Treatment guesses in the Treatment for Adolescents with Depression Study: Accuracy, unblinding and influence on outcomes.

OBJECTIVE: We evaluated the presence and impact of unblinding during the influential Treatment for Adolescents with Depression Study (ClinicalTrials.gov Identifier: NCT00006286). METHOD: Our analysis was part of a Restoring Invisible and Abandoned Trials reanalysis. Treatment for Adolescents with Depression Study trialled fluoxetine, placebo, cognitive behaviour therapy or their combination, in treating adolescents with major depressive disorder. We analysed the accuracy of guesses of fluoxetine or placebo allocation, and their effects on change in Children's Depression Rating Scale-Revised at 12 weeks. RESULTS: Of 221 participants allocated to fluoxetine or placebo, 151 adolescents (68%) had their guess about pill-treatment-arm allocation recorded at week 6, and guesses were recorded for 154 independent evaluators, 159 parents and 164 pharmacotherapists. All of these groups guessed treatment allocation more accurately than would be expected by chance (60-66% accuracy; all p-values ⩽ 0.004). Guesses did not become more accurate between 6 and 12 weeks and were not predicted by adverse events, though event documentation was poor. Treatment guess had a substantial and statistically significant effect on outcome (Children's Depression Rating Scale-Revised change mean difference 9.12 [4.69; 13.55], ß = 0.334, p < 0.001), but actual treatment arm did not (1.53 [-2.83; 5.89], ß = 0.056, p = 0.489). Removing guess from the analysis increased the apparent effect of treatment arm, making it almost statistically significant at the conventional alpha-level of 0.05 (p = 0.06). CONCLUSIONS: For Treatment for Adolescents with Depression Study, treatment guesses strongly predicted outcomes and may have led to the exaggeration of drug effectiveness in the absence of actual effects. The integrity of double-blinding in trials should be routinely assessed and reported.

Dispensing of psychotropic medications to Australian children and adolescents before and during the COVID-19 pandemic, 2013-2021: a retrospective cohort study.

OBJECTIVE: To determine longitudinal patterns of dispensing of antidepressant, anxiolytic, antipsychotic, psychostimulant, and hypnotic/sedative medications to children and adolescents in Australia during 2013-2021. DESIGN: Retrospective cohort study; analysis of 10% random sample of Pharmaceutical Benefits Scheme (PBS) dispensing data. PARTICIPANTS, SETTING: People aged 18 years or younger dispensed PBS-subsidised psychotropic medications in Australia, 2013-2021. MAIN OUTCOME MEASURES: Population prevalence of dispensing of psychotropic medications to children and adolescents, by psychotropic class, gender, and age group (0-6, 7-12, 13-18 years). RESULTS: The overall prevalence of psychotropic dispensing to children and adolescents was 33.8 per 1000 boys and 25.2 per 1000 girls in 2013, and 60.0 per 1000 boys and 48.3 per 1000 girls in 2021. The prevalence of psychotropic polypharmacy was 5.4 per 1000 boys and 3.7 per 1000 girls in 2013, and 10.4 per 1000 boys and 8.3 per 1000 girls in 2021. Prevalent dispensing during 2021 was highest for psychostimulants (boys, 44.0 per 1000; girls, 17.4 per 1000) and antidepressants (boys, 20.4 per 1000; girls, 33.8 per 1000). During 2021, the prevalence of dispensing was higher than predicted by extrapolation of 2013-2019 data for many classes, including antidepressants (boys: +6.1%; 95% CI, 1.1-11.1%; girls: +22.2%; 95% CI, 17.4-26.9%), and psychostimulants (boys: +14.5%; 95% CI, 8.0-21.1%; girls: +27.7%; 95% CI, 18.9-36.6%). The increases were greatest for girls aged 13-18 years (antidepressants: +20.3%; 95% CI, 16.9-23.7%; psychostimulants: +39.0%; 95% CI, 27.9-50.0%). CONCLUSIONS: The prevalence of both psychotropic dispensing and psychotropic polypharmacy for children and adolescents were twice as high in 2021 as in 2013. The reasons and appropriateness of the marked increases in psychotropic dispensing during the COVID-19 pandemic, particularly to adolescent girls, should be investigated.

Trends in prescription of psychotropic medications to children and adolescents in Australian primary care from 2011 to 2018.

OBJECTIVE: To examine trends in prescribing psychotropic medications to children and adolescents in Australian primary care from 2011 to 2018. METHOD: A retrospective cohort study examined prescriptions written by general practitioners using MedicineInsight, a large Australian primary care database, covering approximately 9% of all general practitioner practices. Numbers of patients receiving prescriptions for five main classes of psychotropics (antipsychotics, antidepressants, attention deficit hyperactivity disorder medications, anxiolytics, and hypnotics/sedatives [including benzodiazepines and Z-drugs, but excluding melatonin]) were examined annually by age-group (0-4, 5-9, 10-14, 15-18 years). Melatonin was analysed separately. RESULTS: The number of patients prescribed any psychotropic increased from 25.6 to 36.2 per 1000 individuals from 2011 to 2018 (average annual increase +4.5%, 95% confidence interval [4.1%, 4.9%]; overall +41.4%). Among the five main classes, the largest annual increase was for attention deficit hyperactivity disorder medications (+9.6%, 95% confidence interval [8.8%, 10.5%]; overall +95.8%), followed by antipsychotics (+6.2%, 95% confidence interval [5.0%, 7.3%]; overall +62.8%) and antidepressants (+4.5%, 95% confidence interval [4.0%, 5.0%]; overall +42.8%). Hypnotic/sedative prescribing decreased on average 6.5% per year (95% confidence interval [-8.0%, -5.0%]; overall -40.2%). Anxiolytic prescribing remained steady. Melatonin prescriptions showed the highest increase of all (+24.7%, 95% confidence interval [23.7%, 25.8%]; overall +606.7%). The largest annual increase in antipsychotic, antidepressant or attention deficit hyperactivity disorder medication prescribing occurred in 10- to 14-year-olds (+7.5%, +6.5% and +10.4%, respectively). The largest point prevalence occurred in 2018 among 15- to 18-year-olds, with 98.5 per 1000 prescribed antidepressants. Antidepressants were more frequently prescribed to females; antipsychotics, attention deficit hyperactivity disorder medications and melatonin more often to males. The most prescribed antipsychotics were risperidone (<15 years) and quetiapine (15- to 18-year-olds). Fluoxetine was the most prescribed antidepressant in those aged 5+ years and amitriptyline in 0- to 4-year-olds. CONCLUSION: General practitioner prescribing of melatonin, antipsychotics, antidepressants and attention deficit hyperactivity disorder medications to under-19-year-olds increased markedly from 2011 to 2018. Although benzodiazepine and Z-drug prescriptions declined, this was offset by a substantial increase in melatonin prescribing.

Attention deficit hyperactivity disorder late birthdate effect common in both high and low prescribing international jurisdictions: a systematic review.

BACKGROUND: Multiple studies have found that the youngest children in a classroom are at elevated risk of being diagnosed with, or medicated for, ADHD. This systematic review was conducted to investigate whether this late birthdate effect is the norm and whether the strength of effect is related to the absolute risk of being diagnosed/medicated. METHODS: A literature search of the PubMed and ERIC databases and snowball and grey literature searching were conducted. RESULTS: A total of 19 studies in 13 countries covering over 15.4 million children investigating this relationship were identified. Three other studies exploring related topics were identified. The diversity of methodologies prevented a meta-analysis. Instead a systematic review of the 22 studies was conducted. A total of 17 of the 19 studies found that the youngest children in a school year were considerably more likely to be diagnosed and/or medicated than their older classmates. Two Danish studies found either a weak or no late birth date effect. There was no consistent relationship between per-capita diagnosis or medication rates and the strength of the relative age effect, with strong effects reported in most jurisdictions with comparatively low rates. CONCLUSIONS: It is the norm internationally for the youngest children in a classroom to be at increased risk of being medicated for ADHD, even in jurisdictions with relatively low prescribing rates. A lack of a strong effect in Denmark may be accounted for by the common practice of academic 'redshirting', where children judged by parents as immature have a delayed school start. Redshirting may prevent and/or disguise late birthdate effects and further research is warranted. The evidence of strong late birthdate effects in jurisdictions with comparatively low diagnosis/medication rates challenges the notion that low rates indicate sound diagnostic practices.

Mental Health Messages in Prominent Mental Health Apps.

PURPOSE: Many who seek primary health care advice about mental health may be using mobile applications (apps) claiming to improve well-being or relieve symptoms. We aimed to identify how prominent mental health apps frame mental health, including who has problems and how they should be managed. METHODS: We conducted a qualitative content analysis of advertising material for mental health apps found online in the United States, the United Kingdom, Canada, and Australia during late 2016. Apps were included if they explicitly referenced mental health diagnoses or symptoms and offered diagnosis and guidance, or made health claims. Two independent coders analyzed app store descriptions and linked websites using a structured, open-ended instrument. We conducted interpretive analysis to identify key themes and the range of messages. RESULTS: We identified 61 mental health apps: 34 addressed predominantly anxiety, panic, and stress (56%), 16 addressed mood disorders (26%), and 11 addressed well-being or other mental health issues (18%). Apps described mental health problems as being psychological symptoms, a risk state, or lack of life achievements. Mental health problems were framed as present in everyone, but everyone was represented as employed, white, and in a family. Explanations about mental health focused on abnormal responses to mild triggers, with minimal acknowledgment of external stressors. Therapeutic strategies included relaxation, cognitive guidance, and self-monitoring. Apps encouraged frequent use and promoted personal responsibility for improvement. CONCLUSIONS: Mental health apps may promote medicalization of normal mental states and imply individual responsibility for mental well-being. Within the health care clinician-patient relationship, such messages should be challenged, where appropriate, to prevent overdiagnosis and ensure supportive health care where needed.

A health app developer's guide to law and policy: a multi-sector policy analysis.

BACKGROUND: Apps targeted at health and wellbeing sit in a rapidly growing industry associated with widespread optimism about their potential to deliver accessible and cost-effective healthcare. App developers might not be aware of all the regulatory requirements and best practice principles are emergent. Health apps are regulated in order to minimise their potential for harm due to, for example, loss of personal health privacy, financial costs, and health harms from delayed or unnecessary diagnosis, monitoring and treatment. We aimed to produce a comprehensive guide to assist app developers in producing health apps that are legally compliant and in keeping with high professional standards of user protection. METHODS: We conducted a case study analysis of the Australian and related international policy environment for mental health apps to identify relevant sectors, policy actors, and policy solutions. RESULTS: We identified 29 policies produced by governments and non-government organisations that provide oversight of health apps. In consultation with stakeholders, we developed an interactive tool targeted at app developers, summarising key features of the policy environment and highlighting legislative, industry and professional standards around seven relevant domains: privacy, security, content, promotion and advertising, consumer finances, medical device efficacy and safety, and professional ethics. We annotated this developer guidance tool with information about: the relevance of each domain; existing legislative and non-legislative guidance; critiques of existing policy; recommendations for developers; and suggestions for other key stakeholders. CONCLUSIONS: We anticipate that mental health apps developed in accordance with this tool will be more likely to conform to regulatory requirements, protect consumer privacy, protect consumer finances, and deliver health benefit; and less likely to attract regulatory penalties, offend consumers and communities, mislead consumers, or deliver health harms. We encourage government, industry and consumer organisations to use and publicise the tool.

Health of grey nomads: On the move and under the health sector radar.

OBJECTIVE: Grey nomads - older people driving long distances recreationally and staying in caravans, tents or motor homes - are common on Australian highways. Although grey nomads report many benefits from their travels, there is anecdotal evidence that they impose a significant burden on rural/remote health services, including general practitioners, pharmacists and hospitals. There have been calls for better resourcing and service provision, but little reference to solid evidence on which to base this. This literature review is the first to integrate existing evidence for a health audience. SETTING: Australia. DESIGN: Narrative literature search and synthesis. RESULTS: There is very little published information about the health and health service utilisation of grey nomads, and almost none in the medical literature. One key exception, a survey at a caravan park in the Kimberley region, found that, like other older Australians, many grey nomads have chronic diseases, and they have high rates of medication use. However, other studies have found that they generally view themselves as relatively healthy. There is some evidence of inadequate preparation for travelling. Issues include lack of health summaries, inadequate medication supplies and suboptimal vaccination. Some experience emergencies, sometimes resulting in hospital admissions. Overall, they place a poorly documented burden on rural/remote services. CONCLUSION: There is a need for further research on the health of grey nomads, their use of self-care strategies, and their uptake of health services both on the road and at home, to inform the provision of health services and optimise their well-being and health care utilisation.

Antipsychotic prescribing patterns in children and adolescents attending Australian general practice in 2011 and 2017.

Background: Antipsychotics are increasingly prescribed to children and adolescents worldwide, but little is known about reasons for prescribing. We aimed to examine patterns of paediatric antipsychotic prescribing in Australian primary care services in 2011 and 2017, including diagnoses, sociodemographic characteristics, off-label prescribing, and psychotropic co-prescribing. Methods: Retrospective analysis of electronic health records (EHRs) using a large Australian general practice database (MedicineInsight). Diagnoses of mental disorders were extracted from EHRs and associated with antipsychotic prescriptions within the same calendar year for three age-groups: 0-9, 10-14, and 15-18-year-olds. Results: In 2017, children/adolescents with mental health diagnoses were more likely to be prescribed antipsychotics (2.9% of 27,412 patients) than in 2011 (2.0% of 8418 patients; absolute difference +0.9, 95% CI + 0.5, +1.4). The likelihood was greater for patients with bipolar disorders (21.6% vs. 41.5%), eating disorders (1.1% vs. 7.2%), and autism without behavioural problems (3.7% vs. 6.1%). Depression/anxiety (adjusted 26.8% of patients 2011; 30.8% 2017) was the most common diagnosis associated with antipsychotics in both years. Most antipsychotics were prescribed off-label (69.8% 2011; 79.7% 2017; absolute difference +9.8, 95% CI + 1.54, +18.4). Off-label prescribing increased most among those aged 15-18-years, females, and patients living in outer regional/remote/very remote communities and the most disadvantaged areas. The three most frequently prescribed antipsychotics in both years were risperidone, quetiapine, and olanzapine. Psychotropic co-prescribing among patients receiving antipsychotic prescriptions was approximately 69% in both years. Conclusions: Prescribing antipsychotics for mental health diagnoses to children/adolescents attending Australian general practices was more frequent in 2017 than 2011, and most commonly associated with depression/anxiety diagnoses. In both years, most prescribing was off-label. The majority of patients were co-prescribed other classes of psychotropics along with antipsychotics.

Video-based telehealth in Australian primary health care: current use and future potential.

Many Australians have limited access to health-care services due to a range of barriers, including geographic distance and restricted mobility, which telehealth can potentially address. This paper reviews the current and potential use of video consultation in primary health care in Australia, drawing on international literature. There is substantial evidence of high patient satisfaction, but many studies have methodological limitations. Overall, evidence of effectiveness and cost-effectiveness is weak. There is reasonable evidence for diagnosis, home care and specialist consultations by GPs with patients present. Two telehealth initiatives using video consultation are briefly presented. Both provide evidence that video consultation has a valuable role to play, but does not obviate the need for face-to-face consultations. Video consultation challenges traditional professional roles, particularly those of nurses, and can improve health workers' skills and job satisfaction. More fundamentally, telehealth challenges the traditional distinction between primary and secondary care. This can be a source of resistance but may ultimately be one of its strengths. Appropriately targeted video consultation has much potential to improve the delivery of primary health care in Australia, particularly in rural and remote regions.

Psychotropic marketing practices and problems: implications for DSM-5.

The descriptive diagnostic model since DSM-III has often led to "cookbook" diagnosis and assumptions of "chemical imbalance" for psychiatric disorders. Pharmaceutical companies have exploited this in their marketing. This includes promoting self-diagnosis with online checklists. Significant overprescribing of psychotropics has resulted. DSM-5 will provide new disorders and broader diagnostic criteria that will likely exacerbate this. Most psychotropic prescribing is done by primary care physicians, who are problematically excluded from DSM-5 field trials and are influenced by industry funded key opinion leaders who may promote diagnosis of subthreshold cases. More lax criteria will increase diagnosis of subthreshold cases. Expansion of not otherwise specified (NOS) categories can be used to justify off-label promotion. Pediatric bipolar disorder, constructed within the bipolar disorder NOS category, became an "epidemic" in the United States, fuelled by diagnostic upcoding pressures. Disruptive mood dysregulation disorder may similarly cause overdiagnosis and excessive prescribing, as will other new disorders and lower diagnostic thresholds.

The increased use of antidepressants has contributed to the worldwide reduction in suicide rates.

Numerous ecological studies have shown an inverse association between antidepressant use and suicide rates and a smaller number of individual-based studies have shown an association between current antidepressant use and reduced suicide risk. Such evidence is often cited in support of the notion that antidepressants prevent suicide. However, more recently, the premises underlying this proposition, namely that suicide is caused by depression and that antidepressants relieve depression, have been challenged and the potential harm caused by antidepressants has been highlighted. In this article, Goran Isacsson and Charles Rich debate with Jon Jureidini and Melissa Raven the motion that the increased use of antidepressants has contributed to the worldwide reduction in suicide rates.

Antidepressant Prescribing and Suicide/Self-Harm by Young Australians: Regulatory Warnings, Contradictory Advice, and Long-Term Trends.

In 2004, the US Food and Drug Administration (FDA) controversially issued a black box warning that antidepressants were associated with an increased risk of suicidal thoughts and behaviours in people aged under 18 years. In 2007, the warning was expanded to include young adults aged under 25 years. In 2005, the Australian Therapeutic Goods Administration responded to the FDA warning by requiring Product and Consumer Information leaflets to be updated to reflect the risk. However, there was considerable debate, and at times emotive backlash, in academic journals and the international media. Prominent US and Australian mental health organisations and psychiatrists challenged the FDA warning. They argued that, on balance, antidepressant use was likely to reduce the risk of suicide. Several ecological studies were cited misleadingly as evidence that decreasing antidepressant use increases suicide risk. From 2008 to 2018, Australian per-capita child, adolescent and young adult antidepressant dispensing (0-27 years of age) and suicide (0-24 years) rates have increased approximately 66% and 49%, respectively. In addition, there was a 98% increase in intentional poisonings among 5 to 19 year-olds in New South Wales and Victoria between 2006 and 2016, with substantial overlap between the most commonly dispensed psychotropics and the drugs most commonly used in self-poisoning. These results do not support claims that increased antidepressant use reduces youth suicide risk. They are more consistent with the FDA warning and the hypothesis that antidepressant use increases the risk of suicide and self-harm by young people. Causal relationships cannot be established with certainty until there is a vast improvement in post-marketing surveillance. However, there is clear evidence that more young Australians are taking antidepressants, and more young Australians are killing themselves and self-harming, often by intentionally overdosing on the very substances that are supposed to help them.

The "Hot Potato" of Mental Health App Regulation: A Critical Case Study of the Australian Policy Arena.

BACKGROUND: Health apps are a booming, yet under-regulated market, with potential consumer harms in privacy and health safety. Regulation of the health app market tends to be siloed, with no single sector holding comprehensive oversight. We sought to explore this phenomenon by critically analysing how the problem of health app regulation is being presented and addressed in the policy arena. METHODS: We conducted a critical, qualitative case study of regulation of the Australian mental health app market. We purposively sampled influential policies from government, industry and non-profit organisations that provided oversight of app development, distribution or selection for use. We used Bacchi's critical, theoretical approach to policy analysis, analysing policy solutions in relation to the ways the underlying problem was presented and discussed. We analysed the ways that policies characterised key stakeholder groups and the rationale policy authors provided for various mechanisms of health app oversight. RESULTS: We identified and analysed 29 policies from Australia and beyond, spanning 5 sectors: medical device, privacy, advertising, finance, and digital content. Policy authors predominantly framed the problem as potential loss of commercial reputations and profits, rather than consumer protection. Policy solutions assigned main responsibility for app oversight to the public, with a heavy onus on consumers to select safe and high-quality apps. Commercial actors, including powerful app distributors and commercial third parties were rarely subjects of policy initiatives, despite having considerable power to affect app user outcomes. CONCLUSION: A stronger regulatory focus on app distributors and commercial partners may improve consumer privacy and safety. Policy-makers in different sectors should work together to develop an overarching regulatory framework for health apps, with a focus on consumer protection.