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.

Recruitment to a trial of antipsychotic reduction: impact of an acceptability study.

OBJECTIVES: Pre-trial acceptability studies may boost recruitment, especially in trials comparing distinctly different interventions. We evaluated the impact of an acceptability study on recruitment to a randomised trial of antipsychotic reduction versus maintenance treatment and explored demographic and clinical predictors of subsequent enrolment. METHODS: Participants with a diagnosis of a schizophrenia spectrum disorder who were taking antipsychotic medication were interviewed about their views of taking part in a future trial. RESULTS: In a sample of 210 participants, 151 (71.9%) expressed an interest in taking part in the future trial, 16 (7.6%) said they might be interested, and 43 (20.5%) said they were not. Altruistic reasons were most commonly given for wanting to take part, and concern about randomisation for not wanting to. Ultimately 57 people enrolled in the trial (27.1% of the original sample). Eighty-five people who initially expressed an interest did not enrol due to declining or not being eligible (for clinical reasons). Women and people from a white ethnic background were more likely to enrol in the trial, but no illness or treatment-related characteristics were associated with enrolment. CONCLUSION: An acceptability study can be a useful tool for recruitment to challenging trials, but it may over-estimate recruitment.

Effects of lithium on suicide and suicidal behaviour: a systematic review and meta-analysis of randomised trials.

AIMS: Lithium has long been believed to reduce the risk of suicide and suicidal behaviour in people with mood disorders. Previous meta-analyses appeared to support this belief, but excluded relevant data due to the difficulty of conducting meta-analysis of rare events. The current study is an updated systematic review and meta-analysis that includes all eligible data, and evaluates suicide, non-fatal suicidal behaviour (including suicidal ideation) and suicide attempts. METHODS: We searched PubMed, PsycINFO and Embase and some trial registers. We included all randomised trials comparing lithium and placebo or treatment as usual in mood disorders published after 2000, to ensure suicide was reliably reported. Trial quality was assessed using the Cochrane Risk of Bias tool. Pooled data were analysed using Fisher's Exact test. In addition, meta-analysis was conducted using various methods, prioritizing the Exact method. All trials were included in the analysis of suicide initially, regardless of whether they reported on suicide or not. We conducted a sensitivity analysis with trials that specifically reported on suicides and one that included trials published before 2000. Pre-specified subgroup analyses were performed involving suicide prevention trials, trials excluding people already taking lithium, trials involving people with bipolar disorder exclusively and those involving people with mixed affective diagnoses. Non-fatal suicidal behaviour and suicide attempts were analysed using the same methods, but only trials that reported these outcomes were included. PROSPERO registration: CRD42021265809. RESULTS: Twelve eligible studies involving 2578 participants were included. The pooled suicide rate was 0.2% for people randomised to lithium and 0.4% with placebo or treatment as usual, which was not a statistically significant difference; odds ratio (OR) = 0.41 (95% confidence interval 0.03-2.49), p = 0.45. Meta-analysis using the Exact method produced an OR of 0.42 (95% confidence interval 0.01-4.5). The result was not substantially different when restricted to 11 trials that explicitly reported suicides and remained statistically non-significant when including 15 trials published before 2000 (mostly in the 1970s). There were no significant differences in any subgroup analysis. There was no difference in rates of all non-fatal suicidal behaviour in seven trials that reported this outcome, or in five trials that reported suicide attempts specifically. Meta-analyses using other methods also revealed no statistically significant differences. CONCLUSIONS: Evidence from randomised trials is inconclusive and does not support the idea that lithium prevents suicide or suicidal behaviour.

A qualitative exploration of family members' perspectives on reducing and discontinuing antipsychotic medication.

BACKGROUND: Antipsychotics are routinely prescribed to people diagnosed with schizophrenia or psychosis on a long-term basis. Considerable literature explores service users' opinions and experiences of antipsychotics, but studies investigating family members' views are lacking. AIMS: To explore family members' perspectives on antipsychotics, particularly their views on long-term use, reduction and discontinuation of antipsychotics. METHODS: Semi-structured interviews were conducted with 11 family members of people experiencing psychosis. Participants were recruited through community support groups and mental health teams. Interviews were analysed thematically. RESULTS: The majority of family members valued antipsychotic medication primarily in supporting what they saw as a fragile stability in the person they cared for. Their views of medication were ambivalent, combining concerns about adverse effects with a belief in the importance of medication due to fears of relapse. They described a need for constant vigilance in relation to medication to ensure it was taken consistently, and often found changes, particularly reduction in medication difficult to contemplate. CONCLUSIONS: Findings highlight that family members' attitudes to medication sometimes conflict with those of the people they care for, impacting on their health and the caring relationship. Family members may need more support and could be usefully involved in medication decision-making.

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.

A systematic review of social functioning outcome measures in schizophrenia with a focus on suitability for intervention research.

Social functioning is an important part of recovery and a key treatment target in clinical research in schizophrenia. Evaluating and comparing interventions is challenged by the choice of many measures which focus on different aspects of functioning, with little to guide selection. This results in difficulties comparing outcomes of treatment where studies have used different measures. To improve the measurement of social functioning in intervention research, we aimed to provide practical information on suitability of measures. We conducted a systematic review of measures developed or psychometrically evaluated since 2007, and assessed and discussed the structure, content, quality, and the use of the measures in intervention research. Thirty-two measures of social functioning and 22 validation papers were identified. Measures included structured questionnaires, semi-structured interviews, and assessment of performance on specific tasks. The content of measures was organised into eight categories, which are in order of frequency with which they were covered by measures: activities of daily living, productive activity, relationships, leisure activities, cognition, anti-social behaviour, psychosis symptoms and self-esteem and empowerment. In terms of quality, most measures were rated as moderate, with the Personal and Social Performance Scale gaining the highest rating. However, there was little data on responsiveness of measures, or how they compare to objective or 'real-world' indicators of functioning. The Social Functioning Scale and Personal and Social Performance Scale have been most frequently used in intervention studies to date. Future research should aim to provide further data on psychometric properties relevant to intervention research.

How do participants in clinical trials compare with other patients with schizophrenia?

We aimed to explore the clinical relevance of a multicentre, pragmatic randomised trial of antipsychotic reduction in people diagnosed with schizophrenia or psychosis The sample recruited for the antipsychotic reduction study (n = 69 people) was compared with the population of patients with an eligible diagnosis undergoing treatment in the same service (n = 3067 people), using routinely-collected, anonymised data. The trial sample was found to resemble the wider population in terms of the number of past admissions, the likelihood of having been subject to legal detention and the level of risk the patient was perceived to pose to themselves or others. There was a lower proportion of people from minority ethnic backgrounds in the trial sample. The results provide some reassurance that trial recruits were similar to the wider population in terms of the severity of their condition and did not comprise a highly select sample of people with milder problems. The different ethnic composition of the research sample is consistent with other research.

Community Occupational Therapy for people with dementia and family carers (COTiD-UK) versus treatment as usual (Valuing Active Life in Dementia [VALID]) study: A single-blind, randomised controlled trial.

BACKGROUND: We aimed to estimate the clinical effectiveness of Community Occupational Therapy for people with dementia and family carers-UK version (Community Occupational Therapy in Dementia-UK version [COTiD-UK]) relative to treatment as usual (TAU). We hypothesised that COTiD-UK would improve the ability of people with dementia to perform activities of daily living (ADL), and family carers' sense of competence, compared with TAU. METHODS AND FINDINGS: The study design was a multicentre, 2-arm, parallel-group, assessor-masked, individually randomised controlled trial (RCT) with internal pilot. It was conducted in 15 sites across England from September 2014 to January 2018. People with a diagnosis of mild to moderate dementia living in their own home were recruited in pairs with a family carer who provided domestic or personal support for at least 4 hours per week. Pairs were randomised to either receive COTiD-UK, which comprised 10 hours of occupational therapy delivered over 10 weeks in the person with dementia's home or TAU, which comprised the usual local service provision that may or may not include standard occupational therapy. The primary outcome was the Bristol Activities of Daily Living Scale (BADLS) score at 26 weeks. Secondary outcomes for the person with dementia included the following: the BADLS scores at 52 and 78 weeks, cognition, quality of life, and mood; and for the family carer: sense of competence and mood; plus the number of social contacts and leisure activities for both partners. Participants were analysed by treatment allocated. A total of 468 pairs were recruited: people with dementia ranged from 55 to 97 years with a mean age of 78.6 and family carers ranged from 29 to 94 with a mean of 69.1 years. Of the people with dementia, 74.8% were married and 19.2% lived alone. Of the family carers, 72.6% were spouses, and 22.2% were adult children. On randomisation, 249 pairs were assigned to COTiD-UK (62% people with dementia and 23% carers were male) and 219 to TAU (52% people with dementia and 32% carers were male). At the 26 weeks follow-up, data were available for 364 pairs (77.8%). The BADLS score at 26 weeks did not differ significantly between groups (adjusted mean difference estimate 0.35, 95% CI -0.81 to 1.51; p = 0.55). Secondary outcomes did not differ between the groups. In total, 91% of the activity-based goals set by the pairs taking part in the COTiD-UK intervention were fully or partially achieved by the final COTiD-UK session. Study limitations include the following: Intervention fidelity was moderate but varied across and within sites, and the reliance on primarily proxy data focused on measuring the level of functional or cognitive impairment which may not truly reflect the actual performance and views of the person living with dementia. CONCLUSIONS: Providing community occupational therapy as delivered in this study did not improve ADL performance, cognition, quality of life, or mood in people with dementia nor sense of competence or mood in family carers. Future research should consider measuring person-centred outcomes that are more meaningful and closely aligned to participants' priorities, such as goal achievement or the quantity and quality of activity engagement and participation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10748953.

Reasons for nonparticipation in the Valuing Active Life in Dementia randomised controlled trial of a dyadic occupational therapy intervention: An interview study.

OBJECTIVES: There is currently little known about why people decline to participate in dyadic, psychosocial dementia research. This interview study aims to explore the reasons why people declined to participate in the Valuing Active Life in Dementia research trial. METHODS: Ten family carers of people with dementia, who were part of a dyad that had declined to take part in the randomised controlled trial, participated in qualitative telephone interviews to explore their reasons for declining. Inductive thematic analysis was used to identify themes. FINDINGS: Two themes with related sub-themes were identified: (1) Protectiveness - protecting the person with dementia, themselves as carers and their current lifestyle; (2) 'It's not for us' - the time commitment, and the possible unsuitability of the intervention, was seen to outweigh the perceived benefit of taking part. People with dementia were not always involved in the decision-making process, with carers stating the decision not to participate was made in the usual way as all their decisions. No apparent differences between the spousal and the child carers were apparent in the small sample. CONCLUSION: Recruitment to randomised controlled trials can be considered difficult or unfair because some participants will miss out on the desired intervention. However, this study shows that concern about the time and inconvenience of being involved in the trial can put people off research participation. Identifying possible reasons for declining research participation contributes to the design of future trials and recruitment strategies, so that the potential benefit is considered relative to the time and effort involved. Offering research opportunities to people with dementia and their families at the right stage of the dementia trajectory for their needs, facilitating personalised recruitment strategies with finely tailored researcher communication skills should help maximise recruitment, reduce attrition and deliver a more successful trial.

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.

Sense of coherence in family caregivers of people living with dementia: a mixed-methods psychometric evaluation.

BACKGROUND: Family caregivers of people living with dementia can experience feelings of burden and stress but the concept of sense of coherence has been identified as an important protective trait against the negative impact of caregiving. Despite this, there has been no psychometric evaluation of the Sense of Coherence scale-13 with this population. Therefore, a psychometric evaluation was conducted using a mixed-methods approach. METHOD: Five hundred and eighty-three caregivers of people living with dementia participated in the study. We examined the feasibility, internal consistency, construct validity, floor and ceiling effects, concurrent validity and face validity of the Sense of Coherence scale-13. RESULTS: The Sense of Coherence scale-13 demonstrated adequate internal consistency. Sense of coherence was positively related to resilience, sense of competence and health related quality of life, demonstrating good concurrent validity. However, the face validity of the scale was assessed as poor. CONCLUSION: The sense of coherence scale performed well under psychometric evaluation however guidance for caregivers should be examined and revised to reflect feedback from caregivers who completed this study, which could lead to improved face validity for this scale. TRIAL REGISTRATION NUMBER: ISRCTN10748953 . Registered 18th September 2014.

Factors related to sense of competence in family caregivers of people living with dementia in the community: a narrative synthesis.

ABSTRACTObjectives:Sense of competence defines a caregiver's feeling of being capable to manage the caregiving task and is an important clinical concept in the caregiving literature. The aim of this review was to identify the factors, both positive and negative, associated with a caregiver's perception of their sense of competence. DESIGN: A systematic review of the literature was conducted, retrieving both quantitative and qualitative papers from databases PsycINFO, CINAHL, EMBASE, and Medline. A quality assessment was conducted using the STROBE and CASP checklists, and the quality rating informed the inclusion of papers ensuring the evidence was robust. Narrative synthesis was employed to synthesize the findings and to generate an updated conceptual model of sense of competence. RESULTS: Seventeen papers were included in the review, all of which were moderate to high quality. These included 13 quantitative, three mixed-methods and one qualitative study. Factors associated with sense of competence included: behavioral and psychological symptoms of dementia (BPSD), caregiver depression, gratitude, and the ability to find meaning in caregiving. CONCLUSIONS: The results of this review demonstrate that both positive and negative aspects of caring are associated with caregiver sense of competence. Positive and negative aspects of caregiving act in tandem to influence caregiver perception of their competence. The proposed model of sense of competence aims to guide future research and clinical interventions aimed at improving this domain but requires further testing, as due to the observational nature of the include papers, the direction of causality could not be inferred.

Positive psychology outcome measures for family caregivers of people living with dementia: a systematic review.

BACKGROUND: Family caregivers of people living with dementia can have both positive and negative experiences of caregiving. Despite this, existing outcome measures predominately focus on negative aspects of caregiving such as burden and depression. This review aimed to evaluate the development and psychometric properties of existing positive psychology measures for family caregivers of people living with dementia to determine their potential utility in research and practice. METHOD: A systematic review of positive psychology outcome measures for family caregivers of people with dementia was conducted. The databases searched were as follows: PsychINFO, CINAHL, MEDLINE, EMBASE, and PubMed. Scale development papers were subject to a quality assessment to appraise psychometric properties. RESULTS: Twelve positive outcome measures and six validation papers of these scales were identified. The emerging constructs of self-efficacy, spirituality, resilience, rewards, gain, and meaning are in line with positive psychology theory. CONCLUSIONS: There are some robust positive measures in existence for family caregivers of people living with dementia. However, lack of reporting of the psychometric properties hindered the quality assessment of some outcome measures identified in this review. Future research should aim to include positive outcome measures in interventional research to facilitate a greater understanding of the positive aspects of caregiving and how these contribute to well-being.

ImpRess: an Implementation Readiness checklist developed using a systematic review of randomised controlled trials assessing cognitive stimulation for dementia.

BACKGROUND: Research reporting results of clinical trials, psychosocial or technological interventions frequently omit critical details needed to inform implementation in practice. The aim of this article is to develop an Implementation Readiness (ImpRess) checklist, that includes criteria deemed useful in measuring readiness for implementation and apply it to trials of cognitive stimulation in dementia, providing a systematic review of their readiness for widespread implementation. METHODS: Five electronic databases were searched. After initial screening of papers, two reviewers assessed quality and scored the included studies based on the ImpRess checklist specifically developed for this review. RESULTS: Twenty studies met the inclusion criteria. As determined by the ImpRess checklist, scores ranged from 11 to 29 out of 52. According to the checklist the most comprehensive and ready to implement version of cognitive stimulation was Cognitive Stimulation Therapy. CONCLUSIONS: Reports of interventions rarely include consideration of implementation in practice. Contrary to the growing number of reporting guidelines, crucial items within the ImpRess checklist have been frequently overlooked. This study was able to show that the ImpRess checklist was feasible in practice and reliable. The checklist may be useful in evaluating readiness for implementation for other manualised interventions.