Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed.

To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au.

This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5–0.9 mg/kg or midazolam 0.025–0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4.

The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1–69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2–8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h.

Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.

Internalising disorders are highly prevalent emotional dysregulations during preadolescence but clinical decision-making is hampered by high heterogeneity. During this period impulsivity represents a major risk factor for psychopathological trajectories and may act on this heterogeneity given the controversial anxiety–impulsivity relationships. However, how impulsivity contributes to the heterogeneous symptomatology, neurobiology, neurocognition and clinical trajectories in preadolescent internalising disorders remains unclear.

The aim was to determine impulsivity-dependent subtypes in preadolescent internalising disorders that demonstrate distinct anxiety–impulsivity relationships, neurobiological, genetic, cognitive and clinical trajectory signatures.

We applied a data-driven strategy to determine impulsivity-related subtypes in 2430 preadolescents with internalising disorders from the Adolescent Brain Cognitive Development study. Cross-sectional and longitudinal analyses were employed to examine subtype-specific signatures of the anxiety–impulsivity relationship, brain morphology, cognition and clinical trajectory from age 10 to 12 years.

We identified two distinct subtypes of patients who internalise with comparably high anxiety yet distinguishable levels of impulsivity, i.e. enhanced (subtype 1) or decreased (subtype 2) compared with control participants. The two subtypes exhibited opposing anxiety–impulsivity relationships: higher anxiety at baseline was associated with higher lack of perseverance in subtype 1 but lower sensation seeking in subtype 2 at baseline/follow-up. Subtype 1 demonstrated thicker prefrontal and temporal cortices, and genes enriched in immune-related diseases and glutamatergic and GABAergic neurons. Subtype 1 exhibited cognitive deficits and a detrimental trajectory characterised by increasing emotional/behavioural dysregulations and suicide risks during follow-up.

Our results indicate impulsivity-dependent subtypes in preadolescent internalising disorders and unify past controversies about the anxiety–impulsivity interaction. Clinically, individuals with a high-impulsivity subtype exhibit a detrimental trajectory, thus early interventions are warranted.

One size does not fit all in assessment and intervention for people with convictions for sexual offences. Crime scene indicators and risk-related variables have been used to identify distinct clusters of people with convictions for sexual offences, but there is a need for more robust typologies that identify clusters based on psychologically meaningful risk factors that can be targeted in treatment.

To use robust modelling techniques to identify latent profiles of people with convictions for sexual offences based on indicators of dynamic risk.

Adult male participants, who had been convicted for sexual offences and assessed for eligibility for the prison-based Core Sex Offender Treatment Programme delivered by His Majesty's Prison and Probation Service (UK), were randomly allocated to a test (n = 1577: 70.2%) or validation (n = 668: 29.8%) data-set. Exploratory factor analysis (EFA) was used to select measures of dynamic risk from psychological test data. EFA indicated four factors, from which six measures were selected for inclusion in latent profile analysis.

Five latent profiles were identified in the test and validation data-sets. These were labelled low psychological impairment, impulsive, distorted thinker, rape preoccupied and child fantasist. Profiles varied in individual characteristics, offence histories, victim preferences and level of risk.

Our findings should be used to guide assessment and intervention practices that are tailored to distinct psychological profiles consistent with principles of risk, need and responsivity.

The UK and USA currently report their highest number of drug-related deaths since records began, with higher rates among individuals experiencing homelessness.

Given that overdose prevention in homeless populations may require unique strategies, we evaluated whether substances implicated in death differed between (a) housed decedents and those experiencing homelessness and (b) between US and UK homeless populations.

We conducted an internationally comparative retrospective cohort study utilising multilevel multinomial regression modelling of coronial/medical examiner-verified drug-related deaths from 1 January 2012 to 31 December 2021. UK data were available for England, Wales and Northern Ireland; US data were collated from eight county jurisdictions. Data were available on decedent age, sex, ethnicity, housing status and substances implicated in death.

Homeless individuals accounted for 16.3% of US decedents versus 3.4% in the UK. Opioids were implicated in 66.3 and 50.4% of all studied drug-related deaths in the UK and the USA respectively. UK homeless decedents had a significantly increased risk of having only opioids implicated in death compared with only non-opioids implicated (relative risk ratio RRR = 1.87, 95% CI 1.76–1.98, P < 0.001); conversely, US homeless decedents had a significantly decreased risk (RRR = 0.37, 95% CI 0.29–0.48, P < 0.001). Methamphetamine was implicated in two-thirds (66.7%) of deaths among US homeless decedents compared with 0.4% in the UK.

Both the rate and type of drug-related deaths differ significantly between homeless and housed populations in the UK and USA. The two countries also differ in drugs implicated in death. Targeted programmes for country-specific implicated drug profiles appear warranted.