Improving the Detection, Assessment, Management and Prevention of Delirium in Hospices (the DAMPen-D study): Feasibility study of a flexible and scalable implementation strategy to deliver guideline-adherent delirium care.

BACKGROUND: Delirium is a complex condition, stressful for all involved. Although highly prevalent in palliative care settings, it remains underdiagnosed and associated with poor outcomes. Guideline-adherent delirium care may improve its detection, assessment and management. AIM: To inform a future definitive study that tests whether an implementation strategy designed to improve guideline-adherent delirium care in palliative care settings improves patient outcomes (reduced proportion of in-patient days with delirium). DESIGN: With Patient Involvement members, we conducted a feasibility study to assess the acceptability of and engagement with the implementation strategy by hospice staff (intervention), and whether clinical record data collection of process (e.g. guideline-adherent delirium care) and clinical outcomes (evidence of delirium using a validated chart-based instrument;) pre- and 12-weeks post-implementation of the intervention would be possible. SETTING/PARTICIPANTS: In-patient admissions in three English hospices. RESULTS: Between June 2021 and December 2022, clinical record data were extracted from 300 consecutive admissions. Despite data collection during COVID-19, target clinical record data collection (n = 300) was achieved. Approximately two-thirds of patients had a delirium episode during in-patient stay at both timepoints. A 6% absolute reduction in proportion of delirium days in those with a delirium episode was observed. Post-implementation improvements in guideline-adherent metrics include: clinical delirium diagnosis 15%-28%; delirium risk assessment 0%-16%; screening on admission 7%-35%. CONCLUSIONS: Collection of data on delirium outcomes and guideline-adherence from clinical records is feasible. The signal of patient benefit supports formal evaluation in a large-scale study.

New UK palliative medicine consultants: clinical and non-clinical preparedness after higher specialty training.

OBJECTIVES: Higher specialty trainees are expected to achieve clinical and non-clinical skills during training in preparation for a consultant role. However, evidence from many specialties from different countries suggests that new consultants are less prepared in non-clinical skills. The transition from trainee to a consultant phase can be challenging. The study aims to identify if new UK Palliative Medicine consultants, within 5 years of their appointment, feel prepared in clinical and non-clinical skills after completing specialty training and understand the support available for them. METHOD: An online survey, designed using previous literature, was distributed via the Association for Palliative Medicine email and social media. Five-point Likert scales and drop-down options to record preparedness were used. Ethics approval was obtained. RESULTS: Forty-four participants from different UK regions completed the survey; 80% were female. The majority felt very/extremely prepared in audit (84%), clinical skills (71%), interaction with colleagues (70%). Majority moderate preparation was human resources (50%), organisation structure (68%) and leadership (52%). Most were not at all or slightly prepared in financial management (70%) and in complaint management (43%). The majority (75%) reported that departmental colleagues gave the most support in stressful situations but almost 49% did not have formal support. CONCLUSION: New palliative medicine consultants require support with some non-clinical roles such as management of complaints and finances. This is consistent with findings from other specialties. New consultants would benefit from formal support. Future research could focus on how trainees could be supported to gain more experience in non-clinical domains.

Exploring pathways to optimise care in malignant bowel obstruction (EPOC): Protocol for a three-phase critical realist approach to theory-led intervention development for shared decision-making.

INTRODUCTION: Malignant bowel obstruction is a distressing complication of cancer, causing pain, nausea and vomiting, and often has a poor prognosis. Severe and rapidly developing symptoms, a lack of robust clinical guidelines and the need for multidisciplinary input make treatment decision-making challenging. Sharing decision-making with people with malignant bowel obstruction and their caregivers can be difficult, and inconsistent communication creates serious deficiencies in care by amplifying patients' distress and uncertainty. Little attention has been paid to the implicit influences on this process-for example, the role of discipline-related norms and the beliefs of decision-makers. This study will explore how these processes work and develop interventions to improve shared decision-making. METHODS AND ANALYSIS: Exploring Pathways to Optimise Care (EPOC) is a three-phase study set within a critical realist framework: (i) realist review, to develop explanatory theory describing collaborative decision-making in the management of malignant bowel obstruction; (ii) an in-depth interview study using modified grounded theory to explore the active ingredients of this collaboration in practice settings; and (iii) the presentation to stakeholders (practitioners, patients and caregivers) of integrated results from Phase I (theory developed from the literature) and Phase II (theory developed from current practice) as a basis for intervention mapping. We aim to produce recommendations to address the challenges, and to develop a set of tools to (i) aid interaction around shared decision-making and (ii) aid interprofessional interaction around the management of this condition. Registration details: The realist review is registered with PROSPERO (CRD42022308251).

Non-steroidal anti-inflammatory drugs for pain in hospice/palliative care: an international pharmacovigilance study.

OBJECTIVES: To describe the current, real-world use of non-steroidal anti-inflammatory drugs for pain and the associated benefits and harms. METHODS: A prospective, multicentre, consecutive cohort pharmacovigilance study conducted at 14 sites across Australia, Aotearoa/New Zealand and the UK including hospital, hospice inpatient and outpatient services. Pain scores and harms were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events at baseline, 2 days and 14 days. Ad-hoc safety reporting continued until day 28. RESULTS: Data were collected from 92 patients between March 2018 and October 2021. Most patients had cancer (91%) and were coprescribed opioids (90%). At 14 days, 83% of patients had benefit from non-steroidal anti-inflammatory drugs and 22% had harm. The most common harms were nausea (8%), vomiting (3%), acute kidney injury (3%) and non-gastrointestinal bleeding (3%); only 2% were severe and no patients ceased their non-steroidal anti-inflammatory drugs due to toxicity. Overall, 65% had benefit without harm and 3% had harm without benefit. CONCLUSIONS: Most patients benefited from non-steroidal anti-inflammatory drugs with only one in five patients experiencing tolerable harm. This suggests that short-term use of non-steroidal anti-inflammatory drugs in patients receiving palliative care is safer than previously thought and may be underused.

Educational impact of COVID-19 on foundation doctors and the decision to take a break from structured approved training programmes in the United Kingdom.

INTRODUCTION: The COVID-19 pandemic impacted the Foundation Programme for doctors in the United Kingdom. Foundation doctors were working under increased pressure and significant changes were made to their training. AIMS: The aim of this study is to explore the educational impact the COVID-19 pandemic had on foundation doctors and to understand how this resulted in doctors choosing to take time away from structured training programmes within the United Kingdom to make up for lost educational opportunities. METHODS: In this phenomenological research, semi-structured interviews were carried out with post-foundation doctors who had completed their training during the pandemic. The data collected from these interviews were coded to carry out a thematic analysis. RESULTS: All 12 participants reported that their formalised teaching had been cancelled, and due to the pandemic, many doctors felt that service provision was prioritised over their postgraduate education. Some doctors had positive experiences of informal teaching; however, many felt they missed out on educational opportunities. Doctors acknowledged that this was a contributing factor when deciding to take time out of training. This also resulted in doctors seeking educational opportunities outside of training. DISCUSSION: The pandemic created many educational challenges for foundation doctors; this has contributed to doctors deciding to take time away from training. In some cases, due to a focus on service provision and their 'lost education', doctors are using time away from training to address their own specific educational needs. The impact of this 'lost education' requires further research and needs to be considered when doctors do apply to speciality training.

Experiences of a Novel Integrated Service for Older Adults at Risk of Frailty: A Qualitative Study.

The UK has a significant and growing population of older adults with frailty and complex healthcare needs, necessitating innovative care solutions. This study aimed to explore patients' and carers' experiences of a novel integrated service that was set up to address the increasing healthcare needs of older people living with frailty. A qualitative study that combined free-text survey questions with in-depth interviews. This study is part of a larger non-randomized trial of the service, with evaluation of wellbeing and quality of life at baseline, 2 to 4 weeks, and 10 to 14 weeks. Patients (aged 65 and above) with an electronic Frailty Index in the severe range and their informal family carers participated in this study. Data were collected between April 2019 and March 2020. Free text survey responses and interview data were subjected to reflexive thematic analyses. Four themes were generated: the overall experience of the service; interactions within the service; treatment and interventions; and outcomes due to the service. Most participants wanted further follow-up and more extensive integration with other services. Most participants described their overall experience positively, especially the available time to address their full range of concerns, but opportunities to integrate the service more fully and to extend follow-up remain.

Development of a Core Outcome Set for the research and assessment of inoperable malignant bowel obstruction.

BACKGROUND: Malignant bowel obstruction is experienced by 15% of people with advanced cancer, preventing them from eating and drinking and causing pain, nausea and vomiting. Surgery is not always appropriate. Management options include tube or stent drainage of intestinal contents and symptom control using medication. Published literature describing palliative interventions uses a broad range of outcome measures, few of which are patient-relevant. This hinders evidence synthesis, and fails to consider the perspectives of people undergoing treatment. AIMS: To develop a Core Outcome Set for the assessment of inoperable malignant bowel obstruction with clinician, patient and caregiver involvement, using COMET methodology (Core Outcome Measures in Effectiveness Trials). METHODS: A systematic review of clinical trials and observational studies, a rapid review of the qualitative literature and in-depth patient and clinician interviews were conducted to identify a comprehensive list of outcomes. Outcomes were compared and consolidated by the study Steering Group and Patient and Public Involvement contributors, and presented to an international clinical Expert Panel for review. Outcomes from the finalised list were rated for importance in a three-round international Delphi process: results of two survey rounds were circulated to respondents, and two separate consensus meetings were conducted with clinicians and with patients and caregivers via virtual conferencing, using live polling to reach agreement on a Core Outcome Set. RESULTS: 130 unique outcomes were identified. Following the independent Expert Panel review, 82 outcomes were taken into round 1 of the Delphi survey; 24 outcomes reached criteria for critical importance across all stakeholder groups and none reached criteria for dropping. All outcomes rated critically important were taken forward for re-rating in round 2 and all other outcomes dropped. In round 2, all outcomes were voted critically important by at least one stakeholder group. Round 2 outcomes were presented again at online consensus meetings, categorised as high ranking (n = 9), middle ranking (n = 7) or low ranking (n = 8). Stakeholders reached agreement on 16 core outcomes across four key domains: Symptom control, Life impact, Treatment outcomes, and Communication and patient preferences. CONCLUSION: Use of this Core Outcome Set can help to address current challenges in making sense of the evidence around treatment for inoperable malignant bowel obstruction to date, and underpin a more robust future approach. Clearer communication and an honest understanding between all stakeholders will help to provide a basis for responsible decision-making in this distressing situation in clinical practice.

Non-pharmacological interventions to manage psychological distress in patients living with cancer: a systematic review.

BACKGROUND: Psychological distress is common in patients with cancer; interfering with physical and psychological wellbeing, and hindering management of physical symptoms. Our aim was to systematically review published evidence on non-pharmacological interventions for cancer-related psychological distress, at all stages of the disease. METHODS: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review was registered on PROSPERO (CRD42022311729). Searches were made using eight online databases to identify studies meeting our inclusion criteria. Data were collected on outcome measures, modes of delivery, resources and evidence of efficacy. A meta-analysis was planned if data allowed. Quality was assessed using the Mixed Methods Appraisal Tool (MMAT). RESULTS: Fifty-nine studies with 17,628 participants were included. One third of studies included mindfulness, talking or group therapies. Half of all studies reported statistically significant improvements in distress. Statistically significant intervention effects on distress were most prevalent for mindfulness techniques. Four of these mindfulness studies had moderate effect sizes (d = -0.71[95% CI: -1.04, -0.37] p < 0.001) (d = -0.60 [95% CI: -3.44, -0.89] p < 0.001) (d = -0.77 [CI: -0.146, -1.954] p < 0.01) (d = -0.69 [CI: -0.18, -1.19] p = 0.008) and one had a large effect size (d = -1.03 [95% CI: -1.51, -0.54] p < 0.001). Heterogeneity of studies precluded meta-analysis. Study quality was variable and some had a high risk of bias. CONCLUSIONS: The majority of studies using a mindfulness intervention in this review are efficacious at alleviating distress. Mindfulness-including brief, self-administered interventions-merits further investigation, using adequately powered, high-quality studies. SYSTEMATIC REVIEW REGISTRATION: This systematic review is registered on PROSPERO, number CRD42022311729.

Effects of Opioids on Immune and Endocrine Function in Patients with Cancer Pain.

OPINION STATEMENT: Opioids are an important treatment in managing cancer pain. Uncontrolled pain can be detrimental to function and quality of life. Common adverse effects of opioids such as sedation, constipation and nausea are well recognised, but opioid effects on the endocrine and immune systems are less apparent. The evidence for the immunomodulatory effects of opioids suggest that some opioids might be immunosuppressive and that their use might be associated with reduced survival and increased rates of infection in patients with cancer. However, the quality of this evidence is limited. Opioid-induced endocrinopathies, in particular opioid-induced hypogonadism, may also impact cancer survival and impair quality of life. But again, evidence in patients with cancer is limited, especially with regard to their management. There are some data that different opioids influence immune and endocrine function with varying outcomes. For example, some opioids, such as tramadol and buprenorphine, demonstrate immune-sparing qualities when compared to others. However, most of this data is preclinical and without adequate clinical correlation; thus, no opioid can currently be recommended over another in this context. Higher opioid doses might have more effect on immune and endocrine function. Ultimately, it is prudent to use the lowest effective dose to control the cancer pain. Clinical presentations of opioid-induced endocrinopathies should be considered in patients with cancer and assessed for, particularly in long-term opioid users. Hormone replacement therapies may be considered where appropriate with support from endocrinology specialists.

Tapentadol for the management of cancer pain in adults: an update.

PURPOSE OF REVIEW: Tapentadol is the first of a new class of analgesics, having synergistic µ-opioid receptor agonist and noradrenaline reuptake inhibitory actions. It has been widely researched in many areas of pain, often in noninferiority studies against potent opioids. This review describes all randomized and recent nonrandomized studies of tapentadol in adults with cancer pain. RECENT FINDINGS: Tapentadol has been shown to be at least as effective as morphine and oxycodone in five randomized (two of which were multicenter and double-blind) and a range of nonrandomized trials, although caution is needed when interpreting these results. It is effective in both opioid-naive patients and those already taking opioids. By having a lower µ-opioid receptor binding affinity, it has fewer opioid-related toxicities such as constipation and nausea. A recent randomized trial comparing tapentadol to tapentadol plus duloxetine in patients with chemotherapy-induced peripheral neuropathy shows similar improvement in both groups in a range of pain relieving and quality of life measures, with similar adverse effects. SUMMARY: Tapentadol has been shown in a range of studies to be an effective analgesic and thus should be considered as an alternative to morphine and oxycodone, especially when opioid toxicities are an issue.

Over a third of palliative medicine physicians meet burnout criteria: Results from a survey study during the COVID-19 pandemic.

BACKGROUND: Palliative medicine physicians may be at higher risk of burnout due to increased stressors and compromised resilience during the COVID-19 pandemic. Burnout prevalence and factors influencing this among UK and Irish palliative medicine physicians is unknown. AIM: To determine the prevalence of burnout and the degree of resilience among UK and Irish palliative medicine physicians during the COVID-19 pandemic, and associated factors. DESIGN: Online survey using validated assessment scales assessed burnout and resilience: The Maslach Burnout Inventory Human Services Survey for Medical Personnel [MBI-HSS (MP)] and the Connor-Davidson Resilience Scale (CD-RISC). Additional tools assessed depressive symptoms, alcohol use, and quality of life. SETTING/PARTICIPANTS: Association of Palliative Medicine of UK and Ireland members actively practising in hospital, hospice or community settings. RESULTS: There were 544 respondents from the 815 eligible participants (66.8%), 462 provided complete MBI-HSS (MP) data and were analysed. Of those 181/462 (39.2%) met burnout criteria, based on high emotional exhaustion or depersonalisation subscales of the MBI-HSS (MP). A reduced odds of burnout was observed among physicians who worked ⩽20 h/week (vs 31-40 h/week, adjusted odds ratio (aOR) 0.03, 95% confidence interval (CI) 0.002-0.56) and who had a greater perceived level of clinical support (aOR 0.70, 95% CI 0.62-0.80). Physicians with higher levels of depressive symptoms had higher odds of burnout (aOR 18.32, 95% CI 6.75-49.73). Resilience, mean (SD) CD-RISC score, was lower in physicians who met burnout criteria compared to those who did not (62.6 (11.1) vs 70.0 (11.3); p < 0.001). CONCLUSIONS: Over one-third of palliative medicine physicians meet burnout criteria. The provision of enhanced organisational and colleague support is paramount in both the current and future pandemics.

A non-randomised controlled study to assess the effectiveness of a new proactive multidisciplinary care intervention for older people living with frailty.

BACKGROUND: Integrated care may improve outcomes for older people living with frailty. We aimed to assess the effectiveness of a new, anticipatory, multidisciplinary care service in improving the wellbeing and quality of life (QoL) of older people living with severe frailty. METHODS: A community-based non-randomised controlled study. Participants (≥65 years, electronic Frailty Index ≥0.36) received either the new integrated care service plus usual care, or usual care alone. Data collection was at three time points: baseline, 2-4 weeks, and 10-14 weeks. The primary outcome was patient wellbeing (symptoms and other concerns) at 2-4 weeks, measured using the Integrated Palliative care Outcome Scale (IPOS); the secondary outcome was QoL, measured using EQ-5D-5L. To test duration of effect and safety, wellbeing and QoL were also measured at 10-14 weeks. Descriptive statistics were used to characterise and compare intervention and control groups (eligible but had not accessed the new service), with t-test, Chi-Square, or Mann-Whitney U tests (as appropriate) to test differences at each time point. Generalised linear modelling, with propensity score matching, was used for further group comparisons. Data were analysed using STATA v17. RESULTS: 199 intervention and 54 control participants were recruited. At baseline, intervention and control groups were similar in age, gender, ethnicity, living status, and body mass index, but not functional status or area deprivation score. At 2-4 weeks, wellbeing had improved in the intervention group but worsened in the control (median IPOS -5 versus 2, p<0.001). QoL improved in the intervention group but was unchanged in the control (median EQ-5D-5L 0.12, versus 0.00, p<0.001). After adjusting for age, gender, and living status, the intervention group had an average total IPOS score reduction at 2-4 weeks of 6.34 (95% CI: -9.01: -4.26, p<0.05); this improvement was sustained, with an average total IPOS score reduction at 10-14 weeks of 6.36 (95% CI: -8.91:-3.80, p<0.05). After propensity score matching based on functional status/area deprivation, modelling showed similar results, with a reduction in IPOS score at 2-4 weeks in the intervention group of 7.88 (95% CI: -12.80: -2.96, p<0.001). CONCLUSIONS: Our findings suggest that the new, anticipatory, multidisciplinary care service may have improved the overall wellbeing and quality of life of older people living with frailty at 2-4 weeks and the improvement in wellbeing was sustained at three months. ETHICS APPROVAL: NHS Research Ethics Committee 18/YH/0470 and IRAS-250981. TRIAL REGISTRATION: The trial was retrospectively registered at the International Standard Randomised Controlled Trial Number (ISRCTN) registry (registration date: 01/08/2022, registration number: ISRCTN10613839).

Effect of Opioids on Survival in Patients with Cancer.

Opioids are commonly used for pain management in patients with cancer. They have a range of unwanted effects, including some that potentially influence cancer growth. This article reviews the data assessing the effects of opioids on survival in patients with cancer. Many studies assessing this show an association between opioids and decreased survival. This effect is present even at very low doses of opioids. These studies do not assess causality, so it is not known if it is a direct effect of opioids on survival. As the control groups are not matched to the opioid group it might be that opioids are being used to control pain and patients receiving opioids have more aggressive cancers and it is the underlying cancer which is causing the decreased survival. Furthermore, although some studies allude to different opioids having different effects on survival, often all opioids are pooled in analysis. Future work needs to try to ascertain causality and differentiate between different opioids, pain, and cancer-mediated effects on survival in specific cancer types. Until then, opioids should continue to be used in patients with cancer as part of measures to optimise comfort and quality of life.

Parental death: a systematic review of support experiences and needs of children and parent survivors.

BACKGROUND: Bereaved people need a supportive response from those around them. Knowing children's and surviving parents' needs following parental death is the first step to ensuring a supportive response. However, no systematic review has reported on this phenomenon. AIM: To systematically identify and synthesise qualitative literature exploring support experiences of parentally bereaved children and surviving parents. METHODS: Systematic review with thematic synthesis, following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. MEDLINE, Embase, PsycINFO, CINAHL and the British Nursing Database were searched for relevant papers to September 2021. Included studies were appraised for quality and thematically synthesised using Thomas and Harden's thematic synthesis framework. RESULTS: Fifteen qualitative studies from nine countries were included. There were four analytical themes from the children's perspectives (1) Openness of communication with children about death and dying, (2) Children's challenges of managing change, (3) Navigating emotions, and (4) Children's acceptability, access and engagement with support. There were three analytical themes from the parents' perspectives: (1) Adjusting as a parent, (2) Supporting their children, and (3) Parent's acceptability, access and engagement with support. CONCLUSIONS: Following a parental death, open and honest communication and involvement in what is happening within the family will help children cope. Both children and parents suppress emotions and avoid conversations to protect each other and those around them. A taboo around death exists and constrains the support some families receive. Childhood bereavement is a public health issue, with a need for professionals and communities to better understand and respond to the needs of bereaved families.CRD42020166179.

The range and suitability of outcome measures used in the assessment of palliative treatment for inoperable malignant bowel obstruction: A systematic review.

BACKGROUND: Malignant bowel obstruction, a complication of certain advanced cancers, causes severe symptoms which profoundly affect quality of life. Clinical management remains complex, and outcome assessment is inconsistent. AIM: To identify outcomes evaluating palliative treatment for inoperable malignant bowel obstruction, as part of a four-phase study developing a core outcome set. DESIGN: The review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA); PROSPERO (ID: CRD42019150648). Eligible studies included at least one subgroup with obstruction below the ligament of Treitz undergoing palliative treatment for inoperable malignant bowel obstruction. Study quality was not assessed because the review does not evaluate efficacy. DATA SOURCES: Medline, Embase, the Cochrane Database, CINAHL, PSYCinfo Caresearch, Open Grey and BASE were searched for trials and observational studies in October 2021. RESULTS: A total of 4769 studies were screened, 290 full texts retrieved and 80 (13,898 participants) included in a narrative synthesis; 343 outcomes were extracted verbatim and pooled into 90 unique terms across six domains: physiological, nutrition, life impact, resource use, mortality and survival. Prevalent outcomes included adverse events (78% of studies), survival (54%), symptom control (39%) and mortality (31%). Key individual symptoms assessed were vomiting (41% of studies), nausea (34%) and pain (33%); 19% of studies assessed quality of life. CONCLUSIONS: Assessment focuses on survival, complications and overall symptom control. There is a need for definitions of treatment 'success' that are meaningful to patients, a more consistent approach to symptom assessment, and greater consideration of how to measure wellbeing in this population.

Pharmacovigilance in hospice/palliative care: Net effect of amitriptyline or nortriptyline on neuropathic pain: UTS/IMPACCT Rapid programme international consecutive cohort.

BACKGROUND: Real-world effectiveness of interventions in palliative care need to be systematically quantified to inform patient/clinical decisions. Neuropathic pain is prevalent and difficult to palliate. Tricyclic antidepressants have an established role for some neuropathic pain aetiologies, but this is less clear in palliative care. AIM: To describe the real-world use and outcomes from amitriptyline or nortriptyline for neuropathic pain in palliative care. DESIGN: An international, prospective, consecutive cohort post-marketing/phase IV/pharmacovigilance/quality improvement study of palliative care patients with neuropathic pain where the treating clinician had already made the decision to use a tricyclic antidepressant. Data were entered at set times: baseline, and days 7 and 14. Likert scales graded benefits and harms. SETTING/PARTICIPANTS: Twenty-one sites (inpatient, outpatient, community) participated in six countries between June 2016 and March 2019. Patients had clinician-diagnosed neuropathic pain. RESULTS: One hundred and fifty patients were prescribed amitriptyline (110) or nortriptyline (40) of whom: 85% had cancer; mean age 73.2 years (SD 12.3); mean 0-4 scores for neuropathic pain at baseline were 1.8 (SD 1.0). By day 14, doses of amitriptyline were 57 mg (SD 21) and nortriptyline (48 mg (SD 21). Fifty-two (34.7%) patients had pain improvement by day 14 (amitriptyline (45/110 (43.3%); nortriptyline (7/40 (18.9%)). Thirty-nine (27.7%) had new harms; (amitriptyline 29/104 (27.9%); nortriptyline 10/37 (27.0%); dizziness (n = 23), dry mouth (n = 20), constipation (n = 14), urinary retention (n = 10)). Benefits without harms occurred (amitriptyline (26/104 (25.0%); nortriptyline (4/37 (10.8%)). CONCLUSIONS: Benefits favoured amitriptyline while harms were similar for both medications.