Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain

Use of chronic opioid therapy for chronic noncancer pain has increased substantially. The American Pain Society and the American Academy of Pain Medicine commissioned a systematic review of the evidence on chronic opioid therapy for chronic noncancer pain and convened a multidisciplinary expert panel to review the evidence and formulate recommendations. Although evidence is limited, the expert panel concluded that chronic opioid therapy can be an effective therapy for carefully selected and monitored patients with chronic noncancer pain. However, opioids are also associated with potentially serious harms, including opioid-related adverse effects and outcomes related to the abuse potential of opioids. The recommendations presented in this document provide guidance on patient selection and risk stratification; informed consent and opioid management plans; initiation and titration of chronic opioid therapy; use of methadone; monitoring of patients on chronic opioid therapy; dose escalations, high-dose opioid therapy, opioid rotation, and indications for discontinuation of therapy; prevention and management of opioid-related adverse effects; driving and work safety; identifying a medical home and when to obtain consultation; management of breakthrough pain; chronic opioid therapy in pregnancy; and opioid-related polices.PerspectiveSafe and effective chronic opioid therapy for chronic noncancer pain requires clinical skills and knowledge in both the principles of opioid prescribing and on the assessment and management of risks associated with opioid abuse, addiction, and diversion. Although evidence is limited in many areas related to use of opioids for chronic noncancer pain, this guideline provides recommendations developed by a multidisciplinary expert panel after a systematic review of the evidence.     

Research Gaps on Use of Opioids for Chronic Noncancer Pain: Findings From a Review of the Evidence for an American Pain Society and American Academy of Pain Medicine Clinical Practice Guideline

Chronic noncancer pain is common and use of opioids is increasing. Previously published guidelines on use of opioids for chronic noncancer pain have been based primarily on expert consensus due to lack of strong evidence. We conducted searches on Ovid MEDLINE and the Cochrane databases through July 2008 to identify studies that addressed one or more of 37 Key Questions that a multidisciplinary expert panel identified as important to be answered to generate evidence-based recommendations on the use of opioids for chronic noncancer pain. A total of 14 systematic reviews, 38 randomized trials not included in a previously published systematic review, and 13 other studies met inclusion criteria. Almost all of the randomized trials of opioids for chronic noncancer pain were short-term efficacy studies. Critical research gaps on use of opioids for chronic noncancer pain include: lack of effectiveness studies on long-term benefits and harms of opioids (including drug abuse, addiction, and diversion); insufficient evidence to draw strong conclusions about optimal approaches to risk stratification, monitoring, or initiation and titration of opioid therapy; and lack of evidence on the utility of informed consent and opioid management plans, the utility of opioid rotation, the benefits and harms specific to methadone or higher doses of opioids, and treatment of patients with chronic noncancer pain at higher risk for drug abuse or misuse.PerspectiveCurrently, clinical decisions regarding the use of opioids for chronic noncancer pain need to be made based on weak evidence. Research funding priorities need to be set to address these critical research needs if the care of patients with chronic noncancer pain is to improve.     

Medikamentöse Therapie bei Rückenschmerzen

Today, a wide range of efficient analgesic and non-analgesic drugs for the treatment of back pain are available. However, drugs should never be the only mainstay of a back pain treatment program. Non-steroidal antiinflammatory drugs (NSAID) are widely used in acute back pain. NSAIDs prescribed at regular intervals are effective to reduce simple back pain. The different NSAIDs are effective for the reduction of this pain. They have serious adverse effects, particularly at high doses, in the elderly, and on long-term administration. The new cyclooxygenase II-inhibitors have less gastrointestinal complications. But the long-term experiences are limited up to now. Considerable controversy exists about the use of opioid analgesics in chronic noncancer pain. Many physicians are concerned about the effectiveness and adverse effects of opioids. Other clinicians argue that there is a role for opioid therapy in chronic noncancer pain, e. g. especially in chronic low back pain. There is a low incidence of organ toxicity in patients who respond to opioids. The incidence of abuse and addiction is likewise relatively low. The potential for increased function and improved quality of life seems to outweigh the risks. However, there is a lack of randomised controlled trials (RCT) on opioid therapy in a multimodal pain treatment approach. Clinical experience and some studies suggest administration of sustained release opioids because of better comfort for the patient and less risks for addiction. The opioids should be selected due to the specific side effects of the different drugs. For patients with pre-existing constipation transdermal fentanyl should be preferred. Antidepressant medications have been used for the treatment of chronic back pain, though there is only little scientific evidence for their effectiveness. There is no evidence for the use of antidepressants in acute low back pain. Trials of muscle relaxants for patients with acute back pain have used a wide range of agents, e. g. benzodiazepines. They mostly reduce acute back pain, but they have significant adverse effects including drowsiness and psychological and physical dependence even after relatively short treatment. Benzodiazepines are not indicated in the treatment of chronic back pain. Drugs are sometimes necessary for the patients to begin and persevere a multimodal treatment program. Drug therapy should be terminated as soon as other treatment strategies succeed. Unfortunately, no studies exist evaluating the place of analgesics within a multimodal treatment program.     

Clinician beliefs about opioid use and barriers in chronic nonmalignant pain

A survey of the medical directors of multidisciplinary pain clinics and multidisciplinary pain centers listed in the American Pain Society Pain Facilities Directory was conducted to define those pain specialists' beliefs about the role of opioid analgesia in 14 types of chronic nonmalignant pain. Respondents also reported their perceptions of barriers to their prescribing opioids for chronic nonmalignant pain and what they perceived as barriers to opioid prescribing for chronic nonmalignant pain by other, non-pain specialist clinicians in their communities. The respondents are characterized by demographics, disciplines, specialties, and time in practice. The percentage of time that a pharmacist was available in the pain programs also is reported. There is increasing acceptance of opioids for most of the listed types of chronic nonmalignant pain, but the acceptance varies by types of pain syndromes. Opioids were most consistently accepted for sickle cell disease pain and least commonly endorsed for headaches, myofascial pain, and fibromyalgia. Factors that may influence clinicians' perceptions about opioids are discussed.     

Clinician Beliefs About Opioid Use and Barriers in Chronic Nonmalignant Pain

A survey of the medical directors of multidisciplinary pain clinics and multidisciplinary pain centers listed in the American Pain Society Pain Facilities Directory was conducted to define those pain specialists' beliefs about the role of opioid analgesia in 14 types of chronic nonmalignant pain. Respondents also reported their perceptions of barriers to their prescribing opioids for chronic nonmalignant pain and what they perceived as barriers to opioid prescribing for chronic nonmalignant pain by other, non-pain specialist clinicians in their communities. The respondents are characterized by demographics, disciplines, specialties, and time in practice. The percentage of time that a pharmacist was available in the pain programs also is reported. There is increasing acceptance of opioids for most of the listed types of chronic nonmalignant pain, but the acceptance varies by types of pain syndromes. Opioids were most consistently accepted for sickle cell disease pain and least commonly endorsed for headaches, myofascial pain, and fibromyalgia. Factors that may influence clinicians' perceptions about opioids are discussed.     

Evaluation of Chronic,Noncancer Pain Management Initiative in a Multidisciplinary Pain Clinic

BackgroundChronic pain management is a major challenge for primary care providers (PCPs). PCPs manage many patients with chronic pain and other comorbidities including mental health problems like post-traumatic stress disorder (PTSD) and depression. Chronic pain and opioid problems are a national crisis, particularly among veterans (U.S. Department of Veterans Affairs, 2019). There are many veterans with chronic non-cancer pain who are being treated with opioids. Chronic opioid use has contributed to an epidemic of opioid-related adverse events (VA, 2017). Opioids not only result in poor pain control, but have associated risks such as misuse, overdose, and diversion which may be fatal (Frieden & Houry, 2016).AimsThe aim of this project was to evaluate chronic non-cancer pain management of veterans using an advanced practice registered nurse (APRN)-led multidisciplinary team approach to incorporate non-opioid and non-pharmacologic modalities to affect self-reported pain and use of prescribed opioids.MethodsA retrospective quality improvement (QI) project was conducted in the multidisciplinary pain (MDP) clinic. The APRN used a biopsychosocial approach for chronic pain management guided by the Plan, Do, Study, Act (PDSA) cycle framework. Thirty-four patients who were utilizing opioids for pain management were included using convenience sampling from the MDP clinic. The APRN educated and treated patients with non-opioid medications and non-pharmacolog therapies. A 10-point pain scale and morphine equivalent daily dose (MEDD) were utilized pre- and post-intervention to evaluate the MDP clinic.ResultsParticipants were predominantly male (91.8%), with a mean age of 63.18 ± 15.39 years, and 36.4% of whom were retired. Only 20.6% of the participants reported the use of opioids for <12 months. Low back pain (93%) was the most common pain location. The mean baseline MEDD was 41.04 and the post tapered MEDD was 23.05; this revealed a significant decline in MEDD (p < .0001). A decline was also found between pre- and post-pain scores (ranges 0-8). There was a significant reported decline in pain scores with a baseline of 6.11 to post tapering pain of 3.1 (t = 4.99, df = 28, p < .0001). Participants preferred non-opioid medications 94% and non-pharmacologic therapy 86%, like physical therapy, yoga, and acupuncture. Fifty-one percent of patients were referred for injections and 46% were referred to primary care behavior health, which includes pain school, sleep hygiene classes, and cognitive behavior therapy.ConclusionsAPRNs are in a key position to assess and treat patients based on current evidence while facilitating opioid titration. This initiative highlights that safe tapering of opioids is possible when utilizing a multidisciplinary approach for chronic pain management. Findings support the use of non-pharmacologic and non-opioid therapy for chronic pain management which can result in reduced patient-reported pain. Further research is warranted to examine both pharmacologic (non-opioid) and non-pharmacologic strategies that promote pain management while tapering opioids.     

Neuropsychological assessment of chronic non-malignant pain patients treated in a multidisciplinary pain centre.

The aim of the study was to investigate the influence of pain, sedation, pain medications and socio-demographics on cognitive functioning in chronic non-malignant pain patients. Chronic non-malignant pain patients (N=91) treated in a multidisciplinary pain centre were compared with age and sex matched healthy volunteers (N=64). Furthermore four subgroups of patients were examined: Group 1 (N=21) received no pain medications, group 2 (N=19) were in long-term oral opioid treatment, group 3 (N=18) were treated with antidepressants and/or anticonvulsants and group 4 (N=33) were treated with a combination of long-term oral opioids and antidepressants and/or anticonvulsants. Assessments comprised pain (PVAS) and sedation (SVAS), Continuous Reaction Time (CRT) testing for sustained attention, Finger Tapping Test (FTT) testing for psychomotor speed, Paced Auditory Serial Addition Task (PASAT) testing for information processing and working memory and Mini Mental State Examination (MMSE). CRT and FTT were impaired in the total patient sample. Treatment with opioids was associated with poorer performance of PASAT. High scores of PVAS and SVAS were associated with poor performance of PASAT and CRT, respectively. MMSE seems to be too insensitive for detecting the milder forms of cognitive impairment found in chronic non-malignant patients.     

Long-term opioid therapy for chronic noncancer pain: a systematic review and meta-analysis of efficacy and safety

Opioid therapy for chronic noncancer pain (CNCP) is controversial due to concerns regarding long-term efficacy and adverse events (including addiction). We systematically reviewed the clinical evidence on patients treated with opioids for CNCP for at least six months. Of 115 studies identified by our search of eleven databases (through April 7, 2007), 17 studies (patients [n]=3,079) met inclusion criteria. Studies evaluated oral (studies [k]=7; n=1,504), transdermal (k=3; n=1, 993), and/or intrathecal (k=8; n=177) opioids. Many patients withdrew from the clinical trials due to adverse effects (oral: 32.5% [95% confidence interval (CI), 26.1%-39.6%]; intrathecal: 6.3% [95% CI, 2.9%-13.1%]; transdermal: 17.5% [95% CI, 6.5%-39.0%]), or due to insufficient pain relief (oral: 11.9% [95% CI, 7.8%-17.7%]; intrathecal: 10.5% [95% CI, 3.5%-27.4%]; transdermal: 5.8% [95% CI, 4.2%-7.3%]). Signs of opioid addiction were reported in only 0.05% (1/2,042) of patients and abuse in only 0.43% (3/685). There was an insufficient amount of data on transdermal opioids to quantify pain relief. For patients able to remain on oral or intrathecal opioids for at least six months, pain scores were reduced long-term (oral: standardized mean difference [SMD] 1.99, 95% CI, 1.17-2.80; intrathecal: SMD 1.33, 95% CI, 0.97-1.69). We conclude that many patients discontinue long-term opioid therapy due to adverse events or insufficient pain relief; however, weak evidence suggests that oral and intrathecal opioids reduce pain long-term in the relatively small proportion of individuals with CNCP who continue treatment.     

Use and efficacy of low-dose ketamine in the management of acute postoperative pain: a review of current techniques and outcomes.

Ketamine hydrochloride is a well known general anesthetic and short acting analgesic in use for almost 3 decades. The role of the NMDA receptor in the processing of nociceptive input has led naturally to renewed clinical interest in N-methyl-D-aspartate (NMDA) receptor antagonists such as ketamine. This paper reviews the use and efficacy of low-dose ketamine in the management of acute postoperative pain. The literature was obtained from a computer search of the MEDLINE database from 1966 through December 1998. Studies were included for review if they were randomized, prospective, controlled, double-blind and reported pain scores. We evaluate the clinical literature and discuss the efficacy of low-dose ketamine in the management of acute postoperative pain when administered alone or in conjunction with other agents via the oral, intramuscular, subcutaneous, intravenous and intraspinal routes. Low-dose ketamine is defined as a bolus dose of less than 2 mg/g when given intramuscularly or less than 1 mg/kg when administered via the intravenous or epidural route. For continuous i.v. administration low-dose ketamine is defined as a rate of < or =20 microg/kg per min. We conclude that ketamine may provide clinicians with a tool to improve postoperative pain management and to reduce opioid related adverse effects. The evidence suggests that low-dose ketamine may play an important role in postoperative pain management when used as an adjunct to local anesthetics, opioids, or other analgesic agents. Further research is required in the following areas: (a) dose-finding studies for ketamine as an adjunct to opioids and local anesthetics (b) efficacy and optimal route of administration (c) the role of S(+)-ketamine; (d) the influence of ketamine on long-term outcome such as chronic pain (e) long-term physical and chemical stability of mixtures containing ketamine (f) spinal toxicity of ketamine and (g) effects of low-dose ketamine on cognitive and memory functioning after surgery.     

Veränderte Schmerzschwellen während und nach Opioidentzug bei Patienten mit chronischen Rückenschmerzen

Background

Opioids as the strongest pain drugs are often used for chronic pain although their long-term efficacy has not yet been clarified. In this longitudinal study, we compared the pain sensitivity of patients with chronic low back pain (cLBP) under long-term opioid use and treated with multidisciplinary pain therapy.

Methods

The pain sensitivity was measured by the quantitative sensory testing (QST) technique at admission, discharge and 6 months after the beginning of the study in 34 patients with both cLBP and opioid medication, 33 opioid-naive cLBP patients and those neither with pain nor opioid use (HC). Both patient groups underwent a 3-week multidisciplinary pain therapy (MDPT).

Results

Under opioid use, the patients showed significantly lower cold and heat pain thresholds compared to HC and delayed reaction to warm stimuli. After 3 weeks of MDPT, opioid-positive patients still had a lower pain threshold to cold and heat stimuli, while opioid-naive patients normalised their pain perception.

Conclusion

Our findings suggest that long-term use of opioids intensifies the peripheral sensitisation of cLBP. The MDPT can counteract this process.     

Comparative efficacy and safety of long-acting oral opioids for chronic non-cancer pain: a systematic review

Opioids have been endorsed as appropriate treatment for refractory chronic non-cancer pain when used according to published guidelines. They are widely used for this indication. However, there appear to be gaps in our understanding of the efficacy and safety of individual long-acting opioids compared to each other or as a class compared to short-acting opioids. This systematic review summarizes and assesses the evidence for the comparative efficacy and safety of long-acting opioids in the management of chronic non-cancer pain. Randomized trials (for comparative efficacy and adverse events) and observational studies (for adverse events only) that included non-parenteral long-acting opioids were sought using electronic databases, handsearching reference lists, and soliciting pharmaceutical company submissions. Searches were performed through October 2002. The validity of each included study was assessed using a data abstraction form and predefined criteria. An overall grade was allocated for the body of evidence for each key question. A total of 16 randomized trials (comparative efficacy and adverse events), enrolling 1427 patients, and 8 observational studies (adverse events) of 1190 patients were included in this review. No randomized trial was rated good quality; observational studies were generally of poorer quality than the trials. There was insufficient evidence to prove that different long-acting opioids are associated with different efficacy or safety profiles. There was also insufficient evidence to determine whether long-acting opioids as a class are more effective or safer than short-acting opioids. A subgroup of three studies on long-acting versus short-acting oxycodone was more homogeneous and provided fair evidence that these formulations are equally effective for pain control.     

Opioids in chronic non-cancer pain: systematic review of efficacy and safety

Opioids are used increasingly for chronic non-cancer pain. Controversy exists about their effectiveness and safety with long-term use. We analysed available randomised, placebo-controlled trials of WHO step 3 opioids for efficacy and safety in chronic non-cancer pain. The Oxford Pain Relief Database (1950-1994) and Medline, EMBASE and the Cochrane Library were searched until September 2003. Inclusion criteria were randomised comparisons of WHO step 3 opioids with placebo in chronic non-cancer pain. Double-blind studies reporting on pain intensity outcomes using validated pain scales were included. Fifteen randomised placebo-controlled trials were included. Four investigations with 120 patients studied intravenous opioid testing. Eleven studies (1025 patients) compared oral opioids with placebo for four days to eight weeks. Six of the 15 included trials had an open label follow-up of 6-24 months. The mean decrease in pain intensity in most studies was at least 30% with opioids and was comparable in neuropathic and musculoskeletal pain. About 80% of patients experienced at least one adverse event, with constipation (41%), nausea (32%) and somnolence (29%) being most common. Only 44% of 388 patients on open label treatments were still on opioids after therapy for between 7 and 24 months. The short-term efficacy of opioids was good in both neuropathic and musculoskeletal pain conditions. However, only a minority of patients in these studies went on to long-term management with opioids. The small number of selected patients and the short follow-ups do not allow conclusions concerning problems such as tolerance and addiction.     

Methadone Safety: A Clinical Practice Guideline From the American Pain Society and College on Problems of Drug Dependence,in Collaboration With the Heart Rhythm Society

Methadone is used for the treatment of opioid addiction and for treatment of chronic pain. The safety of methadone has been called into question by data indicating a large increase in the number of methadone-associated overdose deaths in recent years that has occurred in parallel with a dramatic rise in the use of methadone for chronic pain. The American Pain Society and the College on Problems of Drug Dependence, in collaboration with the Heart Rhythm Society, commissioned an interdisciplinary expert panel to develop a clinical practice guideline on safer prescribing of methadone for treatment of opioid addiction and chronic pain. As part of the guideline development process, the American Pain Society commissioned a systematic review of various aspects related to safety of methadone. After a review of the available evidence, the expert panel concluded that measures can be taken to promote safer use of methadone. Specific recommendations include the need to educate and counsel patients on methadone safety, use of electrocardiography to identify persons at greater risk for methadone-associated arrhythmia, use of alternative opioids in patients at high risk of complications related to corrected electrocardiographic QTc interval prolongation, careful dose initiation and titration of methadone, and diligent monitoring and follow-up. Although these guidelines are based on a systematic review, the panel identified numerous research gaps, most recommendations were based on low-quality evidence, and no recommendations were based on high-quality evidence.PerspectiveThis guideline, based on a systematic review of the evidence on methadone safety, provides recommendations developed by a multidisciplinary expert panel. Safe use of methadone requires clinical skills and knowledge in use of methadone to mitigate potential risks, including serious risks related to risk of overdose and cardiac arrhythmias.