Global Burden Disease Estimates for Major Depressive Disorders (MDD): A review of diagnostic instruments used in studies of prevalence.

Global Burden of Disease (GBD) estimates have significant policy implications nationally and internationally. Disease burden metrics, particularly for depression, have played a critical role in raising governmental awareness of mental health and in calculating the economic cost of depression. Recently, the World Health Organization ranked depression as the single largest contributor to global disability. The main aim of this paper was to assess the basis upon which GBD prevalence estimates for major depressive disorder (MDD) were made. We identify the instruments used in the 2019 GBD estimates and provide a descriptive assessment of the five most frequently used instruments. The majority of country studies, 356/566 (62.9%), used general mental health screeners or structured/semi-structured interview guides, 98/566 (17.3%) of the studies used dedicated depression screeners, and 112 (19.8%) used other tools for assessing depression. Thus, most of the studies used instruments that were not designed to make a diagnosis of depression or assess depression severity. Our results are congruent with and extend previous research that has identified critical flaws in the data underpinning the GBD estimates for MDD. Despite the widespread promotion of these prevalence estimates, caution is needed before using them to inform public policy and mental health interventions. This is particularly important in lower-income countries where resources are scarce.

Nabilone treatment for severe behavioral problems in adults with intellectual and developmental disabilities: Protocol for a phase I open-label clinical trial.

Severe behavioral problems (SBPs) are common contributors to morbidity and reduced quality of life for adults with intellectual and developmental disabilities (IDD) and their families. Current medications for SBPs show equivocal effectiveness and are associated with a high risk of side effects. New and safe treatments are urgently needed. While preliminary studies suggest that medical cannabinoids, particularly the synthetic cannabinoid nabilone, are plausible treatment options for SBPs in adults with IDD, data on the tolerability, safety and efficacy of nabilone in this population has never been investigated. Thus, we propose this first-ever Phase I pre-pilot open-label clinical trial to obtain preliminary data on the adherence, tolerability and safety profiles of nabilone in adults with IDD, and explore changes in SBPs pre- to post-treatment. We hypothesize that nabilone has favorable tolerability and safety profile for adults with IDD. The preliminary results will inform the next-stage pilot randomized controlled trials, followed by fully powered clinical trials eventually. This research helps fill the evidence gap in the use of cannabinoids in individuals with IDD to meet the needs of patients, families, and service providers.

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.

TikTok and Attention-Deficit/Hyperactivity Disorder: A Cross-Sectional Study of Social Media Content Quality.

OBJECTIVES: Social media platforms are increasingly being used to disseminate mental health information online. User-generated content about attention-deficit/hyperactivity disorder (ADHD) is one of the most popular health topics on the video-sharing social media platform TikTok. We sought to investigate the quality of TikTok videos about ADHD. METHOD: The top 100 most popular videos about ADHD uploaded by TikTok video creators were classified as misleading, useful, or personal experience. Descriptive and quantitative characteristics of the videos were obtained. The Patient Education Materials Assessment Tool for Audiovisual Materials (PEMAT-A/V) and Journal of American Medical Association (JAMA) benchmark criteria were used to assess the overall quality, understandability, and actionability of the videos. RESULTS: Of the 100 videos meeting inclusion criteria, 52% (n = 52) were classified as misleading, 27% (n = 27) as personal experience, and 21% (n = 21) as useful. Classification agreement between clinician ratings was 86% (kappa statistic of 0.7766). Videos on the platform were highly understandable by viewers but had low actionability. Non-healthcare providers uploaded the majority of misleading videos. Healthcare providers uploaded higher quality and more useful videos, compared to non-healthcare providers. CONCLUSIONS: Approximately half of the analyzed TikTok videos about ADHD were misleading. Clinicians should be aware of the widespread dissemination of health misinformation on social media platforms and its potential impact on clinical care.

An International Survey of Health Care Services Available to Patients With Tourette Syndrome.

Objective: Tourette syndrome (TS) is a neuropsychiatric disorder that is highly associated with several comorbidities. Given the complex and multifaceted nature of TS, the condition is managed by a wide variety of practitioners in different disciplines. The goal of this study was to investigate health service delivery and care practices by clinicians who see TS patients across different geographic settings internationally. Methods: A comprehensive questionnaire was developed to assess clinical care resources for patients with TS and was sent to clinicians in Canada (CA), the United States (US), Europe (EU), and the United Kingdom (UK). Responses were compared quantitatively between geographic regions. Results: The majority of respondents, regardless of region, reported that fewer than 40% of their case-load are patients with tics. The accessibility of TS services varied among regions, as indicated by differences in wait times, telemedicine offerings, comorbidity management and the availability of behavioral therapies. First-line pharmacotherapy preferences varied among physicians in different geographical regions with CA respondents preferring alpha-2-adrenergic agonists and respondents from the UK and EU preferring dopamine receptor antagonists. Discussion: The results suggest that there is a scarcity of specialized TS clinics, potentially making access to services challenging, especially for patients newly diagnosed with TS. Differences in regional pharmacotherapeutic preferences are reflected in various published treatment guidelines in EU and North America. The lack of dedicated specialists and telemedicine availability, coupled with differences in comorbidity management, highlight the need for interprofessional care and holistic management to improve health care delivery to patients with TS.

Selective serotonin reuptake inhibitor 'discontinuation syndrome' or withdrawal.

Attempts to define selective serotonin reuptake inhibitor (SSRI) withdrawal with the term 'discontinuation syndrome' are not supported by evidence. Acknowledging that SSRI use can result in dependence and withdrawal allows patients to be better informed around decisions related to these drugs, and helps inform strategies for safe tapering as appropriate.

Neuroimaging the emotional modulation of urge inhibition in Tourette Syndrome.

Tourette Syndrome (TS) is a neuropsychiatric condition characterized by tics that are typically preceded by uncomfortable urges that build until the tic is performed. Both tics and their associated urges are commonly exacerbated during states of heightened emotion. However, the neural substrates that are responsible for the development of urges have not been fully elucidated, particularly with regards to the influence of emotion. In this study, we investigate the brain areas associated with the development of urges and their modulation by emotion in patients with TS. Moreover, we explore the influence of obsessive-compulsive symptoms (OCS) which are commonly comorbid in TS. Forty patients with TS and 20 healthy controls completed an emotional blink suppression paradigm while undergoing functional magnetic resonance imaging. For the paradigm, participants completed alternating blocks of blink inhibition and free blinking while viewing pictures of angry and neutral facial expressions. Compared to controls, patients exhibited greater activity in the superior temporal gyrus and midcingulate during the inhibition of urges. Within the patient group, tic severity was associated with activity in the superior frontal gyrus during the angry inhibition contrast as compared to neutral; greater premonitory urge severity was associated with greater activity in the hippocampus, middle temporal gyrus and in the subcortex; blink inhibition ability was negatively associated with activity in the thalamus and insula. There were no significant associations with OCS severity for the emotion-related contrasts. The observed activated regions may represent a network that produces urges in patients, or alternatively, could represent compensatory cortical activity needed to keep urges and tics under control during emotional situations. Additionally, our findings suggest that OCS in the context of TS is similar to traditional obsessive-compulsive disorder and is neurobiologically dissociable from tics.

The functional connectivity profile of tics and obsessive-compulsive symptoms in Tourette Syndrome.

Tourette Syndrome (TS) is characterized by the presence of tics and sensory phenomena, such as premonitory urges, and is often accompanied by significant obsessive-compulsive symptoms (OCS). The goal of this exploratory study was to determine the association between functional connectivity and the different symptom domains of TS, as little is currently known about how they differ. Resting-state functional magnetic resonance imaging was performed in 39 patients with TS and 20 matched healthy controls. Seed-based functional connectivity of the supplementary motor area (SMA), orbitofrontal cortex (OFC), insula, caudate and putamen were compared between the groups, and correlated with clinical measures within the patient group. When compared to controls, patients with TS exhibited greater connectivity between the temporal gyri, insula and putamen, and between the OFC and cingulate cortex. Tic severity was associated with greater connectivity between the putamen and the sensorimotor cortex; OCS severity was associated with less connectivity between the SMA and thalamus and between the caudate and precuneus; and premonitory urge severity was associated with less connectivity between the OFC and sensorimotor cortex and between the inferior frontal gyrus and the putamen and insula seeds. Functional connectivity within sensorimotor processing regions were associated with all of the investigated symptom domains, including OCS, suggesting dysfunctions in the sensorimotor system may explain most of the observed symptoms in TS, and not just tics.

Examining the functional activity of different obsessive-compulsive symptom dimensions in Tourette syndrome.

OBJECTIVES: Tourette syndrome (TS) is commonly comorbid with obsessive-compulsive disorder (OCD) and many phenomenological similarities exist between tics and obsessive-compulsive symptoms (OCS). Therefore, due to the clinical importance of comorbid OCD, the goal of this study was to investigate the neural substrates of OCS in TS using functional magnetic resonance imaging. METHODS: Forty patients with TS and 20 healthy controls underwent functional magnetic resonance imaging while viewing blocks of OCS-provoking pictures relating to washing, checking and symmetry symptoms, as well as generally disgusting and neutral scenes. Statistical comparisons were made between patients with moderate/severe OCS, absent/mild OCS and healthy controls. As well, within the entire TS patient group, significant associations with clinical measures were assessed for each of the provocation conditions. RESULTS: Group differences in the insula, sensorimotor cortex, supramarginal gyrus and visual processing regions were common among the checking, washing and disgust conditions. In the patient group, negative associations between OCS severity and activity in the supramarginal gyrus, inferior frontal gyrus, sensorimotor cortex, precuneus and visual processing regions were common among the provocation conditions. Tic severity was only associated with activity in the anterior cingulate cortex for the symmetry condition. CONCLUSION: Our findings implicate areas previously reported to be involved in OCD, as well as areas not typically implicated in OCD, suggesting that the neurobiological profile of TS+OCD is intermediate to pure TS and pure OCD.

The Neural Correlates of Self-Regulatory Fatigability During Inhibitory Control of Eye Blinking.

The capacity to regulate urges is an important human characteristic associated with a range of social and health outcomes. Self-regulatory capacity has been postulated to have a limited reserve, which when depleted leads to failure. The authors aimed to investigate the neural correlates of self-regulatory fatigability. Functional MRI was used to detect brain activations in 19 right-handed healthy subjects during inhibition of eye blinking, in a block design. The increase in number of blinks during blink inhibition from the first to the last block was used as covariate of interest. There was an increase in the number of eye blinks escaping inhibitory control across blink inhibition blocks, whereas there was no change in the number of eye blinks occurring during rest blocks. Inhibition of blinking activated a wide network bilaterally, including the inferior frontal gyrus, dorsolateral prefrontal cortex, dorsal anterior cingulate cortex, supplementary motor area, and caudate. Deteriorating performance was associated with activity in orbitofrontal cortex, ventromedial prefrontal cortex, rostroventral anterior cingulate cortex, precuneus, somatosensory, and parietal areas. As anticipated, effortful eye-blink control resulted in activation of prefrontal control areas and regions involved in urge and interoceptive processing. Worsening performance was associated with activations in brain areas involved in urge, as well as regions involved in motivational evaluation. These findings suggest that self-regulatory fatigability is associated with relatively less recruitment of prefrontal cortical regions involved in executive control.

Preliminary Evidence on Cannabis Effectiveness and Tolerability for Adults With Tourette Syndrome.

The authors retrospectively evaluated effectiveness and tolerability of cannabis in 19 adults with Tourette syndrome. Tics scores decreased by 60%, and 18 of the 19 participants were at least "much improved." Cannabis was generally well tolerated, although most participants reported side effects.

OCD: obsessive-compulsive disgust? The role of disgust in obsessive-compulsive disorder.

Recent research has identified the important role of disgust in the symptomatology of obsessive-compulsive disorder (OCD). Exaggerated and inappropriate disgust reactions may drive some of the symptoms of OCD, and in some cases, may even eclipse feelings of anxiety. This paper reviews behavioural and neuroimaging research that recognizes the prominent role of disgust in contributing to OCD symptoms, especially contamination-based symptoms. We discuss how elevated behavioural and biological markers of disgust reported in OCD populations support the need for alternative clinical treatment strategies and theoretical models of OCD.

Study 329 continuation phase: Safety and efficacy of paroxetine and imipramine in extended treatment of adolescent major depression.

OBJECTIVE: This is an analysis of the unpublished continuation phase of Study 329, the primary objective of which was to compare the efficacy and safety of paroxetine and imipramine with placebo in the treatment of adolescents with unipolar major depression. The objectives of the continuation phase were to assess safety and relapse rates in the longer term. The objective of this publication, under the Restoring Invisible and Abandoned Trials (RIAT) initiative, was to see whether access to and analysis of the previously unpublished dataset from the continuation phase of this randomized controlled trial would have clinically relevant implications for evidence-based medicine. METHODS: The study was an eight-week double-blind randomized placebo-controlled trial with a six month continuation phase. The setting was 12 North American academic psychiatry centres, from 20 April 1994 to 15 February 1998. 275 adolescents with major depression were originally enrolled in Study 329, with 190 completing the eight-week acute phase. Of these, 119 patients (43%) entered the six-month continuation phase (paroxetine n = 49; imipramine n = 39; placebo n = 31), in which participants were continued on their current treatment, blinded. As per the protocol, we have looked at rates of relapse (based on Hamilton Depression Scale scores) across both acute and continuation phases, and generated a safety profile for paroxetine and imipramine compared with placebo for up to six months.ANOVA testing (generalized linear model) using a model including effects of site, treatment and site x treatment interaction was applied. Otherwise we used only descriptive statistics. RESULTS: Of patients entering the continuation phase, 15 of 49 for paroxetine (31%), 12 of 39 for imipramine (31%) and 12 of 31 for placebo (39%) completed as responders. Across the study, 25 patients on paroxetine relapsed (41% of those showing an initial response), 15 on imipramine (26%), and 10 on placebo (21%). In the continuation and taper phases combined there were 211 adverse events in the paroxetine group, 147 on imipramine and 100 on placebo. The taper phase had a higher proportion of severe adverse events per week of exposure than the acute phase, with the continuation phase having the fewest events. CONCLUSIONS: The continuation phase did not offer support for longer-term efficacy of either paroxetine or imipramine. Relapse and adverse events on both active drugs open up the risks of a prescribing cascade. The previously largely unrecognised hazards of the taper phase have implications for prescribing practice and need further exploration.