Gerhard H. H. Müller-Schwefe

Sublingual fentanyl orally disintegrating tablet in daily practice: efficacy, safety and tolerability in patients with breakthrough cancer pain.

Abstract Background and objectives: Breakthrough cancer pain (BTcP) affects more than half of patients with cancer pain and has severe detrimental impacts on quality of life (QoL). This study evaluated the efficacy, QoL impact and safety of sublingual fentanyl orally disintegrating tablet (sublingual fentanyl ODT), for the treatment of BTcP in a clinical setting. Research design and methods: This was a prospective, multi-center phase IV study. Opioid-tolerant adult patients with BTcP received sublingual fentanyl ODT in the course of routine clinical practice, and completed questionnaires over a 28-day observation period. Efficacy was assessed using measures of maximum BTcP intensity and the times to first effect and maximum effect of sublingual fentanyl ODT. Changes in QoL were evaluated using the modified pain disability index (mPDI) and the hospital anxiety and depression scale (HADS). Adverse events were recorded throughout. Results: Of 217 enrolled patients, 181 (83.4%) completed the observation period. During the study, 3163 episodes were treated with a mean dose of 401.4 μg per episode. The study recorded a significant improvement in maximum BTcP intensity with sublingual fentanyl ODT, compared with baseline (p < 0.0001). Patients reported experiencing the first effects of the study drug within 5 minutes of administration in 67.7% of episodes, and maximum effect within 30 minutes in 63.2% of episodes. mPDI and HADS scores significantly improved during the observation period (p < 0.0001). Sublingual fentanyl ODT was well-tolerated, with 12 patients (5.5%) experiencing ≥1 study drug-related adverse event. Study limitations include a modest size and duration, and the single-arm design. Conclusions: Under the conditions of a phase IV study, sublingual fentanyl ODT was effective and well-tolerated for the treatment of BTcP in opioid-tolerant cancer patients. Study treatment was associated with significant improvements in BTcP intensity and QoL scores, and patients reported rapid onset of action in the majority of episodes.

Managing chronic pain in elderly patients requires a CHANGE of approach

Abstract In many countries, the number of elderly people has increased rapidly in recent years and this is expected to continue; it has been predicted that almost a quarter of the population in the European Union will be over 65 years of age in 2035. Many elderly people suffer from chronic pain but it is regularly under-treated, partly because managing these patients is often complex. This paper outlines the extent of untreated pain in this population and the consequent reduction in quality of life, before articulating the reasons why it is poorly or inaccurately diagnosed. These include the patient’s unwillingness to complain, atypical pain presentations, multiple morbidities and cognitive decline. Successful pain management depends upon accurate diagnosis, which is based upon a complete history and thorough physical examination, as well as an assessment of psychosocial functioning. Poor physician/patient communication can be improved by using standardized instruments to establish individual treatment targets and measure progress towards them. User-friendly observational instruments may be valuable for patients with dementia. In line with the widely accepted biopsychosocial model of pain, a multidisciplinary approach to pain management is recommended, with pharmacotherapy, psychological support, physical rehabilitation and interventional procedures available if required. Declining organ function and other physiological changes require lower initial doses of analgesics and less frequent dosing intervals, and the physician must be aware of all medications that the patient is taking, in order to avoid drug/drug interactions. Non-adherence to treatment is common, and various strategies can be employed to improve it; involving the elderly patient’s caregivers and family, using medication systems such as pill-boxes, or even sending text messages. In the long term, the teaching of pain medicine needs to be improved – particularly in the use of opioids – both at undergraduate level and after qualification.

A holistic approach to chronic pain management that involves all stakeholders: change is needed

Abstract Chronic pain affects a large proportion of the population, imposing significant individual distress and a considerable burden on society, yet treatment is not always instituted and/or adequate. Comprehensive multidisciplinary management based on the biopsychosocial model of pain has been shown to be clinically effective and cost-efficient, but is not widely available. A literature review of stakeholder groups revealed many reasons for this, including: i) many patients believe healthcare professionals lack relevant knowledge, and consultations are rushed, ii) general practitioners consider that pain management has a low priority and is under-resourced, iii) pain specialists cite non-adherence to evidence-based treatment, sub-optimal prescribing, and chronic pain not being regarded as a disease in its own right, iv) nurses’, pharmacists’ and physiotherapists’ skills are not fully utilized, and v) psychological therapy is employed infrequently and often too late. Many of the issues relating to physicians could be addressed by improving medical training, both at undergraduate and postgraduate levels – for example, by making pain medicine a compulsory core subject of the undergraduate medical curriculum. This would improve physician/patient communication, increase the use of standardized pain assessment tools, and allow more patients to participate in treatment decisions. Patient care would also benefit from improved training for other multidisciplinary team members; for example, nurses could provide counseling and follow-up support, psychologists offer coping skills training, and physiotherapists have a greater role in rehabilitation. Equally important measures include the widespread adoption of a patient-centered approach, chronic pain being recognized as a disease in its own right, and the development of universal guidelines for managing chronic non-cancer pain. Perhaps the greatest barrier to improvement is lack of political will at both national and international level. Some powerful initiatives and collaborations are currently lobbying policy-making bodies to raise standards and reduce unnecessary pain – it is vital they continue.

Pain in the cancer patient: Different pain characteristics CHANGE pharmacological treatment requirements

Abstract Twenty years ago, the main barriers to successful cancer pain management were poor assessment by physicians, and patients’ reluctance to report pain and take opioids. Those barriers are almost exactly the same today. Cancer pain remains under-treated; in Europe, almost three-quarters of cancer patients experience pain, and almost a quarter of those with moderate to severe pain do not receive any analgesic medication. Yet it has been suggested that pain management could be improved simply by ensuring that every consultation includes the patient’s rating of pain, that the physician pays attention to this rating, and a plan is agreed to increase analgesia when it is inadequate. After outlining current concepts of carcinogenesis in some detail, this paper describes different methods of classifying and diagnosing cancer pain and the extent of current under-treatment. Key points are made regarding cancer pain management. Firstly, the pain may be caused by multiple different mechanisms and therapy should reflect those underlying mechanisms – rather than being simply based on pain intensity as recommended by the WHO three-step ladder. Secondly, a multidisciplinary approach is required which combines both pharmacological and non-pharmacological treatment, such as psychotherapy, exercise therapy and electrostimulation. The choice of analgesic agent and its route of administration are considered, along with various interventional procedures and the requirements of palliative care. Special attention is paid to the treatment of breakthrough pain (particularly with fast-acting fentanyl formulations, which have pharmacokinetic profiles that closely match those of breakthrough pain episodes) and chemotherapy-induced neuropathic pain, which affects around one third of patients who receive chemotherapy. Finally, the point is made that medical education should place a greater emphasis on pain therapy, both at undergraduate and postgraduate level.

Low-dose 7-day transdermal buprenorphine in daily clinical practice – perceptions of elderly patients with moderate non-malignant chronic pain

Abstract Objective: To assess patients’ perceptions regarding the low-dose 7-day buprenorphine transdermal patch for treatment of moderate non-malignant chronic pain. Methods: Patient-reported outcome data were collected in clinical practices in Germany in a prospective, multicenter, non-interventional observation using the German Pain Questionnaire/German Pain Diary. Questionnaires were completed by the patients without influence from the attending physician. Mean change in pain intensity (lowest, average, and highest pain intensity in the previous 24 h), changes in Hospital Anxiety and Depression Scale scores (HADS-A and HADS-D), in impairments of daily activities (modified pain disability index, mPDI), in quality of life (quality of life impairment by pain inventory, QLIP), and in overall burden of pain over a 12-week treatment period were evaluated. Results: Data of 891 patients were assessed (mean age 72.8 years). Buprenorphine starting doses were mainly 5 µg/h (67.1% of patients) and 10 µg/h (27.3%). At the end of week 12, the majority received either 5 µg/h (41%) or 10 µg/h (42.3%) buprenorphine. Mean average pain intensity was reduced by 5.1 points to 1.7 ± 1.3 from 6.8 ± 1.5 points at baseline (76% improvement). Amelioration was observed in HADS-A (59% from 7.8 ± 3.3 at baseline) and HADS-D (56% from 9.2 ± 3.1), in mPDI sum score (76%; from 31.1 ± 9.8), and in quality of life (165%; from 13.9 ± 10.1). Mean burden of pain continuously decreased. Limitations: All those inherent in open-label observations and pain studies using subjective and patient-reported outcome parameters (such as the lack of a control group). Conclusions: Our results indicate that the 7-day buprenorphine patch might be considered an effective treatment option for moderate non-malignant chronic pain management in daily clinical practice. The mostly elderly patient population of this patient survey experienced sustained pain relief and improvements in pain-related impairments of daily activities and quality of life, leading to a substantial reduction in overall burden of pain.

Patient perceptions associated with the 5% lidocaine medicated plaster in daily practice

Abstract Objective: To evaluate patients’ perceptions of 5% lidocaine medicated plaster for treatment of chronic neuropathic pain in daily clinical practice. Research design and methods: In a prospective, multicentre, non-interventional observation, patient-reported outcome data were collected in clinical practices in Germany using the German Pain Questionnaire for pre-treatment documentation and the German Pain Diary for documentation of weekly treatment-associated changes. Questionnaires were completed by the patients without input from their physicians. Main outcome measures: Mean changes over the 12-week treatment period in pain intensity, in impairments of daily activities (modified pain disability index, mPDI) and of quality of life (quality of life impairment by pain inventory, QLIP), in Hospital Anxiety and Depression Scale scores (HADS-A and HADS-D), and in overall burden of pain. Results: Data of 922 patients were evaluated. Mean average pain intensity over 24 h improved by 5.1 points (74%) from 6.9 ± 1.6 points at baseline. A 30% reduction in overall pain intensity was already observed within the first 2–3 weeks with continuous further reductions until end of observation. Marked improvements in anxiety and depression scores (40% and 52%, respectively), and in pain-related restrictions in daily life activities (66%) and quality of life (157%) were also noted. Burden of pain was reduced by 56.2 points (73%) from 77.5 points at baseline. Stratification by diagnosis showed a treatment effect of lidocaine plaster for all underlying conditions with highest treatment effects for diabetic polyneuropathy and postherpetic neuralgia. Conclusions: In a patient population where 46% of individuals already suffered from chronic to markedly chronic pain, patients perceive the 5% lidocaine medicated plaster as an efficacious topical treatment of chronic neuropathic pain in daily clinical practice. Strongest pain relief as well as associated improvements in pain-related restrictions were observed within the first five treatment weeks; however, beneficial effects continued until end of observation.

Treatment for chronic low back pain: the focus should change to multimodal management that reflects the underlying pain mechanisms

Abstract Chronic low back pain: Chronic pain is the most common cause for people to utilize healthcare resources and has a considerable impact upon patients’ lives. The most prevalent chronic pain condition is chronic low back pain (CLBP). CLBP may be nociceptive or neuropathic, or may incorporate both components. The presence of a neuropathic component is associated with more intense pain of longer duration, and a higher prevalence of co-morbidities. However, many physicians’ knowledge of chronic pain mechanisms is currently limited and there are no universally accepted treatment guidelines, so the condition is not particularly well managed. Diagnosis: Diagnosis should begin with a focused medical history and physical examination, to exclude serious spinal pathology that may require evaluation by an appropriate specialist. Most patients have non-specific CLBP, which cannot be attributed to a particular cause. It is important to try and establish whether a neuropathic component is present, by combining the findings of physical and neurological examinations with the patients history. This may prove difficult, however, even when using screening instruments. Multimodal management: The multifactorial nature of CLBP indicates that the most logical treatment approach is multimodal: i.e. integrated multidisciplinary therapy with co-ordinated somatic and psychotherapeutic elements. As both nociceptive and neuropathic components may be present, combining analgesic agents with different mechanisms of action is a rational treatment modality. Individually tailored combination therapy can improve analgesia whilst reducing the doses of constituent agents, thereby lessening the incidence of side effects. Conclusions: This paper outlines the development of CLBP and the underlying mechanisms involved, as well as providing information on diagnosis and the use of a wide range of pharmaceutical agents in managing the condition (including NSAIDs, COX-2 inhibitors, tricyclic antidepressants, opioids and anticonvulsants), supplemented by appropriate non-pharmacological measures such as exercise programs, manual therapies, behavioral therapies, interventional pain management and traction. Surgery may be appropriate in carefully selected patients.

Dysport® for the treatment of myofascial back pain: Results from an open-label, Phase II, randomized, multicenter, dose-ranging study

Abstract Background and purpose Botulinum toxin type A (BoNT-A) has antinociceptive and muscle-relaxant properties. The objectives of this study were to investigate the efficacy and safety of a single BoNT-A (Dysport®) treatment in myofascial back pain. Methods In this randomized, open-label, multicenter study, adults with myofascial lower back pain received Dysport® injections at four trigger points (60,80 or 120 units per injection point). Patients were followed for 12 weeks. The a priori primary endpoint was a pooled evaluation, at Week 6, of seven measures of efficacy, including pain intensity (patient diary), modified Pain Disability Index (PDI) score, use of interfering concomitant analgesics, and patient-rated global efficacy. Optional assessments of pressure thresholds and tissue compliance were conducted. Safety was also assessed. Results A total of 202 patients were randomized to treatment and 189 patients received a low (n = 57), medium (n = 57), or high (n = 75) total dose of Dysport® at 34 centers in Germany between October 2002 and October 2003. All treated patients were included in the safety population; 8 patients were excluded from the intention-to-treat population. Patients had moderate to severe pain at baseline. At baseline, 120 patients were receiving concomitant analgesic therapy; 6.7%, 74.2% and 19.2% were considered to cause mild, moderate and severe interference with pain measurements, respectively. There was no difference between doses for the a priori combined primary endpoint. Patient-reported pain intensity scores at rest and on movement decreased significantly after treatment for all groups combined (p < 0.0001 at all visits). At Week 6, reductions in pain intensity at rest were 29%, 19% and 26% for the low-, medium- and high-dose groups, respectively; reductions in pain intensity on movement were 27%, 18% and 26%, respectively. Overall, patients who reported pain intensity reductions at Week 6 were evident within 3 weeks of treatment and were maintained for the 12 weeks of the study. In the total population, significant decreases in mean PDI sum scores from baseline were observed from Week 3 and were maintained through to the end of treatment (Week 12); no differences between the dose groups were observed. Pressure thresholds and tissue compliance also increased during the study. Adverse events were generally as expected for BoNT-A; the majority were mild or moderate in severity. Conclusions Dysport® treatment was associated with reductions in myofascial back pain and was well tolerated. Nodose-response relationship was observed; treatment with Dysport® using a four-trigger-point injection protocol at 60 units per trigger point was associated with a clinically relevant and statistically significant improvement in pain and pain-related disability; there was no additional benefit from the higher doses. Implications Our findings are limited by the lack of a control group and further research is warranted to confirm the value of Dysport® for the treatment of myofascial back pain and confirm the optimum dosing in this indication.

Struktur der schmerzmedizinischen Versorgung in Deutschland

ZusammenfassungIm Auftrag der schmerzmedizinischen/psychologischen Fachgesellschaften, der Selbsthilfeorganisation der Schmerzpatienten und des Berufsverbandes der Schmerztherapeuten und Schmerzpsychologen hat die Gemeinsame Kommission der Fachgesellschaften und Verbände für Qualität in der Schmerzmedizin unter Mitwirkung der jeweiligen Präsidenten überprüfbare Struktur- sowie Prozesskriterien entwickelt, um schmerzmedizinische Einrichtungen in Deutschland klassifizieren zu können. Grundlage sind das in Deutschland etablierte System der abgestuften Versorgung sowie bestehende Qualifikationen, Weiterbildungen und Zusatzbezeichnungen. Die Einführung eines Fachkundenachweises Schmerzmedizin wird empfohlen. Neben den erstmals beschriebenen schmerzpsychotherapeutischen Einrichtungen können anhand der Kriterien fünf Ebenen von der Einrichtung mit Fachkunde Schmerzmedizin über spezialisierte Einrichtungen bis zum Zentrum für interdisziplinäre Schmerzmedizin definiert werden. Ziel der Empfehlungen ist es, verbindliche und überprüfbare Kriterien zur Qualitätssicherung in der Schmerzmedizin zu etablieren und die Versorgung zu verbessern.AbstractOn behalf of the Medical/Psychological Pain Associations, Pain Patients Alliance and the Professional Association of Pain Physicians and Psychologists, the Joint Commission of Professional Societies and Organizations for Quality in Pain Medicine, working in close collaboration with the respective presidents, has developed verifiable structural and process-related criteria for the classification of medical and psychological pain treatment facilities in Germany. Based on the established system of graded care in Germany and on existing qualifications, these criteria also argue for the introduction of a basic qualification in pain medicine. In addition to the first-ever comprehensive description of psychological pain facilities, the criteria presented can be used to classify five different levels of pain facilities, from basic pain management facilities, to specialized institutions, to the Centre for Interdisciplinary Pain Medicine. The recommendations offer binding and verifiable criteria for quality assurance in pain medicine and improved pain treatment.On behalf of the Medical/Psychological Pain Associations, Pain Patients Alliance and the Professional Association of Pain Physicians and Psychologists, the Joint Commission of Professional Societies and Organizations for Quality in Pain Medicine, working in close collaboration with the respective presidents, has developed verifiable structural and process-related criteria for the classification of medical and psychological pain treatment facilities in Germany. Based on the established system of graded care in Germany and on existing qualifications, these criteria also argue for the introduction of a basic qualification in pain medicine. In addition to the first-ever comprehensive description of psychological pain facilities, the criteria presented can be used to classify five different levels of pain facilities, from basic pain management facilities, to specialized institutions, to the Centre for Interdisciplinary Pain Medicine. The recommendations offer binding and verifiable criteria for quality assurance in pain medicine and improved pain treatment.

Die Diagnostik des Rückenschmerzes ist vielfarbig

ZusammenfassungRückenschmerzen gehören zu den kostenintensivsten Gesundheitsproblemen in den westlichen Ländern. Schuld daran sind nach Ansicht unserer Autoren vor allem eindimensionale Diagnostik- und Therapiekonzepte. Sie vernachlässigen komplexe psychosoziale Aspekte und begünstigen eine Chronifizierung der Beschwerden. Das „Farbleitsystem“ unserer Autoren verdeutlicht die Zusammenhänge.