The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin concentration or activity in a systematic umbrella review of the principal relevant areas of research. PubMed, EMBASE and PsycINFO were searched using terms appropriate to each area of research, from their inception until December 2020. Systematic reviews, meta-analyses and large data-set analyses in the following areas were identified: serotonin and serotonin metabolite, 5-HIAA, concentrations in body fluids; serotonin 5-HT 1A receptor binding; serotonin transporter (SERT) levels measured by imaging or at post-mortem; tryptophan depletion studies; SERT gene associations and SERT gene-environment interactions. Studies of depression associated with physical conditions and specific subtypes of depression (e.g. bipolar depression) were excluded. Two independent reviewers extracted the data and assessed the quality of included studies using the AMSTAR-2, an adapted AMSTAR-2, or the STREGA for a large genetic study. The certainty of study results was assessed using a modified version of the GRADE. We did not synthesise results of individual meta-analyses because they included overlapping studies. The review was registered with PROSPERO (CRD42020207203). 17 studies were included: 12 systematic reviews and meta-analyses, 1 collaborative meta-analysis, 1 meta-analysis of large cohort studies, 1 systematic review and narrative synthesis, 1 genetic association study and 1 umbrella review. Quality of reviews was variable with some genetic studies of high quality. Two meta-analyses of overlapping studies examining the serotonin metabolite, 5-HIAA, showed no association with depression (largest n = 1002). One meta-analysis of cohort studies of plasma serotonin showed no relationship with depression, and evidence that lowered serotonin concentration was associated with antidepressant use ( n = 1869). Two meta-analyses of overlapping studies examining the 5-HT 1A receptor (largest n = 561), and three meta-analyses of overlapping studies examining SERT binding (largest n = 1845) showed weak and inconsistent evidence of reduced binding in some areas, which would be consistent with increased synaptic availability of serotonin in people with depression, if this was the original, causal abnormaly. However, effects of prior antidepressant use were not reliably excluded. One meta-analysis of tryptophan depletion studies found no effect in most healthy volunteers ( n = 566), but weak evidence of an effect in those with a family history of depression ( n = 75). Another systematic review ( n = 342) and a sample of ten subsequent studies ( n = 407) found no effect in volunteers. No systematic review of tryptophan depletion studies has been performed since 2007. The two largest and highest quality studies of the SERT gene, one genetic association study ( n = 115,257) and one collaborative meta-analysis ( n = 43,165), revealed no evidence of an association with depression, or of an interaction between genotype, stress and depression. The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration.

Background Peer support roles in mental health services are significantly increasing in the United Kingdom and internationally. However, there is wide variation in these roles and limited research exploring the ways in which Peer Support Workers (PSWs) are currently working. We aimed to explore: 1) the values underpinning the PSW role; 2) the distinctive features of the work that PSWs' do; and 3) the perceived impact of the PSW role. Methods We conducted semi-structured qualitative interviews with paid mental health PSWs working across a range of settings. We took a co-produced, participatory approach: interviews were carried out by researchers with lived experience of mental health conditions and data were analysed using collaborative methods, guided by general principles of thematic analysis. Results We interviewed 35 PSWs. Overarching themes identified from iterative analysis included: 1) Underpinning values: (i) Recovery is possible: fostering hope, role-modelling and encouraging change, (ii) Mutuality: sharing lived experiences to bring empathy and build connection, (iii) Person-centred approach: adapting ways of working to the individual, (iv) Empowering instead of'fixing'service users. 2) Distinctive features:The centrality of an individualised approach, facilitating recovery through sharing lived experiences and building connection. PSWs advocated for service-user needs and most worked in non-clinical ways, offering holistic, recovery-orientated support. Tensions could arise with more clinical approaches. 3) Impacts: Participants thought that peer support helped service users feel understood, leading to greater openness and facilitating recovery, although some felt that it may not be right for everyone. The role had benefits for participants' own recovery, although its emotional demands could lead to burnout. Participants felt that PSWs could bring systemic improvements to services and use their lived experience to help teams meet service user needs. Conclusion PSWs work in a range of ways, but, a unifying feature is a flexible, person-centred approach, facilitating recovery through shared lived experience. A range of potential benefits of peer work were identified for PSWs and for service users, as well as reports of positive systemic change. These could be facilitated by recovery-orientated models in services, space for shared learning with PSWs, and flexibility to incorporate PSWs'unique ways of working. Clinical trial number Not applicable.

Background Antipsychotic medication is beneficial for people with psychosis or schizophrenia in the short term, but the balance of risks and benefits in the long term is less clear. Many patients remain functionally impaired, experience significant and distressing side effects and physical health problems. Evidence in people with first episode psychosis suggests that social functioning may be improved for some patients following a gradual reduction or discontinuation of antipsychotics, but there is no evidence in people with recurrent conditions. Objectives To assess patients’ attitudes to long-term use of antipsychotic medication (work package 1a). To develop a gradual strategy of antipsychotic reduction and discontinuation and to design a trial to assess its benefits and harms (work packages 1a and 1b). To evaluate the antipsychotic reduction strategy in a randomised pilot trial (work package 2). To conduct a full randomised trial (work package 3a) of the antipsychotic reduction strategy in patients with multie pisode psychosis. To explore the experiences of people enrolled in the antipsychotic reduction strategy (work package 3b). Methods Design Objective 1: A mixed-methods survey of attitudes to long-term treatment and (work package 1a). Objective 2: Survey of attitudes to participation in a randomised trial, expert consultation, lived experience consultation, literature review, including a systematic review of definitions of relapse in previous trials of antipsychotics, focus groups (work packages 1a and 1b). Objectives 3 and 4: Multicentre, pragmatic, open, parallel group randomised controlled trial (with blinded assessors) (work packages 2 and 3a). Objective 5: qualitative study using semistructured interviews (work package 3b). Participants Patients with schizophrenia or recurrent, non-affective psychotic episodes, taking antipsychotics. Setting English community mental health services. Interventions A gradual strategy of antipsychotic reduction, with discontinuation where possible (evaluated in work packages 2 and 3, developed during work package 1). Main outcome measures In work package 1a: Patients’ views of antipsychotic medication and participation in a randomised trial of antipsychotic reduction. In work package 2: Recruitment rates and adherence to trial procedures. In work package 3a: Primary outcome was the Social Functioning Scale. The principal secondary outcome was severe relapse (admission to mental health inpatient care). Other outcomes included any relapse, symptoms, and a full economic analysis was performed. Results Work package 1a – 269 participants were interviewed. Only 33% were content with taking antipsychotic medication for long term, and 31% and 45% wished to try and stop or reduce it, respectively, with clinical support. Seventy-nine per cent indicated that they would or might be interested in taking part in a future trial. Work package 1b – Trial recruitment strategy and intervention protocol, procedures and adherence protocols were developed, along with definitions and procedures for determining relapse. The systematic review failed to identify a previous definition of relapse that was reliable, clinically relevant and feasibly to apply. Work package 2 – Recruitment was 65% of the projected target and the trial was approved to continue to a full trial. Work package 3a – 253 participants were randomised, 126 to supported reduction, 127 to maintenance antipsychotic treatment. At 24 months, there was no statistically significant difference between groups in change on the Social Functioning Scale (b: 0.19, 95% confidence interval −1.94 to 2.33, p = 0.859). The rate of severe relapse was significantly higher in the intervention group (25%) compared to the maintenance group (13%) (odds ratio, b: 2.39, 95% confidence interval 1.25 to 4.56). The risk of any relapse was also higher, but there was no difference in other outcomes. There were 93 serious adverse events in 49 individuals in the reduction arm (mostly admissions to hospital for a mental health relapse) and there were 64 in 29 individuals in the maintenance arm. In the economic analysis, at 24 months, there was no significant difference between the two arms in costs (£5619; 95% confidence interval −£386 to £11,625) or quality-adjusted life-years (−0.035, 95% confidence interval −0.125 to 0.054). There were significantly fewer years of full capability in the supported reduction arm (−0.103, 95% confidence interval −0.191 to −0.015). Work package 3b – 26 patients were interviewed. Analysis indicated that patients experienced improvements in adverse effects, social functioning and sense of self. However, some experienced increased symptoms, challenging emotional intensity and relapse. For some patients, supported medication reduction provided an opportunity for learning and empowerment. Work package 3c – 15 clinicians provided feedback on their experiences. They felt that antipsychotic reduction had been beneficial for some but had led to negative outcomes for other patients. Some reported that the trial enabled more collaborative relationships with patients. Limitations Recruitment was challenging, and some participants did not adhere to their randomised treatment programme. The number recruited was a small proportion of the number screened, which means the sample may differ from the general population of people considered likely to be suitable to take part in a trial of this sort. The COVID pandemic affected the social functioning measure. Conclusions Quantitative analysis showed that antipsychotic reduction and discontinuation over a period of months does not improve social functioning at 24 months, and increases the risk of severe relapse. There is a low probability that supported reduction is cost-effective compared to maintenance. In qualitative findings, patients and clinicians noted positive and negative effects of antipsychotic reduction. Future work Future work should include long-term follow-up of the trial cohort and investigation of more gradual reduction strategies. Trial registration The trial is registered as ISRCTN90298520 on 7 February 2017 and at ClinicalTrials.gov on 18 June 2018. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research Programme (NIHR award ref: RP-PG-0514-20004) and is published in full in Programme Grants for Applied Research; Vol. 14, No. 5. See the NIHR Funding and Awards website for further award information. Plain language summary Schizophrenia and other psychotic conditions are common and can cause considerable suffering. The widely established treatment is long-term antipsychotic medication, but this can cause harmful and unpleasant side effects. In this programme, we designed a ‘clinical trial’ to test the benefits and harms of helping people to gradually reduce and stop their antipsychotic medication. In the trial, people were randomly assigned to have their antipsychotic medication dose reduced or to continue on their current dose. We followed up people and assessed their ability to live their daily lives (social functioning) and other outcomes. In the first part of the research, we interviewed 269 patients and found that almost a third (31%) would welcome an opportunity to try to stop their antipsychotic medication with support from their psychiatrist. Just under half (45%) would like to reduce it. We enrolled 253 participants in the clinical trial and followed up 190 people 2 years later. At 2 years, there were no differences in social functioning between people who were assigned to antipsychotic reduction and those assigned to continue their antipsychotic treatment. People assigned to antipsychotic reduction were approximately twice as likely to have a severe relapse of their condition. At 2 years, there were no differences in the levels of symptoms or side effects. Antipsychotic reduction was more costly and did not lead to financial savings. In-depth interviews showed that people experienced some beneficial effects from reducing antipsychotics, including reduced side effects and increased empowerment, and some negative effects, including intense emotions, worsening of symptoms and relapse. Psychiatrists felt that antipsychotic reduction had been beneficial for some patients but had led to negative outcomes for others. Psychiatrists felt that the reduction process had enabled them to develop a more equal partnership with some patients. Scientific summary Background Antipsychotic medication suppresses acute symptoms and prevents relapse in the short term, but the balance of risks and benefits in the long term is less clear. Many patients remain functionally impaired, experience significant and distressing side effects and physical health problems, leading to dissatisfaction with treatment and non-adherence. Evidence in people with first episode psychosis suggests that social functioning may be improved for some patients following a gradual and supported reduction and discontinuation, but there is no evidence in people with recurrent psychotic conditions. Work package 1a Objective To explore patients’ attitudes to long-term use of antipsychotic medication and to reduction and discontinuation of antipsychotics. Methods Design A mixed-methods survey of attitudes to long-term treatment and willingness to participate in a randomised controlled trial (RCT) of an antipsychotic reduction programme. Participants Patients with schizophrenia or recurrent, non-affective psychosis, taking antipsychotics, aged ≥ 18 years with sufficient English to complete assessments, who have capacity to consent and are not legally compelled to take medication recruited from community mental health services in four London-based mental health trusts and general practices. Setting Community mental health services in four mental health Trusts in London and London-based general practices. Interventions A survey of attitudes to antipsychotics and antipsychotic reduction and discontinuation. Main outcomes Views about use of long-term antipsychotic medication, reduction and discontinuation of antipsychotic medication. Views about participation in a randomised trial of a clinically supported antipsychotic reduction strategy. Results A total of 269 participants with psychosis were interviewed. Of these, 31% wished to try and stop their antipsychotic with professional support, and 45% tried to reduce it. Only 33% were content with taking antipsychotic medication for long term. People who wanted to discontinue had more negative attitudes towards the medication but were otherwise similar to other participants. Wanting to stop or reduce medication was motivated mainly by adverse effects and health concerns. Professional support was identified as potentially helpful to achieve reduction. Seventy-nine per cent indicated that they would or might be interested in taking part in a future trial. Altruistic reasons were most commonly given for wanting to take part and concern about randomisation for not wanting to. Limitations The survey sample was influenced by clinician’s decisions to put people forward and patients’ interest and consent. The majority of participants had used antipsychotics for many years, so the sample does not necessarily reflect the views of shorter-term users. Conclusions A substantial proportion of people using long-term antipsychotics would like support to try to reduce their dose or discontinue treatment, mainly due to adverse effects. The survey was a useful recruitment strategy for the main trial even though fewer people eventually enrolled in the trial than had indicated they would be interested. Work package 1b Objectives To explore how antipsychotics should be reduced in clinical practise and how a trial could be designed to evaluate such a process. Methods Methods consisted of: expert consultation with national and international experts, lived experience consultation with the programme’s Lived Experience Advisory Committee members, literature review and focus groups with staff members from two London-based mental health trusts. These were conducted to inform trial design, recruitment and outcomes. A systematic review of relapse definitions in antipsychotic discontinuation trials was conducted. Results The systematic review failed to identify a previous definition of relapse that was reliable, clinically relevant and feasibly to apply. The trial recruitment strategy, the intervention protocol, procedures and monitoring protocols were developed. Eligibility criteria were determined and definitions and procedures for determining relapse were developed, including terms of reference for an end-point committee to assess non-severe relapses. Conclusions Procedures to conduct a randomised trial comparing gradual antipsychotic reduction and discontinuation with maintenance treatment were developed. Work package 2 Objective To ascertain whether a trial of a supported antipsychotic reduction programme is feasible. Methods Design Pilot trial of a multicentre, pragmatic, open, parallel group RCT of antipsychotic reduction in people with schizophrenia and recurrent psychotic conditions. Participants Patients with schizophrenia or recurrent, non-affective psychosis, aged ≥ 18 years, taking antipsychotics, with sufficient English to complete assessments, who have capacity to consent and are not legally compelled to take medication recruited from community mental health services in two London-based mental health trusts. Setting Two London-based mental health trusts. Intervention Evaluation of a strategy of gradual antipsychotic reduction and discontinuation overseen by a clinician. Outcomes Recruitment rate and feasibility of monitoring. Results The recruitment during the 4 months of the pilot trial was 65% of the projected target. Intervention monitoring was judged to be feasible. Conclusions The trial was approved to continue to a full trial. Work package 3a Some text in this section has been reproduced with permission from Moncrieff J, Crellin N, Stansfeld J, Cooper R, Marston L, Freemantle N, et al. Randomised controlled trial of antipsychotic dose reduction and discontinuation versus maintenance treatment in people with schizophrenia and other recurrent psychotic disorders in England (the RADAR trial). Lancet Psychiatry 2023;10:848–59. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) licence, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: https://creativecommons.org/licenses/by/4.0/. The text below includes minor additions and formatting changes to the original text. Objectives To evaluate the benefits and harms of an antipsychotic reduction programme compared to maintenance treatment in patients with multiepisode psychosis. Methods Design A full RCT of antipsychotic reduction in people with schizophrenia and recurrent psychotic conditions. Participants Patients with schizophrenia or recurrent, non-affective psychosis, taking antipsychotics, with sufficient English to complete assessments, who have capacity to consent and are not legally compelled to take medication recruited from community mental health services in 19 mental health trusts in England. Setting Community mental health services in 19 mental health trusts in England. Interventions A strategy of gradual antipsychotic reduction and discontinuation overseen by a clinician. Outcomes The primary outcome was social functioning at 24-month follow-up, measured using the Social Functioning Scale (SFS). The principal secondary outcome was severe relapse, which was defined as hospital admission for psychiatric inpatient treatment. An expert end-point committee was convened to assess the presence or absence of relapse more broadly, which was based on blinded information from clinical case-notes, using predefined criteria and guidance. Other secondary outcomes were mental state, measured by the Positive and Negative Syndrome Scale, quality of life, measured by the Manchester Short Assessment of quality of life, and the Objective Social Outcomes Index (SIX), which is derived from it. Adverse effects of antipsychotics were measured using a modified version of the Glasgow Antipsychotic Side-Effect Scale, body weight and sexual dysfunction using the Arizona Sexual Experiences Scale. Other assessments included the Questionnaire about the Process of Recovery, the Client Satisfaction Questionnaire and the Medication Adherence Report Scale. Neuropsychological function was measured using a brief battery of tests designed for this trial. Health economics outcome measures included the EuroQol-5 Dimensions, five-level version and the ICEpop CAPability measure for Adults. Results A total of 253 participants were randomised: 126 were assigned to antipsychotic dose reduction and 127 to maintenance. One hundred and ninety participants were interviewed at a 24-month follow-up. The difference between the groups on the primary outcome, the SFS, was small and not statistically significant (0.19, −1.9 to 2.3: Table a). Sensitivity analyses, including the degree of COVID-19 lockdown and predictors of missingness, did not change this. The time to severe relapse was shorter in the reduction group compared with the maintenance group [hazard ratio 2.2, 95% confidence interval (CI) 1.2 to 4.0, p = 0.007]. At 24 months, 32 participants (25.4%) in the reduction group had had at least 1 severe relapse compared with 17 (13.4%) of the maintenance group (odds ratio 2.2, 95% CI 1.2 to 4.2). Rates of non-severe and overall relapse were also higher in the reduction group. There was no difference in median bed-days between groups. TABLE aBaseline demographic and clinical characteristics of randomised trial participants Characteristic Antipsychotic dose reduction/discontinuation, maximum, N = 126 Antipsychotic maintenance treatment, maximum, N = 127 N n (%) or mean (SD) or median (IQR) N n (%) or mean (SD) or median (IQR) Male 126 85 (67.4%) 127 83 (65.3%) Female 126 40 (31.7%) 127 42 (33.1%) Transgender 126 1 (0.79%) 127 2 (1.6%) Age 126 Mean 46.6 (SD 12.2) 127 Mean 46.0 (SD 11.5) Marital status Single, separated, divorced, widowed 126 106 (84.1%) 127 110 (86.6%) Married, cohabiting, civil partnership 126 20 (15.9%) 127 17 (13.4%) Ethnicity White 126 89 (70.6%) 125 82 (65.6%) Black 126 25 (19.8%) 125 27 (21.6%) Asian 126 8 (6.3%) 125 8 (6.4%) Other 126 4 (3.2%) 125 8 (6.4%) First language English 126 107 (84.9%) 127 114 (89.8%) Highest educational achievement Primary and secondary education to age 16 years 125 49 (39.2%) 126 36 (28.6%) Primary and secondary education to age 18 years 125 22 (17.6%) 126 27 (21.4%) Tertiary or further education 125 40 (32.0%) 126 56 (44.4%) Other general education 125 14 (11.2%) 126 7 (5.6%) Years of completed education 121 Mean 14 (SD 3.3) 125 Mean 14 (SD 3.9) Employment Employed, voluntary or in education 126 38 (30.2%) 125 36 (28.8%) Not working or in education 126 88 (69.8%) 125 89 (71.2%) Length of time in contact with mental health services 0–3 years 126 11 (8.7%) 127 6 (4.7%) 4–10 years 126 34 (27.0%) 127 28 (22.0%) 11–15 years 126 20 (15.9%) 127 23 (18.1%) 16–20 years 126 20 (15.9%) 127 22 (17.3%) > 20 years 126 41 (32.5%) 127 48 (37.8%) Age when first referred to mental health services < 20 years 126 26 (20.6%) 127 27 (21.3%) 20–30 years 126 57 (45.2%) 127 67 (52.7%) 31–40 years 126 25 (19.8%) 127 22 (17.3%) ≥ 41 years 126 18 (14.3%) 127 11 (8.7%) Number of previous mental health admissions Median 3 (IQR 1–5) Median 3 (IQR 1–5) Recreational drugs used in the last month 126 11 (8.7%) 126 14 (11.1%) Alcohol use over the past month Once a month or less 126 80 (63.5%) 126 82 (65.1%) Two to four times a month 126 24 (19.0%) 126 20 (15.9%) Two or more times a week 126 22 (17.5%) 126 19 (19.0%) Antipsychotic medication dose in chlorpromazine equivalents 126 Median 300 (IQR 200–450) 127 Median 300 (IQR 200–400) Outcome measures at baseline SFS overall 123 Mean 107.7 (SD 8.6) 120 Mean 108.2 (SD 10.2) PANSS positive symptom subscale 124 Median 10 (IQR 8–14) 127 Median 11 (8–16) PANSS negative symptom subscale 124 Median 11 (IQR 9–15) 124 Median 11 (8–15) PANSS total 122 Median 48 (IQR 41–59) 123 Median 48 (IQR 40–61) MANSA 126 Mean 4.7 (SD 0.82) 127 Mean 4.6 (SD 0.83) SIX 125 Mean 3.4 (SD 1.3) 127 Mean 3.4 (SD 1.3) Modified GASS 105 Mean 27.6 (SD 15.2) 104 Mean 29.0 (SD 17.1) Body weight in kg 114 Mean 90.9 (SD 20.2) 116 Mean 89.7 (SD 19.1) CSQ-8 125 Median 20 (IQR 20–21) 122 Median 20 (IQR 19–21) MARS-5 124 Median 24 (IQR 22–25) 124 Median 25 (IQR 23–25) QPR-15 123 Mean 55.7 (SD 9.9) 122 Mean 56.6 (SD 10.0) ASEX 42 Mean 16.3 (SD 6.1) 39 Mean 15.5 (SD 5.0) Cognitive tests Digit span 124 Mean 14.8 (SD 4.5) 126 Mean 14.7 (SD 4.7) Digit symbol substitution 117 Mean 47.2 (SD 17.4) 121 Mean 47.3 (SD 18.2) Rey Auditory Verbal Learning 121 Mean 35.7 (SD 12.0) 120 Mean 36.1 (SD 12.4) Trail making 121 Median 45 (IQR 35–62) 121 Median 50 (IQR 36–64) Verbal fluency 124 Mean 16.5 (SD 4.9) 126 Mean 16.6 (SD 5.2) ASEX, Arizona Sexual Experience Scale; CSQ, Client Satisfaction Questionnaire; GASS, Glasgow Antipsychotic Side-Effect Scale; IQR, interquartile range; MANSA, Manchester Short Assessment of quality of life; MARS, Medication Adherence Report Scale; PANSS, Positive and Negative Syndrome Scale; QPR, Questionnaire about the Process of Recovery; SD, standard deviation. Other secondary outcomes showed no difference between the groups at 24 months, including measures of symptoms, quality of life, adverse effects scales, body weight and employment. The median dose reduction at any point during the trial was 67% in the reduction arm and 0% in the maintenance arm. At 24 months, it was 33% versus 0%. Thirty-four people (27.0%) randomised to reduction stopped their antipsychotic medication completely at some time during the 24-month follow-up period, and 13 (10.2%) of those randomised to maintenance treatment did so. Eighty-eight (69.8%) participants in the reduction group reduced their antipsychotic dose by 50% or more when compared with 21 (16.5%) of the maintenance participants. Serious adverse events were more common in the reduction group, largely due to a higher number of hospitalisations for relapse. There were no significant differences between arms in total costs for any perspectives. There were no significant difference in quality-adjusted life-years (−0.035, 95% CI −0.123 to 0.052), whereas years of full capability were significantly lower in the reduction arm compared to the maintenance arm (baseline-adjusted difference: −0.103, 95% CI −0.192 to −0.014). The reduction strategy was dominated by maintenance and was not likely to be cost-effective for all perspectives taken and outcomes employed. Limitations Recruitment was challenging, and some participants did not adhere to their randomised treatment programme. The COVID pandemic affected the social functioning measure. Conclusions The current trial provides data on the pros and cons of a gradual strategy of antipsychotic reduction and discontinuation in people with recurrent psychotic disorders. The findings demonstrate that a strategy of reducing and stopping antipsychotic medication over several months increases the risk of relapse compared with maintenance treatment but does not measurably improve social functioning or affect other clinical and social outcomes after 2 years. Further follow-up data will provide information about longer-term outcomes. Trial registration The trial is registered as ISRCTN90298520 on 7 February 2017 and at ClinicalTrials.gov on 18 June 2018. Work package 3b Some text in this section has been reproduced with permission from Morant N, Long M, Jayacodi S, Cooper R, Akther-Robertson J, Stansfeld J, et al. Experiences of reduction and discontinuation of antipsychotics: a qualitative investigation within the ‘RADAR’ trial. eClinicalMedicine 2023;64:102135. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) licence, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: https://creativecommons.org/licenses/by/4.0/. The text below includes minor additions and formatting changes to the original text. Objectives To explore the experiences of people enrolled in an antipsychotic reduction programme in a clinical trial. Methods Design Qualitative study using semistructured interviews. Participants Participants in the full trial in work package 3a who were randomised to the antipsychotic reduction arm. Setting Community mental health services involved in the randomised trial. Outcomes Qualitative data on patients’ experiences of antipsychotic reduction within the randomised trial. Results Twenty-six participants from the antipsychotic reduction arm of the trial were interviewed. Most reported reduced adverse effects of antipsychotics with dose reductions, primarily in mental clouding, emotional blunting and sedation, and some positive impacts on social functioning and sense of self. Over half experienced deteriorations in mental health, including psychotic symptoms and intolerable levels of emotional intensity. Nine had a psychotic relapse. The trial context in which medication reduction was explicitly part of clinical care provided various learning opportunities. Some participants were highly engaged with reduction processes, and despite difficulties, including relapses, they developed novel perspectives on medication, dose optimisation and how to manage their mental health. Others were more ambivalent about reduction or experienced less overall impact. Experiences of antipsychotic reductions over 2 years were dynamic and diverse, shaped by variations in dose reduction profiles, reduction effects, personal motivation and engagement levels, and relationships with prescribers. Relapse risks and challenges were apparent, but some people experienced medication reduction done with clinical guidance as empowering. Limitations The sample may have excluded people with more negative experiences. Conclusions Participants described both positive and negative effects of reducing antipsychotics. Some gained a deeper understanding of their condition and felt empowered to take a more active role in managing their medication. Work package 3c Objectives To explore clinician’s experiences of being involved in a trial of supported antipsychotic reduction. Methods Design Qualitative study using semistructured interviews. Outcomes Clinician’s experiences of taking part in a randomised trial of antipsychotic reduction. Results Fifteen psychiatrists were interviewed. They described the positive and negative effects of antipsychotic reduction. Some felt that the trial had enabled them to establish more collaborative relationships with patients. Limitations The sample may have excluded clinicians with more negative experiences. Conclusions Clinicians have mixed views about antipsychotic reduction. Trial registration The trial is registered as ISRCTN90298520 on 7 February 2017 and at ClinicalTrials.gov on 18 June 2018. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research Programme (NIHR award ref: RP-PG-0514-20004) and is published in full in Programme Grants for Applied Research; Vol. 14, No. 5. See the NIHR Funding and Awards website for further award information.

Inpatient mental health care is an integral part of the continuum of mental health care in many countries, though it can be associated with challenges, such as reliance on coercive practices, negative patient experiences, and limited therapeutic options. Given these issues, there is a growing interest in exploring alternative approaches for individuals experiencing a mental health crisis. This research aimed to identify models which offer an alternative to standard inpatient mental health care across all age groups, both nationally and internationally, and to develop a typology for these alternative models. A dual literature search and expert consultation research methodology was adopted to identify relevant models. Three typologies of models were developed according to age group and acuity, including: alternatives to standard acute inpatient services for adults; alternatives to longer-stay inpatient services for adults, including rehabilitation and forensic inpatient services; and alternatives to standard inpatient services for children and young people. We identified an array of service models in each typology, some in community settings, some hospital-based and some working across settings. Models varied greatly in characteristics, extent of implementation and supporting evidence. Through this mapping exercise, we have developed three novel typologies of alternatives to standard inpatient care. A range of community-based, hospital-based and cross-setting approaches were identified. The identification of services providing inpatient care in a substantially different way to the standard suggests that some improvements could be provided within existing structures. Potential inequities in access to alternatives were identified for certain groups, such as people who are compulsorily detained, younger children, and young people transitioning between children’s and adults' services. These typologies can inform future description, evaluation and comparison of different service models. This research also yields some key considerations for the design, development and implementation of alternative mental health service models and service arrays.

Obective: Ketamine and esketamine have been claimed to possess anti-suicidal effects and potentially to transform suicide prevention. This study provides an updated overview of evidence from clinical trials to establish whether ketamine or esketamine reduce death, suicides, suicide attempts or suicidal ideation, compared to active or inert placebo among people with psychiatric disorders. Design: Systematic review and meta-analysis. Data sources: We searched EMBASE, PubMed and PsycINFO from inception until 02.12.2025. Eligibility criteria for selecting studies: Eligible for inclusion were randomised controlled trials which compared the effect of ketamine or esketamine with active or inert placebo for the treatment of people with psychiatric disorders. We included trials with concomitant treatments and excluded those where ketamine/esketamine were used as anaesthics. Data synthesis and study quality: Data were synthesised with meta-analysis, including methods for double-zero events. Risk of bias was assessed using the Cochrane Risk of Bias Tool and quality of the evidence was evaluated using GRADE guidelines. Results: We included 73 trials with a total of 5671 participants. The majority of trials (56) examined ketamine, 16 esketamine, and 1 arketamine. Twelve of the ketamine trials were cross-over trials and the rest were parallel group trials. A single dose was used in 35 trials. Median length of treatment and follow-up was 45 days. Rates of suicidal behaviour were 1.63% for ketamine/esketamine and 1.72% for placebo, with the 95% credible interval including the null-effect, OR = 0.98 \[0.58 to 1.60\] (Bayesian Analysis with weak priors). There were 42 (1.43%) suicide attempts, 6 (0.20%) suicides and 9 (0.31%) deaths with ketamine/esketamine compared to 41 (1.64%), 2 (0.08%) and 5 (0.20%) on placebo. Ketamine/esketamine significantly reduced suicide ideation up to 4 weeks (standardized mean differences [SMD] at 12h to 24h of -0.31 [-0.45 to -0.18], I2 = 26%), but effects were small after 24 hours and dropped to near zero after 4 weeks. Subgroup analysis for suicide ideation revealed that effects of esketamine were close to zero after 24 hours whereas effects for ketamine were small to medium for the first 4 weeks. Effects tended to be larger in trials involving suicidal patients. Repeated dosings were not superior to single doses. Quality assessment revealed unreliable blinding, selective reporting and - especially for suicidal behaviour - imprecision, leading to low or very low certainty ratings for suicidal behaviour and low or moderate certainty ratings for suicide ideation. Conclusions: There is insufficient evidence for a preventive effect of ketamine/esketamine for suicidal behaviour. The observed immediate but short-term effect on suicide ideation may be overestimated due to unblinding bias. Our review is the most comprehensive on suicidality to date, however, more evidence is needed to draw conclusions on suicidal behaviour. Other: No specific funding was involved. The protocol was registered with PROSPERO (CRD42023364156). ### Competing Interest Statement All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/ and declare: CV, MP, RC, TW, VS no support from any commercial organisation for the submitted work and have no other conflicts of interest to declare; JM has received royalties for books about psychiatric drugs; MH received support from a clinical research fellowship at NELFT (NHS), royalties from the Maudsley Deprescribing Guidelines, and is a co-founder of Outro Health, a digital clinic in the US where he receives consulting fees. ### Clinical Protocols ### Funding Statement No funding was involved ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data used in this study will be made publicly available via the OSF upon publication in a journal.

Abstract Background The use of surveillance technologies is becoming increasingly common in inpatient mental health settings, commonly justified as efforts to improve safety and cost-effectiveness. However, their use has been questioned in light of limited research conducted and the sensitivities, ethical concerns and potential harms of surveillance. This systematic review aims to (1) map how surveillance technologies have been employed in inpatient mental health settings, (2) explore how they are experienced by patients, staff and carers and (3) examine evidence regarding their impact. Methods We searched five academic databases (Embase, MEDLINE, PsycInfo, PubMed and Scopus), one grey literature database (HMIC) and two pre-print servers (medRxiv and PsyArXiv) to identify relevant papers published up to 19/09/2024. We also conducted backwards and forwards citation tracking and contacted experts to identify relevant literature. The Mixed Methods Appraisal Tool assessed quality. Data were synthesised narratively. Results Thirty-two studies met the inclusion criteria. They reported on CCTV/video monitoring (n = 13), Vision-Based Patient Monitoring and Management (n = 9), body-worn cameras (n = 6), GPS electronic monitoring (n = 2) and wearable sensors (n = 2). Sixteen papers (50.0%) were low quality, five (15.6%) medium quality and eleven (34.4%) high quality. Nine studies (28.1%) declared a conflict of interest. Qualitative findings indicate patient, staff and carer views of surveillance technologies are mixed and complex. Quantitative findings regarding the impact of surveillance on outcomes such as self-harm, violence, aggression, care quality and cost-effectiveness were inconsistent or weak. Conclusions There is currently insufficient evidence to suggest that surveillance technologies in inpatient mental health settings are achieving their intended outcomes, such as improving safety and reducing costs. The studies were generally of low methodological quality, lacked lived experience involvement, and a substantial proportion (28.1%) declared conflicts of interest. Further independent coproduced research is needed to more comprehensively evaluate the impact of surveillance technologies in inpatient settings. If they are to be implemented, all key stakeholders should be engaged in the development of policies, procedures and best practice guidance to regulate their use, prioritising patients’ perspectives.

Objective: To examine the evidence and practice of antipsychotic dose reduction from the lens of biomedical ethics (specifically principlism) to support evidence-based practice and patient choice and self-determination. Methods: An overview of the evidence from randomized controlled trials of antipsychotic dose reduction versus maintenance is presented. This is followed by a theoretical examination of the four key biomedical ethical principles of autonomy, nonmaleficence, beneficence, and justice and how they apply in the case of antipsychotic dose reduction. Results: Existing clinical trial research is dominated by relapse as the primary outcome, with dose reduction associated with a higher risk of relapse than maintenance. Few studies have measured other patient-centered outcomes but have shown preliminary evidence for superior cognitive functioning, lower negative symptoms, and better functioning following dose reduction. Respect for autonomy is a cornerstone of psychiatric rehabilitation, and this includes the right of people to choose to reduce or discontinue antipsychotic medication. Reduced capacity for treatment decision making can be supported. Autonomy and appraisal of nonmaleficence and beneficence associated with dose reduction can be facilitated through shared or supported decision making. Clinicians should continue to strive for justice through the fair allocation of resources to support all people who request antipsychotic dose reduction. Conclusions and Implications for Practice: Clinicians have a responsibility to balance the four core ethical principles to the best of their ability when supporting a person in their recovery journey. Exploring, trialing, and supporting antipsychotic dose reduction may be part of this process if that is the patient's choice. Impact and Implications Autonomy and justice are upheld when people are supported to reduce or cease antipsychotic medication if that is their choice. Clinicians can balance the principles of nonmaleficence and beneficence (i.e., minimize harm and promote a person's welfare) by staying up-to-date with and sharing the evidence openly with patients, promoting supported or shared decision making, advanced statements, slow hyperbolic tapering, and providing additional monitoring and psychosocial support.

Abstract Background Peer support for mental health is recommended across international policy guidance and provision. Our systematic umbrella review summarises evidence on the effectiveness, implementation, and experiences of paid peer support approaches for mental health. Methods We searched MEDLINE, EMBASE, PsycINFO, The Campbell Collaboration, and The Cochrane Database of Systematic Reviews (2012–2022) for reviews of paid peer support interventions for mental health. The AMSTAR2 assessed quality. Results were synthesised narratively, with implementation reported using the CFIR (Consolidated Framework for Implementation Research). The protocol was registered with PROSPERO (registration number: CRD42022362099). Results We included 35 reviews (426 primary studies, n = 95–40,927 participants): systematic reviews with (n = 13) or without (n = 13) meta-analysis, or with qualitative synthesis (n = 3), scoping reviews (n = 6). Most reviews were low or critically low (97%) quality, one review was high quality. Effectiveness was investigated in 23 reviews. Results were mixed; there was some evidence from meta-analyses that peer support may improve depression symptoms (particularly perinatal depression), self-efficacy, and recovery. Factors promoting successful implementation, investigated in 9 reviews, included adequate training and supervision, a recovery-oriented workplace, strong leadership, and a supportive and trusting workplace culture with effective collaboration. Barriers included lack of time, resources and funding, and lack of recognised peer support worker (PSW) certification. Experiences of peer support were explored in 11 reviews, with 3 overarching themes: (i) what the PSW role can bring, including recovery and improved wellbeing for service users and PSWs; (ii) confusion over the PSW role, including role ambiguity and unclear boundaries; and (iii) organisational challenges and impact, including low pay, negative non-peer staff attitudes, and lack of support and training. Conclusions Peer support may be effective at improving some clinical outcomes, self-efficacy, and recovery. Certain populations, e.g. perinatal populations, may especially benefit from peer support. Potential strategies to successfully implement PSWs include co-production, clearly defined PSW roles, a receptive hierarchical structure and staff, appropriate PSW and staff training with clinical and/or peer supervision alongside safeguarding. Services could benefit from clear, coproduced, setting specific implementation guidelines for PSW. PSW roles tend to be poorly defined and associations between PSW intervention content and impacts need further investigation. Future research should reflect the priorities of providers/service users involved in peer support.

Background Autistic people have a high likelihood of developing mental health difficulties but a low chance of receiving effective mental healthcare. Therefore, there is a need to identify and examine strategies to improve mental healthcare for autistic people. Aims To identify strategies that have been implemented to improve access, experiences of care and mental health outcomes for autistic adults, and to examine evidence on their acceptability, feasibility and effectiveness. Method A co-produced systematic review was conducted. MEDLINE, PsycINFO, CINHAL, medRxiv and PsyArXiv were searched. We included all study designs reporting acceptability or feasibility outcomes and empirical quantitative study designs reporting effectiveness outcomes. Data were synthesised using a narrative approach. Results A total of 30 articles were identified. These included 16 studies of adapted mental health interventions, eight studies of service improvements and six studies of bespoke mental health interventions developed for autistic people. There was no conclusive evidence on effectiveness. However, most bespoke and adapted approaches appeared to be feasible and acceptable. Identified adaptations appeared to be acceptable and feasible, including increasing knowledge and detection of autism, providing environmental adjustments and communication accommodations, accommodating individual differences and modifying the structure and content of interventions. Conclusion Many identified strategies are feasible and acceptable, and can be readily implemented in services with the potential to make mental healthcare more suitable for autistic people, but important research gaps remain. Future research should address these and investigate a co-produced package of service improvement measures.

Autistic children and young people (CYP) experience mental health difficulties but face many barriers to accessing and benefiting from mental health care. There is a need to explore strategies in mental health care for autistic CYP to guide clinical practice and future research and support their mental health needs. Our aim was to identify strategies used to improve mental health care for autistic CYP and examine evidence on their acceptability, feasibility, and effectiveness. A systematic review and meta-analysis were carried out. All study designs reporting acceptability/feasibility outcomes and empirical quantitative studies reporting effectiveness outcomes for strategies tested within mental health care were eligible. We conducted a narrative synthesis and separate meta-analyses by informant (self, parent, and clinician). Fifty-seven papers were included, with most investigating cognitive behavioral therapy (CBT)-based interventions for anxiety and several exploring service-level strategies, such as autism screening tools, clinician training, and adaptations regarding organization of services. Most papers described caregiver involvement in therapy and reported adaptations to communication and intervention content; a few reported environmental adjustments. In the meta-analyses, parent- and clinician-reported outcomes, but not self-reported outcomes, showed with moderate certainty that CBT for anxiety was an effective treatment compared to any comparison condition in reducing anxiety symptoms in autistic individuals. The certainty of evidence for effectiveness, synthesized narratively, ranged from low to moderate. Evidence for feasibility and acceptability tended to be positive. Many identified strategies are simple, reasonable adjustments that can be implemented in services to enhance mental health care for autistic individuals. Notable research gaps persist, however.

BACKGROUND:Maintenance antipsychotic medication is recommended for people with schizophrenia or recurrent psychosis, but the adverse effects are burdensome, and evidence on long-term outcomes is sparse. We aimed to assess the benefits and harms of a gradual process of antipsychotic reduction compared with maintenance treatment. Our hypothesis was that antipsychotic reduction would improve social functioning with a short-term increase in relapse. METHODS:RADAR was an open, parallel-group, randomised trial done in 19 National Health Service Trusts in England. Participants were aged 18 years and older, had a diagnosis of recurrent, non-affective psychotic disorder, and were prescribed an antipsychotic. Exclusion criteria included people who had a mental health crisis or hospital admission in the past month, were considered to pose a serious risk to themselves or others by a treating clinician, or were mandated to take antipsychotic medication under the Mental Health Act. Through an independent, internet-based system, participants were randomly assigned (1:1) to gradual, flexible antipsychotic reduction, overseen by treating clinicians, or to maintenance. Participants and clinicians were aware of treatment allocations, but assessors were masked to them. Follow-up was for 2 years. Social functioning, assessed by the Social Functioning Scale, was the primary outcome. The principal secondary outcome was severe relapse, defined as requiring admission to hospital. Analysis was done blind to group identity using intention-to-treat data. The trial is completed and has been registered with ISRCTN registry (ISRCTN90298520) and with ClinicalTrials.gov (NCT03559426). FINDINGS:4157 people were screened, of whom 253 were randomly allocated, including 168 (66%) men, 82 (32%) women, and 3 (1%) transgender people, with a mean age of 46 years (SD 12, range 22-79). 171 (67%) participants were White, 52 (21%) were Black, 16 (6%) were Asian, and 12 (5%) were of other ethnicity. The median dose reduction at any point during the trial was 67% in the reduction group and zero in the maintenance group; at 24 months it was 33% versus zero. At the 24-month follow-up, we assessed 90 of 126 people assigned to the antipsychotic dose reduction group and 94 of 127 assigned to the maintenance group, finding no difference in the Social Functioning Scale (β 0·19, 95% CI -1·94 to 2·33; p=0·86). There were 93 serious adverse events in the reduction group affecting 49 individuals, mainly comprising admission for a mental health relapse, and 64 in the maintenance group, relating to 29 individuals. INTERPRETATION:At 2-year follow-up, a gradual, supported process of antipsychotic dose reduction had no effect on social functioning. Our data can help to inform decisions about the use of long-term antipsychotic medication. FUNDING:National Institute for Health Research.

Background:Antipsychotics are a core treatment for psychosis, but the evidence for gradual dose reductions guided by clinicians is under-developed. The RADAR randomised controlled trial (RCT) compared antipsychotic reduction and possible discontinuation with maintenance treatment for people with recurrent psychotic disorders. The current study explored participants' experiences of antipsychotic reduction or discontinuation within this trial. Methods:This qualitative study was embedded within the RADAR RCT (April 2017-March 2022) that recruited 253 participants from specialist community mental health services in 19 public healthcare localities in England. Participants were adults with recurrent non affective psychosis who were taking antipsychotic medication. Semi-structured interviews, lasting 30-90 min, were conducted after the trial final 24-month follow-up with 26 people who reduced and/or discontinued antipsychotics within the trial, sampled purposively for diversity in sociodemographic characteristics, trial variables, and pre-trial medication and clinical factors. Data were analysed using thematic analysis and findings are reported qualitatively. Findings:Most participants reported reduced adverse effects of antipsychotics with dose reductions, primarily in mental clouding, emotional blunting and sedation, and some positive impacts on social functioning and sense of self. Over half experienced deteriorations in mental health, including psychotic symptoms and intolerable levels of emotional intensity. Nine had a psychotic relapse. The trial context in which medication reduction was explicitly part of clinical care provided various learning opportunities. Some participants were highly engaged with reduction processes, and despite difficulties including relapses, developed novel perspectives on medication, dose optimisation, and how to manage their mental health. Others were more ambivalent about reduction or experienced less overall impact. Interpretation:Experiences of antipsychotic reductions over two years were dynamic and diverse, shaped by variations in dose reduction profiles, reduction effects, personal motivation and engagement levels, and relationships with prescribers. There are relapse risks and challenges, but some people experience medication reduction done with clinical guidance as empowering. Clinicians can use findings to inform and work flexibly with service users to establish optimal antipsychotic doses. Funding:National Institute for Health Research.

Background Public Health England recently called for the establishment of services to help people to safely stop prescribed drugs associated with dependence and withdrawal, including benzodiazepines, z-drugs, antidepressants, gabapentinoids and opioids. NICE identified a lack of knowledge about the best model for such service delivery. Therefore, we performed a global survey of existing deprescribing services to identify common practices and inform service development. Methods We identified existing deprescribing services and interviewed key personnel in these services using an interview co-produced with researchers with lived experience of withdrawal. We summarised the common practices of the services and analysed the interviews using a rapid form of qualitative framework analysis. Results Thirteen deprescribing services were included (8 UK, 5 from other countries). The common practices in the services were: gradual tapering of medications often over more than a year, and reductions made in a broadly hyperbolic manner (smaller reductions as total dose became lower). Reductions were individualised so that withdrawal symptoms remained tolerable, with the patient leading this decision-making in most services. Support and reassurance were provided throughout the process, sometimes by means of telephone support lines. Psychosocial support for the management of underlying conditions (e.g. CBT, counselling) were provided by the service or through referral. Lived experience was often embedded in services through founders, hiring criteria, peer support and sources of information to guide tapering. Conclusion We found many common practices across existing deprescribing services around the world. We suggest that these ingredients are included in commissioning guidance of future services and suggest directions for further research to clarify best practice.

BACKGROUND:Antipsychotic medication can reduce psychotic symptoms and risk of relapse in people with schizophrenia and related disorders, but it is not always effective and adverse effects can be significant. We know little of patients' views about continuing or discontinuing antipsychotic treatment.AIMS:To explore the views of people with schizophrenia and other psychotic disorders about continuing their antipsychotic medication or attempting to reduce or discontinue this medication with clinical support.METHODS:We collected quantitative and qualitative data by conducting semi-structured interviews in London, UK. Factors predicting a desire to discontinue medication were explored. Content analysis of qualitative data was undertaken.RESULTS:We interviewed 269 participants. 33% (95% CI, 27 to 39%) were content with taking long-term antipsychotic medication. Others reported they took it reluctantly (19%), accepted it on a temporary basis (24%) or actively disliked it (18%). 31% (95% CI, 25 to 37%) said they would like to try to stop medication with professional support, and 45% (95% CI, 39 to 51%) wanted the opportunity to reduce medication. People who wanted to discontinue had more negative attitudes towards the medication but were otherwise similar to other participants. Wanting to stop or reduce medication was motivated mainly by adverse effects and health concerns. Professional support was identified as potentially helpful to achieve reduction.CONCLUSIONS:This large study reveals that patients are commonly unhappy about the idea of taking antipsychotics on a continuing or life-long basis. Professional support for people who want to try to reduce or stop medication is valued.

This cross-sectional study estimates the costs incurred by the National Health Service (NHS) in England as a consequence of the unnecessary prescribing (i.e. non-indicated or dispensable) of dependency-forming medicines (antidepressants, opioids, gabapentinoids, benzodiazepines, Z-drugs). It assesses prescribing in primary care from April 2015-March 2018. Analyses were based upon the following data sets: the number of adults continuously prescribed dependency forming medications and the duration of prescriptions (obtained from Public Health England); the Net Ingredient Cost (NIC) and the dispensing costs for each medicine (obtained from the NHS Business Service Authority [NHSBSA]). Consultation costs were calculated based on guideline recommendations and the number of consultations evidenced in prior research for long-term medication monitoring. Across opioids, gabapentinoids, benzodiazepines, Z-drugs the total estimated unnecessary cost over three years (April 2015-March 2018) was £1,367,661,104 to £1,555,234,627. For antidepressants the total estimated unnecessary cost for one year was £37,321,783 to £45,765,504. The data indicate that the NHS in England may incur a significant estimated mean annual loss of £455,887,035 to £518,411,542 for opioids, gabapentinoids, benzodiazepines, Z-drugs and an estimated annual loss of £37,321,783 to £45,765,504 for antidepressants. Combined, this gives an estimated annual loss of £493,208,818 to £564,177,046 as a result of non-indicated or dispensable prescribing of dependency-forming medicines. Estimates are conservative and figures could be higher.

The development of severe mental health conditions is strongly linked to our environments, particularly experiences of trauma and adversity. However treatments for severe mental health conditions are often primarily biomedical, centred around medication. For people diagnosed with schizophrenia or psychosis, this is antipsychotic medication. Although antipsychotics have been found to reduce symptoms and risk of relapse, some patients derive little benefit from these drugs, and they can lead to severe adverse effects. Subsequently, a high proportion of people do not want to take antipsychotics and request an alternative. Yet in the UK and in many countries there are currently no guidelines for stopping antipsychotics or formal treatment alternatives, despite such alternatives being available in some countries. For example, in Norway and Vermont (USA), in response to pressure from service user organisations, governments have mandated the establishment of "minimal medication" services. We examine whether everyone with a psychotic condition needs long-term antipsychotic treatment and evidence for alternative models of care. We recommend that healthcare providers should be encouraged to develop a psychosocial treatment package for people with psychosis or schizophrenia that provides a realistic possibility of minimising antipsychotic exposure.

Abstract Body Adults with ADHD describe self-medicating with cannabis. A small number of psychiatrists in the US prescribe cannabis medication for ADHD, despite there being no evidence from trials. The EMA-C trial (Experimental Medicine in ADHD-Cannabinoids) was a pilot randomised placebo-controlled experimental study of a cannabinoid medication, Sativex Oromucosal Spray, in 30 adults with ADHD. The primary outcome was cognitive performance and activity level using the QbTest. Secondary outcomes included ADHD and emotional lability (EL) symptoms. From 17.07.14-18.06.15, 30 participants were randomly assigned to the active (n=15) or placebo (n=15) group. For the primary outcome, no significant difference was found in the intent-to-treat analysis although the overall pattern of scores was such that the active group usually had scores that were better than the placebo group (Est=-0.17,95%CI-0.40-0.07, p=0.16, n=15/11 active/placebo). For secondary outcomes Sativex was associated with a nominally significant improvement in hyperactivity/impulsivity (p=0.03) and a cognitive measure of inhibition (p=0.05), and a trend towards improvement for inattention (p=0.10) and EL (p=0.11). Per-protocol effects were higher. Results did not meet significance following adjustment for multiple testing. One serious (muscular seizures/spasms) and three mild adverse events occurred in the active group and one serious (cardiovascular problems) adverse event in the placebo group. Adults with ADHD may represent a subgroup of individuals who experience a reduction of symptoms and no cognitive impairments following cannabinoid use. While not definitive, this study provides preliminary evidence supporting the self-medication theory of cannabis use in ADHD and the need for further studies of the endocannabinoid system in ADHD. Disclosure During this work-RC was a Ph.D. student funded by a grant to PA from Vifor Pharma. PA received funds (consultancy/sponsored talks/research/education) from Shire, Lilly, Novartis, Janssen, PCMScientific, Vifor Pharma, QBTech. Sativex was free from GW Pharm

Background. Adults with attention deficit hyperactivity disorder (ADHD) frequently suffer from sleep problems and report high levels of daytime sleepiness compared to neurotypical controls, which has detrimental effect on quality of life. Methods. We evaluated daytime sleepiness in adults with ADHD compared to neurotypical controls using an observer-rated sleepiness protocol during the Sustained Attention Response Task as well as electroencephalogram (EEG) slowing, a quantitative electroencephalographic measure collected during a short period of wakeful rest. Results. We found that adults with ADHD were significantly sleepier than neurotypical controls during the cognitive task and that this on-task sleepiness contributed to cognitive performance deficits usually attributed to symptoms of ADHD. EEG slowing predicted severity of ADHD symptoms and diagnostic status, and was also related to daytime sleepiness. Frontal EEG slowing as well as increased frontal delta were especially prominent in adults with ADHD. We have validated and adapted an objective observer-rated measure for assessing on-task sleepiness that will contribute to future sleep research in psychology and psychiatry. Conclusions. These findings indicate that the cognitive performance deficits routinely attributed to ADHD and often conceptualized as cognitive endophenotypes of ADHD are largely due to on-task sleepiness and not exclusively due to ADHD symptom severity. Daytime sleepiness plays a major role in cognitive functioning of adults with ADHD.