Clinical outcome data of anxiety patients treated with cannabis-based medicinal products in the United Kingdom: a cohort study from the UK Medical Cannabis Registry.

RATIONALE: Cannabis-based medicinal products (CBMPs) have been identified as novel therapeutics for generalised anxiety disorder (GAD) based on pre-clinical models; however, there is a paucity of high-quality evidence on their effectiveness and safety. OBJECTIVES: This study aimed to evaluate the clinical outcomes of patients with GAD treated with dried flower, oil-based preparations, or a combination of both CBMPs. METHODS: A prospective cohort study of patients with GAD (n = 302) enrolled in the UK Medical Cannabis Registry prescribed oil or flower-based CBMPs was performed. Primary outcomes were changes in generalised anxiety disorder-7 (GAD-7) questionnaires at 1, 3, and 6 months compared to baseline. Secondary outcomes were single-item sleep quality scale (SQS) and health-related quality of life index (EQ-5D-5L) questionnaires at the same time points. These changes were assessed by paired t-tests. Adverse events were assessed in line with CTCAE (Common Terminology Criteria for Adverse Events) v4.0. RESULTS: Improvements in anxiety, sleep quality and quality of life were observed at each time point (p < 0.001). Patients receiving CBMPs had improvements in GAD-7 at all time points (1 month: difference -5.3 (95% CI -4.6 to -6.1), 3 months: difference -5.5 (95% CI -4.7 to -6.4), 6 months: difference -4.5 (95% CI -3.2 to -5.7)). Thirty-nine participants (12.9%) reported 269 adverse events in the follow-up period. CONCLUSIONS: Prescription of CBMPs in those with GAD is associated with clinically significant improvements in anxiety with an acceptable safety profile in a real-world setting. Randomised trials are required as a next step to investigate the efficacy of CBMPs.

Digital Technology Use and Mental Health Consultations: Survey of the Views and Experiences of Clinicians and Young People.

BACKGROUND: Digital technologies play an increasingly important role in the lives of young people and have important effects on their mental health. OBJECTIVE: We aimed to explore 3 key areas of the intersection between digital technology and mental health: the views and experiences of young people and clinicians about digital technology and mental health; implementation and barriers to the UK national guidance recommendation-that the discussion of digital technology use should form a core part of mental health assessment; and how digital technology might be used to support existing consultations. METHODS: Two cross-sectional web-based surveys were conducted in 2020 between June and December, with mental health clinicians (n=99) and young people (n=320). Descriptive statistics were used to summarize the proportions. Multilinear regression was used to explore how the answers varied by gender, sexuality, and age. Thematic analysis was used to explore the contents of the extended free-text answers. Anxiety was measured using the Generalized Anxiety Disorder Questionnaire-7 (GAD-7). RESULTS: Digital technology use was ubiquitous among young people, with positive and negative aspects acknowledged by both clinicians and young people. Negative experiences were common (131/284, 46.1%) and were associated with increased anxiety levels among young people (GAD-7 3.29; 95% CI 1.97-4.61; P<.001). Although the discussion of digital technology use was regarded as important by clinicians and acceptable by young people, less than half of clinicians (42/85, 49.4%) routinely asked about the use of digital technology and over a third of young people (48/121, 39.6%) who had received mental health care had never been asked about their digital technology use. The conversations were often experienced as unhelpful. Helpful conversations were characterized by greater depth and exploration of how an individual's digital technology use related to mental health. Despite most clinicians (59/83, 71.1%) wanting training, very few (21/86, 24.4%) reported receiving training. Clinicians were open to viewing mental health data from apps or social media to help with consultations. Although young people were generally, in theory, comfortable sharing such data with health professionals, when presented with a binary choice, most reported not wanting to share social media (84/117, 71.8%) or app data (67/118, 56.8%) during consultations. CONCLUSIONS: Digital technology use was common, and negative experiences were frequent and associated with anxiety. Over a third of young people were not asked about their digital technology use during mental health consultations, and potentially valuable information about relevant negative experiences on the web was not being captured during consultations. Clinicians would benefit from having access to training to support these discussions with young people. Although young people recognized that app data could be helpful to clinicians, they appeared hesitant to share their own data. This finding suggests that data sharing has barriers that need to be further explored.

Mental Health Practitioners' and Young People's Experiences of Talking About Social Media During Mental Health Consultations: Qualitative Focus Group and Interview Study.

BACKGROUND: Increasing concerns among mental health care professionals have focused on the impact of young people's use of digital technology and social media on their mental well-being. It has been recommended that the use of digital technology and social media be routinely explored during mental health clinical consultations with young people. Whether these conversations occur and how they are experienced by both clinicians and young people are currently unknown. OBJECTIVE: This study aimed to explore mental health practitioners' and young people's experiences of talking about young people's web-based activities related to their mental health during clinical consultations. Web-based activities include use of social media, websites, and messaging. Our aim was to identify barriers to effective communication and examples of good practice. In particular, we wanted to obtain the views of young people, who are underrepresented in studies, on their social media and digital technology use related to mental health. METHODS: A qualitative study was conducted using focus groups (11 participants across 3 groups) with young people aged 16 to 24 years and interviews (n=8) and focus groups (7 participants across 2 groups) with mental health practitioners in the United Kingdom. Young people had experience of mental health problems and support provided by statutory mental health services or third-sector organizations. Practitioners worked in children and young people's mental health services, statutory services, or third-sector organizations such as a university counseling service. Thematic analysis was used to analyze the data. RESULTS: Practitioners and young people agreed that talking about young people's web-based activities and their impact on mental health is important. Mental health practitioners varied in their confidence in doing this and were keen to have more guidance. Young people said that practitioners seldom asked about their web-based activities, but when asked, they often felt judged or misunderstood. This stopped them from disclosing difficult web-based experiences and precluded useful conversations about web-based safety and how to access appropriate web-based support. Young people supported the idea of guidance or training for practitioners and were enthusiastic about sharing their experiences and being involved in the training or guidance provided to practitioners. CONCLUSIONS: Practitioners would benefit from structured guidance and professional development to enable them to support young people in feeling more willing to disclose and talk about their web-based experiences and their impact on their mental health. This is reflected in practitioners' desire for guidance to improve their confidence and skills to safely support young people in navigating the challenges of the web-based world. Young people want to feel comfortable discussing their web-based activities during their consultations with mental health practitioners, both in tackling the challenges and using the opportunity to discuss their experiences, gain support, and develop coping strategies related to web-based safety.

Hierarchical clustering of prolonged post-concussive symptoms after 12 months: symptom-centric analysis and association with functional impairments.

BACKGROUND: Following a concussion, approximately 15% of individuals experience persistent symptoms that can lead to functional deficits. However, underlying symptom-clusters that persist beyond 12 months have not been adequately characterized, and their relevance to functional deficits are unclear. The aim of this study was to characterize the underlying clusters of prolonged post-concussive symptoms lasting more than 12 months, and to investigate their association with functional impairments. METHODS: Although hierarchical clustering is ideally suited in evaluating subjective symptom severities, it has not been applied to the Rivermead Post-Concussion Questionnaire (RPQ). The RPQ and functional impairments questions were administered via a smartphone application to 445 individuals who self-reported prolonged post-concussive symptoms. Symptom-clusters were obtained using agglomerative hierarchical clustering, and their association with functional deficits were investigated with sensitivity analyses, and corrected for multiple comparisons. RESULTS: Five symptom-clusters were identified: headache-related, sensitivity to light and sound, cognitive, mood-related, and sleep-fatigue. Individuals with more severe RPQ symptoms were more likely to report functional deficits (p < 0.0001). Whereas the headache and sensitivity clusters were associated with at most one impairment, at-least-mild sleeping difficulties and fatigue were associated with four, and moderate-to-severe cognitive difficulties with five (all p < 0.01). CONCLUSIONS: Symptom-clusters may be clinically useful for functional outcome stratification for targeted rehabilitation therapies. Further studies are required to replicate these findings in other cohorts and questionnaires, and to ascertain the effects of symptomatic intervention on functional outcomes.

Developing good practice indicators to assist mental health practitioners to converse with young people about their online activities and impact on mental health: a two-panel mixed-methods Delphi study.

BACKGROUND: Online activity has been linked to poor mental health in children and young people, particularly those with existing vulnerability who may inadvertently or otherwise access harmful content. It is suggested health and social care practitioners should address online activity during mental health consultations, but guidance about acceptable or effective ways to do this is lacking. This study sought to derive good practice guidance to support mental health practitioners to engage young people in conversations about their online activities and impact on mental health. METHODS: A mixed-methods Delphi (consensus) study was conducted with a panel of mental health practitioners (n = 21) and a panel of young people (n = 22). Practitioners worked with children or young adults in the UK, mostly in statutory services (80.9%), in varied clinical roles, with 2 - 30 years of experience and most were female (87.5%). Young people were mostly female (77.3%), 13-22 years old, reported varied mental health diagnoses and had sought help from services. Across 3 rounds, panellists completed questionnaires which involved rating agreement with statements and answering open-ended questions. Iterative analysis informed subsequent questionnaire content. The percentage of participants rating their level of agreement with each statement was calculated. The threshold for inclusion as a good practice indicator (GPI) was 75% across both panels. Thematic analysis was used for free-text data. RESULTS: Twenty-seven GPIs emerged covering 'who' (which young people) should be asked about online activities, 'when', 'what' should be discussed, and with what 'outcome'. Panels agreed conversations should be initiated with all young people from first meeting and regularly thereafter, with 'red flags' indicating a conversation may be pertinent. Core topics were identified with additional areas for patients presenting with disordered eating or self-harm. Panels emphasised conversations should be fluid, normalised, and encourage reflection and self-awareness. CONCLUSIONS: Mental health practitioners could empower young people to exercise agency in relation to online safety and capitalise on positive features. Findings also identify training needs for practitioners. Further research should explore real-world application of the GPIs and transferability to underrepresented groups within our panels, such as males and younger children. Ethnicity and deprivation were not recorded.

Web-based support services to help prevent suicide in young people and students: A mixed-methods, user-informed review of characteristics and effective elements.

The online world may provide an alternative means to engage young people and students with suicidal feelings, who are typically reluctant to seek help. We aimed to map, characterise and obtain user evaluation of current online suicide support for this group in order to assess the usefulness of current provision and how it may be improved. We conducted a mixed-methods study, comprised of an internet search, content analysis of site features and qualitative interviews with site users: 9 young people and 4 general practitioners. Data collection took place in 2019 and 2020 in the UK. Young people participants were recruited through the well-being networks of a large University in South-West England and via a national young person's mental health app. General practitioners were recruited locally through professional networks. We identified a wide range of easily accessible online support, including examples of interactive services, such as live chat and text messaging, but a lack of support that is both suicide-specific and young adult-specific, and an absence of online suicide or mental health crisis support services tailored specifically for students. Qualitative data showed that clarity, brevity and immediacy are the most important facets of engaging crisis help for young people, and that young people may prefer to use text-based rather than verbal forms of communication when seeking help. Few services provided access to active peer support, outside of lived-experience stories, which were evaluated as both valuable and potentially harmful. There is a need to further develop tailored suicide specific online crisis support for young people and students, which is able to 'speak to' their age-specific needs and preferences. While lived experience may provide a valuable means of supporting young audiences, caution is required since this may have unintended negative consequences and further research is needed to understand the safe framing of such material.

Optimizing Existing Mental Health Screening Methods in a Dementia Screening and Risk Factor App: Observational Machine Learning Study.

BACKGROUND: Mindstep is an app that aims to improve dementia screening by assessing cognition and risk factors. It considers important clinical risk factors, including prodromal symptoms, mental health disorders, and differential diagnoses of dementia. The 9-item Patient Health Questionnaire for depression (PHQ-9) and the 7-item Generalized Anxiety Disorder Scale (GAD-7) are widely validated and commonly used scales used in screening for depression and anxiety disorders, respectively. Shortened versions of both (PHQ-2/GAD-2) have been produced. OBJECTIVE: We sought to develop a method that maintained the brevity of these shorter questionnaires while maintaining the better precision of the original questionnaires. METHODS: Single questions were designed to encompass symptoms covered in the original questionnaires. Answers to these questions were combined with PHQ-2/GAD-2, and anonymized risk factors were collected by Mindset4Dementia from 2235 users. Machine learning models were trained to use these single questions in combination with data already collected by the app: age, response to a joke, and reporting of functional impairment to predict binary and continuous outcomes as measured using PHQ-9/GAD-7. Our model was developed with a training data set by using 10-fold cross-validation and a holdout testing data set and compared to results from using the shorter questionnaires (PHQ-2/GAD-2) alone to benchmark performance. RESULTS: We were able to achieve superior performance in predicting PHQ-9/GAD-7 screening cutoffs compared to PHQ-2 (difference in area under the curve 0.04, 95% CI 0.00-0.08, P=.02) but not GAD-2 (difference in area under the curve 0.00, 95% CI -0.02 to 0.03, P=.42). Regression models were able to accurately predict total questionnaire scores in PHQ-9 (R2=0.655, mean absolute error=2.267) and GAD-7 (R2=0.837, mean absolute error=1.780). CONCLUSIONS: We app-adapted PHQ-4 by adding brief summary questions about factors normally covered in the longer questionnaires. We additionally trained machine learning models that used the wide range of additional information already collected in Mindstep to make a short app-based screening tool for affective disorders, which appears to have superior or equivalent performance to well-established methods.

Does anxiety moderate the effectiveness of mirtazapine in patients with treatment-resistant depression? A secondary analysis of the MIR trial.

BACKGROUND: There is a lack of evidence to guide treatment of comorbid depression and anxiety. Preliminary evidence suggests mirtazapine may be effective in treating patients with both depression and anxiety symptoms. METHODS: We undertook a secondary analysis of mirtazapine (MIR): a placebo-controlled trial of the addition of mirtazapine to a selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor in treatment-resistant depression (TRD) in primary care. We subdivided participants into three groups by baseline generalized anxiety disorder score (GAD-7): severe (GAD-7 ⩾ 16), moderate (GAD-7 = 11-15), no/mild (GAD-7 ⩽ 10). We used linear regression including likelihood-ratio testing of interaction terms to assess how baseline anxiety altered the response of participants to mirtazapine as measured by 12-week GAD-7 and Beck Depression Inventory II (BDI-II) scores. RESULTS: Baseline generalized anxiety moderated mirtazapine's effect as measured by GAD-7 (p = 0.041) and BDI-II (p = 0.088) at 12 weeks. Participants with severe generalized anxiety receiving mirtazapine had lower 12-week GAD-7 score (adjusted difference between means (ADM) -2.82, 95% confidence interval (CI) -0.69 to -4.95) and larger decreases in BDI-II score (ADM -6.36, 95% CI -1.60 to -10.84) than placebo. Conversely, there was no anxiolytic benefit (ADM 0.28, 95% CI -1.05 to 1.60) or antidepressant benefit (ADM -0.17, 95% CI -3.02 to 2.68) compared with placebo in those with no/mild generalized anxiety. CONCLUSIONS: These findings extend the evidence for the effectiveness of mirtazapine to reduce generalized anxiety in TRD in primary care. These results may inform targeted prescribing in depression based on concurrent anxiety symptoms, although these conclusions are constrained by the post-hoc nature of this analysis.

Valproate for acute mania.

BACKGROUND: Bipolar disorder is a severe and common mental disorder where patients experience recurrent symptoms of elevated or irritable mood, depression, or a combination of both. Treatment is usually with psychiatric medication, including mood stabilisers, antidepressants and antipsychotics. Valproate is an effective maintenance treatment for bipolar disorder. However, evidence assessing the efficacy of valproate in the treatment of acute mania is less robust, especially when comparing it to some of the newer antipsychotic agents. This review is an update of a previous Cochrane Review (last published 2003) on the role of valproate in acute mania. OBJECTIVES: To assess the efficacy and tolerability of valproate for acute manic episodes in bipolar disorder compared to placebo, alternative pharmacological treatments, or a combination pharmacological treatments, as measured by the treatment of symptoms on specific rating scales for individual episodes in paediatric, adolescent and adult populations. SEARCH METHODS: We searched Ovid MEDLINE (1950- ), Embase (1974- ), PsycINFO (1967- ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 28 September 2018. We had also conducted an earlier search of these databases in the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR) (all years to 6 June 2016). We also searched the World Health Organization (WHO) trials portal (ICTRP) and clinicaltrials.gov in September 2018, to identify any additional unpublished or ongoing studies. SELECTION CRITERIA: Single- and double-blind, randomised controlled trials comparing valproate with placebo, alternative antimanic treatments, or a combination of pharmacological treatments. We also considered studies where valproate was used as an adjunctive treatment in combination with another agent separately from studies where it was used in monotherapy. We included male and female patients of all ages and ethnicity with bipolar disorder. DATA COLLECTION AND ANALYSIS: Two review authors independently performed data extraction and methodological quality assessment. For analysis, we used the odds ratio (OR) for binary efficacy outcomes and the mean difference (MD) or standardised mean difference (SMD) for continuously distributed outcomes. MAIN RESULTS: Twenty-five trials (3252 participants) compared valproate with either placebo or alternative antimanic treatments to alleviate the symptoms of acute mania. For efficacy, our primary outcome was response rate. For tolerability, our primary outcome was the number of participants with any adverse effect. This meta-analysis included studies focusing on children, adolescents, as well as adults with a range of severity of manic symptoms. The majority of studies focused on adult men and women (aged 18 and above), were conducted in inpatient settings and completed in the US. Five studies in this review focused on children and adolescents (aged 18 and under) so that the review covers an age range from 3 - 82 years. Seven studies contained outpatient participants in some form. Nine studies included data that has been collected outside the US, namely Iran (4 studies), India (3 studies), China (1 study), or across several international countries (1 study).In adults, high-quality evidence found that valproate induces a slightly higher response compared to placebo (45% vs 29%, OR 2.05, 95% CI 1.32 to 3.20; 4 studies, 869 participants). Moderate-quality evidence found there was probably little or no difference in response rates between valproate and lithium (56% vs 62%, OR 0.80, 95% CI 0.48 to 1.35; 3 studies, 356 participants). In adults, low-quality evidence found there may be little or no difference in response rate between valproate and olanzapine (38% vs 44%, OR 0.77, 95% CI 0.48 to 1.25; 2 studies, 667 participants).In the children and adolescent population, the evidence regarding any difference in response rates between valproate and placebo was uncertain (23% vs 22%, OR 1.11, 95% CI 0.51 to 2.38; 1 study, 151 participants, very low-quality evidence). Low-quality evidence found that the response rate of participants receiving valproate may be lower compared to risperidone (23% vs 66%, OR 0.16, 95% CI 0.08 to 0.29; 1 study, 197 participants). The evidence regarding any difference in response rates between valproate and lithium was uncertain (23% vs 34%, OR 0.57, 95% CI 0.31 to 1.07; 1 study, 197 participants, very low-quality evidence).In terms of tolerability in adults, moderate-quality evidence found that there are probably more participants receiving valproate who experienced any adverse events compared to placebo (83% vs 75%, OR 1.63, 95% CI 1.13 to 2.36; 3 studies, 745 participants). Low-quality evidence found there may be little or no difference in tolerability between valproate and lithium (78% vs 86%, OR 0.61, 95% CI 0.25 to 1.50; 2 studies, 164 participants). We did not obtain primary tolerability outcome data on the olanzapine comparison.Within the children and adolescent population, the evidence regarding any difference between valproate or placebo was uncertain (67% vs 60%, OR 1.39, 95% CI 0.71 to 2.71; 1 study, 150 participants, very low-quality evidence). We did not obtain primary tolerability outcome data on the lithium or risperidone comparisons. AUTHORS' CONCLUSIONS: There is evidence that valproate is an efficacious treatment for acute mania in adults when compared to placebo. By contrast, there is no evidence of a difference in efficacy between valproate and placebo for children and adolescents. Valproate may be less efficacious than olanzapine in adults, and may also be inferior to risperidone as a monotherapy treatment for paediatric mania. Generally, there is uncertain evidence regarding whether valproate causes more or less side effects than the other main antimanic therapies. However, evidence suggests that valproate causes less weight gain and sedation than olanzapine.