Approaches to improving mental health care for autistic children and young people: a systematic review and meta-analysis.

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.

The effectiveness, implementation, and experiences of peer support approaches for mental health: a systematic umbrella review.

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.

Pediatric Medical Subspecialist Use in Outpatient Settings.

Importance: A first step toward understanding whether pediatric medical subspecialists are meeting the needs of the nation's children is describing rates of use and trends over time. Objectives: To quantify rates of outpatient pediatric medical subspecialty use. Design, Setting, and Participants: This repeated cross-sectional study of annual subspecialist use examined 3 complementary data sources: electronic health records from PEDSnet (8 large academic medical centers [January 1, 2010, to December 31, 2021]); administrative data from the Healthcare Integrated Research Database (HIRD) (14 commercial health plans [January 1, 2011, to December 31, 2021]); and administrative data from the Transformed Medicaid Statistical Information System (T-MSIS) (44 state Medicaid programs [January 1, 2016, to December 31, 2019]). Annual denominators included 493 628 to 858 551 patients younger than 21 years with a general pediatric visit in PEDSnet; 5 million beneficiaries younger than 21 years enrolled for at least 6 months in HIRD; and 35 million Medicaid or Children's Health Insurance Program beneficiaries younger than 19 years enrolled for any amount of time in T-MSIS. Exposure: Calendar year and type of medical subspecialty. Main Outcomes and Measures: Annual number of children with at least 1 completed visit to any pediatric medical subspecialist in an outpatient setting per population. Use rates excluded visits in emergency department or inpatient settings. Results: Among the study population, the proportion of girls was 51.0% for PEDSnet, 51.1% for HIRD, and 49.3% for T-MSIS; the proportion of boys was 49.0% for PEDSnet, 48.9% for HIRD, and 50.7% for T-MSIS. The proportion of visits among children younger than 5 years was 37.4% for PEDSnet, 20.9% for HIRD, and 26.2% for T-MSIS; most patients were non-Hispanic Black (29.7% for PEDSnet and 26.1% for T-MSIS) or non-Hispanic White (44.9% for PEDSnet and 43.2% for T-MSIS). Annual rates for PEDSnet ranged from 18.0% to 21.3%, which were higher than rates for HIRD (range, 7.9%-10.4%) and T-MSIS (range, 7.6%-8.6%). Subspecialist use increased in the HIRD commercial health plans (annual relative increase of 2.4% [95% CI, 1.6%-3.1%]), but rates were essentially flat in the other data sources (PEDSnet, -0.2% [95% CI, -1.1% to 0.7%]; T-MSIS, -0.7% [95% CI, -6.5% to 5.5%]). The flat PEDSnet growth reflects a balance between annual use increases among those with commercial insurance (1.2% [95% CI, 0.3%-2.1%]) and decreases in use among those with Medicaid (-0.9% [95% CI, -1.6% to -0.2%]). Conclusions and Relevance: The findings of this cross-sectional study suggest that among children, 8.6% of Medicaid beneficiaries, 10.4% of those with commercial insurance, and 21.3% of those whose primary care is received in academic health systems use pediatric medical subspecialty care each year. There was a small increase in rates of subspecialty use among children with commercial but not Medicaid insurance. These data may help launch innovations in the primary-specialty care interface.

Experiences of reduction and discontinuation of antipsychotics: a qualitative investigation within the RADAR trial.

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.

Antipsychotic dose reduction and discontinuation versus maintenance treatment in people with schizophrenia and other recurrent psychotic disorders in England (the RADAR trial): an open, parallel-group, randomised controlled trial.

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 (ß 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.

"Stabilise-reduce, stabilise-reduce": A survey of the common practices of deprescribing services and recommendations for future services.

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.

The serotonin theory of depression: a systematic umbrella review of the evidence.

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-HT1A 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-HT1A 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.

An analysis of views about supported reduction or discontinuation of antipsychotic treatment among people with schizophrenia and other psychotic disorders.

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.

Seasonal variation in oestrogenic potency and biological effects of wastewater treatment works effluents assessed using ERE-GFP transgenic zebrafish embryo-larvae.

Effluents from wastewater treatment works (WwTW) exhibit both temporal and spatial variation in oestrogenicity, however few studies have attempted to quantify how this variation affects biological responses in fish. Here we used an oestrogen-responsive green fluorescent protein (ERE-GFP) transgenic zebrafish (Danio rerio) to quantify oestrogenic activity and health effects for exposure to three different WwTW effluents. Endpoints measured included survival/hatching rate, GFP induction (measured in target tissues or gfp mRNA induction in whole embryos) and vtg mRNA induction in whole embryos. Exposure to one of the study effluents (at 100%), resulted in some mortality, and exposure to all three effluents (at 50% and 100%) caused decreases in hatching rates. Higher levels of vtg mRNA corresponded with higher levels of steroidal oestrogens in the different effluents, with lowest-observed-effect concentrations (LOECs) between 31 ng/L and 39 ng/L oestradiol equivalents (EEQs). Tissue patterns of GFP expression for all three WwTWs effluents reflected the known targets for steroidal oestrogens and for some other oestrogenic chemicals likely present in those effluents (i.e. nonylphenol or bisphenolic compounds). GFP induction was similarly responsive to vtg mRNA induction (a well-established biomarker for oestrogen exposure). We thus demonstrate the ERE-GFP transgenic zebrafish as an effective model for monitoring the oestrogenic potency and health effects for exposure to complex mixtures of chemicals contained within WwTW effluents.

Health Effects and Life Stage Sensitivities in Zebrafish Exposed to an Estrogenic Wastewater Treatment Works Effluent.

A wide range of health effects in fish have been reported for exposure to wastewater treatment work (WwTW) effluents including feminized responses in males. Most of these exposure studies, however, have assessed acute health effects and chronic exposure effects are less well established. Using an Estrogen Responsive Element-Green Fluorescent Protein (ERE-GFP)-Casper transgenic zebrafish, we investigated chronic health effects and life stage sensitivities for exposure to an estrogenic WwTW effluent and the synthetic estrogen 17α-ethinylestradiol (EE2). Exposure to the WwTW effluent (at full strength;100%) and to 10 ng/L (nominal) EE2 delayed testis maturation in male fish but accelerated ovary development in females. Exposure to 50% and 100% effluent, and to 10 ng/L EE2, also resulted in skewed sex ratios in favor of females. Differing patterns of green fluorescent protein (GFP) expression, in terms of target tissues and developmental life stages occurred in the ERE-GFP- zebrafish chronically exposed to 100% effluent and reflected the estrogenic content of the effluent. gfp and vitellogenin (vtg) mRNA induction were positively correlated with measured levels of steroidal estrogens in the effluent throughout the study. Our findings illustrate the importance of a fish's developmental stage for estrogen exposure effects and demonstrate the utility of the ERE-GFP zebrafish for integrative health analysis for exposure to estrogenic chemical mixtures.

The Systemic Assessment Clinic, a Novel Method for Assessing Patients in General Adult Psychiatry: Presentation and Preliminary Service Evaluation.

The traditional model of psychiatric assessment and diagnosis can be criticised as reductive. We developed an innovative model for psychiatric assessment of adult patients referred to our adult mental health team, the Systemic Assessment Clinic, incorporating the principles and techniques of systemic family therapy and dialogical practice into standard psychiatric assessment. We conducted a service evaluation, comparing prospective use of mental health services for patients assessed either in the Systemic Assessment Clinic or in standard assessment. Patients assessed in the Systemic Assessment Clinic had more favourable outcomes than those in standard assessment: they were significantly less likely to need multiple follow-up treatment appointments with a psychiatrist and to be re-referred to mental health services once discharged, indicating reduced healthcare costs. Satisfaction rates for participants attending the systemic assessment clinic were high. Our service evaluation gives preliminary evidence that the Systemic Assessment Clinic could be a potential new model for psychiatric assessment; further evaluation is warranted in a randomised controlled trial.

Electrophysiological correlates of spontaneous mind wandering in attention-deficit/hyperactivity disorder.

We recently hypothesised that increased spontaneous mind wandering (MW-S) reflects a core process underlying attention-deficit/hyperactivity disorder (ADHD). Previous studies show that individuals with ADHD and neurotypical individuals with increased MW-S display similar cognitive-performance and electrophysiological (EEG) impairments in attentional processes. However, the cognitive-EEG markers associated with increased MW-S in ADHD remain poorly understood. We therefore investigated such markers in a sample of 69 sex- and age-matched adults with ADHD and 29 controls during the Sustained Attention to Response Task. We compared task performance and EEG measures (P3, time-frequency brain-oscillations) of attentional processes between groups, and examined their association with a validated self-report questionnaire of MW-S. Finally, we tested the hypothesis that MW-S and ADHD diagnosis relate to the same cognitive-EEG impairments using a hierarchical regression model. Compared to controls, adults with ADHD showed attenuations in P3, event-related alpha and beta suppression during response inhibition (No-Go trials), and theta power activations during response execution (Go trials), as well as increased reaction time variability and more commission/omission errors. MW-S was also continuously associated with most cognitive-EEG measures related to ADHD. The hierarchical regressions on measures associated with both ADHD diagnosis and MW-S showed that MW-S did not explain additional variance in the cognitive-EEG markers (except for beta suppression) beyond ADHD diagnosis, and vice versa. These findings are consistent with our hypothesis that ADHD diagnosis and MW-S share common neural deficits, and that MW-S may reflect a core symptom of the disorder.

Glyceryl trinitrate in first-episode psychosis unmedicated with antipsychotics: A randomised controlled pilot study.

BACKGROUND: There is a pressing need for new classes of treatment for psychosis. A key therapeutic target for novel compounds is the NMDA receptor, which may be modulated by nitric oxide donors such as sodium nitroprusside (SNP). Recent studies of SNP in patients with psychosis have mixed results, and the drug has to be administered intravenously. Glyceryl trinitrate (GTN) is a well-established cardiovascular medicine that is also a nitric oxide donor, and can be given orally. AIMS: We explored the safety and potential effects of GTN in unmedicated patients with a first episode of psychosis. METHODS: This was a single-centre, randomised, double-blind, placebo-controlled trial from December 2016 to April 2019 (ClinicalTrials.gov identifier: NCT02906553). Patients received 3 × sprays of GTN or placebo for three consecutive days, and were re-assessed on Days 1, 2, 3 and 7. The primary outcome was cognition (Jumping to Conclusions task), secondary outcomes were symptoms (Positive and Negative Syndrome Scale (PANSS)), verbal memory (Hopkins Verbal Learning task), and mood (Bond-Lader Visual Analogue Scales). RESULTS: Nineteen patients were randomised, and 13 participants were included in the analyses. Compared with placebo, GTN was well tolerated, but was not associated with significant effects on cognition, symptoms, or mood. Bayesian statistics indicate that our results were 2× more likely under the null hypothesis than the alternative hypothesis, providing anecdotal evidence that GTN does not improve psychotic symptoms. CONCLUSIONS: We found no indication of an effect of GTN on symptoms of psychosis or cognition.

The key role of daytime sleepiness in cognitive functioning of adults with attention deficit hyperactivity disorder.

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.

Psychosocial interventions for people with schizophrenia or psychosis on minimal or no antipsychotic medication: A systematic review.

Antipsychotics are the first-line treatment for people with schizophrenia or psychosis. There is evidence that they can reduce the symptoms of psychosis and risk of relapse. However many people do not respond to these drugs, or experience adverse effects and stop taking them. In the UK, clinical guidelines have stressed the need for research into psychosocial interventions without antipsychotics. This systematic review examines the effects of psychosocial interventions for people with schizophrenia or psychosis who are on no/minimal antipsychotics. Databases were searched for empirical studies investigating a psychosocial intervention in people with a schizophrenia spectrum disorder who were not taking antipsychotics or had received an antipsychotic minimisation strategy. We identified nine interventions tested in 17 studies (N = 2250), including eight randomised controlled trials. Outcomes were generally equal to or in a small number of cases better than the control group (antipsychotics/treatment as usual) for Cognitive Behavioural Therapy (CBT), Need Adapted Treatment and Soteria. The remaining interventions provided some encouraging, but overall inconsistent findings and were Psychosocial Outpatient Treatment, Open Dialogue, Psychosocial Inpatient Treatment, Psychoanalysis/Psychodynamic Psychotherapy, Major Role Therapy, and Milieu Treatment. Study quality was generally low with little recent research. In conclusion, nine psychosocial interventions have been studied for patients on no/minimal antipsychotics. The majority of studies reported outcomes for the intervention which were the same as the control group, however, study quality was problematic. Given the adverse effects of antipsychotics and that many people do not want to take them, high quality trials of psychosocial treatments for people on minimal/no antipsychotics are needed.

Definitions of relapse in trials comparing antipsychotic maintenance with discontinuation or reduction for schizophrenia spectrum disorders: A systematic review.

INTRODUCTION: Avoidance of relapse is the main aim of long-term antipsychotic treatment in schizophrenia, yet how 'relapse' is defined in trials is not well-known. METHODS: We conducted a systematic review of definitions of relapse in trials of continuous antipsychotic treatment compared with discontinuation, intermittent treatment or dose reduction for people with schizophrenia spectrum disorders. Trials were identified from previous Cochrane reviews and a new search. The quality of relapse definitions was rated in terms of reliability and clinical relevance and associations between quality of definitions and trial characteristics and outcome were explored. RESULTS: We identified 82 reports of 81 trials which employed 54 different definitions of relapse. There were 33 definitions in the 35 trials published since 1990, with recent trials employing complex definitions often involving alternative criteria. Only ten primary definitions of relapse required the presence of psychotic symptoms in all cases, and only three specified this in combination with a measure of overall severity or functional decline. Only two definitions specified a duration longer than two days. Relapse definitions were rated as showing good reliability in 37 trials, but only seven showed good clinical relevance. Six trials with definitions that were both reliable and clinically relevant were slightly longer, but did not differ from remaining trials in other characteristics or overall or relative risk of relapse. CONCLUSIONS: Antipsychotic trials define relapse in numerous different ways, and few definitions consistently reflect suggested indications of a clinically significant relapse.

Experiences of taking neuroleptic medication and impacts on symptoms, sense of self and agency: a systematic review and thematic synthesis of qualitative data.

PURPOSE: Neuroleptic (antipsychotic) drugs reduce psychotic symptoms, but how they achieve these effects and how the drugs' effects are experienced by people who take them are less well understood. The present study describes a synthesis of qualitative data about mental and behavioural alterations associated with taking neuroleptics and how these interact with symptoms of psychosis and people's sense of self and agency. METHODS: Nine databases were searched to identify qualitative literature concerning experiences of taking neuroleptic medication. A thematic synthesis was conducted. RESULTS: Neuroleptics were commonly experienced as producing a distinctive state of lethargy, cognitive slowing, emotional blunting and reduced motivation, which impaired functioning but also had beneficial effects on symptoms of psychosis and some other symptoms (e.g. insomnia). For some people, symptom reduction helped restore a sense of normality and autonomy, but others experienced a loss of important aspects of their personality. Across studies, many people adopted a passive stance towards long-term medication, expressing a sense of resignation, endurance or loss of autonomy. CONCLUSIONS: Neuroleptic drugs modify cognition, emotions and motivation. These effects may be associated with reducing the intensity and impact of symptoms, but also affect people's sense of self and agency. Understanding how the effects of neuroleptics are experienced by those who take them is important in developing a more collaborative approach to drug treatment in psychosis and schizophrenia.

Randomised controlled trial of gradual antipsychotic reduction and discontinuation in people with schizophrenia and related disorders: the RADAR trial (Research into Antipsychotic Discontinuation and Reduction).

INTRODUCTION: Antipsychotic medication is effective in reducing acute symptoms of psychosis, but it has a range of potentially serious and debilitating adverse effects and is often disliked by patients. It is therefore essential it is only used when benefits outweigh harms. Although multiple trials conducted with people with schizophrenia indicate an increased risk of relapse in the short-term following abrupt antipsychotic discontinuation, there is little evidence about the long-term outcome of a gradual process of reduction and discontinuation on social functioning, relapse and other outcomes. METHODS AND ANALYSIS: This is a multicentre, randomised controlled trial involving people with schizophrenia and related disorders who have had more than one episode. Participants are randomised to have a clinically-supervised, gradual reduction of antipsychotic medication, leading to discontinuation when possible, or to continue with maintenance treatment. Blinded follow-up assessments are conducted at 6, 12 and 24 months and the primary outcome is social functioning, measured by the Social Functioning Scale at 24 months. A minimum of 134 evaluable participants provides 90% power to detect a five-point difference, and 206 to detect a four-point difference. Secondary outcomes include severe relapse (admission to hospital) and the study is also intended to detect a minimum 10% difference in severe relapse, which requires 402 participants, assuming a 15% loss to follow-up. Other secondary outcomes include all relapses, as identified by an independent and blinded endpoint committee, symptoms measured by the Positive and Negative Syndrome Scale, quality of life, adverse effects, self-rated recovery and neuropsychological measures. Enrolment started in 2016. The trial is scheduled to finish in June 2022. ETHICS AND DISSEMINATION: Ethical approval was initially obtained on 27 October 2016 (UK Research Ethics Committee reference 16/LO/1507). Results will be published in peer-reviewed journals and disseminated to the public. TRIAL REGISTRATION NUMBER: ISRCTN90298520. EudraCT: 2016-000709-36. Pre-results.