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Monica Zolezzi,1 Rawan Abouelhassan,1 Yassin Eltorki,2 Peter M Haddad,2 Mahtab Noorizadeh1 1College of Pharmacy, QU Health, Qatar University, Doha, Qatar; 2Mental Health Hospital, Hamad Medical Corporation, Doha, QatarCorrespondence: Monica ZolezziCollege of Pharmacy, Qatar University, PO Box 2713, Doha, QatarEmail mzolezzi@qu.edu.qaIntroduction: Long acting injectable (LAI) antipsychotics are commonly used in the treatment of schizophrenia to improve adherence and clinical outcomes. Concerns have been reported in relation to their non-systemic or injection site adverse effect profile. As such, this study aims to review and evaluate all evidence reporting injection site adverse effects with LAI antipsychotics.Methods: An electronic search was systematically conducted through four databases (PubMed, Embase, SCOPUS, Cochrane) in order to identify studies investigating injection-site reactions associated with LAI antipsychotics. Unpublished studies such as conference proceedings and clinical trial registries were also searched. The search was limited to literature published in English without year limits.Results: Of a total of 189 citations that were identified from the electronic database search, 12 were selected for inclusion in this review. Various injection site reactions were reported in these studies, including pain, bleeding, and swelling. Overall, the studies reported a low incidence of these injection site reactions. Only a minority of the included articles compared injection site reactions between different LAI antipsychotics.Conclusion: Injection site pain was the most commonly reported injection site adverse effect across all articles reviewed. The low incidence of injection site adverse effects associated with LAI antipsychotics indicates that these formulations appear to be well tolerated by patients. More head-to-head trials comparing second generation LAI antipsychotics are needed.Keywords: intramuscular preparations, depot antipsychotics, injection site adverse effects

Francesca D Reeder,1 Nusrat Husain,2 Abdul Rhouma,3 Peter M Haddad,2 Tariq Munshi,4 Farooq Naeem,4 Davit Khachatryan,4 Imran B Chaudhry2 1School of Medicine, 2Neurosciences and Psychiatry Unit, University of Manchester, Manchester, 3Early Intervention Service, Lancashire Care NHS Foundation Trust, Preston, UK; 4Queen’s University, Kingston, Ontario, Canada Aim: There is evidence that childhood trauma is a risk factor for the development of psychosis and it is recommended that childhood trauma is inquired about in all patients presenting with psychosis. This study aimed to determine the prevalence of childhood trauma in patients in the UK Early Intervention Service based on a case note review.Methods: This is a retrospective case note study of 296 patients in an UK Early Intervention Service. Trauma history obtained on service entry was reviewed and trauma experienced categorized. Results were analyzed using crosstab and frequency analysis.Results: The mean age of the sample was 24 years, 70% were male, 66% were White, and 23% Asian (ethnicity not documented in 11% of the sample). Approximately 60% of patients reported childhood trauma, 21% reported no childhood trauma, and data were not recorded for the remaining 19%. Among those reporting trauma, the prevalence of most frequently reported traumas were: severe or repeated disruption (21%), parental mental illness (19%), bullying (18%), absence of a parent (13%), and ‘other’ trauma (24%) – the majority of which were victimization events. Sixty-six percent of those reporting trauma had experienced multiple forms of trauma.Conclusion: A high prevalence of childhood trauma (particularly trauma related to the home environment or family unit) was reported. This is consistent with other studies reporting on trauma and psychosis. The main weakness of the study is a lack of a control group reporting experience of childhood trauma in those without psychosis. Guidelines recommend that all patients with psychosis are asked about childhood trauma; but in 19% of our sample there was no documentation that this had been done indicating the need for improvement in assessment. Keywords: childhood trauma, psychosis, abuse, bullying, family

Usman Adam, Nusrat Husain, Peter M Haddad, Tariq Munshi, Fauzia Tariq, Farooq Naeem, Imran B ChaudhryBackground: Tardive dyskinesia (TD) is a side effect of antipsychotic treatment that often only appears after months or years of treatment. A systematic review of randomized controlled trials lasting more than 1 year showed that second-generation antipsychotics (SGAs) were associated with an approximately fivefold lower risk of TD compared to haloperidol in patients with chronic schizophrenia. In contrast, there is little research on the risk of TD with other first-generation antipsychotics (FGAs), and this applies especially to their use in the treatment of patients with first episode psychosis (FEP).Objectives: To determine the severity and point prevalence of TD in a naturalistic sample of patients with FEP in Pakistan treated with FGAs or SGAs.Methods: This was an observational study. TD was assessed by trained clinicians using the Abnormal Involuntary Movement Scale.Results: In the total sample (number =86) the mean age of patients was 26 years and the prevalence of TD (Schooler Kane criteria) was 29% with no significant difference between those treated with FGAs and SGAs (31% FGAs versus 26% SGAs; P=0.805). The Abnormal Involuntary Movement Scale total score (items 1–7), a measure of the severity of TD, was significantly higher for patients treated with FGAs versus those treated with SGAs (P=0.033). Scores on specific items showed that this reflected higher scores for dyskinesia affecting the muscles of facial expression, as well as of the upper and lower limb, whereas scores did not differ significantly in other body areas. Conclusion: FGAs were associated with greater severity, though not prevalence, of TD than SGAs. The study highlights the relatively high rate of TD in Asian FEP patients and the need for clinicians to monitor for this and other potential antipsychotic side effects during treatment. Keywords: first-generation antipsychotic, second-generation antipsychotic, Abnormal Involuntary Movement Scale

Peter M Haddad,1,2 Cecilia Brain,3,4 Jan Scott5,6 1Neuroscience and Psychiatry Unit, University of Manchester, Manchester, 2Greater Manchester West Mental Health NHS Foundation Trust, Salford, UK; 3Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, 4Nå Ut-teamet, Psychosis Clinic, Sahlgrenska University Hospital, Gothenburg, Sweden; 5Academic Psychiatry, Institute of Neuroscience, Newcastle University, 6Centre for Affective Disorders, Institute of Psychiatry, London, UK Abstract: Nonadherence with medication occurs in all chronic medical disorders. It is a particular challenge in schizophrenia due to the illness's association with social isolation, stigma, and comorbid substance misuse, plus the effect of symptom domains on adherence, including positive and negative symptoms, lack of insight, depression, and cognitive impairment. Nonadherence lies on a spectrum, is often covert, and is underestimated by clinicians, but affects more than one third of patients with schizophrenia per annum. It increases the risk of relapse, rehospitalization, and self-harm, increases inpatient costs, and lowers quality of life. It results from multiple patient, clinician, illness, medication, and service factors, but a useful distinction is between intentional and unintentional nonadherence. There is no gold standard approach to the measurement of adherence as all methods have pros and cons. Interventions to improve adherence include psychoeducation and other psychosocial interventions, antipsychotic long-acting injections, electronic reminders, service-based interventions, and financial incentives. These overlap, all have some evidence of effectiveness, and the intervention adopted should be tailored to the individual. Psychosocial interventions that utilize combined approaches seem more effective than unidimensional approaches. There is increasing interest in electronic reminders and monitoring systems to enhance adherence, eg, Short Message Service text messaging and real-time medication monitoring linked to smart pill containers or an electronic ingestible event marker. Financial incentives to enhance antipsychotic adherence raise ethical issues, and their place in practice remains unclear. Simple pragmatic strategies to improve medication adherence include shared decision-making, regular assessment of adherence, simplification of the medication regimen, ensuring that treatment is effective and that side effects are managed, and promoting a positive therapeutic alliance and good communication between the clinician and patient. These elements remain essential for all patients, not least for the small minority where vulnerability and risk issue dictate that compulsory treatment is necessary to ensure adherence.Keywords: adherence, nonadherence, antipsychotics, schizophrenia, long-acting injections, relapse, risk factors

José Manuel Olivares,1 Köksal Alptekin,2 Jean-Michel Azorin,3 Fernando Cañas,4 Vincent Dubois,5 Robin Emsley,6 Philip Gorwood,7 Peter M Haddad,8 Dieter Naber,9 George Papageorgiou,10 Miquel Roca,11 Pierre Thomas,12 Guadalupe Martinez,13 Andreas Schreiner141Department of Psychiatry, Hospital Meixoeiro, Complejo Hospitalario Universitario de Vigo, Vigo, Spain; 2Department of Psychiatry, Dokuz Eylül University School of Medicine, Izmir, Turkey; 3Department of Psychiatry, Sainte Marguerite Hospital, Marseille, France; 4Department of Psychiatry, Hospital Dr R Lafora, Madrid, Spain; 5Cliniques Universitaires St-Luc, Bruxelles, Belgium; 6Department of Psychiatry, Faculty of Health Sciences, University of Stellenbosch, Cape Town, South Africa; 7Sainte-Anne Hospital, Paris Descartes University and INSERM U894, Paris, France; 8Greater Manchester West Mental Health National Health Service Foundation Trust and Department of Psychiatry, University of Manchester, Manchester, UK; 9Universitätsklinikum Hamburg-Eppendorf, Klinik für Psychiatrie und Psychotherapie, Hamburg, Germany; 10Department of Psychiatry, Evangelismos General Hospital, Athens, Greece; 11Unidad de Psiquiatría, Hospital Juan March, Institut Universitari d’Investigació en Ciències de la Salut, Universitat de les Illes Balears, Palma de Mallorca, Spain; 12Department of Psychiatry, Fontan Hospital CHRU Lille, UDSL, University North of France, Lille, France; 13Medical Affairs, Janssen, Madrid, Spain; 14Medical Affairs, Janssen, Neuss, GermanyBackground: Nonadherence is common among patients with schizophrenia, although the rates vary according to means of assessment and patient population. Failure to adhere to medication can have a major impact on the course of illness and treatment outcomes, including increasing the risk of relapse and rehospitalization. Understanding psychiatrists’ perception of the causes and consequences of nonadherence is crucial to addressing adherence problems effectively.Methods: The Europe, the Middle East, and Africa (EMEA) Spanish Adherencia Terapéutica en la Esquizofrenia (ADHES) survey was conducted by questionnaire during January–March 2010 among psychiatrists treating patients with schizophrenia in 36 countries. The survey comprised 20 questions. In addition to recording the demographic details of the 4722 respondents (~12% response rate), it canvassed their preferred methods of assessing adherence, their perceptions of adherence rates, reasons for nonadherence, and strategies to improve adherence.Results: Psychiatrists estimated that 53% of their patients with schizophrenia were partially/nonadherent during the previous month. They estimated only one-third of patients who deteriorated after stopping medication were able to attribute this to nonadherence. Psychiatrists assessed adherence most often by patient interview. Lack of insight was viewed as the most important cause of medication discontinuation, followed by patients feeling better and thinking their medication unnecessary, and experiencing undesirable side effects. Considerably fewer psychiatrists viewed insufficient efficacy, cognitive impairment, or drug/alcohol abuse as the most important reasons for their patients stopping medication.Conclusion: Psychiatrists throughout EMEA recognize the impact of partial/nonadherence to medication, with patient enquiry being the most commonly used means of assessment. There remains a need for more proactive management of patients with schizophrenia, particularly in increasing patient insight of their illness in order to improve adherence and minimize the consequences of relapse. Strategies focused on raising awareness of the importance of adherence are also warranted, with the aim of improving patient outcomes in schizophrenia.Keywords: adherence, schizophrenia, psychiatrist, survey, ADHES

The British Association for Psychopharmacology guidelines specify the scope and targets of treatment for bipolar disorder. The third version is based explicitly on the available evidence and presented, like previous Clinical Practice Guidelines, as recommendations to aid clinical decision making for practitioners: it may also serve as a source of information for patients and carers, and assist audit. The recommendations are presented together with a more detailed review of the corresponding evidence. A consensus meeting, involving experts in bipolar disorder and its treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from these participants. The best evidence from randomized controlled trials and, where available, observational studies employing quasi-experimental designs was used to evaluate treatment options. The strength of recommendations has been described using the GRADE approach. The guidelines cover the diagnosis of bipolar disorder, clinical management, and strategies for the use of medicines in short-term treatment of episodes, relapse prevention and stopping treatment. The use of medication is integrated with a coherent approach to psychoeducation and behaviour change.

A revision of the 2008 British Association for Psychopharmacology evidence-based guidelines for treating depressive disorders with antidepressants was undertaken in order to incorporate new evidence and to update the recommendations where appropriate. A consensus meeting involving experts in depressive disorders and their management was held in September 2012. Key areas in treating depression were reviewed and the strength of evidence and clinical implications were considered. The guidelines were then revised after extensive feedback from participants and interested parties. A literature review is provided which identifies the quality of evidence upon which the recommendations are made. These guidelines cover the nature and detection of depressive disorders, acute treatment with antidepressant drugs, choice of drug versus alternative treatment, practical issues in prescribing and management, next-step treatment, relapse prevention, treatment of relapse and stopping treatment. Significant changes since the last guidelines were published in 2008 include the availability of new antidepressant treatment options, improved evidence supporting certain augmentation strategies (drug and non-drug), management of potential long-term side effects, updated guidance for prescribing in elderly and adolescent populations and updated guidance for optimal prescribing. Suggestions for future research priorities are also made. [ABSTRACT FROM AUTHOR]

Psychiatrists’ attitudes and knowledge about antipsychotic long-acting injections (LAIs) are important given the increasing emphasis on patient choice in treatment and the availability of second-generation antipsychotic (SGA) LAIs. A cross-sectional study of consultant psychiatrists’ attitudes and knowledge in North West England was carried out. A pre-existing questionnaire on clinicians’ attitudes and knowledge regarding LAIs was updated. Of 102 participants, 50% reported a decrease in their use of LAIs. LAI prescribing was evenly split between first-generation antipsychotic (FGA) and SGA-LAIs. Most regarded LAIs as associated with better adherence (89%) than tablets. A substantial proportion believed that LAIs could not be used in first-episode psychosis (38%) and that patients always preferred tablets (33%). Compared with a previous sample, the current participants scored more favourably on a patient-centred attitude subscale (60.4% vs 63.5%, P = 0.034) and significantly fewer regarded LAIs as being stigmatising and old-fashioned. Reported LAI prescribing rates have decreased in the last 5 years despite an SGA-LAI becoming available and most clinicians regarding LAIs as effective. Most attitudes and knowledge have remained stable although concerns about stigma with LAI use have decreased. Concerns about patient acceptance continue as do negative views about some aspects of LAI use; these may compromise medication choices offered to patients. [ABSTRACT FROM PUBLISHER]

Psychiatric nurses' attitudes to depots have only been explored in the UK. We conducted a cross-sectional attitudinal study for Hong Kong psychiatric nurses and also conducted international comparisons for nurses' views about depots. A pre-existing UK questionnaire on clinicians' attitudes and knowledge regarding depots was updated for the present study. Participants were 98 psychiatric nurses who attended an academic meeting. The majority of respondents had positive views regarding their role in depot administration; most reported that they had sufficient training (84%). However, many did not feel involved in treatment decision making (60%) and other negative views were expressed including: (1) most patients always prefer to have oral (vs. depot) (80%); and (2) force is sometimes required when administering a depot (40%). Interestingly, most reported that patients' friends and family were more accepting of depot (vs. oral) (69%). When compared with a former sample of London community psychiatric nurses, Hong Kong nurses had less favourable patient-focussed attitudes (mean 56% vs. 60%, P = 0.051) and depot-specific attitudes regarding depots (mean 63% vs. 69%, P < 0.001). In conclusion, therefore, international variation exists and encompasses clinical practice aspects for both the patient and the depot formulation per se. Our participants wanted more involvement in treatment decision making. [ABSTRACT FROM AUTHOR]

Antipsychotic drugs can be of great benefit in a range of psychiatric disorders, including schizophrenia and bipolar disorder, but all are associated with a wide range of potential adverse effects. These can impair quality of life, cause stigma, lead to poor adherence with medication, cause physical morbidity and, in extreme cases, be fatal. A comprehensive overview of tolerability requires a review of all available data, including randomised controlled trials (RCTs), observational studies and postmarketing surveillance studies. Assessing the relative tolerability of atypical antipsychotics is hampered by the paucity of RCTs that compare these drugs head-to-head, and limited and inconsistent reporting of adverse effect data that makes cross-study comparisons difficult. Despite methodological problems in assessment and interpretation of tolerability data, important differences exist between the atypical antipsychotics in the relative risk of acute extrapyramidal symptoms (highest risk: higher doses of risperidone), hyperglycaemia and dyslipidaemia (highest risk: clozapine and olanzapine), hyperprolactinaemia (highest risk: amisulpride and risperidone), prolongation of heart rate-corrected QT interval (QTc) [highest risk: ziprasidone and sertindole] and weight gain (highest risk: clozapine and olanzapine). Sedation, antimuscarinic symptoms, postural hypotension, agranulocytosis and seizures are more common with clozapine than with other atypical antipsychotics. The variation in their tolerability suggests that it is misleading to regard the atypical antipsychotics as a uniform drug class, and also means that the term 'atypical antipsychotic' has only limited usefulness. Differences between the atypical agents in terms of efficacy and pharmacodynamic profiles also support this view. As tolerability differs between specific conventional and atypical drugs, we conclude that broad statements comparing the relative risk of specific adverse effects between 'atypical' and 'conventional' antipsychotics are largely meaningless; rather, comparisons should be made between specific atypical and specific conventional drugs. Adverse effects are usually dose dependent and can be influenced by patient characteristics, including age and gender. These confounding factors should be considered in clinical practice and in the interpretation of research data. Selection of an antipsychotic should be on an individual patient basis. Patients should be involved in prescribing decisions and this should involve discussion about adverse effects. [ABSTRACT FROM AUTHOR]

Background: The prevalence of psychosis has been shown to be disproportionately high amongst sexual and gender minority individuals. However, there is currently little consideration of the unique needs of this population in mental health treatment, with LGBTQA+ individuals facing barriers in accessing timely and non-stigmatising support for psychotic experiences. This issue deserves attention as delays to help-seeking and poor engagement with treatment predict worsened clinical and functional outcomes for people with psychosis. The present protocol describes the methodology for a scoping review which will aim to identify barriers and facilitators faced by LGBTQA+ individuals across the psychosis spectrum in help-seeking and accessing mental health support., Methods: A comprehensive search strategy will be used to search Medline, PsycINFO, Embase, Scopus, LGBTQ+ Source, and grey literature. Original studies of any design, setting, and publication date will be included if they discuss barriers and facilitators to mental health treatment access and engagement for LGBTQA+ people with experiences of psychosis. Two reviewers will independently screen titles/abstracts and full-text articles for inclusion in the review. Both reviewers will then extract the relevant data according to pre-determined criteria, and study quality will be assessed using the Joanna Briggs Institute (JBI) critical appraisal checklists. Key data from included studies will be synthesised in narrative form according to the Guidance on the Conduct of Narrative Synthesis in Systematic Reviews., Discussion: The results of this review will provide a comprehensive account of the current and historical barriers and facilitators to mental healthcare faced by LGBTQA+ people with psychotic symptoms and experiences. It is anticipated that the findings from this review will be relevant to clinical and community services and inform future research. Findings will be disseminated through publication in a peer-reviewed journal and presented at conferences., Scoping Review Registration: This protocol is registered in Open Science Framework Registries ( https://doi.org/10.17605/OSF.IO/AT6FC )., (© 2024. The Author(s).)

Introduction: Maintenance antipsychotic treatment improves multiple outcomes in people with schizophrenia. These benefits are challenged by medication nonadherence, which is a common occurrence. Long-acting injectable antipsychotic (LAI) formulations were developed to reduce nonadherence and thereby improve outcomes. This narrative review is based on a PubMed search (January 2000 - August 2022) for studies on LAI antipsychotics., Areas Covered: Opportunities and challenges associated with LAIs are reviewed. Advantages, compared to oral antipsychotics (OAs), include improved adherence, reduced relapse and hospitalization risk, delayed and lower relapse risk after stopping treatment, and the ability to differentiate true treatment resistance from 'pseudo'-resistance. Additionally, LAIs are associated with lower all-cause mortality than OAs. LAIs are under-used in many services, partly reflecting negative attitudes, misconceptions, and lack of knowledge among clinicians, patients, and carers. Practical barriers to LAI use include acquisition costs and inadequate service structures to administer/monitor LAI treatment., Expert Opinion: The education and engagement of clinicians, patients and caregivers can assist more informed decision-making regarding LAIs. Future research regarding LAIs should encompass multiple complementary designs, focus on functionality and recovery outcomes, and include groups at high risk of relapse, including those with comorbid substance use disorders and early in the course of schizophrenia.

Introduction: While there is considerable published evidence regarding the nature and severity of Selective Serotonin Reuptake Inhibitor (SSRI) discontinuation symptoms in the adult population, information relating to the child and adolescent population remains scarce. This narrative review examined the published literature on SSRI withdrawal symptoms in the under-18-year-old age group. MEDLINE and PsycINFO were comprehensively searched from inception to 5 May 2023., Areas Covered: This review highlights the importance of recognizing SSRI withdrawal in children and adolescents and summarizes available literature and guidelines for safe discontinuation., Expert Opinion: Evidence of the presence of SSRI withdrawal phenomenon in children and adolescents mainly originates from case reports and extrapolated adult data. Existing data on SSRI withdrawal syndrome in children and adolescents is therefore limited, and there is a need for formal research in this specific population to establish with more certainty the nature and extent of SSRI withdrawal syndrome. Nevertheless, there is currently enough evidence available for prescribing clinicians to provide psychoeducation to patients and families about the possibility of withdrawal symptoms when SSRI treatment is considered. The need for gradual and planned discontinuation should also be discussed for safe withdrawal.

Background and Objectives: Perceived stigma related to infectious diseases is of public health importance and can adversely impact patients' physical and mental health. This study aims to identify the level of perceived stigma among COVID-19 survivors in Qatar and investigate its predictors., Methods: An analytical cross-sectional design was employed. Four hundred and four participants who had a positive COVID-19 PCR test were randomly selected from medical records. The selected participants were interviewed to collect sociodemographic and health-related information. Perceived stigma was assessed using the COVID-19 perceived stigma scale-22 (CPSS-22) that was developed by the researchers. A descriptive analysis followed by a bivariate analysis investigated possible associations between the perceived stigma levels and independent variables. A multivariable analysis was performed using logistic regression to identify any significant associations with perceived stigma. The validity and reliability of the developed tool were also tested., Results: The prevalence of COVID-19 perceived stigma was twenty-six percent ( n  = 107, 26.4%) at 95% CI [22.4-30.4]. Factors associated with higher COVID-19 perceived stigma were male gender, being a manual worker, non-Arabic ethnicity, low educational level, living alone, and being isolated outside the home. However, only occupation, ethnicity, and low educational level predicted COVID-19 perceived stigma in multivariable analysis. The CPSS-22 showed excellent reliability (Cronbach's alpha 0.92)., Conclusion: Perceived stigma was relatively common among participants. Designing programs and interventions targeting male manual workers and those of low-educational levels may assist policymakers in mitigating the stigma related to COVID-19., Competing Interests: In the last 3 years, PMH has received fees for lecturing from Janssen, Newbridge Pharmaceuticals, and Otsuka. Other authors declared no potential conflicts of interest with respect to the research, authorship, and publication of this article., (© 2022 Asociación Universitaria de Zaragoza para el Progreso de la Psiquiatría y la Salud Mental. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Prevalence trends from Arabic speaking countries on psychiatric symptoms before and after the first wave of the COVID-19 pandemic are lacking. We estimated the point prevalence and change in depression and anxiety symptoms scores in relation to sociodemographic variables following the resolution of the first wave in Qatar compared with before the pandemic., Methods: We conducted a trend analysis using repeated nationally representative cross-sectional surveys spanning 2017, 2018, 2020/2021 and using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) to assess depressive and anxiety symptoms. Negative binomial regression was used to model changes in these symptoms in relation sociodemographics and survey year., Results: The two-week prevalence of depressive symptoms (≥10 on the PHQ-9) was 6.6% in 2017 and 6.5% in 2020/2021 (p = 0.986). The two-week prevalence of anxiety symptoms (≥10 on the GAD-7) was 3.6% in 2018 and 5.1% in 2020/2021 (p = 0.062). The data for 2020/21 showed a 35.1% and 29.2% decrease in depression and anxiety symptoms scores compared to pre-pandemic years (2017/2018) after adjusting for sociodemographic factors., Limitations: Screening tools rather than structured interviews were used to assess depressive and anxiety symptoms CONCLUSIONS: The prevalence of depression and anxiety after the first COVID wave did not differ significantly to pre-pandemic estimates. The end of the first wave of the pandemic weakened the associations of these symptoms with traditional sociodemographic risk factors. The 2020/21 depression and anxiety symptoms scores remained high for Qataris and Arabs, suggesting that these cultural groups may benefit most from public mental health interventions., (Crown Copyright © 2022. Published by Elsevier B.V. All rights reserved.)

WHAT IS KNOWN ON THE SUBJECT?: There is only limited information on how the COVID-19 pandemic has affected people diagnosed with mental health disorders, especially people admitted to psychiatric wards. We surveyed the views of inpatients at Qatar's only psychiatric hospital regarding how the pandemic had affected their mental health and social changes they had experienced during the pandemic. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: Nearly half (43%) of those who completed the survey reported that the pandemic had led to a deterioration in their mental health. Those who reported deterioration in their mental health during the pandemic were significantly more likely to have experienced negative social changes during the pandemic. Examples included increased stress from the home and reduced ability to discuss emotions/feelings with family members. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Mental health services need to ensure ongoing support for patients during and after the pandemic. Mental health nurses have a pivotal role including identifying early warning signs of relapse of mental disorders, delivering talking treatments and providing practical advice and COVID-19-related education. Further work is needed to assess the views of people diagnosed with mental health problems in different countries and at a different time point during the pandemic. ABSTRACT: Introduction The impact of the COVID-19 pandemic on people under the care of mental health services has received relatively little attention in the scientific literature. Aim To assess psychiatric inpatients' views regarding their mental health and experience of social change during the pandemic. Method Cross-sectional survey of consecutive patients admitted to Qatar's only psychiatric hospital between mid-June and mid-October 2020. Results Data were analysed for 114/284 (40%) patients admitted during the study period. 8 (7%) reported a history of COVID-19. 43% reported that the pandemic had led to deterioration in their mental health, 11% to an improvement and 39% that there had been no attributable change. Those reporting worsened mental health, attributable to the pandemic, were significantly more likely to report having experienced four negative social changes during the pandemic, namely reduced ability to discuss emotions/feelings with family members, decreased time spent exercising, decreased time spent relaxing and increased stress from the home. Demographic factors did not distinguish those reporting worsened mental health from those whose mental health was improved or unchanged. Discussion A large proportion of psychiatric inpatients reported negative social and mental health changes during the pandemic. However, the study cannot determine causality. Implications for practice Mental health services should consider the psychological and social aspects of people's lives, including their interactions with family, friends and the community. This is especially relevant during the COVID-19 pandemic due to its wide impact on society. Interventions for people diagnosed with mental health disorders should address their psychological and social needs., (© 2021 John Wiley & Sons Ltd.)

WHAT IS KNOWN ON THE SUBJECT?: Smoking is more common among people with serious mental illness, and it contributes to a reduced life expectancy. Several Western countries have successfully introduced smoke-free policies in inpatient mental health units. There is virtually no information about attitudes to smoking bans in mental health units from countries in the Middle East and North Africa region. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: We surveyed mental health professionals working in Qatar's main mental health service to determine support for and attitudes towards a proposed total smoking ban in psychiatric wards. Most staff who completed the survey supported an inpatient smoking ban. However, further analysis, both quantitative and qualitative, showed markedly ambivalent attitudes, that is staff simultaneously held attitudes that supported and opposed a smoking ban. Professionals who did not support a ban were more likely to have not received smoking cessation training in the last 5 years, to be a psychiatrist rather than a nurse or allied mental health professional, to be current smokers and to be a Middle Eastern and North African national. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Further staff training is necessary to achieve more consistent attitudes that support a total smoking ban and increase the likelihood of successful implementation. The attitudes in this study showed similarities and differences to those reported for mental health professionals in Western countries. This highlights that local research is necessary to help shape training and successfully implement smoke-free policies. ABSTRACT: Introduction Despite the fact that patients with serious mental illness (SMI) have high rates of smoking and an increased standardized mortality, there is virtually no information about attitudes to smoking bans in mental health units from countries in the Middle East and North Africa region. Aim To assess support for, and attitudes towards, a proposed total smoking ban in psychiatric wards among mental health clinicians in Qatar. Method Cross-sectional survey of mental health professionals working in Qatar's primary mental health service. Results The response rate was 68% (353/520). Support for a ban was assessed with a single-item question; 73% of respondents supported a ban with opposition significantly (p < .05) associated with being a current smoker, a Middle Eastern and North African (MENA) national, a psychiatrist versus a mental health nurse or allied health professional and not receiving smoking cessation training in the last 5 years. A 21-item questionnaire assessed attitudes to a total smoking ban. It showed marked ambivalence with multiple linear regression identifying MENA nationality, male gender and current smoking status as independent variables influencing attitudes. The most strongly held attitude supporting a ban was concern about passive smoking and against a ban was concern it may increase patient agitation. Qualitative data confirmed ambivalent views. Discussion The results show similarities and differences to research from other countries suggesting that cultural factors influence some attitudes to smoke-free policies. Implications for Practice Staff support and smoking cessation education are necessary to achieve more consistent staff attitudes to support smoke-free policies., (© 2021 The Authors. Journal of Psychiatric and Mental Health Nursing published by John Wiley & Sons Ltd.)

Rationale: Irritable bowel syndrome (IBS) is a chronic and debilitating functional disorder of the gastrointestinal tract manifested by abdominal pain and bowel habit dysregulation. The pathophysiology is complex and management targets symptom resolution. Therapeutic interventions range from dietary modification, psychological interventions, exercise, to the use of antispasmodics, antibiotics, and antidepressants. Anecdotal reports have suggested that buspirone may be beneficial in the treatment of functional dyspepsia and IBS and its physiological effect of reducing gastric tone provides a rational for its benefit., Patient Concerns: A 28-year-old man with unremarkable past medical and psychiatric history presented with worsening abdominal pain, bloating, and bowel movement dysregulation of over 6-year duration., Diagnoses: Physical examination revealed mild distension and discomfort on deep palpation. Thorough blood investigations, stool analysis and culture, and imaging were unremarkable except for the detection of mucus with stool. The patient was diagnosed with irritable bowel syndrome with mixed habits., Interventions: Dietary adjustment and a range of medications (mebeverine, simethicone, loperamide, rifaximin, sertraline and amitriptyline) yielded unsatisfactory response of were not tolerated. Buspirone was eventually introduced., Outcomes: Buspirone was associated with a significant and sustained improvement in IBS symptoms and quality of life., Lessons: This case suggests that buspirone was effective in treating refractory IBS. Further research is needed to assess the role of buspirone in IBS management., Competing Interests: Competing interests: PMH reports personal fees from Janssen, Lundbeck, Otsuka, NewBridge Pharmaceuticals, and Sunovion, outside the submitted work. The other authors report no conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Delirious mania (the coexistence of delirium and mania) is described in the literature but not recognised in standard nosologies. We report a woman in her late 30s, with no psychiatric history, who presented with concurrent symptoms of mania and delirium. She was diagnosed with COVID-19 pneumonia (positive reverse transcription-PCR test). There was no history of substance misuse or concurrent medical illness. CT head scan was normal as were blood investigations, other than elevated inflammatory markers. She received standard treatment for COVID-19 pneumonia and lorazepam and quetiapine to treat her neuropsychiatric symptoms. She made a full recovery after 9 days. She was apyrexial with normal oxygen saturation throughout her illness. The case shows that severe neuropsychiatric symptoms can complicate otherwise mild COVID-19 pneumonia with neuroinflammation being a possible mechanism. A diagnosis of delirious mania appears to better capture the complexity of the presentation than a diagnosis of mania or delirium alone., Competing Interests: Competing interests: PMH reports personal fees from Janssen, NewBridge Pharmaceuticals and Otsuka, outside the submitted work., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Coronavirus disease 2019 (COVID-19) was first recognised in December 2019. The subsequent pandemic has caused 4.3 million deaths and affected the lives of billions. It has increased psychosocial risk factors for mental illness including fear, social isolation and financial insecurity and is likely to lead to an economic recession. COVID-19 is associated with a high rate of neuropsychiatric sequelae. The long-term effects of the pandemic on mental health remain uncertain but could be marked, with some predicting an increased demand for psychiatric services for years to come. COVID-19 has turned a spotlight on mental health for politicians, policy makers and the public and provides an opportunity to make mental health a higher public health priority. We review longstanding reasons for prioritising mental health and the urgency brought by the COVID-19 pandemic, and highlight strategies to improve mental health and reduce the psychiatric fallout of the pandemic.

Background: Dose reduction of antipsychotic maintenance treatment in individuals with schizophrenia could be desirable to minimise adverse effects, but evidence for this strategy is unclear. We aimed to compare risks and benefits of reduced versus standard doses of antipsychotics., Methods: We searched Embase, Medline, PsycINFO, and the Cochrane Library from database inception until June 17, 2020, for randomised trials in adults with schizophrenia or schizoaffective disorder lasting at least 24 weeks, including individuals clinically stable at baseline, and comparing at least two doses of the same antipsychotic, excluding trials in first-episode psychosis or treatment-resistant schizophrenia. We compared low-dose (within 50-99% of the lower limit of the standard dose) and very-low dose (less than 50% of the lower limit) with standard dose, defined as doses higher than the lower limit of the treatment dose recommended by the International Consensus Study. Data from published reports on number of participants, treatment, sex, age, number of events, and changes in psychopathology scores were extracted independently by at least two authors. Investigators or sponsors were contacted by email to obtain missing information regarding outcomes. Co-primary outcomes were relapse and all-cause discontinuation. Study-level data were meta-analysed using random-effects models, calculating risk ratios (RRs) for dichotomous data, and Hedges' g for continuous data. The protocol was registered with OSF registries., Findings: 7853 references were identified in the database search and one additional reference from a manual review of relevant studies. 5744 abstracts were assessed for eligibility, and 101 references were assessed for full-text review. Of these, 79 were excluded for a variety of reasons, resulting in 22 studies being included in the meta-analysis, reporting on 24 trials and 3282 individuals. Study participants had a median age of 38 years (IQR 36-40) with 2166 (65·9%) males and 1116 (34·0%) females. Compared with standard dose, low dose increased the risk of relapse by 44% (16 trials, 1920 participants; RR 1·44, 95% CI 1·10-1·87; p=0·0076; I 2 =46%) and the risk of all-cause discontinuation by 12% (16 trials, 1932 participants; RR 1·12, 1·03-1·22; p=0·0085; I 2 =0%). Very low dose increased the risk of relapse by 72% (13 trials, 2058 participants; RR 1·72, 95% CI 1·29-2·29; p=0·0002; I 2 =70%) and all-cause discontinuation by 31% (11 trials, 1866 participants; RR 1·31, 1·11-1·54; p=0·0011; I 2 =63%). Compared with low dose, very low dose did not significantly increase the risk of relapse (five trials, 686 participants; RR 1·31, 95% CI 0·96-1·79; p=0·092; I 2 =51%) or all-cause discontinuation (five trials 686 participants; RR 1·11, 95% CI 0·95-1·30; p=0·18; I 2 =43%). Subgroup analyses comparing double-blind versus open-label studies, first-generation versus second-generation antipsychotics, and oral versus long-acting injectable antipsychotics were consistent with the overall results. Most studies were classified as having some concerns in the risk of bias assessment, which was mainly caused by absence of publicly available study registrations., Interpretation: During maintenance treatment in multi-episode schizophrenia, antipsychotic doses should probably not be reduced below the standard dose range recommended for acute stabilisation, because reducing the dose further is associated with an increased risk of both relapse and all-cause discontinuation., Funding: None., Competing Interests: Declaration of interests Since 2018, PMH has received honoraria for lecturing and consultancy from Janssen, Lundbeck, NewBridge Pharmaceuticals, Otsuka and Sunovion. Since 2018, JCN has received honoraria for consultancy from Janssen and Lundbeck. Since 2018, CUC reports personal fees from Acadia, Alkermes, Allergan, Angelini, Axsome, Gedeon Richter-Recordati, Gerson Lehrman Group, IntraCellular Therapies, Janssen and Johnson & Johnson, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Neurocrine, Noven, Otsuka, Pfizer, Rovi, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva; personal fees from Bristol-Myers Squibb, Janssen, and Otsuka; royalties from UpToDate; and stock options from LB Pharma, outside of the submitted work. MH and AFK declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Global COVID-19 pandemic containment necessitates understanding the risk of hesitance or resistance to vaccine uptake in different populations. The Middle East and North Africa currently lack vital representative vaccine hesitancy data. We conducted the first representative national phone survey among the adult population of Qatar, between December 2020 and January 2021, to estimate the prevalence and identify potential determinants of vaccine willingness: acceptance (strongly agree), resistance (strongly disagree), and hesitance (somewhat agree, neutral, somewhat disagree). Bivariate and multinomial logistic regression models estimated associations between willingness groups and fifteen variables. In the total sample, 42.7% (95% CI: 39.5-46.1) were accepting, 45.2% (95% CI: 41.9-48.4) hesitant, and 12.1% (95% CI: 10.1-14.4) resistant. Vaccine resistant compared with hesistant and accepting groups reported no endorsement source will increase vaccine confidence (58.9% vs. 5.6% vs. 0.2%, respectively). Female gender, Arab ethnicity, migrant status/type, and vaccine side-effects concerns were associated with hesitancy and resistance. COVID-19 related bereavement, infection, and quarantine status were not significantly associated with any willingness group. Absence of or lack of concern about contracting the virus was solely associated with resistance. COVID-19 vaccine resistance, hesitance, and side-effects concerns are high in Qatar's population compared with those globally. Urgent public health engagement should focus on women, Qataris (non-migrants), and those of Arab ethnicity.

Background: Restless Legs Syndrome (RLS) is a sensorimotor disorder characterized by unpleasant and distressing sensations in the lower limbs that are more pronounced in the evening, commence or worsen at rest, and show partial or complete relief following movement. It can occur as a primary disorder, secondary to medical conditions or treatment with medications including but not limited to antidepressants or antipsychotics., Case Presentation: A 32-year old man with major depressive disorder showed partial response to Escitalopram 10 mg daily. Agomelatine 25 mg at night was added to Escitalopram to treat his residual depressive symptoms, namely insomnia and tiredness. Within two days he developed restlessness and unpleasant sensations in his legs which were worse at night. Symptom severity increased over the following days, prompting an urgent consultation a week later. The patient's presentation met the criteria for RLS. Agomelatine was discontinued leaving the patient on Escitalopram alone. The patient's symptoms improved within 24 h of stopping Agomelatine, with complete resolution four days later. There was no recurrence of RLS during follow-up. The patient scored 6 on Naranjo's adverse drug reaction probability scale, indicating a probable adverse drug reaction caused by Agomelatine., Conclusions: To the best of our knowledge, this is the first case report of suspected Agomelatine-induced RLS. Clinicians need to be aware of RLS to enable prompt diagnosis and management. We suggest adding Agomelatine to the list of agents that can potentially induce RLS.

Background: Patients with schizophrenia are at least twice as likely to develop diabetes mellitus compared to the general population. This is of significance in Qatar given the high prevalence of obesity and diabetes. Furthermore, the lifespan of people with schizophrenia is shortened by approximately 15 years, partly due to long-term microvascular and macrovascular complications. High quality diabetes care can significantly reduce morbidity and mortality. We assessed the level of diabetes care delivered to patients in Qatar with schizophrenia and diabetes compared to those with diabetes alone., Methods: We performed a retrospective chart review of patients with diabetes mellitus with (n = 73) and without (n = 73) schizophrenia. Demographic information and electronic medical records were reviewed to determine adherence to American Diabetes Association standards of diabetes care in the last 6 and 12 months. Optimal diabetes care was defined as having completed glycated hemoglobin (HbA1c), lipid profile and retinal examination within 12 months., Results: Optimal diabetes care was significantly lower in patients with schizophrenia and diabetes compared to diabetes alone [26.0% (n = 19/73) vs 52.1% (n = 38/73), p = 0.002]. Patients with diabetes and schizophrenia were also significantly less likely to have had body mass index recorded within 6 months (p = 0.008) and HbA1c (p = 0.006), lipid profile (p = 0.015), estimated glomerular filtration rate (eGFR) (p = 0.001) and order for retinal examination (p = 0.004) over 12 months. After adjusting for multiple comparisons, only assessment of eGFR (p = 0.01) and order for retinal examination (p = 0.04) remained significant., Conclusion: Patients in Qatar with schizophrenia and diabetes, receive sub-optimal diabetes care compared to those with diabetes alone.

A 30-year-old man with no significant previous or family psychiatric history became severely anxious about his health after a positive COVID-19 test. Physical symptoms of COVID-19 were mild, with no evidence of hypoxia or pneumonia, throughout his illness. He was admitted to a quarantine facility. He remained highly anxious, and 1 week later, he developed paranoid delusions and auditory hallucinations (his first psychotic episode). He was treated with lorazepam 1 mg four times a day, mirtazapine 30 mg nocte and risperidone 1 mg two times a day. His psychotic symptoms lasted 1 week. He stopped psychiatric medication after 4 weeks and had remained well when reviewed 3 months later. A Diagnostic and Statistical Manual of Mental Disorders fifth edition diagnosis of brief psychotic disorder with marked stressor (brief reactive psychosis) was made. Anxiety about his health and social isolation appeared the main aetiological factors but an inflammatory component cannot be excluded. The case highlights that first episode psychosis can be associated with mild COVID-19., Competing Interests: Competing interests: PMH reports personal fees from Janssen, Lundbeck, Otsuka, NewBridge Pharmaceuticals and Sunovion, outside the submitted work., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

NMDA autoantibody encephalitis presenting as schizophrenia suggests the possible role of adaptive cell-mediated immunity in idiopathic schizophrenia. However, to our knowledge there have been no trials of the immune-suppressant methotrexate in schizophrenia. We tested if low-dose methotrexate as used in the treatment of systemic autoimmune disorders would be tolerable and effective in people with schizophrenia in a feasibility study. Ninety-two participants within 5 years of schizophrenia diagnosis were recruited from inpatient and outpatient facilities in Karachi, Pakistan. They were randomised to receive once weekly 10-mg oral methotrexate (n = 45) or matching placebo (n = 47) both with daily 5-mg folic acid, in addition to treatment as usual for 12 weeks. There were eight dropouts per group. Side effects were non-significantly more common in those on methotrexate and were not severe. One person developed leukopenia. Positive symptom scores improved more in those receiving methotrexate than placebo (β = -2.5; [95% CI -4.7 to -0.4]), whereas negative symptoms were unaffected by treatment (β = -0.39; [95% CI -2.01 to 1.23]). There were no immune biomarkers but methotrexate did not affect group mean leucocyte counts or C-reactive protein. We conclude that further studies are feasible but should be focussed on subgroups identified by advances in neuroimmune profiling. Methotrexate is thought to work in autoimmune disorders by resetting systemic regulatory T-cell control of immune signalling; we show that a similar action in the CNS would account for otherwise puzzling features of the immuno-pathogenesis of schizophrenia.

Background: Reports of psychiatric morbidity associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection tend to be limited by geography and patients' clinical status. Representative samples are needed to inform service planning and research., Aims: To describe the psychiatric morbidity associated with SARS-CoV-2 infection (confirmed by real-time polymerase chain reaction) in referrals to a consultation-liaison psychiatry service in Qatar., Method: Retrospective review of 50 consecutive referrals., Results: Most patients were male. Median age was 39.5 years. Thirty-one patients were symptomatic (upper respiratory tract symptoms or pneumonia) for coronavirus disease 2019 (COVID-19) and 19 were asymptomatic (no characteristic physical symptoms of COVID-19 infection). Seventeen patients (34%) had a past psychiatric history including eight with bipolar I disorder or psychosis, all of whom relapsed. Thirty patients (60%) had physical comorbidity. The principal psychiatric diagnoses made by the consultation-liaison team were delirium (n = 13), psychosis (n = 9), acute stress reaction (n = 8), anxiety disorder (n = 8), depression (n = 8) and mania (n = 8). Delirium was confined to the COVID-19 symptomatic group (the exception being one asymptomatic patient with concurrent physical illness). The other psychiatric diagnoses spanned the symptomatic and asymptomatic patients with COVID. One patient with COVID-19 pneumonia experienced an ischaemic stroke. Approximately half the patients with mania and psychosis had no past psychiatric history. Three patients self-harmed. The commonest psychiatric symptoms were sleep disturbance (70%), anxiety (64%), agitation (50%), depressed mood (42%) and irritability (36%)., Conclusions: A wide range of psychiatric morbidity is associated with SARS-CoV-2 infection and is seen in symptomatic and asymptomatic individuals. Cases of psychosis and mania represented relapses in people with schizophrenia and bipolar disorder and also new onset cases.

Background: Patients with a diagnosis of schizophrenia are at an increased risk for developing metabolic syndrome, which is associated with greater cardiovascular morbidity and mortality. Treatment with some commonly used antipsychotic medications may increase the risk of developing metabolic syndrome. The aim of the study was to evaluate the safety of lurasidone in patients who continued lurasidone or switched from risperidone to lurasidone. A secondary aim was assessment of the effect of long-term lurasidone on the Positive and Negative Syndrome Scale (PANSS)., Methods: The treatment sample in the current study consisted of clinically stable patients with schizophrenia (N = 223) who had completed a 12-month, double-blind study of lurasidone vs. risperidone. In the current extension study, all patients received 6 months of open-label treatment with lurasidone, either continuing lurasidone assigned during the preceding double-blind trial, or switching from double-blind risperidone to lurasidone. Safety and tolerability parameters included body weight, prolactin, and metabolic laboratory tests., Results: Six months of OL treatment with lurasidone was generally well-tolerated, with a low incidence of parkinsonism (4.5%) and akathisia (3.1%). Overall, few adverse events were rated as severe (4.9%), and discontinuation due to an adverse event was low in the lurasidone continuation vs. risperidone switch groups (3.7% vs. 6.9%). In the lurasidone continuation versus risperidone switch groups, change from OL baseline to 6-month endpoint (observed case) was observed in mean body weight (- 0.6 vs. -2.6 kg), median total cholesterol (- 4.0 vs. + 4.5 mg/dL), triglycerides (- 4.5 vs. -5.5 mg/dL), glucose (0.0 vs. -3.0 mg/dL) and prolactin (males, + 0.15 vs. -11.2 ng/mL; females, + 1.3 vs. -30.8 ng/mL). Improvement in PANSS total score was maintained, from OL baseline to endpoint in the continuation vs. switch groups (+ 1.0 vs. -1.0; OC)., Conclusions: In this 6-month extension study, lurasidone treatment was generally well-tolerated and associated with minimal effects on weight, metabolic parameters, and prolactin levels. Patients who switched from risperidone to lurasidone experienced reductions in weight, metabolic parameters and prolactin levels commensurate with increases in these safety parameters experienced during the previous 12 months of treatment with risperidone., Trial Registration: ClinicalTrials.gov NCT00641745 (Date of Registration: March 24, 2008).

These updated guidelines from the British Association for Psychopharmacology replace the original version published in 2011. They address the scope and targets of pharmacological treatment for schizophrenia. A consensus meeting was held in 2017, involving experts in schizophrenia and its treatment. They were asked to review key areas and consider the strength of the evidence on the risk-benefit balance of pharmacological interventions and the clinical implications, with an emphasis on meta-analyses, systematic reviews and randomised controlled trials where available, plus updates on current clinical practice. The guidelines cover the pharmacological management and treatment of schizophrenia across the various stages of the illness, including first-episode, relapse prevention, and illness that has proved refractory to standard treatment. It is hoped that the practice recommendations presented will support clinical decision making for practitioners, serve as a source of information for patients and carers, and inform quality improvement.

Background: Adolescent-onset psychosis is associated with more severe symptoms and poorer outcomes than adult-onset psychosis. The National Institute for Clinical Excellence (NICE) recommend that adolescents with first episode psychosis (FEP) should be offered a combination of antipsychotic medication (APs), cognitive behavioural therapy (CBT) and family intervention (FI). The evidence for APs in treating psychosis is limited in adolescents compared to adults. Nevertheless, it indicates that APs can reduce overall symptoms in adolescents but may cause more severe side effects, including cardiovascular and metabolic effects, than in adults. CBT and FI can improve outcomes in adults, but there are no studies of psychological interventions (PI) in patients under 18 years old. Given this limited evidence base, NICE made a specific research recommendation for determining the clinical and cost effectiveness of APs versus PI versus both treatments for adolescent FEP., Methods/design: The current study aimed to establish the feasibility and acceptability of conducting such a trial by recruiting 14-18-year-olds with a first episode of psychosis into a feasibility prospective randomised open blinded evaluation (PROBE) design, three-arm, randomised controlled trial of APs alone versus PI alone versus a combination of both treatments. We aimed to recruit 90 participants from Early Intervention and Child and Adolescent Mental Health Teams in seven UK sites. APs were prescribed by participants' usual psychiatrists. PI comprised standardised cognitive behavioural therapy and family intervention sessions., Discussion: This is the first study to compare APs to PI in an adolescent population with FEP. Recruitment finished on 31 October 2018. The study faced difficulties with recruitment across most sites due to factors including clinician and service-user treatment preferences., Trial Registration: Current controlled trial with ISRCTN, ISRCTN80567433 . Registered on 27 February 2017.

A number of effective maintenance medication options exist for bipolar disorder (BD) and these are regarded as the foundation of long-term treatment in BD. However, nonadherence to medication is common in BD. For example, a large data base study in the United States of America (USA) showed that approximately half of patients with BD were nonadherent with lithium and maintenance medications over a 12 month period. Such nonadherence carries a high risk of relapse due to the recurrent nature of the illness and the fact that abrupt cessation of treatment, particularly lithium, may cause rebound depression and mania. Indeed, medication nonadherence in BD is associated with significantly increased risks of relapse, recurrence, hospitalization and suicide attempts and a decreased likelihood of achieving remission and recovery, as well as with higher overall treatment costs. Factors associated with nonadherence include adverse effects of medication, complex medication regimens, negative patient attitudes to medication, poor insight, rapid-cycling BD, comorbid substance misuse and a poor therapeutic alliance. Clinicians should routinely enquire about nonadherence in a nonjudgmental fashion. Potential steps to improve adherence include simple pragmatic strategies related to prescribing including shared decision-making, psychoeducation with a clear focus on adherence, reminders (traditional and digital), potentially using a depot rather than an oral antipsychotic, managing comorbid substance misuse and improving therapeutic alliance. Financial incentives have been shown to improve adherence to depot antipsychotics, but this approach raises ethical issues and its long-term effectiveness is unknown. Often a combination of approaches will be required. The strategies that are adopted need to be patient specific, reflecting that nonadherence has no single cause, and chosen by the patient and clinician working together., Competing Interests: Conflict of interest statement: In the last 3 years PMH has received honoraria for lecturing or consultancy work from Allergan, Galen, Janssen, Lundbeck, NewBridge Pharmaceuticals, Otsuka, Sunovion and Teva plus conference support from Janssen, Lundbeck and Sunovion. In the last 3 years PST has received honoraria for attending Advisory Board meetings from Galen Limited; Sunovion Pharmaceuticals Europe Ltd; myTomorrows; LivaNova Ltd. In the last 3 years RHMW has received support for research, expenses to attend conferences and fees for lecturing and consultancy work (including attending advisory boards) from various pharmaceutical companies including Astra Zeneca, Cyberonics, Eli Lilly, Janssen, Liva Nova, Lundbeck, MyTomorrows, Otsuka, Pfizer, Roche, Servier, SPIMACO and Sunovion.

Schizophrenia is the eighth leading cause of disability worldwide in people aged 15-44 years. Before antidopaminergic antipsychotics were introduced in the 1950s, no effective medications existed for the treatment of schizophrenia. This review summarizes key meta-analytic findings regarding antipsychotic efficacy in the acute treatment of schizophrenia, including clozapine in treatment-resistant patients. In the most comprehensive meta-analysis of randomized controlled trials conducted in multi-episode schizophrenia, antipsychotics outperformed placebo regarding total symptoms, positive symptoms, negative symptoms, depressive symptoms, quality of life and social functioning. Amongst these outcomes, the standardized mean difference for overall symptoms was largest, that is, 0.47 (95% credible interval = 0.42-0.51), approaching a medium effect size, being reduced to 0.38 when publication bias and small-trial effects were accounted for. A comparison of two meta-analyses indicated that first-episode patients, compared with multi-episode patients, were more likely to have at least minimal treatment response [⩾20% Positive and Negative Syndrome Scale (PANSS)/Brief Psychiatric Rating Scale (BPRS) score reduction: 81% versus 51%] and good response (⩾50% PANSS/BPRS score reduction: 52% versus 23%). In multi-episode schizophrenia, no response or worsening after 2 weeks of a therapeutic antipsychotic dose was highly predictive of not achieving a good response at endpoint (median treatment = 6 weeks: specificity = 86%; positive predictive value = 90%), suggesting a change in treatment should be considered in such cases. In first-episode psychosis, adequately dosed antipsychotic treatment trials for more than 2 weeks are recommended before using no response or worsening as a decision point for aborting a given antipsychotic. In clearly defined treatment-resistant schizophrenia, clozapine generally outperformed other antipsychotics, especially when dosed appropriately (target = 3-6 months' duration; trough clozapine level ⩾350-400 μg/L) with a response rate (⩾20% PANSS/BPRS) of 33% by 3 months of treatment. High antipsychotic doses and psychotropic combinations are unlikely to be superior to standard doses of antipsychotic monotherapy. Acute antipsychotic efficacy in schizophrenia depends on the targeted symptom domain (greater efficacy: total and positive symptoms, lesser efficacy: negative symptoms, depressive symptoms, social functioning and quality of life). Greater antipsychotic efficacy is associated with higher total baseline symptom severity, treatment-naïveté/first-episode status, shorter illness duration, and trials that are nonindustry sponsored and that have a lower placebo effect. The heterogeneity of antipsychotic response across individuals and key symptom domains, the considerable degree of nonresponse/treatment resistance in multi-episode patients, and the adverse effect potential of antipsychotics are major limitations, underscoring the need to develop new medications for the treatment of schizophrenia. Drug development should include matching patient subgroups, which are identified by means of clinical and biomarker variables, to mechanisms of action of novel medications, targeting specific symptom domains, and investigating mechanisms of action other than dopaminergic blockade., Competing Interests: Conflict of interest statement: In the last 3 years, Dr Haddad has received honoraria for lecturing and consultancy work from Allergan, Galen, Janssen, Lundbeck, NewBridge Pharmaceuticals, Otsuka, Sunovion and Teva, plus conference support from Janssen, Lundbeck, NewBridge Pharmaceuticals and Sunovion. Dr Correll has been a consultant or advisor to or has received honoraria from Alkermes, Allergan, Gerson Lehrman Group, IntraCellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, Medavante, Medscape, Neurocrine, Otsuka, Pfizer, ROVI, Sunovion, Takeda, and Teva. He has provided expert testimony for Bristol-Myers Squibb, Janssen and Otsuka. He served on a Data Safety Monitoring Board for Lundbeck, Pfizer, Roche and ROVI. He received royalties from UpToDate and grant support from Janssen, Neurocrine and Takeda. He is also a shareholder of LB Pharma.

Background: Many modern pharmaceutical products were launched during 1950-1980, as reflected in advertisements in the British Medical Journal ( BMJ). One of the first therapeutic areas to benefit from novel effective medications was psychiatry., Methods: We examined BMJ advertising material between 1950 and 1980, including every other issue over six-month periods (October-March) in 1950/1951, 1955/1956, 1957/1958, 1960/1961, 1962/1963, 1965/1966, 1967/1968, 1970/1971, 1972/1973, 1975/1976, 1980/1981. We recorded numbers of adverts for all pharmaceutical products and for psychiatric drugs; we also recorded trade names, generic names and marketing company., Results: Advertising in BMJ peaked in the 1960s and declined markedly in the 1970s. Adverts for psychiatric drugs as a percentage of total pharmaceutical product advertising was broadly similar during 1955-1980, but with peaks in 1960/1961, 1970/1971 and 1975/1976, reflecting the entry of several novel compounds into the market. The peak marketing of antipsychotic drugs, sedatives and anxiolytic drugs was in 1960 and of antidepressants 1970. The time course of the rise of tricyclics and the switch from barbiturates to benzodiazepines can be seen. Drugs for psychiatry rose from ninth (1955/1956) to fourth (1975/1976) in terms of the number of products in the top 10 therapeutic areas. There is no evidence that they were advertised more aggressively (number of adverts/number of products)., Conclusions: The birth of modern psychopharmacology is reflected in th e advertising of psychiatric drugs in BMJ. Many drugs currently used, or their closely related successors, were launched in the early to mid-1960s. This rise in modern pharmaceuticals preceded several other major therapeutic areas.

Aims: To examine how pharmaceutical products that were first marketed between 1950 and 1980 were promoted to physicians through advertisements and briefly review advertising regulations and accuracy of the advertisements in the light of modern knowledge., Methods: We systematically reviewed advertisements promoting drugs for specific therapeutic areas, namely central nervous system disorders (anxiety and sleep disorders, depression, psychoses, and Parkinson's disease), respiratory disorders, cardiovascular disorders, and gastrointestinal disorders. We examined about 800 issues of the British Medical Journal (1950-1980) and about 150 issues of World Medicine (1965-1984)., Results: Advertising material was minimally regulated until the mid-1970s. Many drugs were marketed with little preclinical or clinical knowledge and some with the expectation that prescribers would obtain further data. The peak of advertising occurred in parallel with the surge in the release of novel drugs during the 1960s, but declined markedly after the mid-1970s. Advertisements generally contained little useful prescribing information. The period we investigated saw the release of many novel pharmaceuticals in the therapeutic areas we examined, and many (or their class successors) still play important therapeutic roles, including benzodiazepines, tricyclic antidepressants, phenothiazines, levodopa, selective and non-selective β-adrenoceptor antagonists, thiazide diuretics, β-adrenoceptor agonists, and histamine H 2 receptor antagonists., Conclusions: Advertising pharmaceuticals in the BMJ and World Medicine in 1950-1980 was poorly regulated and often lacked rigour. However, advertisements were gradually modified in the light of increasing clinical pharmacological knowledge, and they reflect an exciting period for the introduction of many drugs that continue to be of benefit today., (© 2018 The British Pharmacological Society.)