Serotonin and depression - a riposte to Moncrieff et al. (2022).

In their recently published systematic "umbrella" review, Moncrieff and colleagues conclude that there is no consistent evidence that depression is caused by decreased serotonin activity in the central nervous system (CNS). However, this paper - which was extensively publicized and received a lot of attention on the social media - can cause misunderstandings, since the serotonin hypothesis of depression in its original form (i.e. reduced serotonin activity in the CNS = depression) formulated more than 50 years ago has been considered outdated for several decades. It has long been known that depression is a heterogeneous disorder not only genetically, clinically and biologically but also from a pharmacotherapeutic perspective. The decreased activity of serotonin, which undoubtedly plays an essential role in the pathogenesis of depression, is characteristic of only a subgroup of depressed subjects whose clinical picture is mostly dominated by intensified negative emotions, agitation, anxiety, insomnia, decreased appetite, self-blame and suicidality and these individuals are primarily responsive to SSRIs. By contrast, depression cases with reduced positive affects (characterized by anhedonia, anergia, inhibition and reduced cognitive functions) are mainly caused by a disturbance in the metabolism of dopamine and/or noradrenaline. These patients are primarily responsive to dual-action (e.g. SNRI) antidepressants. Results of serotonin and catecholamine (dopamine, noradrenaline) depletion studies also suggest that that the dysregulation of serotonin and dopamine/noradrenaline in the CNS is characteristic of different subgroups of depressed patients. In addition to the serotonergic, dopaminergic and noradrenergic systems, many other neurotransmitter systems (e.g. cholinergic, glutamatergic, GABAergic) and other mechanisms (e.g. neuroinfl ammation) have also been proven to play a role in the development of the disorder. Knowledge of the data presented in our publication is important since the simplistic interpretation by Moncrieffetal. of the role of serotonin in the pathogenesis of depression may undermine confidence in SSRIs in many patients. (Neuropsychopharmacol Hung 2022; 24(3): 120-125).

Mental health in immigration detention: A comparison of foreign national ex-prisoners and other detainees.

BACKGROUND: People held in immigration removal centres have a range of vulnerabilities relating both to disappointment at imminent removal from the country of hoped-for residence and various antecedent difficulties. An important subgroup in the UK is of foreign national ex-prisoners who have served a period of incarceration there. Prisoners generally have higher rates of mental disorders than the general population. It is, however, not clear whether foreign national ex-prisoners in UK immigration removal centres have higher rates of mental disorders than other detainees. AIMS: To compare the screened prevalence of mental disorders, levels of unmet needs and time in detention between foreign national ex-prisoners and others in Immigration Removal Centres in England. METHODS: We conducted a secondary analysis of cross-sectional survey data from a previously published study in one Immigration Removal Centre. RESULTS: The 28 foreign national ex-prisoners had been in immigration detention for longer and reported greater levels of unmet needs than the other 66 detainees. The highest levels of unmet needs among the foreign national ex-prisoners were in the areas of psychological distress and intimate relationships. After adjusting for time spent in detention, there was evidence to suggest that foreign national ex-prisoners had a higher screened prevalence of substance use disorders, autism spectrum disorders and attention-deficit hyperactivity disorder than the other detainees. CONCLUSIONS/IMPLICATIONS FOR CLINICAL PRACTICE: This study supports the view that foreign national ex-prisoners are a vulnerable group within immigration detention who have needs for enhanced and specialist service provision, including appropriate arrangements for health screening and active consideration to alternatives to their detention.

Psychological treatments for post-traumatic stress disorder in adults: a network meta-analysis.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a potentially chronic and disabling disorder affecting a significant minority of people exposed to trauma. Various psychological treatments have been shown to be effective, but their relative effects are not well established. METHODS: We undertook a systematic review and network meta-analyses of psychological interventions for adults with PTSD. Outcomes included PTSD symptom change scores post-treatment and at 1-4-month follow-up, and remission post-treatment. RESULTS: We included 90 trials, 6560 individuals and 22 interventions. Evidence was of moderate-to-low quality. Eye movement desensitisation and reprocessing (EMDR) [standardised mean difference (SMD) -2.07; 95% credible interval (CrI) -2.70 to -1.44], combined somatic/cognitive therapies (SMD -1.69; 95% CrI -2.66 to -0.73), trauma-focused cognitive behavioural therapy (TF-CBT) (SMD -1.46; 95% CrI -1.87 to -1.05) and self-help with support (SMD -1.46; 95% CrI -2.33 to -0.59) appeared to be most effective at reducing PTSD symptoms post-treatment v. waitlist, followed by non-TF-CBT, TF-CBT combined with a selective serotonin reuptake inhibitor (SSRI), SSRIs, self-help without support and counselling. EMDR and TF-CBT showed sustained effects at 1-4-month follow-up. EMDR, TF-CBT, self-help with support and counselling improved remission rates post-treatment. Results for other interventions were either inconclusive or based on limited evidence. CONCLUSIONS: EMDR and TF-CBT appear to be most effective at reducing symptoms and improving remission rates in adults with PTSD. They are also effective at sustaining symptom improvements beyond treatment endpoint. Further research needs to explore the long-term comparative effectiveness of psychological therapies for adults with PTSD and also the impact of severity and complexity of PTSD on treatment outcomes.

When trust is lost: the impact of interpersonal trauma on social interactions.

BACKGROUND: Trauma due to deliberate harm by others is known to increase the likelihood of developing Post-Traumatic Stress Disorder (PTSD). This is the first study investigating basic and dynamic trust in 'interpersonal' PTSD. METHODS: Thirty-two participants with PTSD and 22 healthy controls played a novel multi-round version of a monetary investment protocol, the so-called 'Trust Game', a task from the behavioural economics literature, which is considered to involve trust and reciprocity. We used two 'Trust Games' including cooperative and unfair partners. RESULTS: Findings showed an effect for lower basic investment in PTSD compared to healthy controls, that trended towards significance (p = 0.09). All participants showed behavioural flexibility and modified their trust based on behavioural cues from their cooperative and unfair game partners. However, participants with PTSD made significantly lower investments towards the cooperative partner than controls. Investments towards the unfair partner did not differ between groups. Higher trauma scores were associated with lower levels of trust-related investments towards the cooperative but not the unfair game partner. CONCLUSION: The association between reduced trust towards cooperative others in individuals who experienced interpersonal trauma could indicate acquired insensitivity to social rewards or inflexible negative beliefs about others as a sequel of the traumatic experience, which increases in a dose response relationship with the severity of the trauma. A specific focus on cooperation and trusting behaviour could provide a treatment target for future cognitive and pharmacological interventions.

Cost-effectiveness of donepezil and memantine in moderate to severe Alzheimer's disease (the DOMINO-AD trial).

OBJECTIVE: Most investigations of pharmacotherapy for treating Alzheimer's disease focus on patients with mild-to-moderate symptoms, with little evidence to guide clinical decisions when symptoms become severe. We examined whether continuing donepezil, or commencing memantine, is cost-effective for community-dwelling, moderate-to-severe Alzheimer's disease patients. METHODS: Cost-effectiveness analysis was based on a 52-week, multicentre, double-blind, placebo-controlled, factorial clinical trial. A total of 295 community-dwelling patients with moderate/severe Alzheimer's disease, already treated with donepezil, were randomised to: (i) continue donepezil; (ii) discontinue donepezil; (iii) discontinue donepezil and start memantine; or (iv) continue donepezil and start memantine. RESULTS: Continuing donepezil for 52 weeks was more cost-effective than discontinuation, considering cognition, activities of daily living and health-related quality of life. Starting memantine was more cost-effective than donepezil discontinuation. Donepezil-memantine combined is not more cost-effective than donepezil alone. CONCLUSIONS: Robust evidence is now available to inform clinical decisions and commissioning strategies so as to improve patients' lives whilst making efficient use of available resources. Clinical guidelines for treating moderate/severe Alzheimer's disease, such as those issued by NICE in England and Wales, should be revisited. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.

Donepezil and memantine for moderate-to-severe Alzheimer's disease.

BACKGROUND: Clinical trials have shown the benefits of cholinesterase inhibitors for the treatment of mild-to-moderate Alzheimer's disease. It is not known whether treatment benefits continue after the progression to moderate-to-severe disease. METHODS: We assigned 295 community-dwelling patients who had been treated with donepezil for at least 3 months and who had moderate or severe Alzheimer's disease (a score of 5 to 13 on the Standardized Mini-Mental State Examination [SMMSE, on which scores range from 0 to 30, with higher scores indicating better cognitive function]) to continue donepezil, discontinue donepezil, discontinue donepezil and start memantine, or continue donepezil and start memantine. Patients received the study treatment for 52 weeks. The coprimary outcomes were scores on the SMMSE and on the Bristol Activities of Daily Living Scale (BADLS, on which scores range from 0 to 60, with higher scores indicating greater impairment). The minimum clinically important differences were 1.4 points on the SMMSE and 3.5 points on the BADLS. RESULTS: Patients assigned to continue donepezil, as compared with those assigned to discontinue donepezil, had a score on the SMMSE that was higher by an average of 1.9 points (95% confidence interval [CI], 1.3 to 2.5) and a score on the BADLS that was lower (indicating less impairment) by 3.0 points (95% CI, 1.8 to 4.3) (P<0.001 for both comparisons). Patients assigned to receive memantine, as compared with those assigned to receive memantine placebo, had a score on the SMMSE that was an average of 1.2 points higher (95% CI, 0.6 to 1.8; P<0.001) and a score on the BADLS that was 1.5 points lower (95% CI, 0.3 to 2.8; P=0.02). The efficacy of donepezil and of memantine did not differ significantly in the presence or absence of the other. There were no significant benefits of the combination of donepezil and memantine over donepezil alone. CONCLUSIONS: In patients with moderate or severe Alzheimer's disease, continued treatment with donepezil was associated with cognitive benefits that exceeded the minimum clinically important difference and with significant functional benefits over the course of 12 months. (Funded by the U.K. Medical Research Council and the U.K. Alzheimer's Society; Current Controlled Trials number, ISRCTN49545035.).

Exploring attitudes and preferences for dementia screening in Britain: contributions from carers and the general public.

BACKGROUND: Dementia is becoming one of the most important emerging public health concerns in a generation. In societal approaches to the mitigation of major disease 'burden', population screening can sometimes provide an effective approach to improving detection of disease and outcomes. However the acceptability of a systematic population screening programme for dementia, to the British public, is not known. METHODS: A Patient and Public Involvement (PPI) event was organised to give members of the public from the East of England an opportunity to offer their perspectives and to comment on the findings of a systematic literature review looking at attitudes and preferences towards screening for dementia. The event was attended by 36 members of the public and eight national Alzheimer's Society Research Network volunteers. The morning discussion contained a presentation, which defined population screening for attendees but contained no reference to the findings of the review. In the afternoon, findings of the review were presented and a discussion on the results was facilitated. The discussions were recorded, transcribed and subjected to thematic analysis. The NVivo qualitative data software was used to facilitate this process. RESULTS: A total of 23 key themes emerged in relation to the carer and general population. The most frequent themes which emerged were the low levels of understanding and awareness around the dementia syndrome; the acceptability and validity of any tests; costs to the National Health Service (NHS); an individual's existing health status existing health status; financial/profit motive for screening; the inability to change prognosis; and the importance and availability of support. CONCLUSIONS: Factors such as personal beliefs, experiences and attitudes to health impact on decisions to be screened for dementia. A number of additional concerns were raised which were not previously identified in the systematic literature review. These were around the economic incentives for screening (profit motive), the provision of social support, and the economic/social impacts of screening programmes. This may reflect cultural differences in health and social care funding models between Britain and other countries where previous research was conducted.

Attitudes and preferences towards screening for dementia: a systematic review of the literature.

BACKGROUND: Population screening might provide a mechanism to enable early detection of dementia. Yet the potential benefits, harms or acceptability of such a large-scale intervention are not well understood. This research aims to examine the attitudes and preferences of the general public, health care professionals, people with dementia and their carers towards population screening for dementia. METHODS: A systematic review of the international literature was undertaken. A search of fifteen bibliographic databases was conducted (up to 12 July 2012; no language restriction) using terms related to dementia, screening, specific screening tools, case finding, and attitudes and preferences; genetic screening and biomarkers were excluded. All study designs were included except opinion-based papers. Included papers were doubly quality assessed and thematically analysed using NVivo. RESULTS: 29,910 papers were identified of which 29 met the inclusion criteria. We identified seventeen themes relating to the 3 phases of the screening process (pre-, in- and post-screen) - none emerged as more of a facilitator than a barrier to the acceptance of dementia screening. Seven themes emerged in relation to the patient, carer and general population: existing health state; lifestyle and life view; awareness of dementia; role of clinician; communication; benefit; and role of the family. Ten themes emerged in relation to the clinician and healthcare professional: patient's existing health and comorbidities; awareness of dementia; confidence; duration of patient contact; suitability of screening tool; cost; disclosure; time; treatment and prognosis; and stigma. CONCLUSIONS: As for all screening programmes, screening for dementia raises complex issues around preference and choice for clinicians and the public, and it is unclear what specific factors promote or reduce screening acceptance the most. Overall, the level of evidence is low, few large scale studies have been undertaken and none were conducted in representative samples, all affecting the generalizability of identified themes across healthcare contexts. Nevertheless, our findings suggest that population screening for dementia may not be acceptable to either the general public or health care professionals, and highlight where focused efforts are needed to gain insights into dementia specific issues.

Non-pharmacological interventions for agitation in dementia: systematic review of randomised controlled trials.

BACKGROUND: Agitation in dementia is common, persistent and distressing and can lead to care breakdown. Medication is often ineffective and harmful. AIMS: To systematically review randomised controlled trial evidence regarding non-pharmacological interventions. Method We reviewed 33 studies fitting predetermined criteria, assessed their validity and calculated standardised effect sizes (SES). RESULTS: Person-centred care, communication skills training and adapted dementia care mapping decreased symptomatic and severe agitation in care homes immediately (SES range 0.3-1.8) and for up to 6 months afterwards (SES range 0.2-2.2). Activities and music therapy by protocol (SES range 0.5-0.6) decreased overall agitation and sensory intervention decreased clinically significant agitation immediately. Aromatherapy and light therapy did not demonstrate efficacy. CONCLUSIONS: There are evidence-based strategies for care homes. Future interventions should focus on consistent and long-term implementation through staff training. Further research is needed for people living in their own homes.

Cost-effectiveness analyses for mirtazapine and sertraline in dementia: randomised controlled trial.

BACKGROUND: Depression is a common and costly comorbidity in dementia. There are very few data on the cost-effectiveness of antidepressants for depression in dementia and their effects on carer outcomes. AIMS: To evaluate the cost-effectiveness of sertraline and mirtazapine compared with placebo for depression in dementia. METHOD: A pragmatic, multicentre, randomised placebo-controlled trial with a parallel cost-effectiveness analysis (trial registration: ISRCTN88882979 and EudraCT 2006-000105-38). The primary cost-effectiveness analysis compared differences in treatment costs for patients receiving sertraline, mirtazapine or placebo with differences in effectiveness measured by the primary outcome, total Cornell Scale for Depression in Dementia (CSDD) score, over two time periods: 0-13 weeks and 0-39 weeks. The secondary evaluation was a cost-utility analysis using quality-adjusted life years (QALYs) computed from the Euro-Qual (EQ-5D) and societal weights over those same periods. RESULTS: There were 339 participants randomised and 326 with costs data (111 placebo, 107 sertraline, 108 mirtazapine). For the primary outcome, decrease in depression, mirtazapine and sertraline were not cost-effective compared with placebo. However, examining secondary outcomes, the time spent by unpaid carers caring for participants in the mirtazapine group was almost half that for patients receiving placebo (6.74 v. 12.27 hours per week) or sertraline (6.74 v. 12.32 hours per week). Informal care costs over 39 weeks were £1510 and £1522 less for the mirtazapine group compared with placebo and sertraline respectively. CONCLUSIONS: In terms of reducing depression, mirtazapine and sertraline were not cost-effective for treating depression in dementia. However, mirtazapine does appear likely to have been cost-effective if costing includes the impact on unpaid carers and with quality of life included in the outcome. Unpaid (family) carer costs were lower with mirtazapine than sertraline or placebo. This may have been mediated via the putative ability of mirtazapine to ameliorate sleep disturbances and anxiety. Given the priority and the potential value of supporting family carers of people with dementia, further research is warranted to investigate the potential of mirtazapine to help with behavioural and psychological symptoms in dementia and in supporting carers.

Systematic review of the effectiveness of pharmacologic interventions to improve quality of life and well-being in people with dementia.

OBJECTIVE: To review systematically, for the first time, the effectiveness of all pharmacologic interventions to improve quality of life and well-being in people with dementia. DESIGN: Systematic review and meta-analysis. METHODS: We systematically reviewed the 15 randomized controlled trials and one review that fitted predetermined criteria. We included studies that reported the outcomes quality of life, well-being, happiness, or pleasure. MEASUREMENTS: We rated the validity of studies using a checklist. We calculated mean differences between intervention and control groups at follow-up. RESULTS: None of the evaluated trials reported a significant benefit to quality of life or well-being for people with dementia when comparing those taking a drug or its comparator at follow-up (pooled weighted mean difference: 0.18 [95% confidence interval: -0.82 to 0.46]). CONCLUSION: We found no consistent evidence that any drug improves quality of life in people with dementia. We recommend that all dementia trials should include quality of life as an outcome, as this is important to patients, and cannot be presumed from improvements in cognition or other symptomatic outcomes, especially if the latter are small.

The Modern Slavery Core Outcome Set: A Survivor-Driven Consensus on Priority Outcomes for Recovery, Wellbeing, and Reintegration.

There is no consensus on the outcomes needed for the recovery and reintegration of survivors of modern slavery and human trafficking. We developed the Modern Slavery Core Outcome Set (MSCOS) to address this gap. We conducted three English-language reviews on the intervention outcomes sought or experienced by adult survivors: a qualitative systematic review (4 databases, 18 eligible papers, thematic analysis), a rapid review of quantitative intervention studies (four databases, eight eligible papers, content analysis) and a gray literature review (2 databases, 21 websites, a call for evidence, 13 eligible papers, content analysis). We further extracted outcomes from 36 pre-existing interview transcripts with survivors, and seven interviews with survivors from underrepresented groups. We narrowed down outcomes via a consensus process involving: a three-stage E-Delphi survey (191 respondents); and a final consensus workshop (46 participants). We generated 398 outcomes from our 3 reviews, and 843 outcomes from interviews. By removing conceptual and literal duplicates, we reduced this to a longlist of 72 outcomes spanning 10 different domains. The E-Delphi produced a 14-outcome shortlist for the consensus workshop, where 7 final outcomes were chosen. Final outcomes were: "long-term consistent support," "secure and suitable housing," "safety from any trafficker or other abuser," "access to medical treatment," "finding purpose in life and self-actualisation," "access to education," and "compassionate, trauma-informed services." The MSCOS provides outcomes that are accepted by a wide range of stakeholders and that should be measured in intervention evaluation.

Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial.

BACKGROUND: Depression is common in dementia but the evidence base for appropriate drug treatment is sparse and equivocal. We aimed to assess efficacy and safety of two of the most commonly prescribed drugs, sertraline and mirtazapine, compared with placebo. METHODS: We undertook the parallel-group, double-blind, placebo-controlled, Health Technology Assessment Study of the Use of Antidepressants for Depression in Dementia (HTA-SADD) trial in participants from old-age psychiatry services in nine centres in England. Participants were eligible if they had probable or possible Alzheimer's disease, depression (lasting ≥4 weeks), and a Cornell scale for depression in dementia (CSDD) score of 8 or more. Participants were ineligible if they were clinically critical (eg, suicide risk), contraindicated to study drugs, on antidepressants, in another trial, or had no carer. The clinical trials unit at King's College London (UK) randomly allocated participants with a computer-generated block randomisation sequence, stratified by centre, with varying block sizes, in a 1:1:1 ratio to receive sertraline (target dose 150 mg per day), mirtazapine (45 mg), or placebo (control group), all with standard care. The primary outcome was reduction in depression (CSDD score) at 13 weeks (outcomes to 39 weeks were also assessed), assessed with a mixed linear-regression model adjusted for baseline CSDD, time, and treatment centre. This study is registered, number ISRCTN88882979 and EudraCT 2006-000105-38. FINDINGS: Decreases in depression scores at 13 weeks did not differ between 111 controls and 107 participants allocated to receive sertraline (mean difference 1·17, 95% CI -0·23 to 2·58; p=0·10) or mirtazapine (0·01, -1·37 to 1·38; p=0·99), or between participants in the mirtazapine and sertraline groups (1·16, -0·25 to 2·57; p=0·11); these findings persisted to 39 weeks. Fewer controls had adverse reactions (29 of 111 [26%]) than did participants in the sertraline group (46 of 107, 43%; p=0·010) or mirtazapine group (44 of 108, 41%; p=0·031), and fewer serious adverse events rated as severe (p=0·003). Five patients in every group died by week 39. INTERPRETATION: Because of the absence of benefit compared with placebo and increased risk of adverse events, the present practice of use of these antidepressants, with usual care, for first-line treatment of depression in Alzheimer's disease should be reconsidered. FUNDING: UK National Institute of Health Research HTA Programme.

Systematic review of the effectiveness of non-pharmacological interventions to improve quality of life of people with dementia.

BACKGROUND: People with dementia report lower quality of life, but we know little about what interventions might improve it. METHODS: We systematically reviewed 20 randomized controlled trials reporting the effectiveness of non-pharmacological interventions in improving quality of life or well-being of people with dementia meeting predetermined criteria. We rated study validity with a checklist. We contacted authors for additional data. We calculated standardized mean differences (SMD) and, for studies reporting similar interventions, pooled standardized effect sizes (SES). RESULTS: Pooled analyses found that family carer coping strategy-based interventions (four studies, which did not individually achieve significance; n = 420; SES 0.24 (range 0.03-0.45)) and combined patient activity and family carer coping interventions (two studies, not individually significant; n = 191; SES 0.84 (range 0.54-1.14)) might improve quality of life. In one high-quality study, a care management system improved quality of life of people with dementia living at home. Group Cognitive Stimulation Therapy (GCST) improved quality of life of people with dementia in care homes. CONCLUSION: Preliminary evidence indicated that coping strategy-based family carer therapy with or without a patient activity intervention improved quality of life of people with dementia living at home. GCST was the only effective intervention in a higher quality trial for those in care homes, but we did not find such evidence in the community. Few studies explored whether effects continued after the intervention stopped. Future research should explore the longer-term impact of interventions on, and devise strategies to increase, life quality of people with dementia living in care homes or at home without a family carer.

The mass release of migrants from UK immigration detention during the COVID-19 pandemic: what can be learned?

Convincing international evidence demonstrates that immigration detention adversely affects mental health. During the COVID-19 outbreak, additional concerns were raised about the safety and appropriateness of immigration detention. Consequently, several hundred migrants were released en masse from UK immigration detention centres, and few new detentions took place. Over 70% fewer migrants were held in detention centres in June 2020 compared with December 2019. This large 'natural experiment' has demonstrated that detaining fewer migrants is possible and it provides an opportunity to review the necessity for large-scale detention for the purpose of immigration control, as well as its impact on health inequalities. Additionally, given that detainee release arrangements had already been considered unsafe prior to the pandemic, clinicians and service providers should take into consideration that many of those released may not be receiving adequate post-release continuity of care.

Finding agency in limbo: A qualitative investigation into the impact of occupational engagement on the mental health and wellbeing of asylum seekers in the UK.

The process of seeking asylum is complex and often leads to extended periods of uncertainty and liminality for people awaiting decisions on their status. Occupational engagement-defined as meaningful activities and roles that bring purpose and agency to one's life-may be a key driver for mental health recovery for marginalized populations, including asylum seekers with traumatic experiences pre- and post-migration. This study aimed to clarify how occupational engagement impacts on mental health and wellbeing and how asylum seekers maintain engagement in occupation in the context of socio-political constraints of the asylum process. We explored the occupational experiences of 12 clients of one human-rights charity, utilizing community-based participatory research methods. Participants completed group mapping sessions where they depicted routine journeys taken to perform occupations in London, which included discussion around the significance of their journeys. Four participants also completed additional "walking maps"-semi-structured interviews which occurred along a selected "occupational journey" they identified as meaningful to their wellbeing. All data were analyzed using thematic network analysis. Findings revealed that engagement in routine occupations within safe, social spaces positively affects the mental wellbeing of asylum seekers by promoting competence, agency, and feelings of belonging. The liminal space of the asylum process meant that participants' occupational engagement was limited to 'leisure' activities but was still critical to establishing forms of agency associated with their wellbeing. Implications for programs and interventions responding to the needs of asylum seekers are discussed.

Enforced relocation of older people when Care Homes close: a question of life and death?

Care Homes are usually seen as the last refuge for older people but residents are sometimes required to move between homes for administrative purposes. There is concern that such moves threaten their well-being and survival. Relocations have been contested repeatedly in court. A recent ruling and its review of case-law and literature provides guidance for practitioners who may be consulted for advice in this demanding situation.

The impact of anticholinergic burden in Alzheimer's dementia-the LASER-AD study.

OBJECTIVE: to examine the effect of medications with anticholinergic effects on cognitive impairment and deterioration in Alzheimer's dementia (AD). METHODS: cognitive function was measured at baseline and at 6- and 18-month follow-up using the Mini-Mental State Exam (MMSE), the Severe Impairment Battery (SIB) and the Alzheimer's Disease Assessment Battery, Cognitive subsection (ADAS-COG) in a cohort study of 224 participants with AD. Baseline anticholinergic Burden score (ABS) was measured using the Anticholinergic Burden scale and included all prescribed and over the counter medication. RESULTS: the sample was 224 patients with Alzheimer's dementia and 71.4% were women. Their mean age was 81.0 years [SD 7.4 (range 55-98)]. The mean number of medications taken was 3.6 (SD 2.4) and the mean anticholinergic load was 1.1 (SD 1.4, range 0-7). The total number of drugs taken and anticholinergic load correlated (rho = 0.44; P < 0.01). There were no differences in MMSE and other cognitive functioning at either 6 or 18 months after adjusting for baseline cognitive function, age, gender and use of cholinesterase inhibitors between those with, and those without high anticholinergenic load. CONCLUSIONS: medications with anticholinergic effect in patients with AD were not found to effect deterioration in cognition over the subsequent 18 months. Our study did not support a continuing effect of these medications on people with AD who are established on them.

Are old-old patients with major depression more likely to relapse than young-old patients during continuation treatment with escitalopram?

BACKGROUND: Escitalopram has shown efficacy and tolerability in the prevention of relapse in elderly patients with major depressive disorder (MDD). This post-hoc analysis compared time to relapse for young-old patients (n = 197) to that for old-old patients (n = 108). METHOD: Relapse prevention: after 12-weeks open-label treatment, remitters (MADRS ≤12) were randomised to double-blind treatment with escitalopram or placebo and followed over 24-weeks. Patients were outpatients with MDD from 46 European centers aged ≥75 years (old-old) or 65-74 years of age (young-old), treated with escitalopram 10-20 mg/day. Efficacy was assessed using the Montgomery Åsberg Depression Rating Scale (MADRS). RESULTS: After open-label escitalopram treatment, a similar proportion of young-old patients (78%) and old-old patients (72%) achieved remission. In the analysis of time to relapse based on the Cox model (proportional hazards regression), with treatment and age group as covariates, the hazard ratio was 4.4 for placebo versus escitalopram (χ(2)-test, df = 1, χ(2)= 22.5, p < 0.001), whereas the effect of age was not significant, with a hazard ratio of 1.2 for old-old versus young-old (χ(2)-test, df = 1, χ(2) = 0.41, p = 0.520). Escitalopram was well tolerated in both age groups with adverse events reported by 53.1% of young-old patients and 58.3% of old-old patients. There was no significant difference in withdrawal rates due to AEs between age groups (χ(2)-test, χ(2) = 1.669, df = 1, p = 0.196). CONCLUSIONS: Young-old and old-old patients with MDD had comparable rates of remission after open-label escitalopram, and both age groups had much lower rates of relapse on escitalopram than on placebo.

Prevalence of complex post-traumatic stress disorder in refugees and asylum seekers: systematic review.

BACKGROUND: Refugees and asylum seekers often report having experienced numerous complex traumas. It is important to understand the prevalence of complex post-traumatic stress disorder (CPTSD), which can follow complex traumas. AIMS: This systematic review aims to summarise the available literature reporting the prevalence in refugees and asylum seekers of three operationalised definitions of CPTSD: the ICD-11 diagnostic criteria, the ICD-10 criteria (for enduring personality change after catastrophic experience) and the DSM-IV criteria (for disorders of extreme stress not otherwise specified). METHOD: Six electronic databases were searched for studies reporting the prevalence of CPTSD in adult refugee and/or asylum-seeking samples. Owing to heterogeneity between the studies, a narrative synthesis approach was used to summarise studies. Methodological quality was assessed using the Joanna Briggs Critical Appraisal Checklist for Prevalence Studies. This systematic review has been registered with PROSPERO (registration number CRD42020188422, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=188422). RESULTS: Systematic searches identified 15 eligible studies, with 10 examining treatment-seeking samples and five using population samples. CPTSD prevalence in treatment-seeking samples was between 16 and 38%. Prevalence in population samples ranged from 2.2 to 9.3% in four studies, with the fifth reporting a much higher estimate (50.9%). CONCLUSIONS: This review highlights both the high prevalence of CPTSD in treatment samples and the lack of research aiming to establish prevalence of CPTSD in refugee and asylum-seeking populations. Understanding the prevalence of these disabling disorders has implications for policy and healthcare services for the appropriate promotion, planning and provision of suitable treatment and interventions for this highly traumatised population.