Annabel Price

The development of evidence-based European guidelines on the management of depression in palliative cancer care.

Depression is common in cancer patients, particularly those with advanced disease. It is associated with adverse outcomes such as increased pain, disability and poorer prognosis. Our aim was to produce a European evidence-based clinical guideline on the management of depression in patients receiving palliative care to inform practice, establish policy, promote European consensus and ultimately improve patient outcomes. Recommendations were devised using the best available evidence. Where evidence was absent or equivocal, Delphi consensus methods were implemented to elicit and refine expert opinion. Evidence was graded according to the process proposed by GRADE. The resulting guideline has three main sections: (1) prevention; (2) detection, diagnosis and assessment; and (3) treatment. The prevention section outlines strategies such as optimal palliative care and support, effective communication and information-giving. The detection section provides recommendations on symptoms, screening, diagnosis and severity assessment. The treatment section gives guidance on treatment decisions including choice of psychological therapy and antidepressant medication. This is the first comprehensive, evidence-based guideline on managing depression in palliative care. It has the potential to improve patient outcomes by enabling clinicians to access and implement evidence-based knowledge quickly and easily.

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.

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 Parkinsons 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.

The treatment of depression in patients with advanced cancer undergoing palliative care.

Purpose of reviewDepression is a common condition affecting those with advanced cancer, but evidence for effective treatment has been sparse. In recent years, there has been a welcome increase in research activity, with both pharmacological and nonpharmacological treatments being trialled. Recent findingsThis review assesses recent studies of pharmacological interventions including antidepressants and psychostimulants and nonpharmacological interventions including cognitive behavioural therapy, supportive expressive group therapy, couples therapy, complex interventions and aromatherapy massage for treatment of depression. Recent published systematic reviews of interventions for depression are also discussed. SummaryRecent research efforts have paid particular attention to psychological interventions, with cognitive behavioural therapy approaches being most evaluated and showing some encouraging results. Pharmacological interventions remain challenging to assess using rigorous clinical trial methodology, and clinicians still rely upon data derived from studies using general populations and those with less advanced disease or other physical illness. Methodologically sound trials of pharmacological interventions for treatment of depression in advanced disease remains an area of research need.

The factor structure of the PHQ-9 in palliative care

OBJECTIVES The Primary Care Evaluation of Mental Disorders Patient Health Questionnaire (PRIME-MD PHQ-9) is a common screening tool designed to facilitate detection of depression according to DSM-IV criteria. However, the factor structure of the PHQ-9 within the palliative care population has not been evaluated. METHODS 300 participants completed the PHQ-9 within one week of referral to a palliative care service. Participants completed the PHQ-9 again four weeks later (n=213). Confirmatory factor analysis (CFA) and multiple-group CFA were undertaken to test the factor structure of the PHQ-9 and evaluate model invariance over time. RESULTS A two-factor model comprising somatic and cognitive-affective latent factors provided the best fit to the data. Multiple-group CFA suggested model invariance over time. Structural equation modelling revealed that follow-up (time 2) cognitive-affective and somatic symptoms were predicted by their baseline (time 1) factors. CONCLUSIONS The PHQ-9 measures two stable depression factors (cognitive-affective and somatic) within the palliative care population. Studies are now required to examine the trajectories of these symptoms over time in relation to clinical intervention and events.

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.

Prevalence, course and associations of desire for hastened death in a UK palliative population: a cross-sectional study

Objectives To determine the prevalence, severity and remission of desire for hastened death (DHD) in a UK representative sample of patients with advanced disease receiving palliative care and to examine the associations of desire for death. Design A cross-sectional survey with 4-week follow-up. Setting St Christophers Hospice, Sydenham, South London, which is a large hospice with homecare, outpatient and inpatient facilities serving five London boroughs. Participants 300 patients newly referred to the hospice for palliative care. Main outcome measures The Desire for Death Rating Scale (DDRS). Results At T1 33/300 (11%) reported DHD and 11/300 (3.7%) had more serious or pervasive DHD. Of those who expressed DHD at T1 and were interviewed at both time points, 35% no longer reported these thoughts. Of those who reported no DHD at T1, 8% reported DHD at T2. The majority of those who had more severe DHD at T1 had a reduced DHD score by T2. Factors associated with T1 DHD included presence of non-malignant disease, depression, more severe physical symptoms, hopelessness and perceived loss of dignity. Conclusions The prevalence of DHD was at the lower end of that seen in previous studies using similar samples. More severe DHD was uncommon and for most part remitted to some extent during the study. The provision of symptom control and timely detection and intervention for depression coupled with a focus on optimising function, instilling hope and preserving dignity are likely to contribute to alleviation of DHD in patients with advanced illness.

Mortality in dementia with Lewy bodies compared with Alzheimer's dementia: a retrospective naturalistic cohort study.

Objectives To use routine clinical data to investigate survival in dementia with Lewy bodies (DLB) compared with Alzheimer’s dementia (AD). DLB is the second most common dementia subtype after AD, accounting for around 7% of dementia diagnoses in secondary care, though studies suggest that it is underdiagnosed by up to 50%. Most previous studies of DLB have been based on select research cohorts, so little is known about the outcome of the disease in routine healthcare settings. Setting Cambridgeshire & Peterborough NHS Foundation Trust, a mental health trust providing secondary mental health care in England. Sample 251 DLB and 222 AD identified from an anonymised database derived from electronic clinical case records across an 8-year period (2005–2012), with mortality data updated to May 2015. Results Raw (uncorrected) median survival was 3.72 years for DLB (95% CI 3.33 to 4.14) and 6.95 years for AD (95% CI 5.78 to 8.12). Controlling for age at diagnosis, comorbidity and antipsychotic prescribing the model predicted median survival for DLB was 3.3 years (95% CI 2.88 to 3.83) for males and 4.0 years (95% CI 3.55 to 5.00) for females, while median survival for AD was 6.7 years (95% CI 5.27 to 8.51) for males and 7.0 years (95% CI 5.92 to 8.73) for females. Conclusion Survival from first presentation with cognitive impairment was markedly shorter in DLB compared with AD, independent of age, sex, physical comorbidity or antipsychotic prescribing. This finding, in one of the largest clinical cohorts of DLB cases assembled to date, adds to existing evidence for poorer survival for DLB versus AD. There is an urgent need for further research to understand possible mechanisms accounting for this finding.

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

BackgroundIn 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.MethodsThis 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.ResultsThere 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.ConclusionIdeas 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.