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Anxiety is a beneficial behavior that assists survival, although when high levels of anxiety persist it can hinder normal functioning. Despite numerous treatment options most individuals with Generalized Anxiety Disorder (GAD) continue to suffer from the disorder. A novel neuromodulatory treatment that safely and non-invasively alters pathological neural circuitry associated with GAD is required. Therefore, this study investigates the feasibility, safety, and effect of a new innovative High-Definition Transcranial Infraslow Gray Noise Stimulation (HD-tIGNS) targeting the anxiety network in people with GAD, in a delayed-start double-blinded randomized sham-controlled pilot trial ( N  = 22). HD-tIGNS was applied three times per week for three [delayed-start (following 3-weeks of actisham)], or six weeks (early-start). Anxiety questionnaires and electroencephalography were taken at baseline, mid-treatment, and post-treatment. On average, six participants were recruited per month with a mean treatment adherence of 99.5%, and an 8.3% dropout rate of enrolled participants. Clinically meaningful changes in GAD-7 were observed in 45% (early-start group) and 36% (delayed-start group) of participants following 6-weeks and 3-weeks of intervention respectively. No significant differences in brain activity or functional connectivity were observed. This study provides evidence supporting HD-tIGNS as a safe and feasible treatment approach for GAD, however future research should consider alternate network targets.

ObjectivesGlobally, one in six older adults in the community will be a victim of abuse (elder abuse; EA). Despite these horrific statistics, EA remains largely undetected and under-reported. Available screening methods and tools fail to accurately identify the phenomenon’s true prevalence. We aimed to test assessment capture rates by altering the criteria for suspicion of EA in the interRAI-HC (International Resident Assessment Instrument–Home Care) in a large national dataset.DesignWe employed secondary analyses of existing data to test a methodology to improve the detection of older adults at risk of EA using the interRAI-HC, which currently underestimates the extent of abuse.SettingThe interRAI is a suite of clinical assessment instruments. In Aotearoa New Zealand, interRAI is mandatory in aged residential care and home and community services for older people living in the community. They are designed to show the assessor opportunities for improvement and any risks to the person’s health.Outcome measureCapture rates of individuals at risk of EA when the interRAI Abuse-Clinical Assessment Protocol (A-CAP) is changed to include the unable to determine abuse (UDA) group shown in a pilot study to increase capture rates of individuals at risk of EA.ResultsAnalysis of 9 years of interRAI-HC data (July 2013–June 2022) was undertaken, encompassing 186 713 individual assessments consisting of 108 992 women (58.4%) and 77 469 men (41.5%). The mean age was 82.1 years (range: 65–109); the majority 161 378 were European New Zealanders (86.4%) and the most common minority ethnicity was Māori (6.1%). Those at high risk of abuse (A-CAP) tended to be male (2402; 51.0%), were 79.2 years old on average (range 65–105), with 49.6% (2335) living alone, 39.4% (1858) suffering from depression and a majority were assessed as not having independent decision making (2942; 62.5%). In comparison, the UDA group showed similar characteristics to the A-CAP group on some measures. They were slightly younger than the general sample, with a mean age 80.1 years (range 65–107), they had higher rates of depression (2123; 33.5%) compared with the general sample (25 936; 14.8%) and a majority were assessed as not having independent decision-making (3855; 60.9%). The UDA group is distinct from the general sample and the UDA group broadly has similar but less extreme characteristics to the A-CAP group. Through altering the criteria for suspicion of EA, capture rates of at-risk individuals could be more than doubled from 2.5% to 5.9%.ConclusionsWe propose that via adapting the interRAI-HC criteria to include the UDA category, the identification of older adults at risk of EA could be substantially improved, facilitating enhanced protection of this vulnerable population.

Fibromyalgia is a chronic pain condition contributing to significant disability worldwide. Neuroimaging studies identify abnormal effective connectivity between cortical areas responsible for descending pain modulation (pregenual anterior cingulate cortex, pgACC) and sensory components of pain experience (primary somatosensory cortex, S1). Neurofeedback, a brain-computer interface technique, can normalise dysfunctional brain activity, thereby improving pain and function. This study evaluates the safety, feasibility, and acceptability of a novel electroencephalography-based neurofeedback training, targeting effective alpha-band connectivity from the pgACC to S1 and exploring its effect on pain and function. Participants with fibromyalgia ( N  = 30; 15 = active, 15 = placebo) received 12 sessions of neurofeedback. Feasibility and outcome measures of pain (Brief Pain Inventory) and function (Revised Fibromyalgia Impact Questionnaire) were collected at baseline and immediately, ten-days, and one-month post-intervention. Descriptive statistics demonstrate effective connectivity neurofeedback training is feasible (recruitment rate: 6 participants per-month, mean adherence: 80.5%, dropout rate: 20%), safe (no adverse events) and highly acceptable (average 8.0/10) treatment approach for fibromyalgia. Active and placebo groups were comparable in their decrease in pain and functional impact. Future fully powered clinical trial is warranted to test the efficacy of the effective connectivity neurofeedback training in people with fibromyalgia with versus without chronic fatigue.

Psychiatric diagnoses currently rely on a patient’s presenting symptoms or signs, lacking much-needed theory-based biomarkers. Our neuropsychological theory of anxiety, recently supported by human imaging, is founded on a longstanding, reliable, rodent ‘theta’ brain rhythm model of human clinical anxiolytic drug action. We have now developed a human scalp EEG homolog—goal-conflict-specific rhythmicity (GCSR), i.e., EEG rhythmicity specific to a balanced conflict between goals (e.g., approach-avoidance). Critically, GCSR is consistently reduced by different classes of anxiolytic drug and correlates with clinically-relevant trait anxiety scores (STAI-T). Here we show elevated GCSR in student volunteers divided, after testing, on their STAI-T scores into low, medium, and high (typical of clinical anxiety) groups. We then tested anxiety disorder patients (meeting diagnostic criteria) and similar controls recruited separately from the community. The patient group had higher average GCSR than their controls—with a mixture of high and low GCSR that varied with, but cut across, conventional disorder diagnosis. Consequently, GCSR scores should provide the first theoretically-based biomarker that could help diagnose, and so redefine, a psychiatric disorder.

Postpartum Depression (PPD) is the most common non-obstetric complications associated with childbearing, but currently has poor diagnostic regimes. Sensory symptoms of PPD are understudied, particularly with regard to the sense of olfaction. The present study addresses this research gap by assessing differences in olfactory abilities between 39 depressed mothers, who were within the perinatal period (i.e., during pregnancy and up to 1-year post pregnancy) and assessed with Edinburgh Postnatal Depression Scale, and their case-matched healthy volunteers. The assessments include two olfactory testing sessions conducted 4-weeks apart, each comprising a standard odour detection threshold test (i.e., Snap & Sniff Olfactory Test System), and intensity and valence ratings for 3 “pleasant” and 3 “unpleasant” odorants. The results revealed no difference between patients (M = 5.6; SE = 0.3) and control group (M = 5.7; SE = 0.4) in terms of olfactory detection threshold. However, the patients group perceived the 3 “unpleasant” odours as significantly less pleasant ( p  < 0.05), and 2 odorants (1 “pleasant” and 1 “unpleasant”) as less intense. Additionally, these results did not appear to be significantly interacted with the individual’s perinatal stage. The present study is the first to evaluate associations between olfactory function and PPD. Findings from the study suggest that, while PPD has little effect on the early stages of olfactory processing, these conditions may have stronger influence on higher-order olfactory perception, including both hedonic and intensity perception. These novel findings add knowledge to sensory symptoms of PPD.

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. To prepare guidelines for ketamine treatment of TRD that are suitable for routine use by publicly funded specialist mental health services. We consulted with senior leadership, clinical pharmacy, psychiatrists, nursing, service users and Māori 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. 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. We have responded to the challenges of translating the evidence base for ketamine treatment into a form suitable for routine care.

Background: Anxiety disorders are common, associated with significant burden of disease, and have high levels of treatment resistance. Low-dose ketamine has been extensively studied in treatment-resistant depression, with fewer reports in treatment-resistant anxiety disorders. Aims: This systematic review and meta-analysis collected efficacy, safety, and tolerability data for ketamine as a treatment for anxiety spectrum disorders. Methods: We conducted a systematic search for randomized controlled trials (RCTs) of acute ketamine treatment for patients with anxiety disorders. Open-label trials of ketamine maintenance therapy were also considered. Qualitative and, where possible, quantitative syntheses of findings were performed using Review Manager software (RevMan). Acute dose-response and maintenance treatment data were also collected. Results: There were six eligible acute RCTs – two in social anxiety disorder (SAD), three in post-traumatic stress disorder (PTSD), and one in obsessive-compulsive disorder (OCD). Four of the six showed significant improvement in anxiety rating scores in ketamine compared with control groups. Pooled analysis showed ketamine was associated with an increased likelihood of treatment response for SAD (odds ratio (OR): 28.94; 95% confidence interval [CI]: 3.45–242.57; p = 0.002) but not for PTSD (OR: 2.03; 95% CI: 0.67–6.15; p = 0.21). A dose-response profile was observed for ketamine and changes in SAD symptoms, with doses ⩾0.5 mg/kg associated with greater reduction in anxiety rating scores than lower doses. Ketamine maintenance therapy was associated with sustained anxiolytic effects and improved social and/or work functioning. Conclusion: These preliminary analyses suggest that acute ketamine may be broadly effective across treatment-resistant anxiety spectrum disorders. These effects can be prolonged with maintenance treatment. Future studies will be needed to provide critical knowledge gaps around off-label use, side effects, and potential risks for abuse in clinical settings.

IntroductionChronic low back pain (CLBP) is a disabling condition worldwide, with unsatisfactory treatment outcomes, warranting newer therapies. Brain imaging demonstrates altered functional connectivity among three pain processing networks; salience network (SN), default mode network (DMN) and somatomotor network (SMN). Treatments targeted to change the functional connectivity among these networks may produce clinical benefits. This trial will evaluate the efficacy of a novel non-invasive brain stimulation technique targeting the functional connectivity among the SN, DMN and SMN for improving pain intensity in people with CLBP.Methods and analysisA single-centre double-blinded randomised two-arm placebo-controlled parallel phase II efficacy trial will be conducted at the University of Otago (Dunedin, New Zealand). Participants (n=164) with CLBP will be randomised (1:1) to receive 12 sessions (three per week) of either sham or active stimulation. The primary endpoint will be the change in average pain intensity from baseline to 1 week post completion of intervention. Secondary outcome measures include clinical, functional, psychological, quantitative sensory testing and electroencephalography collected at baseline, 1 week post completion of intervention and at follow-up of 1, 3, and 6 months post intervention. Linear mixed model analyses will be used to evaluate the efficacy of the intervention on the primary outcome.Ethics and disseminationEthical approval has been obtained from Northern B Health and Disability Ethics Committee, New Zealand (Ref: 2024 FULL 21891). All participants will provide written informed consent. Findings will be reported to the funding and regulatory bodies, presented at national/international conferences and published in scientific journals.Trial registration numberClinicalTrials.gov, NCT06902233.

IntroductionAlthough 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 analysisThis 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 disseminationEthics 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 numberUTN: U1111-1294-9310, ACTRN12623000817640p.

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