Effect of MDMA-assisted therapy on mood and anxiety symptoms in advanced-stage cancer (EMMAC): study protocol for a double-blind, randomised controlled trial.

BACKGROUND: Symptoms of anxiety and depression are common in patients with terminal illness and multiple challenges exist with timely and effective care in this population. Several centres have reported that one dose of the serotonergic psychedelic psilocybin, combined with therapeutic support, improves these symptoms for up to 6 months in this patient group. Drawing upon related therapeutic mechanisms, 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy may have the potential to achieve similar, positive mental health outcomes in this group. Preliminary evidence also supports the tolerability of MDMA-assisted therapy for anxiety and depression in advanced-stage cancer. METHODS: Up to 32 participants with advanced-stage cancer and associated depression and anxiety will be randomised in a 1:1 ratio into one of two blinded parallel treatment arms. The intervention group will receive 120 mg (+ 60 mg optional supplemental dose) MDMA-assisted therapy. The psychoactive control group will receive 20 mg oral (+ 10 mg optional supplemental dose) methylphenidate-assisted therapy. For each medication-assisted therapy session, participants will undergo two 90-min therapeutic support sessions in the week preceding, and one 90-min support session the day after the experimental session. A battery of measures (mood, anxiety, quality of life, mystical experience, spiritual wellbeing, attitudes towards death, personality traits, holistic health and wellbeing, connectedness, demoralisation, expectations, qualitative data and safety measures) will be assessed at baseline and through to the end of the protocol. Participants will be followed up until either 12 months post-randomisation or death, whichever occurs first. DISCUSSION: This study will examine the effect of MDMA-assisted therapy on symptoms of anxiety and depression in advanced-stage cancer. Potential therapeutic implications include establishing the safety and effectiveness of a novel treatment that may relieve mental suffering in patients with life-threatening illness. TRIAL REGISTRATION: Trial registered on Australian New Zealand Clinical Trials Registry. REGISTRATION NUMBER: ACTRN12619001334190p. Date registered: 30/09/2019. URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378153&showOriginal=true&isReview=true.

Assessing general hospital doctors' attitudes toward psychiatric care in multicultural settings.

OBJECTIVE: Psychiatric care in general hospitals depends on collaboration with non-psychiatrist doctors. The Doctors' Attitudes toward Collaborative Care for Mental Health (DACC-MH) is a two-factor scale designed to address this issue and validated in the UK in 2010. However, its applicability in contemporary, culturally diverse settings is unknown and therefore this study was aimed at determining its validity and consistency using data from our 2021 international study. Confirmatory and exploratory factor analyses were used, comparing results from our 2021 study (n = 889) with those from the 2010 UK study (n = 225). RESULTS: The DACC-MH consultation subscale, but not the management subscale, aligned with data from our larger, international study. The 2-factor model failed the Chi-square goodness of fit test (χ2(19) = 53.9, p < 0.001) but had acceptable other fit indices. While the previously identified attitudinal difference between physicians and surgeons was replicated, measurement invariance for this result could not be established. Exploratory factor analysis suggested a 6-factor model, contrasting with the 2-factor model proposed in 2010 for the UK sample. The DACC-MH scale shows significant limitations when applied to a larger, international dataset. Cultural and generational differences in doctors' attitudes appear relevant and should be considered in assessing barriers to psychiatric care in general hospitals.

LSD increases sleep duration the night after microdosing.

Microdosing psychedelic drugs at a level below the threshold to induce hallucinations is an increasingly common lifestyle practice. However, the effects of microdosing on sleep have not been previously reported. Here, we report results from a Phase 1 randomized controlled trial in which 80 healthy adult male volunteers received a 6-week course of either LSD (10 µg) or placebo with doses self-administered every third day. Participants used a commercially available sleep/activity tracker for the duration of the trial. Data from 3231 nights of sleep showed that on the night after microdosing, participants in the LSD group slept an extra 24.3 min per night (95% Confidence Interval 10.3-38.3 min) compared to placebo-with no reductions of sleep observed on the dosing day itself. There were no changes in the proportion of time spent in various sleep stages or in participant physical activity. These results show a clear modification of the physiological sleep requirements in healthy male volunteers who microdose LSD. The clear, clinically significant changes in objective measurements of sleep observed are difficult to explain as a placebo effect. Trial registration: Australian New Zealand Clinical Trials Registry: A randomized, double-blind, placebo-controlled trial of repeated microdoses of lysergic acid diethylamide (LSD) in healthy volunteers; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381476 ; ACTRN12621000436875.

Considerations in the assessment and management of ADHD within the TGDNB population.

AIMS: In this article we consider current literature around Attention Deficit Hyperactivity Disorder (ADHD) in the transgender, gender diverse and non-binary (TGDNB) population. METHODS: Literature review. RESULTS: N/A conclusions: We outline specific considerations pertaining to the assessment and treatment of ADHD in this group and highlight evidential gaps and avenues for future research. We conclude that TGDNB individuals should be considered a "special population" with regards to ADHD and encourage mental health practitioners to consider specific TGDNB mental health needs beyond capacity assessments and gender-affirming care.

Psychedelic medicines for end-of-life care: Pipeline clinical trial review 2022.

OBJECTIVES: People with terminal illnesses often experience psychological distress and associated disability. Recent clinical trial evidence has stimulated interest in the therapeutic use of psychedelics at end of life. Much uncertainty remains, however, mainly due to methodological difficulties that beset existing trials. We conducted a scoping review of pipeline clinical trials of psychedelic treatment for depression, anxiety, and existential distress at end of life. METHODS: Proposed, registered, and ongoing trials were identified from 2 electronic databases (ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform). Recent reviews and both commercial and non-profit organization websites were used to identify additional unregistered trials. RESULTS: In total, 25 studies were eligible, including 13 randomized controlled trials and 12 open-label trials. Three trials made attempts beyond randomization to assess expectancy and blinding effectiveness. Investigational drugs included ketamine (n = 11), psilocybin (n = 10), 3,4-methylenedioxymethamphetamine (n = 2), and lysergic acid diethylamide (n = 2). Three trials involved microdosing, and fifteen trials incorporated psychotherapy. SIGNIFICANCE OF RESULTS: A variety of onging or upcoming clinical trials are expected to usefully extend evidence regarding psychedelic-assisted group therapy and microdosing in the end-of-life setting. Still needed are head-to-head comparisons of different psychedelics to identify those best suited to specific indications and clinical populations. More extensive and rigorous studies are also necessary to better control expectancy, confirm therapeutic findings and establish safety data to guide the clinical application of these novel therapies.

Adverse Effects of Virtual and Augmented Reality Interventions in Psychiatry: Systematic Review.

BACKGROUND: Virtual reality (VR) and augmented reality (AR) are emerging treatment modalities in psychiatry, which are capable of producing clinical outcomes broadly comparable to those achieved with standard psychotherapies. OBJECTIVE: Because the side effect profile associated with the clinical use of VR and AR remains largely unknown, we systematically reviewed available evidence of their adverse effects. METHODS: A systematic review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework across 3 mental health databases (PubMed, PsycINFO, and Embase) to identify VR and AR interventions targeting mental health diagnoses. RESULTS: Of 73 studies meeting the inclusion criteria, 7 reported worsening clinical symptoms or an increased fall risk. Another 21 studies reported "no adverse effects" but failed to identify obvious adverse effects, mainly cybersickness, documented in their results. More concerningly, 45 of the 73 studies made no mention of adverse effects whatsoever. CONCLUSIONS: An appropriate screening tool would help ensure that VR adverse effects are correctly identified and reported.

Brief intervention reduces prescription of sodium valproate in women of childbearing age.

OBJECTIVE: Sodium valproate's teratogenicity has prompted increasing restrictions to its use. Our initial audit 2 years prior demonstrated continuing hazardous prescription to women of childbearing age in a New Zealand psychiatric inpatient unit, consistent with nationwide dispensing data. METHOD: Following a service-wide educational intervention and application of "black box" warnings, we conducted a follow-up audit of valproate prescription in the same inpatient unit by reviewing records of women admitted over a 10-month period (March 2020-January 2021). Results were compared with local and international guidelines, and against data from our initial audit. RESULTS: Two hundred and sixty-one women of childbearing age were admitted over the sampling period, 26 of whom (10%) were prescribed valproate on discharge. Over three quarters (77%) of these patients had diagnoses other than bipolar affective disorder, valproates only approved psychiatric indication in New Zealand. Following intervention, significant improvements were observed in several key indicators of prescribing quality: pregnancy testing, documentation of contraception status, and discussion of teratogenic risk. CONCLUSIONS: Following intervention, re-audit demonstrated reduced prescription of valproate and improved management of its teratogenic risk in women of childbearing age receiving inpatient psychiatric care. These results demonstrate the value of a systematic approach to improve prescribing practice.

Acute Mood-Elevating Properties of Microdosed Lysergic Acid Diethylamide in Healthy Volunteers: A Home-Administered Randomized Controlled Trial.

BACKGROUND: Microdosing psychedelic drugs is a widespread social phenomenon with diverse benefits claimed for mood and cognition. Randomized controlled trials have failed to support these claims, but the laboratory-based dosing in trials conducted to date may have limited ecological validity. METHODS: Healthy male volunteers were randomized into lysergic acid diethylamide (LSD) (n = 40) and placebo (n = 40) groups and received 14 doses of either 10 µg LSD or an inactive placebo every 3 days for 6 weeks. First doses were given in a supervised laboratory setting, with other doses self-administered in a naturalistic setting. Results of safety data, blinding, daily questionnaires, expectancy, and pre-/postintervention psychometrics and cognitive tasks are presented here. RESULTS: The most notable reported adverse event was treatment-related anxiety, which prompted the withdrawal of 4 participants from the LSD group. Daily questionnaires showed credible evidence (>99% posterior probability) of improved ratings of creativity, connectedness, energy, happiness, irritability, and wellness on dose days compared with nondose days, and these effects remained when controlling for preintervention expectancy. No questionnaire or cognitive task showed a credible change between baseline and 6-week assessment time points. CONCLUSIONS: Microdosing LSD appears to be relatively safe in healthy adult men, notwithstanding a risk of anxiety. While microdosing elicited transient increases in scales associated with mood-elevating effects, it was not sufficient to promote enduring changes to overall mood or cognition in healthy adults. Future microdosing trials in clinical populations will require the use of active placebos to control for placebo effects and dose titration to adjust for interindividual variability in drug response.

The prescriber's guide to classic MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid) for treatment-resistant depression.

This article is a clinical guide which discusses the "state-of-the-art" usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion-this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy-while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward "bridging" methods that may be used to transition simply and safely from other antidepressants to MAOIs.

What stops Korean immigrants from accessing child and adolescent mental health services?

BACKGROUND: Access to child and adolescent mental health services by ethnic minorities has been poorly studied. Despite rapid growth of the immigrant Korean population, evidence indicates that few Korean families utilise these services in New Zealand. Those that do tend to present late and with significant morbidity. We sought to understand barriers to service access from Korean parents' perspectives. METHOD: Seven focus groups were undertaken with 31 Korean parents of children aged 18 and under. The focus groups were semi-structured, held in the Korean language and utilised two case scenarios of common childhood/adolescent mental illnesses around which a set of broad, open-ended questions were posed. All conversations were audiorecorded, transcribed and translated into English. Thematic analysis was conducted using NVivo software. RESULTS: Both attitudinal and structural barriers were identified. Attitudinal barriers included attribution of mental illness to external stressors or parenting problems, social stigma, denial or normalization of children's behaviour, fear of family disempowerment, and mistrust of public mental health services. Structural barriers included parents' lack of information regarding available services, logistical difficulties in access, communication difficulties, concerns over the quality of translators, and cultural competence of service providers. CONCLUSION: Significant barriers prevent Korean immigrant families from accessing child and adolescent mental health services in New Zealand. Measures to improve access, for example by countering stigma, are urgently required.