicenter Studies as Topic; Psychotherapy; Randomized Controlled Trials as Topic; Tic Disorders; Treatment Outcome
PubMed: 35419080
DOI: 10.1155/2022/2365210