Exploration of pain assessment and management processes in oncology outpatient services with healthcare professionals: a qualitative study.

OBJECTIVES: This study explored cancer pain management practices and clinical care pathways used by healthcare professionals (HCPs) to understand the barriers and facilitators for standardised pain management in oncology outpatient services (OS). DESIGN: Data were collected using semistructured interviews that were audio-recorded and transcribed. The data were analysed using thematic analysis. SETTING: Three NHS trusts with oncology OS in Northern England. PARTICIPANTS: Twenty HCPs with varied roles (eg, oncologist and nurse) and experiences (eg, registrar and consultant) from different cancer site clinics (eg, breast and lung). Data were analysed using thematic analysis. RESULTS: HCPs discussed cancer pain management practices during consultation and supporting continuity of care beyond consultation. Key findings included : (1) HCPs' level of clinical experience influenced pain assessments; (2) remote consulting impeded experienced HCPs to do detailed pain assessments; (3) diffusion of HCP responsibility to manage cancer pain; (4) nurses facilitated pain management support with patients and (5) continuity of care for pain management was constrained by the integration of multidisciplinary teams. CONCLUSIONS: These data demonstrate HCP cancer pain management practices varied and were unstructured. Recommendations are made for a standardised cancer pain management intervention: (1) detailed evaluation of pain with a tailored self-management strategy; (2) implementation of a structured pain assessment that supports remote consultations, (3) pain assessment tool that can support both experienced and less experienced clinicians. These findings will inform the development of a cancer pain management tool to integrate within routine oncology OS.

Experience of an NIHR Clinical Lectureship (medical/dental) and the determining factors for a clinical academic career post lectureship: a mixed-method evaluation.

OBJECTIVES: The objective of this study is to investigate early-to-late postdoctoral clinical academic progression and the experiences of NIHR Clinical Lectureship (CL) fellows, considering enablers and barriers to success, and identifying the factors associated with immediate progression to a clinical academic role following completion of the award. SETTING: Datasets of CL awardees across the UK. PARTICIPANTS: For semistructured interviews, n=40 CL awardees that had finished their award within the previous 5 years. For quantitative analysis, n=1226 completed or currently active CL awardees. OUTCOME MEASURES: The responses from the semistructured interviews to the defined questions on experiences during the award, postaward progression, and enablers and barriers to academic progression. Other primary outcome measures were quantitative data on first destinations postaward, demographic data, and whether an awardee had previously held an NIHR Academic Clinical Fellowship (ACF) or was a recipient of the Academy of Medical Sciences (AMS) Starter Grant. RESULTS: CL awardees identified numerous benefits to the award, with the majority achieving their aims. Most awardees progressed to a clinical academic role; however, some returned to a clinical only position, citing concerns around the time pressure associated with balancing clinical and academic responsibilities, and the competition to attain further postdoctoral awards. The region of the award partnership, year of award end and success in applying for an AMS Starter Grant were associated with progression to a clinical academic role. Gender, holding an ACF and having a craft or non-craft specialty had no independent statistical association with clinical academic progression. CONCLUSIONS: The CL is a valued element of the Integrated Academic Pathway. By addressing issues around later postdoctoral progression opportunities, responding to challenges experienced by CLs, and by understanding the factors identified in this study associated with clinical academic progression, it should be possible to increase the proportion of CLs that become fully independent clinical academic research leaders. PARTICIPANTS: 1226 NIHR CLs active or completed on the award between 2006 and 2020.

A systematic review of subcutaneous versus intramuscular or intravenous routes of opioid administration on pain outcomes in cancer and post-surgical clinical populations - challenging current assumptions in palliative care practice.

Objective: The objective of this review is to investigate the use of the subcutaneous route of administration of analgesics, common practice within palliative medicine. Design: Systematic review using consensus approach, direct comparison of subcutaneous route with intravenous and intramuscular routes. Results: The limited available evidence demonstrates non-inferiority of the subcutaneous route in both cancer patients and those post-surgery. Pain management is comparable to other routes. Route-related side effects are rare and systemic side effects are comparable. Conclusion: Pain management is a critical role of palliative medicine. The subcutaneous route of administration offers a viable option for the delivery of parenteral analgesia within all settings, including the community. This review supports current practice, demonstrating equivalence with more invasive routes of administration.

Designing a clinical trial of non-steroidal anti-inflammatory drugs for cancer pain: a survey of UK palliative care physicians.

OBJECTIVES: Insufficient quality evidence exists to support or refute the use of non-steroidal anti-inflammatory drugs (NSAIDs) in the management of cancer pain. We aimed to determine the most clinically pragmatic design of a future randominsed controlled trial (RCT), based on how NSAIDs are currently used and perceived efficacy. METHODS: An online survey was distributed to members of the Association for Palliative Medicine of Great Britain and Ireland examining NSAID use, indications and perceived efficacy, as well as duration of respondents' experience in palliative medicine. RESULTS: 23% of 968 members responded. A placebo-controlled trial of NSAIDs as a strong opioid adjunct in cancer-related bone pain was considered the most clinically pragmatic design. Concerning current practice, oral administration was the preferential route (79.4%), dosed regularly (79.5%). Selective cyclooxygenase-2 (COX-2) inhibitors and non-selective COX-2 inhibitors were considered similarly effective by 45% in cancer pain; ibuprofen being the first line oral NSAID of choice (42.6%). Treatment efficacy is generally determined within 1 week (94.3%). On a Likert scale, most physicians consider NSAIDs improve cancer pain either 'sometimes' (57.7%) or 'often' (40%). Years of specialist palliative care experience did not affect perception of efficacy (p=0.353). CONCLUSIONS: A randomised controlled trial of NSAIDs as opioid adjuncts for cancer-related bone pain would be the most pragmatic design supported by palliative care clinicians to benefit clinical practice.

Non-steroidal anti-inflammatory drugs (NSAIDs) in cancer pain: A database analysis to determine recruitment feasibility for a clinical trial.

BACKGROUND: Insufficient evidence exists to support or refute use of NSAIDs for managing cancer pain. Palliative physicians support a placebo-controlled trial of NSAIDs as strong opioid adjuncts for cancer-induced bone pain as the most pragmatic design to benefit clinical practice. AIM: We aimed to determine patient numbers receiving palliative radiotherapy for cancer-induced bone pain, estimate the suitability of NSAID prescription and determine survival, guiding future trial feasibility. DESIGN: A retrospective observational database analysis was undertaken using 5 years of routinely collected regional radiotherapy and healthcare data, filtered to achieve a cohort with cancer-induced bone pain. Demographics and survival were linked to available serology and co-morbidity data. SETTING/PARTICIPANTS: Data was sourced from the regional Leeds Cancer Centre, a tertiary care setting. Patients who underwent palliative single fraction 8 gray (Gy) radiotherapy treatment for cancer-induced bone pain were included, totalling 2411 over 5 years. RESULTS: A mean of 478 patients received palliative radiotherapy for cancer-induced bone pain annually. Median age (IQR) was 70 (62-77); negatively skewed (-0.69). 65.3% died within 1 year of radiotherapy; 48.0% within 6 months. Age was not associated with survival on univariable analysis (HR 0.999 (95% CI 0.996-1.003)). Serology from 1063 patients (44.2%) were available; eGFR was ⩾60 mL/min/1.73 m2 in 83.0%. From available data (1352 pts; 51.6% of sample), 20.2% had a coded co-morbidity contra-indicating NSAIDs. Combining serology and co-morbidities, 68.5% could be considered for NSAID prescription. CONCLUSIONS: Patient numbers at a regional radiotherapy centre support the feasibility of trial recruitment. Available serology and co-morbidity data suggest two-thirds may be suitable for NSAID prescription.

Characterising the Features of 381 Clinical Studies Evaluating Transcutaneous Electrical Nerve Stimulation (TENS) for Pain Relief: A Secondary Analysis of the Meta-TENS Study to Improve Future Research.

Background and Objectives: Characterising the features of methodologies, clinical attributes and intervention protocols, of studies is valuable to advise directions for research and practice. This article reports the findings of a secondary analysis of the features from studies screened as part of a large systematic review of TENS (the meta-TENS study). Materials and Methods: A descriptive analysis was performed on information associated with methodology, sample populations and intervention protocols from 381 randomised controlled trials (24,532 participants) evaluating TENS delivered at a strong comfortable intensity at the painful site in adults with pain, irrespective of diagnosis. Results: Studies were conducted in 43 countries commonly using parallel group design (n = 334) and one comparator group (n = 231). Mean ± standard deviation (SD) study sample size (64.05 ± 58.29 participants) and TENS group size (27.67 ± 21.90 participants) were small, with only 13 of 381 studies having 100 participants or more in the TENS group. Most TENS interventions were 'high frequency' (>10 pps, n = 276) and using 100 Hz (109/353 reports that stated a pulse frequency value). Of 476 comparator groups, 54.2% were active treatments (i.e., analgesic medication(s), exercise, manual therapies and electrophysical agents). Of 202 placebo comparator groups, 155 used a TENS device that did not deliver currents. At least 216 of 383 study groups were able to access other treatments whilst receiving TENS. Only 136 out of 381 reports included a statement about adverse events. Conclusions: Clinical studies on TENS are dominated by small parallel group evaluations of high frequency TENS that are often contaminated by concurrent treatment(s). Study reports tended focus on physiological and clinical implications rather than the veracity of methodology and findings. Previously published criteria for designing and reporting TENS studies were neglected and this should be corrected in future research using insights gleaned from this analysis.

Efficacy and safety of transcutaneous electrical nerve stimulation (TENS) for acute and chronic pain in adults: a systematic review and meta-analysis of 381 studies (the meta-TENS study).

OBJECTIVE: To investigate the efficacy and safety of transcutaneous electrical nerve stimulation (TENS) for relief of pain in adults. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Cochrane Central, Embase (and others) from inception to July 2019 and updated on 17 May 2020. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials (RCTs) comparing strong non-painful TENS at or close to the site of pain versus placebo or other treatments in adults with pain, irrespective of diagnosis. DATA EXTRACTION AND SYNTHESIS: Reviewers independently screened, extracted data and assessed risk of bias (RoB, Cochrane tool) and certainty of evidence (Grading and Recommendations, Assessment, Development and Evaluation). Mean pain intensity and proportions of participants achieving reductions of pain intensity (≥30% or >50%) during or immediately after TENS. Random effect models were used to calculate standardised mean differences (SMD) and risk ratios. Subgroup analyses were related to trial methodology and characteristics of pain. RESULTS: The review included 381 RCTs (24 532 participants). Pain intensity was lower during or immediately after TENS compared with placebo (91 RCTs, 92 samples, n=4841, SMD=-0·96 (95% CI -1·14 to -0·78), moderate-certainty evidence). Methodological (eg, RoB, sample size) and pain characteristics (eg, acute vs chronic, diagnosis) did not modify the effect. Pain intensity was lower during or immediately after TENS compared with pharmacological and non-pharmacological treatments used as part of standard of care (61 RCTs, 61 samples, n=3155, SMD = -0·72 (95% CI -0·95 to -0·50], low-certainty evidence). Levels of evidence were downgraded because of small-sized trials contributing to imprecision in magnitude estimates. Data were limited for other outcomes including adverse events which were poorly reported, generally mild and not different to comparators. CONCLUSION: There was moderate-certainty evidence that pain intensity is lower during or immediately after TENS compared with placebo and without serious adverse events. PROSPERO REGISTRATION NUMBER: CRD42019125054.

Ten years of NIHR research training: who got an award? A retrospective cohort study.

OBJECTIVE: In 2017, the National Institute for Health Research (NIHR) academy produced a strategic review of training, which reported the variation in application characteristics associated with success rates. It was noted that variation in applicant characteristic was not independent of one another. Therefore, the aim of this secondary analysis was to investigate the inter-relationships in order to identify factors (or groups of factors) most associated with application numbers and success rates. DESIGN: Retrospective data were gathered from 4388 applications to NIHR Academy between 2007 and 2016. Multinominal logistic regression models quantified the likelihood of success depending on changes in the explanatory factors; relative risk ratios with 95% CIs. A classification tree analysis was built using exhaustive χ2 automatic interaction detection to better understand the effect of interactions between explanatory variables on application success rates. RESULTS: 936 (21.3%) applications were awarded. Applications from males and females were equally likely to be successful (p=0.71). There was an overall reduction in numbers of applications from females as award seniority increased from predoctoral to professorship. Applications from institutions with a medical school had a 2.6-fold increase in likelihood of success (p<0.001). Classification tree analysis revealed key predictors of application success: award level, type of programme, previous NIHR award experience and applying form a medical school. CONCLUSION: Success rates did not differ according to gender, and doctors were not more likely to be successful than applications from other professions. Taken together, these findings suggest an essential fairness in how the quality of a submitted application is assessed, but they also raise questions about variation in the opportunity to submit a high-quality application. The companion qualitative study (Burkshaw et al. (2021) BMJ Open) provides valuable insight into potential candidate mechanisms and discusses how research capacity development initiatives might be targeted in the future.

Ten years of NIHR research training: perceptions of the programmes: a qualitative interview study.

OBJECTIVES: The UK National Institute for Health Research (NIHR) training programmes were created to build and sustain research capacity in healthcare. Following the training programme 10-year strategic review, this qualitative study aimed to deepen understanding of facilitators and barriers for those progressing through NIHR-supported research careers. DESIGN: Semistructured qualitative study. DATA COLLECTION AND ANALYSIS: Telephone interviews conducted between May and August 2017 were digitally recorded, transcribed and analysed using Framework Approach. SETTING: UK National Health Service (NHS) Trusts, university medical schools, District General Hospitals, Integrated Academic Training Programme centres and Research Design Services across the North East, North West, South East and South West of England, London and the Midlands. PARTICIPANTS: Fourteen women and eight men, of whom, 14 were previous or current NIHR personal awardees (seven doctors and seven allied health professionals (AHPs) or nurses) and eight were managers (staff within clinical or university training-related roles). RESULTS: (1) NIHR awards were viewed as transformative for research careers; (2) however, there were perceptions of a biased 'playing field'. (3) Inequalities were perceived for AHPs and nurses, those outside of established research institutes and those in 'unfashionable' specialisms. (4) While support for NIHR awards contributed to a healthy research culture, (5) short-term awards were perceived as a barrier to continuing an independent research career. CONCLUSIONS: Participants perceived many strengths of the NIHR training programmes in terms of developing individual careers and research capacity. Areas in which improvement could enhance the ability to attract, develop and retain researcher were identified. Our findings are of relevance to schemes in other countries, where healthcare researchers experience similar challenges. Further work is needed to overcome barriers and ensure equity of access to, and success within, clinical research training schemes to sustain the research workforce needed to address future global health challenges.

A national survey of hospice pharmacists and a comparison with international models.

BACKGROUND: Pharmacists can contribute to improved patient outcomes, improve medicine knowledge, reduce drug costs and minimise errors. However, their role within hospice-based services is not well described. OBJECTIVE: The objective of this paper was to explore the role of pharmacists within UK hospices. METHODS: Methods include an online survey and follow-up telephone contact of pharmacists working in UK hospices assessing pharmacist provision, duties, communication, medicine sourcing and training. RESULTS: Eighty-nine responses were received from 82 hospices (response rate 50%). Pharmacists had a role in 75% of hospices providing between 6.6 min and 5.5 hrs of pharmacist support per bed per week. The most frequent duty reported was provision of medicines information to the clinical team. Access to patient records varied considerably: 13% had full read and write access to GP records while 29% had no access. Job-specific training had not been received by 36% of the respondents and 47% reported training needs including basic training in palliative care. CONCLUSIONS: Three-quarters of UK hospices have pharmacy provision, although this falls below the recommended levels in the majority. Hospice pharmacists lack access to training and records. Medicines sourcing for hospices is variable and could provide opportunities for efficiencies with further research.

Practice review: Evidence-based and effective management of pain in patients with advanced cancer.

BACKGROUND: Pain of a moderate or severe intensity affects over half of patients with advanced cancer and remains undertreated in at least one-third of these patients. AIM: The aim of this study was to provide a pragmatic overview of the evidence supporting the use of interventions in pain management in advanced cancer and to identify where encouraging preliminary results are demonstrated but further research is required. DESIGN: A scoping review approach was used to examine the evidence supporting the use of guideline-recommended interventions in pain management practice. DATA SOURCES: National or international guidelines were selected if they described pain management in adult cancer patients and were written within the last 5 years in English. The Cochrane Database of Systematic Reviews (January 2014 to January 2019) was searched for 'cancer' AND 'pain' in the title, abstract or keywords. A MEDLINE search was also made. RESULTS: A strong opioid remains the drug of choice for treating moderate or severe pain. Bisphosphonates and radiotherapy are also effective for cancer-related bone pain. Optimal management requires a tailored approach, support for self-management and review of treatment outcomes. There is likely a role for non-pharmacological approaches. Paracetamol should not be used in patients taking a strong opioid to treat pain. Cannabis-based medicines are not recommended. Weak opioids, ketamine and lidocaine are indicated in specific situations only. CONCLUSION: Interventions commonly recommended by guidelines are not always supported by a robust evidence base. Research is required to evaluate the efficacy of non-steroidal anti-inflammatory drugs, anti-convulsants, anti-depressants, corticosteroids, some invasive anaesthetic techniques, complementary therapies and transcutaneous electrical nerve stimulation.

The use of quantitative sensory testing in cancer pain assessment: A systematic review.

OBJECTIVE: To summarize the literature on the use of quantitative sensory testing (QST) in the assessment of pain in people with cancer and to describe which QST parameters consistently demonstrate abnormal sensory processing in patients with cancer pain. DATABASES AND DATA TREATMENT: Medline, EMBASE, AMED, CINAHL, SCOPUS and CENTRAL were searched for observational or experimental studies using QST in patients with a cancer diagnosis and reporting pain. Search strategies were based on the terms "quantitative sensory testing", "cancer", "pain", "cancer pain" and "assessment". Databases were searched from inception to January 2019. Data were extracted and synthesized narratively, structured around the different QST modalities and sub-grouped by cancer pain aetiology (tumour- or treatment-related pain). RESULTS: Searches identified 286 records of which 18 met the eligibility criteria for inclusion. Three studies included patients with tumour-related pain, and 15 studies included patients with pain from chemotherapy-induced peripheral neuropathy (CIPN). Across all studies, 50% (9/18) reported sensory abnormities using thermal detection thresholds (cool and warm), 44% (8/18) reported abnormal mechanical detection thresholds using von-Frey filaments and 39% (7/18) found abnormal pinprick thresholds. Abnormal vibration and thermal pain (heat/cold) thresholds were each reported in a third of included studies. CONCLUSION: This systematic review highlights the lack of published data characterizing the sensory phenotype of tumour-related cancer pain. This has implications for our understanding of the underlying pathophysiological mechanisms of cancer pain. Understanding the multiple mechanisms driving cancer pain will help to move towards rational individualized analgesic treatment choices. SIGNIFICANCE: This systematic review found that pain in cancer patients is associated with abnormal sensory responses to thermal, mechanical and pinprick stimuli. However, these findings are based primarily on studies of chemotherapy-induced peripheral neuropathy and data on tumour-related pain are lacking, warranting further research.

An exploratory randomized-controlled trial of the efficacy of the Src-kinase inhibitor saracatinib as a novel analgesic for cancer-induced bone pain.

Pain is a major symptom of bone metastases from advanced cancer and represents a clinical challenge to treat effectively. Basic neurobiology in preclinical animal models implicates enhanced sensory processing in the central nervous system, acting through N-methyl-D-aspartate (NMDA) glutamate receptors, as an important mechanism underpinning persistent pain. The non-receptor tyrosine kinase Src is thought to act as a hub for regulating NMDA receptor activity and the orally available Src inhibitor saracatinib has shown promise as a potential analgesic in recent animal studies. Here we tested the efficacy of saracatinib as a novel analgesic in an exploratory phase II randomized controlled trial on cancer patients with painful bone metastases. Twelve patients completed the study, with 6 receiving saracatinib 125 mg/day for 28 days and 6 receiving placebo. Pharmacokinetic measurements confirmed appropriate plasma levels of drug in the saracatinib-treated group and Src inhibition was achieved clinically by a significant reduction in the bone resorption biomarker serum cross-linked C-terminal telopeptide of type I collagen. Differences between the saracatinib and placebo groups self-reported pain scores, measured using the short form of the Brief Pain Inventory, were not clinically significant after 4 weeks of treatment. There was also no change in consumption of maintenance analgesia in the saracatinib-treated group and no improvement in Quality-of-Life scores. The data were insufficient to demonstrate saracatinib has efficacy as analgesic, although it may have a role as an anti-bone resorptive agent.

The relationship between regional pain with or without neuropathic symptoms and chronic widespread pain.

This study was performed to test whether the risk of developing chronic widespread pain (CWP) in those with regional pain was augmented in those with symptoms of neuropathic pain (NP). Persons free of CWP completed the Douleur Neuropathique 4 (scores ≥3 indicating NP); demographics; Hospital Anxiety and Depression scale; Pittsburgh Sleep Quality Index; and pain medications. Participants were classified as having no pain, regional pain with no symptoms of NP ((Equation is included in full-text article.)), or regional pain with symptoms of NP (NP). At the 12-month follow-up, participants with CWP were identified. Logistic regression estimated the odds ratio, with 95% confidence intervals, of CWP in the (Equation is included in full-text article.)and NP groups compared with no pain, and NP compared with (Equation is included in full-text article.). Partial population attributable risks estimated the proportion of CWP attributable to baseline (Equation is included in full-text article.)or NP exposure. One thousand one hundred sixty-two participants completed the baseline DN4 and provided pain data at follow-up: 523 (45.0%) had no baseline pain, 562 (48.4%) (Equation is included in full-text article.), and 77 (6.6%) NP. One hundred fifty-three (13.2%) had CWP at 12 months: 19 (3.6%) no pain, 108 (19.2%) (Equation is included in full-text article.), and 26 (33.8%) NP. (Equation is included in full-text article.)(2.9 [1.9-4.3]) and NP (2.1 [1.1-4.0]) predicted CWP after adjusting for demographics, Hospital Anxiety and Depression scale, Pittsburgh Sleep Quality Index, and medications. The partial population attributable risk was 41.3% (25.2-54.0) for (Equation is included in full-text article.)and 6.0% (0.1-11.6) for NP. The NP group were not more likely to develop CWP when compared directly with (Equation is included in full-text article.)(1.5 [0.8-2.8]). Neuropathic pain was relatively rare and predicted a small number of new-onset CWP cases. Using these estimates, treatments targeting NP would at best prevent 6% of CWP cases.

Cancer-Related Neuropathic Pain.

Neuropathic pain in cancer is common and debilitating. It is important to differentiate neuropathic pain from other cancer-related pains as it is associated with worse pain outcomes and requires different treatment strategies. This review summarises recent updates to pain classification, aetiology, pain assessment and current recommendations for treatment in patients with cancer-related neuropathic pain.

Duration and determinants of hospice-based specialist palliative care: A national retrospective cohort study.

BACKGROUND: Understanding service provision for patients with advanced disease is a research priority, with a need to identify barriers that limit widespread integration of palliative care. AIM: To identify patient and organisational factors that influence the duration of hospice-based palliative care in the United Kingdom prior to death. DESIGN: This is a retrospective cohort study. SETTING/PARTICIPANTS: A total of 64 UK hospices providing specialist palliative care inpatient beds and community services extracted data for all adult decedents (aged over 17 years) with progressive, advanced disease, with a prior referral (e.g. inpatient, community teams, and outpatient) who died between 1 January 2015 and 31 December 2015. Data were requested for factors relating to both the patient and hospice site. RESULTS: Across 42,758 decedents, the median time from referral to death was 48 days. Significant differences in referral to death days were found for those with cancer (53 days) and non-cancer (27 days) ( p < 0.0001). As age increases, the median days from referral to death decreases: for those under 50 years (78 days), 50-74 years (59 days), and 75 years and over (39 days) ( p = 0.0001). An adjusted multivariable negative binomial model demonstrated increasing age persisting as a significant predictor of fewer days of hospice care, as did being male, having a missing ethnicity classification and having a non-cancer diagnosis ( p < 0.001). CONCLUSION: Despite increasing rhetoric around early referral, patients with advanced disease are receiving referrals to hospice specialist palliative care very late in their illness trajectory. Age and diagnosis persist as determinants of duration of hospice specialist palliative care before death.

A critical appraisal of gabapentinoids for pain in cancer patients.

PURPOSE OF REVIEW: Gabapentinoids are frequently used in the management of cancer pain. In recent Cochrane systematic reviews, although there was an abundance of evidence relating to non-cancer pain, only a few studies related to cancer pain. This review summarizes recent randomised controlled trials (RCTs) evaluating the use of gabapentinoids for tumour-related (as monotherapy or part of combination therapy) and treatment-related pain. RECENT FINDINGS: For tumour-related pain, ten out of thirteen studies showed statistically significant benefits in favour of gabapentinoids. When used, as part of monotherapy or combination therapy, benefits were observed in five out of six studies evaluating gabapentin, and in six out of eight studies evaluating pregabalin. For treatment-related pain, none of the four studies (two gabapentin, two pregabalin) showed statistically significant benefits in favour of gabapentinoids. Unfortunately, many of the studies included were limited by small sample size, lack of blinding, and inadequate follow-up. SUMMARY: More and better quality studies are required, although it may be challenging to accomplish in this patient population. Gabapentinoids may offer benefits to cancer patients with pain, but careful titration and monitoring of adverse effects is necessary.

Opioids combined with antidepressants or antiepileptic drugs for cancer pain: Systematic review and meta-analysis.

BACKGROUND: Combining antidepressant or antiepileptic drugs with opioids has resulted in increased pain relief when used for neuropathic pain in non-cancer conditions. However, evidence to support their effectiveness in cancer pain is lacking. AIM: To determine if there is additional benefit when opioids are combined with antidepressant or antiepileptic drugs for cancer pain. DESIGN: Systematic review and meta-analysis. Randomised control trials comparing opioid analgesia in combination with antidepressant or antiepileptic drugs versus opioid monotherapy were sought. Data on pain and adverse events were extracted. Data were pooled using DerSimonian-Laird random-effects meta-analyses, and heterogeneity was assessed. RESULTS: Seven randomised controlled trials that randomised 605 patients were included in the review. Patients' pain was described as neuropathic cancer pain, cancer bone pain and non-specific cancer pain. Four randomised controlled trials were included in the meta-analysis in which opioid in combination with either gabapentin or pregabalin was compared with opioid monotherapy. The pooled standardised mean difference was 0.16 (95% confidence interval, -0.19, 0.51) showing no significant difference in pain relief between the groups. Adverse events were more frequent in the combination arms. Data on amitriptyline, fluvoxamine and phenytoin were inconclusive. CONCLUSION: Combining opioid analgesia with gabapentinoids did not significantly improve pain relief in patients with tumour-related cancer pain compared with opioid monotherapy. Due to the heterogeneity of patient samples, benefit in patients with definite neuropathic cancer pain cannot be excluded. Clinicians should balance the small likelihood of benefit in patients with tumour-related cancer pain against the increased risk of adverse effects of combination therapy.