Randomised controlled trials (RCTs) of psilocybin have reported large antidepressant effects in adults with major depressive disorder and treatment-resistant depression (TRD). Given psilocybin's psychedelic effects, all published studies have included psychological support. These effects depend on serotonin 2A (5-HT2A) receptor activation, which can be blocked by 5-HT2A receptor antagonists like ketanserin or risperidone. In an animal model of depression, ketanserin followed by psilocybin had similar symptomatic effects as psilocybin alone.

To conduct a proof-of-concept RCT to (a) establish feasibility and tolerability of combining psilocybin and risperidone in adults with TRD, (b) show that this combination blocks the psychedelic effects of psilocybin and (c) provide pilot data on the antidepressant effect of this combination (compared with psilocybin alone).

In a 4-week, three-arm, ‘double dummy’ trial, 60 adults with TRD will be randomised to psilocybin 25 mg plus risperidone 1 mg, psilocybin 25 mg plus placebo, or placebo plus risperidone 1 mg. All participants will receive 12 h of manualised psychotherapy. Measures of feasibility will include recruitment and retention rates; tolerability and safety will be assessed by rates of drop-out attributed to adverse events and rates of serious adverse events. The 5-Dimensional Altered States of Consciousness Rating Scale will be a secondary outcome measure.

This trial will advance the understanding of psilocybin's mechanism of antidepressant action.

This line of research could increase acceptability and access to psilocybin as a novel treatment for TRD without the need for a psychedelic experience and continuous monitoring.

During the last decade there has been a resurgence of interest on the use of psychedelics as novel treatments for mental disorders, including treatment-resistant depression (TRD). Psilocybin, the chemical component of “magic mushrooms”, has been administered with psychotherapy in randomized clinical trials (RCTs) showing large and sustained antidepressant effects. As the use of psilocybin expands, it is becoming more important to understand whether psilocybin’s psychedelic effects are required for psilocybin’s antidepressant effects. Psilocybin’s psychedelic effects are known to be dependent on serotonin 2A receptor (5-HT2AR) activation. Given the safety concerns associated with psilocybin’s psychedelic effects, all studies have used it in conjunction with at least 12 hours of intensive psychotherapy. This makes psilocybin-assisted psychotherapy (PAP) highly resource intensive and impedes scalability given limited resources and access to trained therapists in most jurisdictions. Studies in healthy volunteers have shown that psilocybin’s psychedelic effects are blocked by 5-HT2AR antagonists like risperidone and ketanserin. In a pre-clinical study using a mouse model of depression, administration of ketanserin followed by psilocybin had the same antidepressant effect as psilocybin alone. We propose to conduct the first study to test in humans whether the antidepressant effects of psilocybin are attenuated by 5-HT2AR blockade from risperidone.

Aim 1: To evaluate the feasibility and tolerability of administering psilocybin with risperidone in adults with TRD by evaluating recruitment, retention, tolerability, and safety.

Aim 2: To evaluate psychedelic effects (measured with the 5-Dimensional Altered States of Consciousness Rating Scale) in the three groups.

Aim 3: To evaluate antidepressant effects (measured with the Montgomery Asberg Depression Rating Scale; MADRS) in the three groups. .

A three-arm, 4-week, double blind, proof-of-concept RCT for patients with a DSM-5 major depressive episode that has failed to respond to at least two adequate trials of antidepressants. Participants will be randomized to: 1) psilocybin 25 mg plus risperidone 1 mg; 2) psilocybin 25 mg plus placebo; 3) placebo plus risperidone 1 mg. All participants will receive 12 hours of manualized psychotherapy.

Ethics approval for the proposed study has been obtained. We will present preliminary feasibility data at the meeting in March.

If the study demonstrates that psilocybin’s psychedelic effects are not necessary for psilocybin’s antidepressant effects, the combination of psilocybin and a 5-HT2AR antagonist, such as risperidone, could increase acceptability and access to the use of psilocybin to treat MDD and related conditions.

None Declared

Among patients diagnosed with COVID-19, a substantial proportion are experiencing ongoing symptoms for months after infection, known as ‘long COVID’. Long COVID is associated with a wide range of physical and neuropsychological symptoms, including impacts on mental health, cognition, and psychological wellbeing. However, intervention research is only beginning to emerge. This systematic review synthesizes currently registered trials examining interventions for mental health, cognition, and psychological wellbeing in patients with long COVID.

Standard systematic review guidelines were followed. Trials registered in two large trial registries in 2020 to May 2022 were reviewed. Included studies were narratively synthesized by type of intervention and a risk-of-bias assessment was conducted.

Forty-two registered trials were included, with a total target sample size of 5814 participants. These include 11 psychological interventions, five pharmacological and other medical interventions, and five evaluating herbal, nutritional, or natural supplement interventions. An additional nine trials are examining cognitive and neurorehabilitation interventions and 12 are examining physiotherapy or physical rehabilitation. Most trials are randomized, but many are feasibility trials; trials are evaluating a wide spectrum of outcomes.

While there is a newly emerging body of research testing interventions for mental health, cognition, and psychological wellbeing in long COVID, the breadth and scope of the research remains limited. It is urgently incumbent on researchers to expand upon the intervention research currently under way, in order to generate high-quality evidence on a wide range of candidate interventions for diverse long COVID patient populations.

Frontal sinus obliteration is often performed using fat, autologous bone or a range of synthetic materials. This paper reports the long-term clinical and radiological outcomes of frontal sinus obliteration using beta-tricalcium phosphate putty.

A retrospective audit was performed of patients who underwent frontal sinus obliteration with beta-tricalcium phosphate putty. Patient-, disease- and procedure-related data were collected. Pre- and post-operative computed tomography scans were reviewed to assess bone integration.

Four patients underwent frontal sinus obliteration using beta-tricalcium phosphate putty for treatment of a cerebrospinal leak, mucocele and recalcitrant frontal sinusitis. All patients had disease resolution, with no intra- or post-operative complications reported in the 16.5-month follow up. Post-operative computed tomography scans confirmed native bone obliteration of the frontonasal ducts in all patients.

Beta-tricalcium phosphate putty is a safe and effective option for bone obliteration of the frontal sinus in a range of pathologies, including cerebrospinal fluid leak.

To compare the treatment of patients with early psychosis, 2 years after the introduction of an integrated model of enhanced management within a public adult mental health service, with an historic cohort from the same service.

Variables examined in the 2001 cohort were compared with 2008 patients. Computer database review and a file audit were conducted for all patients with early psychosis across the first 2 years of the program.

Compared to the historic cohort, patients in the current cohort were 24% less likely to have been admitted (P = 0.004). There were statistically significant reductions in involuntary status and use of a locked unit. Rates of police involvement in admission and use of seclusion were also reduced, though this trend was not significant. Average length of stay was reduced. Median duration of untreated psychosis was 3 months in both 2001 and 2008 cohorts.

The introduction of an integrated model of management within an area mental health service for patients with early psychosis contributed to significant reductions in admissions, involuntary status and use of a locked ward. The data suggests that enhanced treatment of early psychosis patients can be offered within generic services.

Why patients with psychosis use cannabis remains debated. The self-medication hypothesis has received some support but other evidence points towards an alleviation of dysphoria model. This study investigated the reasons for cannabis use in first-episode psychosis (FEP) and whether strength in their endorsement changed over time.

FEP inpatients and outpatients at the South London and Maudsley, Oxleas and Sussex NHS Trusts UK, who used cannabis, rated their motives at baseline (n = 69), 3 months (n = 29) and 12 months (n = 36). A random intercept model was used to test the change in strength of endorsement over the 12 months. Paired-sample t-tests assessed the differences in mean scores between the five subscales on the Reasons for Use Scale (enhancement, social motive, coping with unpleasant affect, conformity and acceptance and relief of positive symptoms and side effects), at each time-point.

Time had a significant effect on scores when controlling for reason; average scores on each subscale were higher at baseline than at 3 months and 12 months. At each time-point, patients endorsed ‘enhancement’ followed by ‘coping with unpleasant affect’ and ‘social motive’ more highly for their cannabis use than any other reason. ‘Conformity and acceptance’ followed closely. ‘Relief of positive symptoms and side effects’ was the least endorsed motive.

Patients endorsed their reasons for use at 3 months and 12 months less strongly than at baseline. Little support for the self-medication or alleviation of dysphoria models was found. Rather, patients rated ‘enhancement’ most highly for their cannabis use.

Associations between childhood abuse and various psychotic illnesses in adulthood are commonly reported. We aim to examine associations between several reported childhood adverse events (sexual abuse, physical abuse, emotional abuse, neglect and interpersonal loss) among adults with diagnosed psychotic disorders and clinical and psychosocial outcomes.

Within a large epidemiological study, the 2010 Australian National Survey of Psychosis (Survey of High Impact Psychosis, SHIP), we used logistic regression to model childhood adverse events (any and specific types) on 18 clinical and psychosocial outcomes.

Eighty percent of SHIP participants (1466/1825) reported experiencing adverse events in childhood (sexual abuse, other types of abuse and interpersonal loss). Participants reporting any form of childhood adversity had higher odds for 12/18 outcomes we examined. Significant associations were observed with all psychosocial outcomes (social dysfunction, victimisation, offending and homelessness within the previous 12 months, and definite psychosocial stressor within 12 months of illness onset), with the strongest association for homelessness (odds ratio (OR) = 2.82). Common across all adverse event types was an association with lifetime depression, anxiety and a definite psychosocial stressor within 12 months of illness onset. When adverse event types were non-hierarchically coded, sexual abuse was associated with 11/18 outcomes, other types of abuse 13/18 and, interpersonal loss occurring in the absence of other forms of abuse was associated with fewer of the clinical and psychosocial outcomes, 4/18. When adverse events types were coded hierarchically (to isolate the effect of interpersonal loss in the absence of abuse), interpersonal loss was associated with lower odds of self-reproach (OR = 0.70), negative syndrome (OR = 0.75) and victimisation (OR = 0.82).

Adverse childhood experiences among people with psychosis are common, as are subsequent psychosocial stressors. Mental health professionals should routinely enquire about all types of adversities in this group and provide effective service responses. Childhood abuse, including sexual abuse, may contribute to subsequent adversity, poor psychosocial functioning and complex needs among people with psychosis. Longitudinal research to better understand these relationships is needed, as are studies which evaluate the effectiveness of preventative interventions in high-risk groups.

Clozapine is the most effective medication for treatment refractory schizophrenia. However, descriptions of the mental health and comorbidity profile and care experiences of people on clozapine in routine clinical settings are scarce. Using data from the 2010 Australian Survey of High Impact Psychosis, we aimed to examine the proportion of people using clozapine, and to compare clozapine users with other antipsychotic users on demographic, mental health, adverse drug reaction, polypharmacy and treatment satisfaction variables.

Data describing 1049 people with a diagnosis of schizophrenia or schizoaffective disorder, who reported taking any antipsychotic medication in the previous 4 weeks, were drawn from a representative Australian survey of people with psychotic disorders in contact with mental health services in the previous 12 months. We compared participants taking clozapine (n = 257, 22.4%) with those taking other antipsychotic medications, on a range of demographic, clinical and treatment-related indicators.

One quarter of participants were on clozapine. Of participants with a chronic course of illness, only one third were on clozapine. After adjusting for diagnosis and illness chronicity, participants taking clozapine had significantly lower odds of current alcohol, cannabis and other drug use despite similar lifetime odds. Metabolic syndrome and diabetes were more common among people taking clozapine; chronic pain was less common. Psychotropic polypharmacy did not differ between groups.

Consistent with international evidence of clozapine underutilisation, a large number of participants with chronic illness and high symptom burden were not taking clozapine. The lower probabilities of current substance use and chronic pain among clozapine users warrant further study.

Rates of the metabolic syndrome in people with psychotic illness are high. Emerging evidence suggests that cannabis use may have a positive impact on cardiometabolic risk factors in the general population, but little is known about its impact for people with psychotic illness. Our aim was to investigate whether the rate of the metabolic syndrome in people with psychotic illness was associated with frequency of cannabis use.

The 2010 Australian psychosis survey used a two-phase design to randomly select a nationally representative sample of 1825 adults with psychotic illness for interview and physical assessment. This study is based on 1813 participants who provided data on cannabis use. Multiple logistic regression was used to model the influence of frequency of cannabis use on the metabolic syndrome, adjusting for potential covariates including antipsychotic medication use, smoking, alcohol use and cognitive function.

One-third (33.0%) of participants had used cannabis in the past year. The proportion of non-users, occasional users and frequent users with the metabolic syndrome was 63.0, 51.7 and 43.5%, respectively (p < 0.001). In unadjusted analyses, both occasional use and frequent cannabis use were associated with significantly lower odds of the metabolic syndrome. In the adjusted analyses, the association between the metabolic syndrome and frequent cannabis use remained significant [odds ratio = 0.56, 95% confidence interval (CI) 0.39–0.80], but not the association with occasional use (odds ratio = 0.75, 95% CI 0.49–1.13).

While cannabis use may be detrimental for mental health, these data suggest that it may also have a cardiometabolic protective effect. Further investigation is required to understand the mechanism underlying this paradoxical finding.

The links between migrant status and psychosis have attracted considerable attention in recent decades. The aim of the study was to explore the demographic and clinical correlates of migrant v. Australia-born status in individuals with psychotic disorders using a large community-based sample.

Data were drawn from a population-based prevalence survey of adults with psychotic disorders. Known as the Survey of High Impact Psychosis (SHIP), it was conducted in seven Australian catchment areas in 2010. Logistic regression was used for the main analyses, examining associations of migrant status with sociodemographic and clinical variables.

Of the 1825 participants with psychotic disorders, 17.8% (n = 325) were migrants, of whom 55.7% (n = 181) were male. Compared to Australia-born individuals with psychosis, migrants were more likely to be currently married, to have completed a higher level at school, to have left school later, and to be employed with full-time jobs. Migrants with psychosis were either no different from or less impaired or disadvantaged compared to their Australian-born counterparts on a range of clinical and demographic variables.

In a sample of individuals with psychotic disorders, there was no evidence to suggest that migrant status was associated with worse clinical or socio-economic outcomes compared to their native-born counterparts.

There are insufficient data from nationwide surveys on the prevalence of specific psychotic disorders and associated co-morbidities.

The 2010 Australian national psychosis survey used a two-phase design to draw a representative sample of adults aged 18–64 years with psychotic disorders in contact with public treatment services from an estimated resident population of 1 464 923 adults. This paper is based on data from 1642 participants with an International Classification of Diseases (ICD)-10 psychotic disorder. Its aim is to present estimates of treated prevalence and lifetime morbid risk of psychosis, and to describe the cognitive, physical health and substance use profiles of participants.

The 1-month treated prevalence of psychotic disorders was 3.10 cases per 1000 population aged 18–64 years, not accounting for people solely accessing primary care services; lifetime morbid risk was 3.45 per 1000. Mean premorbid intelligence quotient was approximately 0.5 s.d.s below the population mean; current cognitive ability (measured with a digit symbol coding task) was 1.6 s.d.s below the population mean. For both cognitive tests, higher scores were significantly associated with better independent functioning. The prevalence of the metabolic syndrome was high, affecting 60.8% of participants, and pervasive across diagnostic groups. Of the participants, two-thirds (65.9%) were current smokers, 47.4% were obese and 32.4% were sedentary. Of the participants, half (49.8%) had a lifetime history of alcohol abuse/dependence and 50.8% lifetime cannabis abuse/dependence.

Our findings highlight the need for comprehensive, integrative models of recovery to maximize the potential for good health and quality of life for people with psychotic illness.

Several neuroimaging studies have investigated brain grey matter in people with body dysmorphic disorder (BDD), showing possible abnormalities in the limbic system, orbitofrontal cortex, caudate nuclei and temporal lobes. This study takes these findings forward by investigating white matter properties in BDD compared with controls using diffusion tensor imaging. It was hypothesized that the BDD sample would have widespread significantly reduced white matter connectivity as characterized by fractional anisotropy (FA).

A total of 20 participants with BDD and 20 healthy controls matched on age, gender and handedness underwent diffusion tensor imaging. FA, a measure of water diffusion within a voxel, was compared between groups on a voxel-by-voxel basis across the brain using tract-based spatial statistics within the FSL package.

Results showed that, compared with healthy controls, BDD patients demonstrated significantly lower FA (p < 0.05) in most major white matter tracts throughout the brain, including in the superior longitudinal fasciculus, inferior fronto-occipital fasciculus and corpus callosum. Lower FA levels could be accounted for by increased radial diffusivity as characterized by eigenvalues 2 and 3. No area of higher FA was found in BDD.

This study provided the first evidence of compromised white matter integrity within BDD patients. This suggests that there are inefficient connections between different brain areas, which may explain the cognitive and emotion regulation deficits within BDD patients.

Large epidemiological studies are needed to better understand the prevalence and profile of offending by people with mental illness. This study used a whole-of-population design to examine the prevalence, type and pattern of offending across all psychiatric diagnoses, including schizophrenia, compared to the general population.

We used whole-of-population longitudinal record-linked data for a cohort of all Western Australians born 1955–1969 to determine arrest history over the period 1985–1996 and to ascertain recorded history of psychiatric illness. Of the cohort, 116 656 had been arrested and 40 478 were on the psychiatric case register.

The period prevalence of arrest for people with any psychiatric illness was 32.1%. The highest arrest prevalence, by diagnostic category, was for substance use disorders (59.4%); the prevalence for schizophrenia was 38.7%. Co-morbid substance use disorders significantly increased risk of arrest in people with schizophrenia. The prevalence of mental illness among offenders was 11.1%: 6.5% of offenders had substance use disorders and 1.7% had schizophrenia. For the majority of offenders with a psychiatric illness, first arrest preceded first contact with mental health services; for schizophrenia only, this proportion was increasing over time. The mean percentage annual change in the number of arrests during 1985–1996 rose significantly for offenders with a psychiatric illness other than schizophrenia and dropped significantly for those with no mental illness. Compared to non-psychiatric offenders, offenders with schizophrenia were more likely to offend alone, to offend in open places and to target strangers.

Our findings open the way to an informed approach to the management of offenders with mental illness.