Challenges in diagnosis and management of delirium in Lewy body disease.

BACKGROUND: Delirium is an acute onset and fluctuating impairment of cognition, attention and arousal, often precipitated by acute illness. Lewy body disease (LBD) is an umbrella term for a range of clinical conditions, including Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB). People living with LBD seem to be more susceptible to delirium than those with other subtypes of dementia. AIM: To describe the challenges in clinical diagnosis and management of LBD. METHODS: A systematic review of published literature on diagnosis and management of delirium in LBD. RESULTS: Delirium is particularly challenging to diagnose in LBD as many of the clinical characteristics which define delirium such as inattention, fluctuating arousal, complex visual hallucinations and delusions, are also common to LBD. Distinguishing delirium from LBD can be very difficult clinically especially in the prodromal stages. Both under and over diagnosis of delirium, and under and over treatment of the symptoms have the potential to compromise the care and safety of people with a diagnosed or undiagnosed LBD. Clinicians are currently working with an extremely limited set of evidence-based management options for those with delirium in the context of a LBD diagnosis. For patients with LBD and their families this is an area of clinical practice that needs focused research.

Mortality rates and proximal causes of death in patients with Lewy body dementia versus Alzheimer's disease: A longitudinal study using secondary care mental health records.

BACKGROUND: Previous studies have shown reduced survival in Lewy body dementia (LBD) compared to Alzheimer's disease (AD), but the reasons for this are not known. We identified cause of death categories accounting for the reduced survival in LBD. METHODS: We linked cohorts of patients with dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD) and AD, with proximal cause of death data. We examined mortality by dementia group and hazard ratios for each death category by dementia group in males and females separately. In a specific focus on the dementia group with the highest mortality rate versus reference, we examined cumulative incidence to identify the main causes of death accounting for the excess deaths. RESULTS: Hazard ratios for death were higher in PDD and DLB compared to AD, for both males and females. PDD males had the highest hazard ratio for death across the dementia comparison groups (HR 2.7, 95% CI 2.2-3.3). Compared with AD, hazard ratios for "nervous system" causes of death were significantly elevated in all LBD groups. Additional significant cause-of-death categories included aspiration pneumonia, genitourinary causes, other respiratory causes, circulatory and a "symptoms and signs" category in PDD males; other respiratory causes in DLB males; mental disorders in PDD females; and aspiration pneumonia, genitourinary and other respiratory causes in DLB females. CONCLUSION: Further research and cohort development is required to investigate differences by age group, to extend cohort follow-up to the whole population and to investigate the risk-balance of interventions which may differ by dementia group.

Association between antidementia medication use and mortality in people diagnosed with dementia with Lewy bodies in the UK: A retrospective cohort study.

BACKGROUND: Dementia with Lewy bodies (DLBs) is a common cause of dementia but has higher mortality than Alzheimer's disease (AD). The reasons for this are unclear, but antidementia drugs (including acetylcholinesterase inhibitors [AChEIs] and memantine) symptomatically benefit people with DLB and might improve outcomes. We investigated whether AChEIs and/or memantine were associated with reduced hospital admissions and mortality. METHODS AND FINDINGS: We performed a retrospective cohort study of those diagnosed with DLB between 1 January 2005 and 31 December 2019, using data from electronic clinical records of secondary care mental health services in Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), United Kingdom (catchment area population approximately 0.86 million), as well as linked records from national Hospital Episode Statistics (HES) data. Eligible patients were those who started AChEIs or memantine within 3 months of their diagnosis (cases) and those who never used AChEIs or memantine (controls). Outcomes included admission, length of stay, and mortality. Cox proportional hazard and linear regression models were used. Of 592 patients with DLB, 219 never took AChEIs or memantine, 100 took AChEIs only, and 273 took both AChEIs and memantine. The cohorts were followed up for an average of 896 days, 981 days, and 1,004 days, respectively. There were no significant differences in the cohorts' baseline characteristics, except for socioeconomic status that was lower in patients who never took AChEIs or memantine (χ2 = 23.34, P = 0.003). After controlling for confounding by sociodemographic factors (age, sex, marital status, ethnicity, socioeconomic status), antipsychotic use, antidepressant use, cognitive status, physical comorbidity, anticholinergic burden, and global health performance, compared with patients who never took AChEIs or memantine, patients taking AChEIs only or taking both had a significantly lower risk of death (adjusted hazard ratio (HR) = 0.67, 95% CI = 0.48 to 0.93, p = 0.02; adjusted HR = 0.64, 95% CI = 0.50 to 0.83, P = 0.001, respectively). Those taking AChEIs or both AChEIs and memantine had significantly shorter periods of unplanned hospital admission for physical disorders (adjusted coefficient -13.48, 95% CI = [-26.87, -0.09], P = 0.049; adjusted coefficient -14.21, 95% CI = [-24.58, -3.85], P = 0.007, respectively), but no difference in length of stay for planned admissions for physical disorders, or for admissions for mental health disorders. No significant additional associations of memantine on admission, length of stay, and mortality were found (all P > 0.05). The main limitation was that this was a naturalistic study and possible confounds cannot be fully controlled, and there may be selection bias resulting from nonrandom prescription behaviour in clinical practice. However, we mimicked the intention-to-treat design of clinical trials, and the majority of baseline characters were balanced between cohorts. In addition, our series of sensitivity analyses confirmed the consistency of our results. CONCLUSION: In this study, we observed that use of AChEIs with or without memantine in DLB was associated with shorter duration of hospital admissions and decreased risk of mortality. Although our study was naturalistic, it supports further the use of AChEIs in DLB.

Study of mirtazapine for agitated behaviours in dementia (SYMBAD): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Agitation is common in people with dementia and negatively affects the quality of life of both people with dementia and carers. Non-drug patient-centred care is the first-line treatment, but there is a need for other treatment when this care is not effective. Current evidence is sparse on safer and effective alternatives to antipsychotics. We assessed the efficacy and safety of mirtazapine, an antidepressant prescribed for agitation in dementia. METHODS: This parallel-group, double-blind, placebo-controlled trial-the Study of Mirtazapine for Agitated Behaviours in Dementia trial (SYMBAD)-was done in 26 UK centres. Participants had probable or possible Alzheimer's disease, agitation unresponsive to non-drug treatment, and a Cohen-Mansfield Agitation Inventory (CMAI) score of 45 or more. They were randomly assigned (1:1) to receive either mirtazapine (titrated to 45 mg) or placebo. The primary outcome was reduction in CMAI score at 12 weeks. This trial is registered with ClinicalTrials.gov, NCT03031184, and ISRCTN17411897. FINDINGS: Between Jan 26, 2017, and March 6, 2020, 204 participants were recruited and randomised. Mean CMAI scores at 12 weeks were not significantly different between participants receiving mirtazapine and participants receiving placebo (adjusted mean difference -1·74, 95% CI -7·17 to 3·69; p=0·53). The number of controls with adverse events (65 [64%] of 102 controls) was similar to that in the mirtazapine group (67 [66%] of 102 participants receiving mirtazapine). However, there were more deaths in the mirtazapine group (n=7) by week 16 than in the control group (n=1), with post-hoc analysis suggesting this difference was of marginal statistical significance (p=0·065). INTERPRETATION: This trial found no benefit of mirtazapine compared with placebo, and we observed a potentially higher mortality with use of mirtazapine. The data from this study do not support using mirtazapine as a treatment for agitation in dementia. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

Serotonin depletion impairs both Pavlovian and instrumental reversal learning in healthy humans.

Serotonin is involved in updating responses to changing environmental circumstances. Optimising behaviour to maximise reward and minimise punishment may require shifting strategies upon encountering new situations. Likewise, autonomic responses to threats are critical for survival yet must be modified as danger shifts from one source to another. Whilst numerous psychiatric disorders are characterised by behavioural and autonomic inflexibility, few studies have examined the contribution of serotonin in humans. We modelled both processes, respectively, in two independent experiments (N = 97). Experiment 1 assessed instrumental (stimulus-response-outcome) reversal learning whereby individuals learned through trial and error which action was most optimal for obtaining reward or avoiding punishment initially, and the contingencies subsequently reversed serially. Experiment 2 examined Pavlovian (stimulus-outcome) reversal learning assessed by the skin conductance response: one innately threatening stimulus predicted receipt of an uncomfortable electric shock and another did not; these contingencies swapped in a reversal phase. Upon depleting the serotonin precursor tryptophan-in a double-blind randomised placebo-controlled design-healthy volunteers showed impairments in updating both actions and autonomic responses to reflect changing contingencies. Reversal deficits in each domain, furthermore, were correlated with the extent of tryptophan depletion. Initial Pavlovian conditioning, moreover, which involved innately threatening stimuli, was potentiated by depletion. These results translate findings in experimental animals to humans and have implications for the neurochemical basis of cognitive inflexibility.

Cost-effectiveness of mirtazapine for agitated behaviors in dementia: findings from a randomized controlled trial.

OBJECTIVES: To examine the costs and cost-effectiveness of mirtazapine compared to placebo over 12-week follow-up. DESIGN: Economic evaluation in a double-blind randomized controlled trial of mirtazapine vs. placebo. SETTING: Community settings and care homes in 26 UK centers. PARTICIPANTS: People with probable or possible Alzheimer's disease and agitation. MEASUREMENTS: Primary outcome included incremental cost of participants' health and social care per 6-point difference in CMAI score at 12 weeks. Secondary cost-utility analyses examined participants' and unpaid carers' gain in quality-adjusted life years (derived from EQ-5D-5L, DEMQOL-Proxy-U, and DEMQOL-U) from the health and social care and societal perspectives. RESULTS: One hundred and two participants were allocated to each group; 81 mirtazapine and 90 placebo participants completed a 12-week assessment (87 and 95, respectively, completed a 6-week assessment). Mirtazapine and placebo groups did not differ on mean CMAI scores or health and social care costs over the study period, before or after adjustment for center and living arrangement (independent living/care home). On the primary outcome, neither mirtazapine nor placebo could be considered a cost-effective strategy with a high level of confidence. Groups did not differ in terms of participant self- or proxy-rated or carer self-rated quality of life scores, health and social care or societal costs, before or after adjustment. CONCLUSIONS: On cost-effectiveness grounds, the use of mirtazapine cannot be recommended for agitated behaviors in people living with dementia. Effective and cost-effective medications for agitation in dementia remain to be identified in cases where non-pharmacological strategies for managing agitation have been unsuccessful.

I've had a good life, what's left is a bonus: factor analysis of the Mental Adjustment to Cancer Scale in a palliative care population.

BACKGROUND: The Mental Adjustment to Cancer Scale is an assessment tool commonly used to measure coping in cancer patients, which characterises adaptive coping under the label of 'fighting spirit'. AIM: This study explores adaptation in patients with advanced cancer, by examining the factor structure of the Mental Adjustment to Cancer Scale. Further aims were to examine associations between types of coping and psychological outcomes measured at the same time (time 1) and 4 weeks after referral to palliative care services (time 2). DESIGN: A cross-sectional study with a follow-up assessment 4 weeks later. Factor analysis examined the structure of the Mental Adjustment to Cancer Scale at time 1. SETTING/PARTICIPANTS: A total of 275 patients with advanced cancer receiving palliative care, of whom 193 took part at follow-up. RESULTS: This study provided evidence for the internal consistency and validity of a new scale of 'acceptance and positivity' for use in advanced cancer patients. Patients with a desire for hastened death had lower acceptance and positivity, and patients with higher global quality of life reported a higher level. Social support was positively associated with acceptance and positivity. Higher scores on the acceptance and positivity scale were associated with reduced odds of a desire for hastened death at time 2. CONCLUSION: Adaptation to advanced cancer differs from adaptation to early stage cancer, comprising a general acceptance of the illness and trying to make the most of the time that is left. Individuals with low social support were less likely to evidence appropriate adaptation to their illness.

Concepts of mental capacity for patients requesting assisted suicide: a qualitative analysis of expert evidence presented to the Commission on Assisted Dying.

BACKGROUND: In May 2013 a new Assisted Dying Bill was tabled in the House of Lords and is currently scheduled for a second reading in May 2014. The Bill was informed by the report of the Commission on Assisted Dying which itself was informed by evidence presented by invited experts.This study aims to explore how the experts presenting evidence to the Commission on Assisted Dying conceptualised mental capacity for patients requesting assisted suicide and examine these concepts particularly in relation to the principles of the Mental Capacity Act 2005. METHODS: This study was a secondary qualitative analysis of 36 transcripts of oral evidence and 12 pieces of written evidence submitted by invited experts to the Commission on Assisted Dying using a framework approach. RESULTS: There was agreement on the importance of mental capacity as a central safeguard in proposed assisted dying legislation. Concepts of mental capacity, however, were inconsistent. There was a tendency towards a conceptual and clinical shift toward a presumption of incapacity. This appeared to be based on the belief that assisted suicide should only be open to those with a high degree of mental capacity to make the decision.The 'boundaries' around the definition of mental capacity appeared to be on a continuum between a circumscribed legal 'cognitive' definition of capacity (in which most applicants would be found to have capacity unless significantly cognitively impaired) and a more inclusive definition which would take into account wider concepts such as autonomy, rationality, voluntariness and decision specific factors such as motivation for decision making. CONCLUSION: Ideas presented to the Commission on Assisted Dying about mental capacity as it relates to assisted suicide were inconsistent and in a number of cases at variance with the principles of the Mental Capacity Act 2005. Further work needs to be done to establish a consensus as to what constitutes capacity for this decision and whether current legal frameworks are able to support clinicians in determining capacity for this group.

Impact of psychotic disorder on transplant eligibility and outcomes.

PURPOSE OF REVIEW: Organ transplantation decisions are complex, and psychosocial assessment is an important part of the process. The impact of pretransplant psychotic disorder on posttransplant outcomes is unclear, but some guidelines cite psychosis as a relative contraindication to organ transplantation because of concerns about medication adherence and poor postoperative outcomes. This review explores the evidence for poorer solid organ transplant outcomes for people with preexisting psychotic disorders and discusses future directions for how research can contribute to a better understanding of how organ transplantation outcomes are affected by psychotic illness. RECENT FINDINGS: When added to the existing small body of literature, recent findings show a continuing insufficient evidence base to suggest that the presence of psychotic disorder increases risk of poorer adherence and outcomes. The evidence points to social isolation being a key factor in poorer adherence posttransplant. SUMMARY: Further research is needed to determine the impact of psychotic disorder on transplant outcomes, but based on current evidence a diagnosis of psychotic disorder should not preclude consideration for organ transplantation.

Proactive and integrated consultation-liaison psychiatry for older medical inpatients: A mixed methods description of training, care provided and clinician experience in the HOME study.

OBJECTIVES: To describe the practical experience of delivering a proactive and integrated consultation-liaison (C-L) psychiatry service model (PICLP). PICLP is designed for older medical inpatients and is explicitly biopsychosocial and discharge-focused. In this paper we report: (a) observations on the training of 15 clinicians (seven senior C-L psychiatrists and eight assisting clinicians) to deliver PICLP; (b) the care they provided to 1359 patients; (c) their experiences of working in this new way. METHOD: A mixed methods observational study using quantitative and qualitative data, collected prospectively over two years as part of The HOME Study (a randomized trial comparing PICLP with usual care). RESULTS: The clinicians were successfully trained to deliver PICLP according to the service manual. They proactively assessed all patients and found that most had multiple biopsychosocial problems impeding their timely discharge from hospital. They integrated with ward teams to provide a range of interventions aimed at addressing these problems. Delivering PICLP took a modest amount of clinical time, and the clinicians experienced it as both clinically valuable and professionally rewarding. CONCLUSION: The experience of delivering PICLP highlights the special role that C-L psychiatry clinicians, working in a proactive and integrated way, can play in medical care.

A pragmatic, multicentre, double-blind, placebo-controlled randomised trial to assess the safety, clinical and cost-effectiveness of mirtazapine and carbamazepine in people with Alzheimer's disease and agitated behaviours: the HTA-SYMBAD trial.

Background: Agitation is common and impacts negatively on people with dementia and carers. Non-drug patient-centred care is first-line treatment, but we need other treatment when this fails. Current evidence is sparse on safer and effective alternatives to antipsychotics. Objectives: To assess clinical and cost-effectiveness and safety of mirtazapine and carbamazepine in treating agitation in dementia. Design: Pragmatic, phase III, multicentre, double-blind, superiority, randomised, placebo-controlled trial of the clinical effectiveness of mirtazapine over 12 weeks (carbamazepine arm discontinued). Setting: Twenty-six UK secondary care centres. Participants: Eligibility: probable or possible Alzheimer's disease, agitation unresponsive to non-drug treatment, Cohen-Mansfield Agitation Inventory score ≥ 45. Interventions: Mirtazapine (target 45 mg), carbamazepine (target 300 mg) and placebo. Outcome measures: Primary: Cohen-Mansfield Agitation Inventory score 12 weeks post randomisation. Main economic outcome evaluation: incremental cost per six-point difference in Cohen-Mansfield Agitation Inventory score at 12 weeks, from health and social care system perspective. Data from participants and informants at baseline, 6 and 12 weeks. Long-term follow-up Cohen-Mansfield Agitation Inventory data collected by telephone from informants at 6 and 12 months. Randomisation and blinding: Participants allocated 1 : 1 : 1 ratio (to discontinuation of the carbamazepine arm, 1 : 1 thereafter) to receive placebo or carbamazepine or mirtazapine, with treatment as usual. Random allocation was block stratified by centre and residence type with random block lengths of three or six (after discontinuation of carbamazepine, two or four). Double-blind, with drug and placebo identically encapsulated. Referring clinicians, participants, trial management team and research workers who did assessments were masked to group allocation. Results: Two hundred and forty-four participants recruited and randomised (102 mirtazapine, 102 placebo, 40 carbamazepine). The carbamazepine arm was discontinued due to slow overall recruitment; carbamazepine/placebo analyses are therefore statistically underpowered and not detailed in the abstract. Mean difference placebo-mirtazapine (-1.74, 95% confidence interval -7.17 to 3.69; p = 0.53). Harms: The number of controls with adverse events (65/102, 64%) was similar to the mirtazapine group (67/102, 66%). However, there were more deaths in the mirtazapine group (n = 7) by week 16 than in the control group (n = 1). Post hoc analysis suggests this was of marginal statistical significance (p = 0.065); this difference did not persist at 6- and 12-month assessments. At 12 weeks, the costs of unpaid care by the dyadic carer were significantly higher in the mirtazapine than placebo group [difference: £1120 (95% confidence interval £56 to £2184)]. In the cost-effectiveness analyses, mean raw and adjusted outcome scores and costs of the complete cases samples showed no differences between groups. Limitations: Our study has four important potential limitations: (1) we dropped the proposed carbamazepine group; (2) the trial was not powered to investigate a mortality difference between the groups; (3) recruitment beyond February 2020, was constrained by the COVID-19 pandemic; and (4) generalisability is limited by recruitment of participants from old-age psychiatry services and care homes. Conclusions: The data suggest mirtazapine is not clinically or cost-effective (compared to placebo) for agitation in dementia. There is little reason to recommend mirtazapine for people with dementia with agitation. Future work: Effective and cost-effective management strategies for agitation in dementia are needed where non-pharmacological approaches are unsuccessful. Study registration: This trial is registered as ISRCTN17411897/NCT03031184. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 23. See the NIHR Journals Library website for further project information.

It is common for people with Alzheimer's disease to experience agitation, for example feeling restless or unsettled. If left untreated, agitation can lead to poorer quality of life and increased hospitalisation and strain for family carers. Often these symptoms are treated with medications that are usually used to manage psychosis (antipsychotic drugs), but such medication has limited effectiveness and can cause serious adverse effects to patients, including risk of increased death. Two medications that are already commonly prescribed for other health issues, mirtazapine (an antidepressant) and carbamazepine (a drug used to treat epilepsy), had been identified as a possible alternative way of treating agitation in Alzheimer's disease that might not have the harms associated with antipsychotic medication. In this study, we compared the effects of giving mirtazapine or carbamazepine with a dummy drug (placebo) in people with Alzheimer's disease who were experiencing agitation. The results of the study showed that neither medication was any more effective than the placebo in reducing agitation over 12 weeks in terms of improving symptoms, or in economic terms. Mirtazapine may lead to additional carer costs as compared to placebo. The study findings are stronger for mirtazapine than carbamazepine because the carbamazepine arm was stopped when it had recruited less than half the numbers needed. That was done because the study was not recruiting quickly enough to support both the mirtazapine and the carbamazepine arms. The findings from this study show that mirtazapine should not be recommended to treat agitation in Alzheimer's disease. More work is needed to formulate effective ways and to test new drug and non-drug treatments for agitation in dementia.

Predictors of non-remission of depression in a palliative care population.

BACKGROUND: Prospective studies of depression in palliative care are rare. Two studies that examine depression prospectively in patients with advanced disease have not looked at predictors of remission. AIMS: to explore prospective predictors of non-remission of depression in palliative care. DESIGN AND PARTICIPANTS: The study design comprised two data collections: initial assessment on referral to a palliative care service in South London, UK, and a four-week follow-up. Seventy six participants met the criteria for 'any depressive syndrome' at the time 1 assessment, using the PRIME-MD, who also participated at time 2. The outcome measure was remission (N = 39) or non-remission (N = 37) of depression by time 2. RESULTS: The findings showed that reporting low social support from family and friends at time of referral was the most powerful risk factor for non-remission. There was also a strong association between improved physical symptoms, from time 1 to 2, and remission of depression. CONCLUSIONS: This study in palliative care is the first of which we are aware to explore factors associated with non-remission of depression. Depressed patients identified with low social support on referral to palliative care services might particularly benefit from additional psychosocial care in the treatment of their depression. This study provides evidence that effective physical symptom management in palliative care may be a valuable intervention for depressive symptoms.

Gender differences in prevalence of depression among patients receiving palliative care: the role of dependency.

BACKGROUND: in community studies the prevalence of depression is higher in women than men; however, in palliative care settings this relationship is usually less strong, absent or reversed. AIM: to identify reasons for excess depression among men receiving palliative care. DESIGN: cross-sectional study. SETTING/PARTICIPANTS: we interviewed 300 patients recruited from a large hospice in South East London. Depression was measured using the Primary Care Evaluation of Mental Disorder. RESULTS: the higher prevalence of depression among men was not explained by a higher prevalence of particular types of cancer nor confounding by other covariates. Possible effect modifiers were examined. Depending on others for help with basic tasks (eating, dressing, washing or using the toilet) was a risk factor for depression in men only, with 37.8% of dependent men being depressed compared to 2.4% of similarly affected women (OR = 24.3, 3.1-193.2, p = 0.003). We observed a dose-response effect between the level of dependency and depression in men (p for trend = 0.01). CONCLUSION: depending on others for help with basic tasks appears to contribute to the burden of depression among men with terminal illness. This gender-specific association may explain why the usual gender differences in depression prevalence are not observed in palliative care.

Antidepressants for the treatment of depression in neurological disorders: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Despite the high prevalence of depression in people with neurological disorders, no previous study has sought to summarise existing evidence on the use of antidepressants in this population. A systematic review and meta-analysis was undertaken to determine whether antidepressants are more effective than placebo in the treatment of depression in neurological disorders, and whether any benefit is associated with improvement in function. METHODS: Embase, Pubmed, Psycinfo and Cochrane trial registers were searched for randomised controlled trials (RCTs) comparing the efficacy of antidepressant and placebo in the treatment of depression in adults with a neurological disorder. FINDINGS: 20 RCTs were included in the review, including patients with Parkinson's disease, multiple sclerosis, brain injury, epilepsy and stroke. Outcomes were analysed at four time points: 4-5 weeks, 6-8 weeks, 9-18 weeks and >18 weeks. The primary outcome was response to treatment at 6-8 weeks. The evidence favoured the use of antidepressants over placebo at all time points although pooled results were not statistically significant at all time points. At 6-8 weeks, antidepressant treatment was associated with a greater than twofold odds of remission (OR 2.23; 95% CI 1.54 to 3.23; number needed to treat=7). Fewer data were available for quality of life, and functional and cognitive outcomes, and there was little evidence of improvement with antidepressant treatment. INTERPRETATION: Antidepressants are effective for the treatment of depression in patients with neurological disorders but the evidence for the efficacy of antidepressants in improving quality of life, and functional and cognitive outcomes is inconclusive.

Assisted suicide: why psychiatrists should engage in the debate.

There is an increasing appetite for a change in the law to allow assisted suicide. This editorial suggests that psychiatrists should engage in the debate because the issues at stake will affect us, and we are likely to have a significant part to play were the law to be changed. We suggest that there are three main areas where psychiatrists' expertise may be informative: (a) the extent to which safeguards to limit the availability of assisted dying to target groups can be applied safely and fairly, including to individuals with psychiatric disorders; (b) the complexities inherent in assessing mental capacity; and (c) the degree to which individuals adapt or change their desires, particularly in relation to suicidal behaviours.

Antidepressants for the treatment of depression in palliative care: systematic review and meta-analysis.

Depression can exacerbate symptoms associated with life-threatening illness and increase disability and distress. In palliative care, depression occurs in a context of multiple symptoms, which complicates detection and treatment. While systematic reviews of antidepressants have been conducted in specific life-threatening diseases, no previous study has synthesized the evidence in palliative care. The objective of this study was to determine the efficacy of antidepressants for the treatment of depression in palliative care. MEDLINE, EMBASE, PSYCINFO and Cochrane trials registers were systematically searched to identify randomized controlled trials comparing antidepressants and placebo for the treatment of depression in palliative care. The primary outcome was efficacy assessed at three time-points. Twenty-five studies were included in the review. At each time-point antidepressants were more efficacious than placebo: 4-5 weeks odds ratio (OR) 1.93 (1.15-3.42) p = 0.001; 6-8 weeks OR 2.25 (1.38-3.67) p = 0.001; 9-18 weeks OR 2.71 (1.50-4.91) p = 0.001. This review provides evidence that antidepressants are effective in treating depression in palliative care. Their superiority over placebo is apparent within 4-5 weeks and increases with continued use. It is probable that the effect sizes yielded in this review overestimate the efficacy of antidepressants due to biases such as selective reporting and publication. Nevertheless, the magnitude and consistency of the effect suggests genuine benefit.

The clinical epidemiology of depression in palliative care and the predictive value of somatic symptoms: cross-sectional survey with four-week follow-up.

This cross-sectional survey aimed to determine the prevalence and remission of depression in patients receiving palliative care and to ascertain the predictive value of somatic symptoms in making the diagnosis. Three hundred consecutive patients were interviewed within one week of their initial assessment by a specialist nurse at a palliative care service with in-patient and homecare facilities in south London, UK. Depression was assessed using the PRIME-MD PHQ-9. Presence of somatic symptoms (fatigue, sleep disturbance, poor appetite) was determined using the EORTC-QLQ-C30 quality of life questionnaire. Fifty-eight (19.3% [15.3 to 23.3]) patients met criteria for Major Depressive Disorder; 109 (36.3% [32.3 to 40.3]) met criteria for 'Any depressive syndrome'. Patients with Major Depressive Disorder were more likely to be male, and to have non-malignant disease, pain, poor performance status and desire for an early death. Of those patients with Major Depressive Disorder at baseline, 69% (27/39) had remitted four weeks later. Of those not depressed at baseline, 11% (19/174) met criteria for depression at follow-up. The positive predictive values of sleep disturbance, poor appetite and fatigue were low (<24%), whereas the negative predictive values of these symptoms were high (>89%). The high prevalence of depression in palliative care attests to the need for psychological assessment and support. Depression in patients receiving palliative care is unstable, suggesting that symptoms should be carefully monitored.

Senior doctors' opinions of rational suicide.

CONTEXT: The attitudes of medical professionals towards physician assisted dying have been widely discussed. Less explored is the level of agreement among physicians on the possibility of 'rational suicide'-a considered suicide act made by a sound mind and a precondition of assisted dying legislation. OBJECTIVE: To assess attitudes towards rational suicide in a representative sample of senior doctors in England and Wales. METHODS: A postal survey was conducted of 1000 consultants and general practitioners randomly selected from a commercially available database. The main outcome of interest was level of agreement with a statement about rational suicide. RESULTS: The corrected participation rate was 50%; 363 questionnaires were analysed. Overall 72% of doctors agreed with the possibility of rational suicide, 17% disagreed, and 11% were neutral. Doctors who identified themselves as being more religious were more likely to disagree. Some doctors who disagreed with legalisation of physician assisted suicide nevertheless agreed with the concept of rational suicide. CONCLUSIONS: Most senior doctors in England and Wales feel that rational suicide is possible. There was no association with specialty. Strong religious belief was associated with disagreement, although levels of agreement were still high in people reporting the strongest religious belief. Most doctors who were opposed to physician assisted suicide believed that rational suicide was possible, suggesting that some medical opposition is best explained by other factors such as concerns of assessment and protection of vulnerable patients.

Expert opinion on detecting and treating depression in palliative care: A Delphi study.

BACKGROUND: There is a dearth of data regarding the optimal method of detecting and treating depression in palliative care. This study applied the Delphi method to evaluate expert opinion on choice of screening tool, choice of antidepressant and choice of psychological therapy. The aim was to inform the development of best practice recommendations for the European Palliative Care Research Collaborative clinical practice guideline on managing depression in palliative care. METHODS: 18 members of an international, multi-professional expert group completed a structured questionnaire in two rounds, rating their agreement with proposed items on a scale from 0-10 and annotating with additional comments. The median and range were calculated to give a statistical average of the experts' ratings. RESULTS: There was contention regarding the benefits of screening, with 'routine informal asking' (median 8.5 (0-10)) rated more highly than formal screening tools such as the Hospital Anxiety and Depression Scale (median 7.0 (1-10). Mirtazapine (median 9 (7-10) and citalopram (median 9 (5-10) were the considered the best choice of antidepressant and cognitive behavioural therapy (median 9.0 (3-10) the best choice of psychological therapy. CONCLUSIONS: The range of expert ratings was broad, indicating discordance in the views of experts. Direct comparative data from randomised controlled trials are needed to strengthen the evidence-base and achieve clarity on how best to detect and treat depression in this setting.