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Background: Long-acting injectable antipsychotics (LAIs) have been shown to improve adherence and prevent relapse in the treatment of schizophrenia and psychotic disorders, though longitudinal data on treatment outcomes are limited. Objectives: To establish the long-term acceptability and effectiveness of paliperidone palmitate once monthly (PP1M). Methods: This independent 10-year mirror image study was carried out in a large urban mental health provider. The study evaluated the retention and hospitalization rates 5 years following initiation of PP1M in a naturalistic patient cohort of all adult patients who were newly initiated on PP1M between 2011 and 2015. Electronic records were used to compare the frequency and length of hospital admissions in the 5 years before and after introduction of PP1M. Switching and discontinuation rates and reasons were also recorded with a separate analysis of patients who continued and discontinued PP1M during the study period. Results: A total of 167 patients were included in the study (70% with schizophrenia, 30% with other diagnoses). Discontinuation rates were 24%, 15%, 17%, 5% and 8% in years 1–5, respectively; poor tolerability was the most common cause for stopping PP1M. Demographic and clinical factors such as age, sex, diagnosis and care setting did not discriminate between continuers and discontinuers. The group that completed 5 years on PP1M (46%) showed an overall reduction of 72% in the mean number and 68% in the mean length of admissions compared to the 5-year period before initiation, with more than half of the patients requiring no admission at all during this period of time (median = 0). On the contrary, discontinuers demonstrated worse outcomes in overall bed occupancy than continuers. Findings were overall similar across the total cohort and schizophrenia-only group. Conclusions: Our study has one of the longest durations of follow up of a naturalistic cohort treated with LAIs confirming sustained improvements for patients who continued treatment for up to 5 years with implicit implications for cost effectiveness. Study findings may facilitate shared decision making in this area, overcoming some of the common barriers for use.

Aim: Early intervention services are the established and evidence-based treatment option for individuals with first-episode psychosis. They are time-limited, and care pathways following discharge from these services have had little investigation. We aimed to map care pathways at the end of early intervention treatment to determine common trajectories of care. Methods: We collected health record data for all individuals treated by early intervention teams in two NHS mental health trusts in England. We collected data on individuals’ primary mental health care provider for 52 weeks after the end of their treatment and calculated common trajectories of care using sequence analysis. Results: We identified 2224 eligible individuals. For those discharged to primary care we identified four common trajectories: Stable Primary Care, Relapse and return to CMHT, Relapse and return to EIP, and Discontinuity of Care. We also identified four trajectories for those transferred to alternative secondary mental health care: Stable Secondary Care, Relapsing Secondary Care, Long-term Inpatient, and Discharged Early. The Long-term Inpatient trajectory (1% of sample) accounted for 29% of all inpatient days in the year follow-up, with Relapsing Secondary Care (2% of sample and 21% of inpatient days), and Relapse and return to CMHT (5% of sample, 15% of inpatient days) the second and third most frequent. Conclusions: Individuals have common care pathways at the end of early intervention in psychosis treatment. Understanding common individual and service features that lead to poor care pathways could improve care and reduce hospital use.

The Covid-19 outbreak has taken a substantial toll on the mental and physical wellbeing of healthcare workers (HCWs), impacting healthcare systems at a global scale. One year into the pandemic, the need to establish the prevalence of sleep dysfunction and psychological distress in the face of COVID-19, identify risk and protective factors and explore effective countermeasures remains of critical importance. Despite implicit limitations relating to the quality of available studies, a plethora of evidence to-date suggests that a considerable proportion of HCWs experience significant sleep disturbances (estimated to afflict every two in five HCWs) as well as mood symptoms (with more than one in five reporting high levels of depression or anxiety). Younger age, female gender, frontline status, fear or risk of infection, occupation, current or past mental health concerns, and a lower level of social support were all associated with a greater risk of disturbed sleep and adverse psychological outcomes. Furthermore, we discuss the link between sleep deprivation, susceptibility to viral infections and psychosocial wellbeing, in relevance to COVID-19 and summarize the existing evidence regarding the presence and predictors of traumatic stress/PTSD and burnout in HCWs. Finally, we highlight the role of resilience and tailored interventions in order to mitigate vulnerability and prevent long-term physical and psychological implications. Indeed, promoting psychological resilience through an enhanced social support network has proven crucial for HCWs in coping under these strenuous circumstances. Future research should aim to provide high quality information on the long-term consequences and the effectiveness of applied interventions.

Background: Schizophrenia is a severe psychiatric disorder with periods of remission and relapse. As discontinuation of antipsychotic medication is the most important reason for relapse, long-term maintenance treatment is key. Whether intramuscular long-acting (depot) antipsychotics are more efficacious than oral medication in preventing medication discontinuation is still unresolved. We aimed to compare time to all-cause discontinuation in patients randomly allocated to long-acting injectable (LAI) versus oral medication. Methods: EULAST was a pragmatic, randomised, open-label trial conducted at 50 general hospitals and psychiatric specialty clinics in 15 European countries and Israel. Patients aged 18 years and older, with DSM-IV schizophrenia (as confirmed by the Mini International Neuropsychiatric Interview 5 plus) and having experienced their first psychotic episode from 6 months to 7 years before screening, were randomly allocated (1:1:1:1) using block randomisation to LAI paliperidone, LAI aripiprazole, or the respective oral formulations of these antipsychotics. Randomisation was stratified by country and duration of illness (6 months up to 3 years vs 4 to 7 years). Patients were followed up for up to 19 months. The primary endpoint was discontinuation, regardless of the reason, during 19 months of treatment. We used survival analysis to assess the time until all-cause discontinuation in the intention-to-treat (ITT) group, and per protocol analyses were also done. This trial is registered with ClinicalTrials.gov, NCT02146547, and is complete. Findings: Between Feb 24, 2015, and Dec 15, 2018, 533 individuals were recruited and assessed for eligibility. The ITT population included 511 participants, with 171 (33%) women and 340 (67%) men, and a mean age of 30·5 (SD 9·6) years. 410 (80%) of 511 participants were White, 35 (7%) were Black, 20 (4%) were Asian, and 46 (9%) were other ethnicity. In the combined oral antipsychotics treatment group of 247 patients, 72 (29%) patients completed the study and 175 (71%) met all-cause discontinuation criteria. In the combined LAI treatment arm of 264 patients, 95 (36%) completed the study and 169 (64%) met the all-cause discontinuation criteria. Cox regression analyses showed that treatment discontinuation for any cause did not differ between the two combined treatment groups (hazard ration [HR] 1·16, 95% CI 0·94–1·43, p=0·18). No significant difference was found in the time to all-cause discontinuation between the combined oral and combined LAI treatment groups (log rank test χ 2=1·87 [df 1]; p=0·17). During the study, 121 psychiatric hospitalisations occurred in 103 patients, and one patient from each of the LAI groups died; the death of the patient assigned to paliperidone was assessed to be unrelated to the medication, but the cause of other patient's death was not shared with the study team. 86 (25%) of 350 participants with available data met akathisia criteria and 70 (20%) met parkinsonism criteria at some point during the study. Interpretation: We found no substantial advantage for LAI antipsychotic treatment over oral treatment regarding time to discontinuation in patients with early-phase schizophrenia, indicating that there is no reason to prescribe LAIs instead of oral antipsychotics if the goal is to prevent discontinuation of antipsychotic medication in daily clinical practice. Funding: Lundbeck and Otsuka.

Arturas Kalniunas,1 Ipsita Chakrabarti,1 Rakhee Mandalia,1 Jasna Munjiza,2,3 Sofia Pappa1,2 1West London NHS Trust, London, UK; 2Division of Psychiatry, Imperial College London, London, UK; 3Central and North West London NHS Foundation Trust, London, UKCorrespondence: Sofia PappaRecovery Team East, Avenue House, 43-47 Avenue Road, London, W3 8NJ, UKEmail sofia.pappa@westlondon.nhs.uk; s.pappa@imperial.ac.ukObjective: We aim to systematically review evidence for a relationship between antipsychotic-induced akathisia and suicidal behaviour, in order to guide further clinical decision making in this area.Methods: Several electronic databases (Embase, Medline, Cochrane and PsychINFO) were systemically searched for articles published up to February 2021, using search terms related to akathisia, antipsychotics and suicidal behaviour. Two reviewers independently evaluated all the relevant studies using predetermined criteria and assessed the risk of bias for each included study. The systematic review was conducted in line with PRISMA methodology and reporting.Results: Following de-duplication, screening and application of exclusion criteria, four eligible studies were identified. All of the available studies were in English and included adult patients. Nevertheless, there was significant variability regarding methodology and overall quality was deemed low due to small sample sizes. There was insufficient data to perform statistical analyses of the results. Of the four studies, two found a weak correlation between antipsychotic-related akathisia and suicidal behaviour, a finding that was not supported by the remaining two studies.Conclusion: The search yielded very few studies for inclusion. On the basis of the existing evidence, akathisia cannot be reliably linked to the presence of suicidal behaviour in patients treated with antipsychotic medication. However, proactive screening for emerging suicidal behaviour in this vulnerable patient group is advisable. Our findings highlight the pressing need for further research in this area.Keywords: antipsychotic medication, akathisia, restlessness, suicidal behaviour

Background Difficult-to-treat depression (DTD) presents a substantial health care challenge, with around one-third of people diagnosed with a depressive episode in the UK finding that their symptoms persist following treatment. This study aimed to identify priority research questions (RQs) that could inform the development of new and improved treatments, interventions, and support for people with DTD. Methods Using an adapted Child Health and Nutrition Research Initiative (CHNRI) method, this national prioritisation exercise engaged 60 leading researchers and health care professionals in the UK, as well as 25 wider stakeholders with relevant lived experience to produce a ranked list of priority RQs in DTD. The final list of 99 distinct RQs was independently scored by 42 individuals against a list of five criteria: answerability, effectiveness, impact on health, deliverability, and equity. Results Highly ranked RQs covered a range of novel and existing treatments. The three highest scoring RQs included evaluation of psychological and pharmacological therapies (eg, behavioural activation, and augmentation therapies), as well as social interventions to reduce loneliness or increase support for people with DTD. Conclusions This exercise identified and prioritised 99 RQs that could inform future research and funding decisions over the next five years. The results of this research could improve treatment and support for people affected by DTD. It also serves as an example of ways in which the CHNRI method can be adapted in a collaborative manner to provide a more active role for patients, carers, and health care professionals.

Aims: The Covid-19 pandemic has had a substantial impact on the mental health of the general public and high-risk groups across the globe. Southeast Asia, one of the first regions to be affected by the outbreak, is of particular interest given its proximity and close links to China, experience with recent epidemics (i.e. SARS), and the variable course of the outbreak in the region thus far. The aim of this study was to systemically review and assess the prevalence of anxiety, depression and insomnia symptoms in the general adult population, frontline and general healthcare workers (HCWs), and adult students in Southeast Asia during the course of the first year of the Covid-19 pandemic. Methods: Several literature databases (PubMed, Embase, PsycINFO, Web of Science, and medRxiv) were systemically searched for articles published up to February 2021. Two reviewers independently evaluated all the relevant studies using pre-determined criteria and assessed the risk of bias for each included study. The prevalence rates of mental health symptoms were estimated using a random-effect meta-analysis model. Results: In total, 32 samples from 25 studies with 20,352 participants were included. Anxiety symptoms was assessed in all 25 studies and depressive symptoms in 15 studies with pooled prevalence rates of 22% and 16% respectively. Only two studies evaluated insomnia, whose prevalence was estimated to be 19%. The overall prevalence of mental health disorders was similar amongst frontline HCWs (18%), general HCWs (17%), and students (20%) whilst being noticeably higher in the general population (27%). Conclusions: The results indicate that a considerable proportion of participants report the presence of anxiety, depression and insomnia symptoms. However, the pooled prevalence rates in Southeast Asia are significantly lower than those reported in other meta-analyses from other areas such as China and Europe. This meta-analysis may provide valuable evidence for more targeted identification of mental health needs and guide future research of long-term outcomes. Keywords: meta-analysis; Covid-19; mental health; pandemic; general population; healthcare workers; students; anxiety; depression; insomnia

COVID-19 Long Haulers, an estimated 3% to 12% of people infected globally with coronavirus having latter devasting symptoms 12 weeks after the initial infection is on the rise. We conducted a collaborative study with the long covid patient organization in Greece in order to estimate the prevalence, symptoms and problems that adult long haulers experience and then propose a management plan for these patients. Symptoms were obtained from 208 patients using unstructured qualitative free text entries in an anonymized online questionnaire. The majority of respondents (68.8%) were not hospitalized and had been diagnosed more than six months ago with lingering symptoms (66,8%). Eighteen different symptoms (fatigue, tachycardia, shortness of breath, parosmia etc) were mentioned in both hospitalized and community patients. Interestingly, patients with initial mild symptoms suffer from the same persistent symptoms as those who were hospitalized. Awareness of long covid sequelae seems to be low even among medical doctors. Treatment options incorporating targeted rehabilitation programs are either not available or still excluded from the management plan of long covid patients. Since long COVID is a multi-systemic entity, we propose a holistic interventional approach using a multidisciplinary medical team in order to securely and effectively diagnose and treat these specific patients. Academic and medical community must collaborate with long covid patients’ organizations so as to provide personalized medicine.

Evidence to date suggests that a significant proportion of COVID-19 patients experience adverse psychological outcomes and neuropsychiatric complications. The aim of this study was to evaluate the effect of SARS-CoV-2 infection and subsequent hospitalization on the mental health, sleep, and quality of life of COVID-19 survivors. Patients were assessed 1–2 months after hospital discharge using standardized screening tools for depression and anxiety (HADS), post-traumatic stress disorder (IES-R), insomnia (AIS), and quality of life (EQ-5D-5L). Sociodemographic factors, comorbidities, disease severity and type of hospitalization were also collected. Amongst the 143 patients included, mental health symptoms were common (depression—19%; anxiety—27%; traumatic stress—39%; insomnia—33%) and more frequently reported in female than in male patients. Age, smoking status, comorbidities and illness severity were not found to significantly correlate with the presence of mood, sleep, or stress disorders. Finally, quality of life was worse for patients requiring ICU (p = 0.0057) or a longer hospital stay (p < 0.001) but was unaffected by factors such as sex and other measured outcomes. These findings highlight the need for appropriate intervention to properly manage the immediate and enduring mental health complications of COVID-19.

Worldwide, there are now three marketed dopamine D2 partial agonists: aripiprazole, brexpiprazole and cariprazine. These three drugs share a number of properties other than their action at D2 receptors. Pharmacologically, they are 5HT2 antagonists and D3 and 5HT1A partial agonists but with little or no alpha-adrenergic, anticholinergic or antihistaminic activity. They also share a long duration of action. Clinically, D2 partial agonists are effective antipsychotics and generally have useful antimanic and antidepressant activity. They are usually well tolerated, causing akathisia and insomnia only at the start of treatment, and are non-sedating. These drugs also share a very low risk of increased prolactin and of weight gain and accompanying metabolic effects. They may also have a relatively low risk of tardive dyskinesia. There is some evidence that they are preferred by patients to dopamine antagonists. Individual dopamineD2 partial agonists have much in common and as a group they differ importantly from dopamine D2 antagonists. Dopamine D2 partial agonists should be considered a distinct class of antipsychotics.Key pointsD2 partial agonists share many pharmacological and clinical propertiesD2 partial agonists differ in several important respects from D2 antagonistsD2 partial agonists should be considered a discrete class of antipsychotics D2 partial agonists share many pharmacological and clinical properties D2 partial agonists differ in several important respects from D2 antagonists D2 partial agonists should be considered a discrete class of antipsychotics

During the COVID-19 pandemic, the need to establish the prevalence of sleep dysfunction and psychological distress, identify predisposing and protective factors, and explore effective management strategies remains an important priority. Evidence to date suggests that a considerable proportion of COVID-19 patients experience significant sleep disturbances (estimated to afflict up to 50–75%) as well as psychological distress such as depression, anxiety, and traumatic stress. Duration of hospitalization, pre-existing mental health concerns, lower absolute lymphocyte count, and increased neutrophil-to-lymphocyte ratio have been all associated with a greater risk of sleep dysfunction in infected and hospitalized patients. Furthermore, in this review, we discuss the link between sleep deprivation, susceptibility to viral infections, and psychosocial wellbeing in relevance to COVID-19 and summarize the existing evidence regarding the presence and role of sleep apnea in infected individuals. Finally, we highlight the importance of suitable interventions in order to prevent and manage sleep dysfunction and avoid long-term physical and psychological implications. Future research should aim to provide high-quality information including in high risk, underserved, or difficult to reach populations and on the long-term consequences and effectiveness of applied interventions.

Long COVID-19 syndrome refers to persisting symptoms (>12 weeks) after the initial coronavirus infection and is estimated to affect 3% to 12% of people diagnosed with the disease globally. Aim: We conducted a collaborative study with the Long COVID patient organization in Greece, in order to estimate the characteristics, symptoms, and challenges these patients confront. Methods: Data were collected from 208 patients using unstructured qualitative free-text entries in an anonymized online questionnaire. Results: The majority of respondents (68.8%) were not hospitalized and reported lingering symptoms (66.8%) for more than six months. Eighteen different symptoms (fatigue, palpitations, shortness of breath, parosmia, etc.) were mentioned in both hospitalized and community patients. Awareness of Long COVID sequelae seems to be low even among medical doctors. Treatment options incorporating targeted rehabilitation programs are either not available or still not included inthe management plan of Long COVID patients. Conclusions: Patients infected with coronavirus with initial mild symptoms suffer from the same persistent symptoms as those who were hospitalized. Long COVID syndrome appears to be a multi-systemic entity and a multidisciplinary medical approach should be adopted in order to correctly diagnose and successfully manage these patients.