Protocol for a randomised controlled trial of ketamine versus ketamine and behavioural activation therapy for adults with treatment-resistant depression in the community.

INTRODUCTION: Although short-term benefits follow parenteral ketamine for treatment-resistant major depressive disorder (TR-MDD), there are challenges that prevent routine use of ketamine by clinicians. These include acute dissociative effects of parenteral ketamine, high relapse rates following ketamine dosing and the uncertain role of psychotherapy. This randomised controlled trial (RCT) seeks to establish the feasibility of evaluating repeated oral doses of ketamine and behavioural activation therapy (BAT), compared with ketamine treatment alone, for TR-MDD. We also aim to compare relapse rates between treatment arms to determine the effect size of adding BAT to oral ketamine. METHODS AND ANALYSIS: This is a prospectively registered, two-centre, single-blind RCT. We aim to recruit 60 participants with TR-MDD aged between 18 and 65 years. Participants will be randomised to 8 weeks of oral ketamine and BAT, or 8 weeks of oral ketamine alone. Feasibility will be assessed by tracking attendance for ketamine and BAT, acceptability of treatment measures and retention to the study follow-up protocol. The primary efficacy outcome measure is the Montgomery-Asberg Depression Rating Scale (MADRS) measured weekly during treatment and fortnightly during 12 weeks of follow-up. Other outcome measures will assess the tolerability of ketamine and BAT, cognition and activity (using actigraphy). Participants will be categorised as non-responders, responders, remitters and relapsed during follow-up. MADRS scores will be analysed using a linear mixed model. For a definitive follow-up RCT study to be recommended, the recruitment expectations will be met and efficacy outcomes consistent with a >20% reduction in relapse rates favouring the BAT and ketamine arm will be achieved. ETHICS AND DISSEMINATION: Ethics approval was granted by the New Zealand Central Health and Disability Ethics Committee (reference: 2023 FULL18176). Study findings will be reported to participants, stakeholder groups, conferences and peer-reviewed publications. TRIAL REGISTRATION NUMBER: UTN: U1111-1294-9310, ACTRN12623000817640p.

Dispensing of attention-deficit hyperactivity disorder medications for adults in Aotearoa New Zealand.

AIM: To report dispensing trends for attention-deficit hyperactivity disorder (ADHD) in Aotearoa New Zealand, focussing on adults in order to highlight increasing demand for ADHD treatment by adults and to prompt discussion. METHOD: Demographic and dispensing data for ADHD were obtained from the Pharmaceutical Collection between the years 2006 and 2022. This was stratified according to child (<18 years) and adult (≥18 years) populations. Population dispensing rates for methylphenidate and atomoxetine were calculated. Key findings are reported to reveal demographic and dispensing trends for medication treated ADHD in Aotearoa New Zealand. RESULTS: More males are dispensed ADHD medication than females, although this is less evident for adults (54.8% male). Maori adults are dispensed ADHD medication at a lower rate (10.1%) than Maori children (22.9%). There was a 10-fold increase in dispensing of ADHD medication for adults compared to a three-fold increase for children over the study period. New dispensing for adults doubled between 2011 and 2022. CONCLUSION: Medication treatment for adult ADHD is increasing in Aotearoa New Zealand and includes treatment for persisting childhood ADHD and new diagnoses made in adulthood. Despite increases, dispensing rates for ADHD remain lower than prevalence estimates, suggesting a significant treatment gap. Addressing the treatment gap for ADHD may reduce negative effects of ADHD, but wider social influences should also be considered.

Ketamine for treatment-resistant major depressive disorder: Double-blind active-controlled crossover study.

BACKGROUND: The N-methyl-D-aspartate antagonist ketamine has rapid onset antidepressant activity in treatment-resistant depression (TRD). AIMS: To evaluate mood rating, safety and tolerability data from patients with TRD treated with ketamine and the psychoactive control fentanyl, as part of a larger study to explore EEG biomarkers associated with mood response. METHODS: We evaluated the efficacy and safety of intramuscular racemic ketamine in 25 patients with TRD, using a double-blind active-controlled randomized crossover design. Ketamine doses were 0.5 and 1 mg/kg, and the psychoactive control was fentanyl 50 mcg, given at weekly intervals. RESULTS/OUTCOMES: Within 1 h of ketamine dosing, patients reported reduced depression and anxiety ratings, which persisted for up to 7 days. A dose-response profile for ketamine was noted for dissociative side effects, adverse events and changes in blood pressure; however, changes in mood ratings were broadly similar for both ketamine doses. Overall, 14/25 patients (56%) were responders (⩾50% reduction at 24 h compared with baseline) for either ketamine dose for the Hospital Anxiety and Depression Scale (HADS), and 18/25 (72%) were responders for the HADS-anxiety scale. After fentanyl, only 1/25 (HADS-depression) and 3/25 (HADS-anxiety) were responders. Ketamine was generally safe and well tolerated in this population. CONCLUSIONS: Our findings add to the literature confirming ketamine's activity against depressive and anxiety symptoms in patients with TRD.

Research following trauma in minority ethnic and faith communities: lessons from a study of the psychosocial sequelae of the Christchurch mosque terror attacks.

Recruiting participants for research from highly traumatised ethnic and faith communities requires a participatory and trauma-informed approach that considers logistic barriers, as well as trauma-related and culture-specific issues. Active community engagement through every stage of the project and employing community members in research roles can help build trust, identify and mitigate concerns early, prevent re-traumatization, and ensure that findings will be of value to the community. Some of these research challenges are discussed in the context of the Christchurch mosque terror attacks. These insights may be helpful for researchers and clinicians working in similarly challenging environments.

Toku Oranga: the subjective wellbeing and psychological functioning of postgraduate and medical students in Otautahi Christchurch.

AIMS: Postgraduate and medical students are at risk of psychological distress and burnout, which can cause significant functional and occupational impairment. We aimed to report subjective wellbeing, psychological distress and burnout in postgraduate and medical students in Otautahi Christchurch, Aotearoa (New Zealand), and identify any associations between participant and course information and outcome measures including exposure to major earthquakes in 2010/2011 and the 2019 terrorist attack. METHODS: A self-report online survey was completed by 140 students between November 2019 and March 2020. Life satisfaction, psychological distress and burnout were primary outcomes. Data were analysed using univariate and multivariable analysis. RESULTS: High levels of psychological distress were present in both student groups. Burnout was reported by 78% of respondents. There were no significant associations found between exposure to the Christchurch earthquakes or terrorist attack with primary outcomes. Personality factors, resilience and perceived support and success were weakly associated with wellbeing, distress and burnout. CONCLUSIONS: Postgraduates and medical students reported high levels of psychological distress and burnout. The earthquakes and terrorist attack do not appear to be associated with negative effects in these cohorts. Personality and resilience characteristics may assist in predicting students at risk of morbidity and evaluating potentially relevant interventions.

Polypharmacy in the treatment of people diagnosed with borderline personality disorder: repeated cross-sectional study using New Zealand's national databases.

BACKGROUND: There is insufficient evidence to support the pharmacological treatment of borderline personality disorder. However, previous out-patient cohorts have described high rates of polypharmacy in this group. So far, there have been no national studies that have considered polypharmacy in borderline personality disorder. AIMS: To describe psychotropic polypharmacy in people with borderline personality disorder in New Zealand. METHOD: New Zealand's national databases have been used to link psychotropic medication dispensing data and diagnostic data for borderline personality disorder. Annual dispensing data for 2014 and 2019 have been compared. RESULTS: Fifty percent of people with borderline personality disorder who were dispensed medications had three or more psychotropic medications in 2014. This increased to 55.9% in 2019 (P < 0.001). Those on seven or more psychotropics increased from 8.4 to 10.7% (P < 0.023). Quetiapine was the most dispensed psychotropic medication, being given to 53.8% of people dispensed medication with borderline personality disorder in 2019. Lorazepam dispensing showed the largest increase, going from 15.5 to 26.7% between 2014 and 2019 (P < 0.001). CONCLUSIONS: There is a large burden of psychotropic polypharmacy in people with borderline personality disorder. This is concerning because of the lack of evidence regarding the efficacy of these medications in this group.

Multidisciplinary development of guidelines for ketamine treatment for treatment-resistant major depression disorder for use by adult specialist mental health services in New Zealand.

BACKGROUND: The evidence base for racemic ketamine treatment for treatment-resistant major depressive disorder (TRD) continues to expand, but there are major challenges translating this evidence base into routine clinical care. AIM: To prepare guidelines for ketamine treatment of TRD that are suitable for routine use by publicly funded specialist mental health services. METHOD: We consulted with senior leadership, clinical pharmacy, psychiatrists, nursing, service users and Maori mental health workers on issues relating to ketamine treatment. We prepared treatment guidelines taking the evidence base for ketamine treatment and the consultation into account. RESULTS: Ketamine treatment guidance is reported. This offers two treatment pathways, including a test of ketamine responsiveness with intramuscular ketamine and the dominant use of oral ketamine for a 3-month course to maximise the opportunity for the short-term benefits of ketamine to accumulate. CONCLUSIONS: We have responded to the challenges of translating the evidence base for ketamine treatment into a form suitable for routine care.

The COVID Psychosocial Impacts Scale: A Reliable and Valid Tool to Examine the Psychosocial Impacts of the COVID-19 Pandemic.

This paper reports on the development and validation of the COVID Psychosocial Impacts Scale (CPIS), a self-report measure that comprehensively examines both positive and negative psychosocial impacts from the COVID-19 pandemic. This is the first part of the program of work in which the CPIS was administered and compared with a measure of psychological distress (Kessler Psychological Distress Scale, K-10) and wellbeing (World Health Organization Well-Being Index, WHO-5). The data were obtained online in 2020 and 2022 at two distinct time points to capture different exposures to the pandemic in the New Zealand population to a non-representative sample of 663 and 687 adults, respectively. Two hundred seventy-one participants took part in both surveys. Findings indicate a unidimensional structure within CPIS subscales and inter-relatedness among CPIS stress-related subscales. The scatter plots and correlation matrix indicate CPIS having a positive moderate correlation with K10 and a negative moderate correlation with WHO-5, indicative of construct validity. The paper outlines contextual factors surrounding CPIS development and makes suggestions for future iterations of CPIS. Further work will examine its psychometric properties across cultures.

Ketamine and psychotherapy for the treatment of psychiatric disorders: systematic review.

BACKGROUND: Ketamine is an effective short-term treatment for a range of psychiatric disorders. A key question is whether the addition of psychotherapy to ketamine treatment improves outcomes or delays relapse. AIM: To identify all studies combining psychotherapy with ketamine for the treatment of psychiatric disorders to summarise their effects and make recommendations for future research. METHOD: The review protocol was prospectively registered with PROSPERO (registration number CRD42022318120). Potential studies were searched for in MEDLINE, Embase, PsycINFO, SCOPUS, the Cochrane library and Google Scholar. Eligible studies combined ketamine and psychotherapy for the treatment of psychiatric disorders and did not use case reports or qualitative designs. Key findings relating to psychotherapy type, diagnosis, ketamine protocol, sequencing of psychotherapy and study design are reported. Risk of bias was assessed using modified Joanna Briggs critical appraisal tools. RESULTS: Nineteen studies evaluating 1006 patients were included in the systematic review. A variety of supportive individual and group, manualised and non-manualised psychotherapies were used. The majority of studies evaluated substance use disorders, post-traumatic stress disorder and treatment-resistant depression. Ketamine protocols and sequencing of ketamine/psychotherapy treatment varied substantially between studies. Outcomes were largely positive for the addition of psychotherapy to ketamine treatment. CONCLUSION: The combination of psychotherapy and ketamine offers promise for the treatment of psychiatric disorders, but study heterogeneity prevents definitive recommendations for their integration. Larger randomised controlled trials using manualised psychotherapies and standardised ketamine protocols are recommended to clarify the extent to which the addition of psychotherapy to ketamine improves outcomes over ketamine treatment alone.

[Compulsory community treatment orders (CTOs): recent research and future directions].

SUMMARY: Compulsory community treatment orders (CTOs) are controversial because the right to refuse treatment is overridden, even when patients may not be acutely unwell. Scrutiny of outcomes associated with CTOs is therefore required. This editorial provides an overview of the evidence for CTOs. It also discusses recent papers reporting outcomes associated with CTOs and makes recommendations for researchers and clinicians to consider.

Examining the psychosocial impacts of the COVID-19 pandemic: an international cross-sectional study protocol.

INTRODUCTION: The COVID-19 pandemic exposed people to significant and prolonged stress. The psychosocial impacts of the pandemic have been well recognised and reported in high-income countries (HICs) but it is important to understand the unique challenges posed by COVID-19 in low- and middle-income countries (LMICs) where limited international comparisons have been undertaken. This protocol was therefore devised to study the psychosocial impacts of the COVID-19 pandemic in seven LMICs using scales that had been designed for or translated for this purpose. METHODS AND ANALYSIS: This cross-sectional study uses an online survey to administer a novel COVID Psychosocial Impacts Scale (CPIS) alongside established measures of psychological distress, post-traumatic stress, well-being and post-traumatic growth in the appropriate language. Participants will include adults aged 18 years and above, recruited from Indonesia, Iraq, Iran, Malaysia, Pakistan, Somalia and Turkey, with a pragmatic target sample size of 500 in each country.Data will be analysed descriptively on sociodemographic and study variables. In addition, CPIS will be analysed psychometrically (for reliability and validity) to assess the suitability of use in a given context. Finally, within-subjects and between-subjects analyses will be carried out using multi-level mixed-effect models to examine associations between key sociodemographic and study variables. ETHICS AND DISSEMINATION: Ethical approval was granted by the Human Ethics Committee, University of Otago, New Zealand (Ref. No. 21/102). In addition, international collaborators obtained local authorisation or ethical approval in their respective host universities before data collection commenced.Participants will give informed consent before taking part. Data will be collected and stored securely on the University of Otago, New Zealand Qualtrics platform using an auto-generated non-identifiable letter-number string. Data will be available on reasonable request. Findings will be disseminated by publications in scientific journals and/or conference presentations. TRIAL REGISTRATION NUMBER: NCT05052333.

Feasibility study of brief Group Transdiagnostic Cognitive Behavioural Treatment delivered via Zoom for anxiety and depression in primary care.

AIM: To report the feasibility of delivering and the effectiveness of brief Group Transdiagnostic Cognitive Behavioural Therapy (TCBT) via Zoom for anxiety and/or depression in primary care. METHODS: Participants were eligible for this open-label study if their primary care clinician recommended brief psychological intervention for clinically diagnosed anxiety and/or depression. Group TCBT included an individual assessment followed by four x 2-hour manualised therapy sessions. Primary outcome measures assessed recruitment, adherence to treatment and reliable recovery measured using the PHQ-9 and GAD-7. RESULTS: Twenty-two participants received TCBT over three groups. Recruitment and adherence to TCBT met feasibility thresholds for delivering group TCBT via Zoom. Improvements in the PHQ-9, GAD-7 and reliable recovery were present 3 and 6 months following treatment commencement. CONCLUSION: Brief TCBT delivered using Zoom is a feasible treatment for anxiety and depression diagnosed in primary care. Definitive RCTs are required to provide confirmatory evidence of efficacy for brief group TCBT in this setting.

Variation in the use of compulsory community treatment orders between district health boards in New Zealand.

OBJECTIVE: To report rates of Compulsory Community Treatment Order (CTO) use by District Health Boards (DHBs) in New Zealand and analyse whether socio-demographic factors explain any variability. METHODS: The annualised rate of CTO use per 100,000 population was calculated for the years 2009-2018 using national databases. Rates were adjusted for age, gender, ethnicity, and deprivation and are reported according to DHBs to allow comparisons between regions. RESULTS: The annualised rate of CTO use for New Zealand was 95.5 per 100,000 population. CTO use varied between DHBs from 53 to 184 per 100,000 population. Standardising for demographic variables and deprivation made little difference to this variation. CTO use was higher in males and young adults. Rates for Maori were more than three times that of Caucasian people. CTO use increased as deprivation became more severe. CONCLUSIONS: CTO use increases with Maori ethnicity, young adulthood, and deprivation. Adjusting for socio-demographic factors does not explain the wide variation in CTO use between DHBs in New Zealand. Other regional factors appear to be the major driver of variation in CTO use.

The association between Compulsory Community Treatment Order status and mortality in New Zealand.

BACKGROUND: Compulsory Community Treatment Orders (CTOs) enable psychiatric medication without the need for consent. Careful scrutiny of outcomes including mortality is required to ensure compulsory treatment is evidence-based and ethical. AIMS: To report mortality for patients placed on CTOs and analyse data according to CTO status, mortality cause and diagnosis. METHOD: Data for all patients placed under CTOs between 1 January 2009 and 31 December 2018 was provided by the Ministry of Health, New Zealand. Data included diagnostic and demographic information, dates of CTOs, and any dates and causes of death. Deaths were categorised into suicides, accidents and assaults, and medical causes. Mortality data are reported according to CTO status and diagnosis. RESULTS: A total of 14 726 patients were placed on CTOs over the study period, during which there were 1328 deaths. The mortality rate was 2.97 on and 2.31 off CTOs (rate ratio 1.29, 95% CI 1.14-1.45; P < 0.01). The mortality rate for accidents and assaults was 0.44 on and 0.25 off CTOs (rate ratio 1.73, 95% CI 1.23-2.42; P < 0.01). The mortality rate for medical causes was 2.33 on and 1.90 off CTOs (rate ratio 1.22, 95% CI 1.07-1.40; P < 0.01). The suicide rate was 0.20 on and 0.15 off of CTOs (rate ratio 1.33, 95% CI 0.81-2.12; P = 0.22). CONCLUSIONS: Increased care and medication provided during compulsory treatment does not the modify the course of illness sufficiently to reduce mortality during CTOs. Higher mortality rates during CTO periods compared with non-CTO periods may reflect greater unwellness during CTOs.

The long-term impacts of the Canterbury earthquakes on the mental health of the Christchurch Health and Development Study cohort.

OBJECTIVE: Long-term studies following disasters are rare. It is important to quantify long-term effects of disasters to determine impacts on populations over time. We therefore aim to report the long-term associations between exposure to the Canterbury earthquakes and common mental disorders, taking into account potential confounding factors. METHODS: The Christchurch Health and Development Study is a 40-year longitudinal study of a birth cohort of New Zealand children (635 males and 630 females). The Christchurch Health and Development Study includes 884 participants with data on earthquake exposure and mental health outcomes at ages 34 and 40 years. Rates of Diagnostic and Statistical Manual of Mental Disorders (4th ed.) disorders were measured categorically and using an expanded definition that included sub-syndromal symptoms. The current impact of the earthquakes is reported using 12-month prevalence data 7 years after the earthquakes. The cumulative impact of the earthquakes over the 7 years since onset is also reported. RESULTS: There was a linear trend towards increasing rates of disorder with increasing exposure to the earthquakes. After adjusting for covariates, the 12-month prevalence of anxiety disorder symptoms was significantly increased (p = 0.003). The earthquakes were also associated with cumulative increases in symptoms of post-traumatic stress disorder (p < 0.001), anxiety disorder (p = 0.016), nicotine dependence (p = 0.012), and the total number of disorders (p = 0.039). CONCLUSION: The Canterbury earthquakes were associated with persistent increases in Anxiety Disorder symptoms 7 years after their onset. The earthquakes were also associated with cumulative increases in symptoms of common psychiatric disorders. The magnitude of these effects is small, may no longer be clinically significant and has decreased over time.

oVRcome - Self-guided virtual reality for specific phobias: A randomised controlled trial.

OBJECTIVE: Mobile health applications for mental health are widely accessible but most have had limited research evaluation. Virtual reality exposure therapy is an emerging treatment for specific phobias. Most virtual reality studies have investigated high-end virtual reality devices, typically only available in research and limited clinical settings for a single phobia. This study evaluated the effectiveness of oVRcome, a mobile health application combining self-guided virtual reality exposure and cognitive behaviour therapy, for five specific phobias. METHODS: This is a 2-arm 6-week randomised controlled trial, with a waitlist control group and follow-up at week 12. Participants were required to live in New Zealand; be aged 18-64 years; have a fear of flying, heights, spiders, dogs and needles; score above 4 on the Brief Standard Self-rating scale for phobic patients; and have access to a smartphone and Internet. oVRcome consists of six modules of psychoeducation, relaxation, mindfulness, cognitive techniques, exposure through virtual reality and relapse prevention over 6 weeks. The primary outcome was the change from baseline to week 6 on the Severity Measures for Specific Phobia - Adults. All analyses were performed on intention-to-treat set. RESULTS: A total of 126 participants were randomised, and 109 completed the follow-up at week 6, for a retention rate of 86.5%. The mean change in Severity Measures for Specific Phobia - Adults score from baseline to week 6 was greater in the active group compared with the waitlist group (active group -20.53 [standard deviation = 8.24]; waitlist group: - 12.31 [standard deviation = 10.66]; p < 0.001). The effect size for this difference was 0.86. CONCLUSION: Self-guided use of the oVRcome app was effective at reducing severity of specific phobia symptoms in a sample of people with a self-reported fear of flying, heights, spiders, dogs or needles.Trial registry clinicaltrials.gov NCT04909177.