David S. Baldwin

Summary: Anxiety disorders are distressing and impairing and may be becoming more prevalent. There remains much uncertainty about key factors in the development and maintenance of anxiety disorders, which may underpin some of the limitations of existing psychological, pharmacological and other treatments.

Summary: Distressing and impairing separation anxiety symptoms with onset in adult life can be diagnosed as an anxiety disorder. Advances in understanding in epidemiology and possible neuropsychobiology make the condition worthy of further detailed consideration, but the absence of robustly evidence-based treatments limits the current utility of diagnosis in clinical practice.

Background: We need to identify novel, tractable therapeutic targets for anxiety disorders. Converging evidence suggests the endogenous opioid system plays a role in modulating affective processing, but its contribution to regulation of threat processing in humans remains unclear. Aims: We investigated the neural correlates of non-specific opioid antagonism on explicit and implicit regulation of threatening stimuli in healthy volunteers, using functional magnetic resonance imaging (fMRI). Method: In a randomised, double-blind, placebo-controlled, crossover design, 38 healthy participants received the opioid antagonist naltrexone (50 mg) or placebo before completing two tasks during fMRI: (a) a cognitive emotional reappraisal task probing explicit regulation and (b) a face-viewing task probing implicit processing. Results: Contrary to our hypothesis, we found naltrexone reduced distress ratings during the reappraisal task ( p = 0.044) without impairing regulation success. Explicit regulation in the reappraisal task engaged lateral prefrontal regions similarly across drug conditions. However, naltrexone attenuated ventromedial prefrontal cortex, thalamus and caudate activation when viewing negative images. Naltrexone additionally altered ventromedial prefrontal cortex activity and in task-positive regions including right premotor area and frontal pole compared with placebo when viewing emotional faces. In particular, naltrexone increased left middle frontal gyrus activity when viewing fearful faces. Conclusions: Our results support a role for opioid signalling in automatic emotional regulation, but not in explicit regulation. Furthermore, naltrexone appeared to diminish activity in task-positive regions in response to emotional faces. These findings are consistent with a model where endogenous opioids ‘fine-tune’ affective responses to both negative and positive stimuli. Future research should explore dose–response effects, kappa-opioid contributions and whether similar results are seen in clinical populations.

Background: Eye movement desensitisation and reprocessing (EMDR) is a guideline-recommended treatment for post-traumatic stress disorder (PTSD) but has not been evaluated in survivors of critical illness, whose symptoms may arise from prolonged and complex medical exposures. We assessed the feasibility, safety, and preliminary clinical effectiveness of EMDR for critical care survivors with post-traumatic symptoms. Methods: We conducted a randomised, parallel-group, single-blind feasibility trial at three UK National Health Service hospitals. Adults (≥18 years) with an intensive care stay >24 h were approached before hospital discharge and followed within an observational cohort. At 2–3 months, participants were screened for post-traumatic stress symptoms (Impact of Event Scale–Revised); those scoring ≥22 were invited to randomisation (1:1) to EMDR plus treatment as usual (TAU) versus TAU. EMDR comprised up to 16 sessions delivered face-to-face or online by accredited therapists. Primary outcomes were feasibility (recruitment, retention, intervention uptake, fidelity) and safety. Symptoms were assessed using Clinician-administered PTSD Scale for DSM-5 (CAPS-5) at 3 and 12 months. Analyses followed intention-to-treat principles. The trial was registered on ClinicalTrials.gov (NCT05591625) and is closed to recruitment. Findings: Between Feb 20, 2023, and May 13, 2024, 160 patients were recruited; 40 were randomised (20 EMDR, 20 TAU). Median age was 59 years; 21 (53%) were female. At 12 months, 39/40 (98%) participants completed CAPS-5 follow-up. In the EMDR arm, 18/20 (90%) initiated treatment; mean sessions attended was 10·4 and 15/20 (75%) completed a full therapeutic course. Mean CAPS-5 score change was −15·6 (SD 12.4) in the EMDR group versus −1·6 (SD 11.8) in the TAU group (between-group difference −14·1, 95% CI −21.9 to −6.2; p=0·007). No treatment-related adverse events occurred. Interpretation: EMDR was feasible, safe, and associated with greater reductions in clinician-rated PTSD symptoms compared with treatment as usual, supporting progression to a definitive multicentre trial.

Background: Poor nurse well‐being is a significant concern, adversely affecting patient care quality and satisfaction and contributing to poor job satisfaction, increased sickness absence and workforce retention issues. There are calls for evidence‐based policies and interventions to address poor nurse well‐being, but no consensus exists on which outcomes should be captured to assess nurse well‐being. We used a salutogenic and consensus approach to develop a Core Outcome Set (COS) for nurse well‐being. Methods: A Delphi methodology was employed. Participants were recruited from two stakeholder groups: (1) nurse well‐being professionals, identified through relevant publications, conference/meeting attendance lists and peer recommendations, and (2) registered nurses working in the UK National Health Service (NHS), recruited via social media, professional nursing bodies and practitioner networks. The stakeholder panel completed two rounds of an online Delphi survey, rating 43 previously identified well‐being outcomes on a nine‐point Likert scale, from ‘not important’ to ‘critical.’ Consensus was defined as ≥ 75% of stakeholders agreeing a well‐being outcome was critical for inclusion in the COS. Results: Fifty‐four stakeholders completed the first Delphi round, and 45 participated in both rounds. Thirteen well‐being outcomes met the a priori threshold for inclusion in the COS: general well‐being, health, sleep, positive relationships, personal safety, psychological need satisfaction, psychological safety, job satisfaction, morale, life–work balance, compassion satisfaction, satisfaction with patient care and good nursing practice. The final COS was agreed by the stakeholder panel, without amendments. Conclusion: This study establishes a COS defining the nurse well‐being outcomes that should be captured when assessing nurse well‐being. Appropriate existing measurement instruments can be selected to capture these outcomes; future research is needed to identify and evaluate the most appropriate instruments and assess the feasibility of routinely capturing all 13 outcomes. Implications for Nursing Management: The COS provides nurse managers and workforce leaders with an agreed set of outcomes to support consistent nurse well‐being measurement, benchmarking and workforce monitoring. Its use can support evaluation of well‐being interventions, evidence‐informed decision‐making and the development of strategies and workplaces that enable nurses to thrive.

Background: Anxiolytic medications, particularly benzodiazepines, are widely prescribed, giving impetus to long‐standing debates about how often these agents should be employed in clinical practice. There are, however, few cross‐country studies of the pharmacoepidemiology of these agents. We report on the frequency of anxiolytic medication use, reasons for use, and perceived effectiveness of use in general population surveys across 20 countries. Methods: Face‐to‐face interviews with community samples totaling n = 49,919 respondents in the World Health Organization World Mental Health (WMH) Surveys asked about anxiolytic medication use anytime in the prior 12 months in conjunction with validated fully structured diagnostic interviews. Treatment questions were administered independently of diagnoses to all respondents. Results: A weighted 5.6% ( n = 4079) of respondents reported anxiolytic medication use within the past 12 months; the vast majority comprised benzodiazepine use, and use was highest amongst respondents with a subthreshold major depressive episode (MDE) (25.2%) and a 12‐month MDE (19.8%). Rates were significantly higher in high‐income countries (HICs) than low‐ and middle‐income countries (LMICs) (8.5% vs. 2.2%, χ ² ₁ = 559.6, p < 0.001). Short‐acting benzodiazepines and z‐drugs were most commonly used for sleep (66.5% and 85.5%), while intermediate‐acting benzodiazepines and long‐acting benzodiazepines were most commonly used either for sleep (37.9% and 30.1%) or anxiety (33.3% and 32.0%). Across all conditions, anxiolytic medications were reported as very effective by 55.7% of users and somewhat effective by an additional 32.2% of users, with similar proportions in HICs and LMICs. Negative predictors of high perceived effectiveness were a 12‐month MDE and taking anxiolytic medication for comorbid anxiety and depression. Conclusion: These data do not definitely answer the question of how often benzodiazepines should be prescribed in clinical practice, but they usefully inform discussions of how to optimize their use. It is noteworthy that anxiolytic medications, particularly benzodiazepines, are largely prescribed for anxiety and sleep, and that they are widely perceived to be either very or somewhat effective by users. However, more targeted prescription of these agents may be necessary; in particular antidepressant intervention should be prioritized in the pharmacotherapy of major depressive disorder.

Over twenty years ago, an editorial in this journal called for further studies of the epidemiological and psychopathological characteristics of ‘recurrent brief depression’ in clinical samples in primary and secondary care settings. At that time, relatively little was known about the epidemiology or potential neuropsychobiology of the condition, and no evidence-based treatments had been identified. Two decades have passed, but there have been no substantial developments in understanding in the last ten years. The seeming withdrawal from research into recurrent brief depression is regrettable, given widespread concerns about the burden of depressive symptoms in young people. It seems reasonable to call once again for further investigations in clinical samples, this time with a focus on younger individuals.