chronic pain

A meta-analysis of the benefits and adverse effects of tramadol for the treatment of chronic pain. It looks like the adverse effects outweigh the meager benefits in RCTs at least.

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Objectives The objective of our study was to assess the benefits and harms of tramadol vs placebo in adults with chronic pain.

Design The research method was a systematic review of randomised clinical trials with meta-analysis. The review followed the Trial Sequential Analysis and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Data sources The Cochrane Library, MEDLINE, Embase, Science Citation Index and BIOSIS were searched for trials published from inception to 6 February 2025.

Eligibility criteria for selecting studies Studies were eligible for inclusion if they were published and unpublished randomised clinical trials comparing tramadol vs placebo in adults with any type of chronic pain. Risk of bias was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions.

Main outcome measures The main outcome measures were pain level, adverse events, quality of life, dependence, abuse and depressive symptoms.

Results We included 19 randomised placebo-controlled clinical trials enrolling 6506 participants. All outcome results were at high risk of bias. Meta-analysis and Trial Sequential Analysis showed evidence of a beneficial effect of tramadol on chronic pain (mean difference numerical rating scale (NRS) −0.93 points; 97.5% CI −1.26 to −0.60; p<0.0001; low certainty of evidence). However, the effect size was below our predefined minimal important difference of 1.0 point on NRS. Beta binomial regression showed evidence of a harmful effect of tramadol on serious adverse events (OR 2.13; 97.5% CI 1.29 to 3.51; p=0.001; moderate certainty of evidence), mainly driven by a higher proportion of cardiac events and neoplasms. It was not possible to conduct a meta-analysis of the quality of life due to a lack of data. Meta-analysis and Trial Sequential Analysis showed that tramadol increased the risk of several non-serious adverse events including nausea (number needed to harm (NNH) 7), dizziness (NNH 8), constipation (NNH 9), and somnolence (NNH 13) (all very low certainty of evidence).

Conclusion Tramadol may have a slight effect on reducing chronic pain levels (low certainty of evidence) while likely increasing the risk of both serious (moderate certainty of evidence) and non-serious adverse events (very low certainty of evidence). The potential harms associated with tramadol use for pain management likely outweigh its limited benefits.

Author/s:

Jehad Ahmad Barkji, Mathias Maagaard, Johanne Juul Petersen, Yousef Ahmad Barakji, Emil Ørskov Ipsen, Christian Gluud, Ole Mathiesen, Janus Christian Jakobsen

Long-Term Use of Muscle Relaxant Medications for Chronic Pain: A Systematic Review

Alex Haga — Wed, 25 Sep 2024 13:18:36 +0000

Date Added:

September 25, 2024

Journal/Publication:

JAMA Network Open

Publication Date:

September 19, 2024

Issue:

Volume:

URL:

Long-Term Use of Muscle Relaxant Medications for Chronic Pain: A Systematic Review

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jamanetworkopen.2024.34835

Keywords

chronic pain

muscle relaxants

PMID (1):

39298168

MeSH

Chronic Pain* / therapy

Muscle Relaxants

Central / therapeutic use

Humans

Aside from a few specific indications, muscle relaxants do not benefit patients with chronic pain. James W. Mold, MD, MPH

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Importance: Stricter opioid prescribing guidelines have increased prescriptions of skeletal muscle relaxants (SMRs) for chronic pain, but the efficacy of long-term use of SMRs for chronic pain is unknown.

Objective: To systematically review the effectiveness or efficacy of long-term use of SMRs for chronic pain.

Evidence review: Two reviewers systematically searched Ovid MEDLINE, Embase (Ovid), Web of Science, CINAHL, and Cochrane through December 4, 2023. They included articles published in English, Spanish, or Italian. Only randomized clinical trials (RCTs) and cohort studies with comparator groups evaluating at least 1-month duration of SMRs for chronic pain were included. The reviewers dually reviewed data abstraction, risk-of-bias, and quality. They characterized studies by chronic pain syndrome: low back pain, fibromyalgia, headaches, painful cramps or spasticity, and other syndromes.

Findings: A total of 30 RCTs with 1314 participants and 14 cohort studies with 1168 participants assessed SMRs for chronic pain. Studies were primarily short-term (4-6 weeks). Nine unique SMRs were represented by the studies identified. Eleven studies (25%) examined baclofen, 8 (18%) examined tizanidine, and 7 (16%) examined cyclobenzaprine. Evidence for effectiveness was strongest for SMRs used for trigeminal neuralgia, neck pain, and painful cramps; evidence suggested SMRs for fibromyalgia, low back pain, and other syndromes were not more beneficial than placebo. The most common adverse effects were sedation and dry mouth. RCTs had a low to moderate risk of bias, and the quality of cohort studies was fair to good.

Conclusions and relevance: In this systematic review of long-term use of SMRs for chronic pain, findings suggest that their long-term use may benefit patients with painful spasms or cramps and neck pain; their long-term use for low back pain, fibromyalgia, and headaches did not appear to be beneficial. Clinicians should be vigilant for adverse effects and consider deprescribing if pain-related goals are not met.

Author/s:

Benjamin J Oldfield, Brynna Gleeson, Kenneth L Morford, Zoe Adams, Melissa C Funaro, William C Becker, Jessica S Merlin

Multimodal non-invasive non-pharmacological therapies for chronic pain: mechanisms and progress

Rowan Hutchins — Sun, 08 Oct 2023 05:00:00 +0000

Date Added:

October 8, 2023

Journal/Publication:

BMC Medicine

Publisher:

BMC

Publication Date:

September 29, 2023

Issue:

372

Volume:

URL:

Multimodal non-invasive non-pharmacological therapies for chronic pain: mechanisms and progress

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1186/s12916-023-03076-2

Keywords

chronic pain

PMID (1):

37775758

MeSH

Clinical Protocols

chronic disease

Chronic Pain* / therapy

A lengthy review of nonpharmacologic treatments for chronic pain including proposed mechanisms and current evidence. James W. Mold, MD, MPH

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Chronic pain conditions impose significant burdens worldwide. Pharmacological treatments like opioids have limitations. Non-invasive non-pharmacological therapies (NINPT) encompass diverse interventions including physical, psychological, complementary and alternative approaches, and other innovative techniques that provide analgesic options for chronic pain without medications.
Main body

This review elucidates the mechanisms of major NINPT modalities and synthesizes evidence for their clinical potential across chronic pain populations. NINPT leverages peripheral, spinal, and supraspinal mechanisms to restore normal pain processing and limit central sensitization. However, heterogeneity in treatment protocols and individual responses warrants optimization through precision medicine approaches.
Conclusion

Future adoption of NINPT requires addressing limitations in standardization and accessibility as well as synergistic combination with emerging therapies. Overall, this review highlights the promise of NINPT as a valuable complementary option ready for integration into contemporary pain medicine paradigms to improve patient care and outcomes.

Author/s:

Shi, Yu, Wu, Wen

Clin-STAR corner: 2021 update in musculoskeletal pain in older adults with a focus on osteoarthritis-related pain

Rowan Hutchins — Sun, 17 Sep 2023 05:00:00 +0000

Date Added:

September 17, 2023

Journal/Publication:

Journal of the American Geriatrics Society

Publisher:

American Geriatrics Society

Publication Date:

April 25, 2023

Issue:

Volume:

Pages:

2373-2380

URL:

Clin-STAR corner: 2021 update in musculoskeletal pain in older adults with a focus on osteoarthritis-related pain

Type:

Meta-analyses, Reviews, and Guidelines

DOI (1):

https://doi.org/10.1111/jgs.18369

Keywords

PMID (1):

37186060

MeSH

Musculoskeletal Pain* / drug therapy

osteoarthritis

Knee* / complications

Knee* / therapy

A summary of what we know about managing chronic musculoskeletal pain in older people. James W. Mold, MD, MPH

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Chronic musculoskeletal (MSK) pain remains a leading cause of disability and functional impairment among older adults and is associated with substantial societal and personal costs. Chronic pain is particularly challenging to manage in older adults because of multimorbidity, concerns about treatment-related harm, as well as older adults' beliefs about pain and its management. This narrative review presents data on nine high-quality, peer-reviewed clinical trials published primarily over the past two years that focus on MSK pain management in older adults, of which four were comprehensively reviewed. These studies address contributors to knee osteoarthritis (OA) pain (insomnia), provide evidence for digital delivery or artificial intelligence driven behavioral interventions and potentially more efficient/equally effective modes of delivering glucocorticoids for OA; each of the selected studies have potential for scalability and meaningful impact in the care of older adults.

Author/s:

Owoicho Adogwa, M. Cary Reid, Sai Chilakapati, Una E. Makris

Living Systematic Review on Cannabis and Other Plant-Based Treatments for Chronic Pain

Aubrey Delammermore — Thu, 13 Oct 2022 05:00:00 +0000

Date Added:

October 13, 2022

Journal/Publication:

Agency for Healthcare Research and Quality

Publisher:

US Department of Health and Human Services

Publication Date:

October 6, 2022

URL:

Living Systematic Review on Cannabis and Other Plant-Based Treatments for Chronic Pain

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.23970/AHRQEPCCER250

Keywords

PMID (1):

34882379

MeSH

An updated version of a systematic review previously posted to RPR Exchange. James W. Mold, MD, MPH

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In an effort to address the opioid epidemic, a prominent goal of current research is to identify alternative treatments with equal or better benefits for pain while avoiding potential unintended consequences that could result in harms.

This 'living' systematic review assesses the effectiveness and harms of cannabis and other plant-based treatments for chronic pain conditions. For the purposes of this review, plant-based compounds (PBCs) included are those that are similar to opioids in effect and that have the potential for addiction, misuse, and serious adverse effects; other PBCs such as herbal treatments are not included. The intended audience includes policy and decision makers, funders and researchers of treatments for chronic pain, and clinicians who treat chronic pain.

The report will be updated on a quarterly basis.

Author/s:

McDonagh, M. S., Wagner, J., Ahmed, A. Y., Fu, R., Morasco, B., Kansagara, D., Chou, R.

Chronic anal pain: A review of causes, diagnosis, and treatment

Saige Blanchard — Tue, 14 Jun 2022 05:00:00 +0000

Date Added:

June 14, 2022

Journal/Publication:

Cleveland Clinic Journal of Medicine

Publisher:

Cleveland Clinic Journal of Medicine

Publication Date:

June 1, 2022

Issue:

Volume:

Pages:

336-343

URL:

Chronic anal pain: A review of causes, diagnosis, and treatment

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.3949/ccjm.89a.21102

Keywords

PMID (1):

35649568

MeSH

Levator syndrome

Pudendal Neuralgia

diagnostic tests, routine

Syndrome

pain

A nice review of the causes of chronic anal pain. James W. Mold, MD, MPH

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Chronic anal pain is diffi cult to diagnose and treat, especially with no obvious anorectal cause apparent on clinical examination. This review identifi es 3 main diagnostic
categories for chronic anal pain: local causes, functional
anorectal pain, and neuropathic pain syndromes. Conditions covered within these categories include proctalgia
fugax, levator ani syndrome, pudendal neuralgia, and coccygodynia. The signs, symptoms, relevant diagnostic tests,
and main treatments for each condition are reviewed.

Author/s:

Knowles, C. H., Cohen, R. C.

Evaluation of a Chronic Pain Screening Program Implemented in Primary Care

Saige Blanchard — Fri, 06 Aug 2021 05:00:00 +0000

Date Added:

August 6, 2021

Journal/Publication:

Journal of the American Medical Association

Publisher:

JAMA

Publication Date:

July 1, 2021

Issue:

Volume:

URL:

Evaluation of a Chronic Pain Screening Program Implemented in Primary Care

Type:

Clinical Research Results

Format:

Article

DOI (1):

https://doi.org/10.1001/jamanetworkopen.2021.18495

Keywords

PMID (1):

34313738

MeSH

Cross-Sectional Studies

Activities of Daily Living

chronic pain

Pleasure

Pain Measurement

Electronic Health Records

It is possible to screen for chronic pain using two questions. One-third of patients being seen in community health centers have chronic pain. In 40% of them the problem had not been previously identified. James W. Mold, MD, MPH

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Importance: Although pain is among the most common symptoms reported by patients, primary care practitioners (PCPs) face substantial challenges identifying and assessing pain.

Objective: To evaluate a 2-step process for chronic pain screening and follow-up in primary care.

Design, setting, and participants: A cross-sectional study of patients with a primary care visit between July 2, 2018, and June 1, 2019, was conducted at a statewide, multisite federally qualified health center. Participants included 68 PCPs and 58 medical assistants from 13 sites who implemented the screening process in primary care, and 38 866 patients aged 18 years or older with a primary care visit during that time.

Exposures: Single-question assessment of pain frequency, followed by a 3-question PEG (pain, enjoyment of life, general activity) functional assessment for patients with chronic pain.

Main outcomes and measures: Adherence to a 2-step chronic pain screening and PEG process, proportion of patients with positive screening results, mean PEG pain severity greater than or equal to 7, and documented chronic painful condition diagnosis in patient's electronic health record between 1 year before and 90 days after screening.

Results: Of 38 866 patients with a primary care visit, 31 600 patients (81.3%) underwent screening. Mean (SD) age was 46.2 (15.4) years, and most were aged 35 to 54 years (12 987 [41.1%]), female (18 436 [58.3%]), Hispanic (14 809 [46.9%]), and English-speaking (22 519 [71.3%]), and had Medicaid insurance (18 442 [58.4%]). A total of 10 262 participants (32.5%) screened positive and, of these, 9701 (94.5%) completed the PEG questionnaire. PEG responses indicated severe pain interference with activities of daily living (PEG ≥7) in 5735 (59.1%) participants. A chronic painful condition had not been diagnosed in 4257 (43.9%) patients in the year before screening. A new chronic painful condition was diagnosed at screening or within 90 days in 2250 (52.9%) patients. Care teams found the workflow acceptable, but cited lengthy administration time, challenges with comprehension of the PEG questions, and limited comprehensiveness as implementation barriers.

Conclusions and relevance: A systematic, 2-step process for chronic pain screening and functional assessment in primary care appeared to identify patients with previously undocumented chronic pain and was feasible to implement. Patient-provided information on the frequency of pain, pain level, and pain interference can help improve the assessment and monitoring of pain in primary care.

Author/s:

Bifulco, L., Anderson, D. R., Blankson, M. L, Channamsetty, V., Blaz, J. W., Nguyen-Louie, T., Scholle, S. H.

Challenges and Approaches to Population Management of Long-Term Opioid Therapy Patients

Devin Evans — Wed, 03 Mar 2021 06:00:00 +0000

Date Added:

March 3, 2021

Journal/Publication:

Journal of the American Board of Family Medicine

Publication Date:

February 1, 2021

Issue:

Volume:

Pages:

89-98

URL:

Challenges and Approaches to Population Management of Long-Term Opioid Therapy Patients

Type:

Best Local Practices, Practice Management Research Results

Format:

Article

DOI (1):

10.3122/jabfm.2021.01.190100

Keywords

PMID (1):

33452086

MeSH

analgesics, opioid

Focus Groups

Capacity Building

Medication Therapy Management

chronic pain

opioid-related disorders

drug overdose

prescriptions

Useful tips from a multi-practice initiative to improve management of opioids in primary care. James W. Mold, MD, MPH

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Purpose: Primary care is challenged with safely prescribing opioids for patients with chronic noncancer pain (CNCP), specifically to address risks for overdose, opioid use disorder, and death. We identify sociotechnical challenges, approaches, and recommendations in primary care to effectively track and monitor patients on long-term opioid therapy, a key component for supporting adoption of opioid prescribing guidelines.

Methods: We examined qualitative data (field notes and postintervention interview and focus group transcripts) from 6 rural and rural-serving primary care organizations with 20 clinic locations enrolled in a study evaluating a practice redesign program to improve opioid medication management for CNCP patients. Two independent researchers used content analysis to categorize data into key themes to develop an understanding of sociotechnical factors critical to creating and implementing an approach to tracking and monitoring of patients on long-term opioid therapy in primary care practices.

Results: Four factors were critical to developing a tracking and monitoring system. For each we describe common challenges and approaches used by the clinics to overcome then. The first factor, buy-in and participation, was essential for accomplishing the other 3. The other factors occurred sequentially: 1) cohort identification-finding the right patients, 2) data collection and extraction-tracking the right data, and 3) data use-monitoring patients and adjusting care processes.

Conclusions: We identified common challenges and approaches to tracking and monitoring patients using long-term opioid therapy for CNCP in primary care. Based on these findings we provide recommendations to build capacity for tracking and monitoring for organizations that are engaged in improving safe opioid-prescribing practices for CNCP in primary care.

Author/s:

Stephens, Kari A., Ike, Brooke, Baldwin, Laura-Mae, Packer, Christine, Parchman, Michael

AAFP Chronic Pain Management Toolkit

Devin Evans — Wed, 03 Mar 2021 06:00:00 +0000

Date Added:

March 3, 2021

Journal/Publication:

American Academy of Family Physicians

Publication Date:

March 1, 2021

URL:

AAFP Chronic Pain Management Toolkit

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Web Page

Keywords

MeSH

An AAFP-endorsed toolkit for helping patients who are experiencing chronic pain. James W. Mold, MD, MPH

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Chronic pain is common in the U.S., with anywhere from 11% to 40% of the adult population reporting daily pain.1 Approximately one-third of patients experiencing pain receive a pain medication.2 While the number of prescriptions for pain management have declined in recent years3, opioid misuse remains a significant public health crisis. Roughly 21-29% of patients who are prescribed opioids for chronic pain will misuse them.4

This increase leads to a rise in opioid overdoses—at least half are attributed to prescription medications—and morbidity and mortality. Numerous groups—including the AAFP, other medical societies, the National Academy of Medicine and the U.S. Congress—are emphasizing the need to improve chronic pain care.

Noninvasive Nonpharmacological Treatment for Chronic Pain: A Systematic Review Update. Comparative Effectiveness Review No. 227

John Bayhi — Fri, 17 Apr 2020 18:16:34 +0000

Date Added:

April 17, 2020

Journal/Publication:

AHRQ Publication No. 20-EHC009

Publisher:

Agency for Healthcare Research and Quality

Publication Date:

April 16, 2020

URL:

Noninvasive Nonpharmacological Treatment for Chronic Pain: A Systematic Review Update. Comparative Effectiveness Review No. 227

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.23970/AHRQEPCCER227

Keywords

nonpharmacological treatment

MeSH

tension-type headache

Mindfulness

Low-Level Light Therapy

MEDLINE

follow-up studies

AHRQ evidence review of non-invasive, non-pharmacologic treatments for relief of chronic pain. James W. Mold, MD, MPH

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Objectives. We updated the evidence from our 2018 report assessing persistent improvement in outcomes following completion of therapy for noninvasive nonpharmacological treatment for selected chronic pain conditions.

Data sources. Electronic databases (Ovid MEDLINE®, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews) through November 2017 (for prior report) and from September 2017 through September 2019 (for this update report), reference lists, ClinicalTrials.gov, and our previous report.

Review methods. Using predefined criteria, we selected randomized controlled trials (RCTs) of noninvasive nonpharmacological treatments for five common chronic pain conditions (chronic low back pain; chronic neck pain; osteoarthritis of the knee, hip, or hand; fibromyalgia; and tension headache) that reported results for a at least 1 month postintervention. We analyzed effects and assessed strength of evidence (SOE) at short term (1 to <6 months following treatment completion), intermediate term (≥6 to <12 months), and long term (≥12 months).

Results. We included 233 RCTs (31 new to this update). Many were small (N<70), and evidence beyond 12 months after treatment completion was sparse. The most common comparison was with usual care. Evidence on harms was limited, with no evidence suggesting increased risk for serious treatment-related harms for any intervention. Effect sizes were generally small for function and pain.

Chronic low back pain: Psychological therapies were associated with small improvements compared with usual care or an attention control for both function and pain at short-term, intermediate-term, and long-term followup (SOE: moderate). Function improved over short and/or intermediate term for exercise, low-level laser therapy, spinal manipulation, massage, yoga, acupuncture, and multidisciplinary rehabilitation (SOE moderate at short term for exercise, massage, and yoga; low for all others). Improvements in pain at short term were seen for massage, mindfulness-based stress reduction, acupuncture, and multidisciplinary rehabilitation (SOE: moderate), and exercise, low-level laser therapy, and yoga (SOE: low). At intermediate term, spinal manipulation, yoga, multidisciplinary rehabilitation (SOE: moderate) and exercise and mindfulness-based stress reduction (SOE: low) were associated with improved pain. Compared with exercise, multidisciplinary rehabilitation improved both function and pain at short and intermediate terms (small effects, SOE: moderate.)

Chronic neck pain: In the short term, low-level laser therapy (SOE: moderate) and massage (SOE: low) improved function and pain. Exercise in general improved function long term, and combination exercise improved function and pain both short and long term compared with usual care (SOE: low). Acupuncture improved function short and intermediate term, but there was no pain improvement compared with sham acupuncture (SOE: low). Compared with acetaminophen, Pilates improved both function and pain (SOE: low).

Osteoarthritis pain: Exercise resulted in small improvements in function and pain at short-term (SOE: moderate) and long-term (SOE: low), and moderate improvement at intermediate-term (SOE: low) followup for knee osteoarthritis versus nonactive comparators. Small improvements in function and pain with exercise were seen for hip osteoarthritis short term (SOE: low). Functional improvement persisted into intermediate term, but pain improvement did not (SOE: low).

Fibromyalgia: Functional improvements were seen with exercise, mind-body practices, multidisciplinary rehabilitation (SOE: low) and acupuncture (SOE: moderate) short term compared with usual care, attention control, or sham treatment. At intermediate term, there was functional improvement with exercise and acupuncture (SOE: moderate), cognitive-behavioral therapy (CBT), mindfulness-based stress reduction, myofascial release, and multidisciplinary rehabilitation (SOE: low). Long term, functional improvements persisted for multidisciplinary rehabilitation without improvement in pain (SOE: low). Compared with exercise, tai chi conferred improvement in function short and intermediate term (SOE: low). Pain was improved with exercise (short and intermediate term, SOE moderate), and for CBT (short term), mindfulness practices, and multidisciplinary rehabilitation (intermediate term) (SOE low).

Chronic tension headache: Evidence was sparse and the majority of trials were of poor quality. Spinal manipulation resulted in moderate improvement in pain short term.

Conclusions. Trials identified subsequent to the earlier report largely support previous findings—namely that exercise, multidisciplinary rehabilitation, acupuncture, CBT, mindfulness practices, massage, and mind-body practices most consistently improve function and/or pain beyond the course of therapy for specific chronic pain conditions. Additional research, including comparisons with pharmacological and other active controls, on effects beyond the immediate post-treatment period is needed, particularly for conditions other than low back pain.

Author/s:

Skelly, AC, Chou, R, Dettori, JR, Turner, JA, Friedly, JL, Rundell, SD, Fu, Brodt, ED, Wasson, N, Kantner, S, Ferguson, AJR

Nonopioid Pharmacologic Treatments for Chronic Pain. Comparative Effectiveness Review No. 228

John Bayhi — Fri, 17 Apr 2020 17:56:57 +0000

Date Added:

April 17, 2020

Journal/Publication:

AHRQ Publication No. 20-EHC010

Publisher:

Agency for Healthcare Research and Quality

Publication Date:

April 16, 2020

URL:

Nonopioid Pharmacologic Treatments for Chronic Pain. Comparative Effectiveness Review No. 228

Type:

Meta-analyses, Reviews, and Guidelines

Keywords

chronic pain

non-opioid treatment

anticonvulsants

serotonin-norepinephrine reuptake inhibitor

nonsteroidal anti-inflammatory drugs

MeSH

duloxetine hydrochloride

Diclofenac

Capsaicin

Celecoxib

Anti-Inflammatory Agents

AHRQ evidence review of non-opioids analgesics for relief of chronic pain. James W. Mold, MD, MPH

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Objectives. To evaluate the effectiveness and comparative effectiveness of nonopioid pharmacologic agents in patients with specific types of chronic pain, considering effects on pain, function, quality of life, and adverse events.

Data sources. Electronic databases (Ovid® MEDLINE®, Embase®, PsycINFO®, CINAHL®, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews) through September 10, 2019, reference lists, data requests, and previous reviews.

Review methods. Randomized controlled trials (RCTs) of nonopioid pharmacologic agents in patients with chronic pain were selected using predefined criteria and dual review. This review focused on seven common chronic pain conditions (neuropathic pain, fibromyalgia, osteoarthritis, inflammatory arthritis, low back pain, chronic headache, sickle cell disease), with effects analyzed at short term (1 to <6 months following treatment completion), intermediate term (≥6 to <12 months), and long term (≥12 months). Magnitude of effects were described as small, moderate, or large using previously defined criteria, and strength of evidence was assessed. Meta-analyses were conducted where data allowed, stratified by duration within each intervention type, using random effects models. We evaluated effect modification through subgroup and sensitivity analyses, including specific drug, dose, study quality, and pain type.

Results. We included 185 RCTs in 221 publications and 5 systematic reviews. In the short term, anticonvulsants (pregabalin, gabapentin, and oxcarbazepine for neuropathic pain, pregabalin/gabapentin for fibromyalgia), serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressants (duloxetine for neuropathic pain, fibromyalgia, osteoarthritis, and low back pain, milnacipran for fibromyalgia), and nonsteroidal anti-inflammatory drugs (NSAIDs) (for osteoarthritis and inflammatory arthritis) were associated with mostly small improvements (e.g., 5 to 20 points on a 0 to 100 scale) in pain and function. Function was not found to be improved with duloxetine for low back pain or pregabalin/gabapentin for neuropathic pain. Moderate improvement in quality of life was seen with duloxetine in patients with neuropathic pain, and small improvements in patients with osteoarthritis, but evidence was insufficient to draw conclusions for other drugs and conditions. While most comparisons of drugs and doses did not identify differences, diclofenac improved pain and function moderately more than celecoxib. In the intermediate term, limited evidence (1 RCT) showed memantine moderately improved pain, function, and quality of life in patients with fibromyalgia; improvements in pain, but not function, were maintained in the intermediate term with duloxetine and milnacipran for fibromyalgia. Other drugs studied, including acetaminophen (osteoarthritis), capsaicin (neuropathic pain), cannabis (neuropathic pain), amitriptyline (fibromyalgia, neuropathic pain), and cyclobenzaprine (fibromyalgia) had no clear effects. Withdrawal from study due to adverse events was significantly increased with nonopioid drugs, with the greatest increase over placebo seen with cannabis. Large increases in risk of adverse events were seen with pregabalin (blurred vision, cognitive effects, dizziness, peripheral edema, sedation, and weight gain), gabapentin (blurred vision, cognitive effects, sedation, weight gain), and cannabis (nausea, dizziness). Dose viii reductions reduced the risk of some adverse events with SNRI antidepressants. In the short term small increases in risk of major coronary events and moderate increases in serious gastrointestinal events (both short and long term) were found with NSAIDs.

Conclusions. In the short term, small improvements in pain and/or function were seen with SNRI antidepressants for neuropathic pain, fibromyalgia, osteoarthritis, and low back pain; pregabalin/gabapentin for neuropathic pain and fibromyalgia; oxcarbazepine for neuropathic pain; and NSAIDs for osteoarthritis and inflammatory arthritis. Improvement in function was not found with duloxetine for low back pain and pregabalin/gabapentin for neuropathic pain. Intermediate- and long-term outcomes were mostly not assessed. Increased incidence of drug class–specific adverse events led to withdrawal from treatment in some patients, suggesting that careful consideration of patient characteristics is needed in selecting nonopioid drug treatments.

Author/s:

McDonagh, MS, Selph, SS, Buckley, DI, Holmes, RS, Mauer, K, Ramirez, S, Hsu, FC, Dana, T, Fu, R, Chou

Opioid Treatments for Chronic Pain. Comparative Effectiveness Review No. 229

John Bayhi — Fri, 17 Apr 2020 17:45:13 +0000

Date Added:

April 17, 2020

Journal/Publication:

AHRQ Publication No. 20-EHC011

Publisher:

Agency for Healthcare Research and Quality

Publication Date:

April 16, 2020

URL:

Opioid Treatments for Chronic Pain. Comparative Effectiveness Review No. 229

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.23970/AHRQEPCCER229

Keywords

MeSH

opioid-related disorders

drug overdose

analgesics, non-narcotic

AHRQ evidence review of opioids for relief of chronic pain. James W. Mold, MD, MPH

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Objectives. Chronic pain is common, and opioid therapy is frequently prescribed for this condition. This report updates and expands on a prior Comparative Effectiveness Review on long-term (≥1 year) effectiveness and harms of opioid therapy for chronic pain, including evidence on shorter term (1 to 12 months) outcomes.

Data sources. A prior systematic review (searches through January 2014), electronic databases (Ovid MEDLINE®, Embase®, PsycINFO®, Cochrane CENTRAL, and Cochrane Database of Systematic Reviews through August 2019), reference lists, and clinical trials registries.

Review methods. Predefined criteria were used to select studies of patients with chronic pain prescribed opioids that addressed effectiveness or harms versus placebo, no opioid use, or nonopioid pharmacological therapies; different opioid dosing methods; or risk mitigation strategies. Effects were analyzed at short-term (1 to <6 months), intermediate-term (≥6 to <12 months), and long-term (≥12 months) followup. Studies on the accuracy of risk prediction instruments for predicting opioid use disorder or misuse were also included. Random effects meta-analysis was conducted on short-term trials of opioids versus placebo, opioids versus nonopioids, and opioids plus nonopioids versus an opioid or nonopioid alone. Magnitude of effects was classified as small, moderate, or large using predefined criteria, and strength of evidence was assessed.

Results. We included 115 randomized controlled trials (RCTs), 40 observational studies, and 7 studies of predictive accuracy; 134 were new to this update. Opioids were associated with small benefits versus placebo in short-term pain, function, and sleep quality. There was a small dose-dependent effect on pain, and effects were attenuated at longer (3 to 6 month) versus shorter (1 to 3 month) followup. Opioids were associated with increased risk of discontinuation due to adverse events, gastrointestinal adverse events, somnolence, dizziness, and pruritus versus placebo. In observational studies, opioids were associated with increased risk of an opioid abuse or dependence diagnosis, overdose, all-cause mortality, fractures, falls, and myocardial infarction versus no opioid use; there was evidence of a dose-dependent risk for all outcomes except fracture and falls.

There were no differences between opioids and nonopioid medications in pain, function, or other short-term outcomes. Opioid plus nonopioid combination therapy was associated with little improvement in pain at short-term followup versus an opioid alone. Co-prescription of benzodiazepines or gabapentinoids was associated with increased risk of overdose versus an opioid alone. No RCT evaluated intermediate- or long-term benefits of opioids versus placebo. One trial found stepped therapy starting with opioids to be associated with higher pain intensity and no difference in function or other outcomes versus stepped therapy starting with nonopioid therapy.

Limited evidence indicated no differences between long- and short-acting opioids in effectiveness, but long-acting opioids were associated with increased risk of overdose. One RCT found a taper support intervention associated with greater improvement in function but no difference in pain versus usual care.

Estimates of diagnostic accuracy for various risk prediction instruments were highly inconsistent, and there was no evidence on the effectiveness of risk mitigation strategies for improving clinical outcomes, with the exception of one study that found provision of naloxone associated with decreased emergency department visits.

Trials of patients with prescription opioid dependence found buprenorphine maintenance associated with better outcomes than buprenorphine taper and similar effects of methadone versus buprenorphine. Evidence was insufficient to evaluate benefits and harms of opioid therapy in patients at higher risk for opioid use disorder.

Conclusions. At short-term followup, for patients with chronic pain, opioids are associated with small beneficial effects versus placebo but are associated with increased risk of short-term harms and do not appear to be superior to nonopioid therapy. Evidence on intermediate-term and long-term benefits remains very limited, and additional evidence confirms an association between opioids and increased risk of serious harms that appears to be dose-dependent. Research is needed to develop accurate risk prediction instruments, determine effective risk mitigation strategies, clarify risks associated with co-prescribed medications, and identify optimal opioid tapering strategies.

Author/s:

Chou, R, Hartung, D, Turner, J, Blazina, I, Chan, B, Levander, X, McDonagh, M, Selph, S, Fu, Pappas

Craniosacral therapy for chronic pain: a systematic review and meta-analysis of randomized controlled trials

John Bayhi — Fri, 03 Jan 2020 17:40:28 +0000

Date Added:

January 3, 2020

Journal/Publication:

BMC Musculoskeletal Disorders

Publisher:

BioMed Central Ltd

Publication Date:

December 31, 2019

Issue:

Volume:

URL:

Craniosacral therapy for chronic pain: a systematic review and meta-analysis of randomized controlled trials

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1186/s12891-019-3017-y

Keywords

chronic pain

Complementary Therapies

Craniosacral therapy

meta-analysis

systematic review

PMID (1):

31892357

MeSH

Craniosacral therapy is an apparently effective therapy, about which many of you may be unfamiliar, for patients with chronic pain syndromes. James W. Mold, MD, MPH

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OBJECTIVES:

To systematically assess the evidence of Craniosacral Therapy (CST) for the treatment of chronic pain.

METHODS:

PubMed, Central, Scopus, PsycInfo and Cinahl were searched up to August 2018. Randomized controlled trials (RCTs) assessing the effects of CST in chronic pain patients were eligible. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for pain intensity and functional disability (primary outcomes) using Hedges' correction for small samples. Secondary outcomes included physical/mental quality of life, global improvement, and safety. Risk of bias was assessed using the Cochrane tool.

RESULTS:

Ten RCTs of 681 patients with neck and back pain, migraine, headache, fibromyalgia, epicondylitis, and pelvic girdle pain were included. CST showed greater post intervention effects on: pain intensity (SMD = -0.32, 95%CI = [- 0.61,-0.02]) and disability (SMD = -0.58, 95%CI = [- 0.92,-0.24]) compared to treatment as usual; on pain intensity (SMD = -0.63, 95%CI = [- 0.90,-0.37]) and disability (SMD = -0.54, 95%CI = [- 0.81,-0.28]) compared to manual/non-manual sham; and on pain intensity (SMD = -0.53, 95%CI = [- 0.89,-0.16]) and disability (SMD = -0.58, 95%CI = [- 0.95,-0.21]) compared to active manual treatments. At six months, CST showed greater effects on pain intensity (SMD = -0.59, 95%CI = [- 0.99,-0.19]) and disability (SMD = -0.53, 95%CI = [- 0.87,-0.19]) versus sham. Secondary outcomes were all significantly more improved in CST patients than in other groups, except for six-month mental quality of life versus sham. Sensitivity analyses revealed robust effects of CST against most risk of bias domains. Five of the 10 RCTs reported safety data. No serious adverse events occurred. Minor adverse events were equally distributed between the groups.

DISCUSSION:

In patients with chronic pain, this meta-analysis suggests significant and robust effects of CST on pain and function lasting up to six months. More RCTs strictly following CONSORT are needed to further corroborate the effects and safety of CST on chronic pain.

Author/s:

Haller, H, Lauche, R, Sundberg, T, Dobos, G, Cramer, H

Exercise interventions and patient beliefs for people with hip, knee or hip and knee osteoarthritis: a mixed methods review

Jeffrey Wilson — Wed, 03 Apr 2019 14:50:52 +0000

Date Added:

April 3, 2019

Journal/Publication:

Cochrane Database of Systematic Reviews

Publisher:

Cochrane Library

Publication Date:

April 17, 2018

URL:

Exercise interventions and patient beliefs for people with hip, knee or hip and knee osteoarthritis: a mixed methods review

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1002/14651858.CD010842.pub2

Keywords

exercise therapy

chronic pain

osteoarthritis

PMID (1):

29664187

MeSH

Many patients with osteoarthritis of the knee and hip believe that physical activity could further damage their joints. Providing reassurance and clear advice about the value of exercise in controlling symptoms, and opportunities to participate in activities that people regard as enjoyable and relevant, may encourage more physical activity, which brings a range of health benefits to a large population of people. James W. Mold, MD, MPH

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BACKGROUND:

Chronic peripheral joint pain due to osteoarthritis (OA) is extremely prevalent and a major cause of physical dysfunction and psychosocial distress. Exercise is recommended to reduce joint pain and improve physical function, but the effect of exercise on psychosocial function (health beliefs, depression, anxiety and quality of life) in this population is unknown.

OBJECTIVES:

To improve our understanding of the complex inter-relationship between pain, psychosocial effects, physical function and exercise.

SEARCH METHODS:

Review authors searched 23 clinical, public health, psychology and social care databases and 25 other relevant resources including trials registers up to March 2016. We checked reference lists of included studies for relevant studies. We contacted key experts about unpublished studies.

SELECTION CRITERIA:

To be included in the quantitative synthesis, studies had to be randomised controlled trials of land- or water-based exercise programmes compared with a control group consisting of no treatment or non-exercise intervention (such as medication, patient education) that measured either pain or function and at least one psychosocial outcome (self-efficacy, depression, anxiety, quality of life). Participants had to be aged 45 years or older, with a clinical diagnosis of OA (as defined by the study) or self-reported chronic hip or knee (or both) pain (defined as more than six months' duration).To be included in the qualitative synthesis, studies had to have reported people's opinions and experiences of exercise-based programmes (e.g. their views, understanding, experiences and beliefs about the utility of exercise in the management of chronic pain/OA).

DATA COLLECTION AND ANALYSIS:

We used standard methodology recommended by Cochrane for the quantitative analysis. For the qualitative analysis, we extracted verbatim quotes from study participants and synthesised studies of patients' views using framework synthesis. We then conducted an integrative review, synthesising the quantitative and qualitative data together.

MAIN RESULTS:

Twenty-one trials (2372 participants) met the inclusion criteria for quantitative synthesis. There were large variations in the exercise programme's content, mode of delivery, frequency and duration, participant's symptoms, duration of symptoms, outcomes measured, methodological quality and reporting. Comparator groups were varied and included normal care; education; and attention controls such as home visits, sham gel and wait list controls. Risk of bias was high in one and unclear risk in five studies regarding the randomisation process, high for 11 studies regarding allocation concealment, high for all 21 studies regarding blinding, and high for three studies and unclear for five studies regarding attrition. Studies did not provide information on adverse effects.There was moderate quality evidence that exercise reduced pain by an absolute percent reduction of 6% (95% confidence interval (CI) -9% to -4%, (9 studies, 1058 participants), equivalent to reducing (improving) pain by 1.25 points from 6.5 to 5.3 on a 0 to 20 scale and moderate quality evidence that exercise improved physical function by an absolute percent of 5.6% (95% CI -7.6% to 2.0%; standardised mean difference (SMD) -0.27, 95% CI -0.37 to -0.17, equivalent to reducing (improving) WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) function on a 0 to 100 scale from 49.9 to 44.3) (13 studies, 1599 participants)). Self-efficacy was increased by an absolute percent of 1.66% (95% CI 1.08% to 2.20%), although evidence was low quality (SMD 0.46, 95% CI 0.34 to 0.58, equivalent to improving the ExBeliefs score on a 17 to 85 scale from 64.3 to 65.4), with small benefits for depression from moderate quality evidence indicating an absolute percent reduction of 2.4% (95% CI -0.47% to 0.5%) (SMD -0.16, 95% CI -0.29 to -0.02, equivalent to improving depression measured using HADS (Hospital Anxiety and Depression Scale) on a 0 to 21 scale from 3.5 to 3.0) but no clinically or statistically significant effect on anxiety (SMD -0.11, 95% CI -0.26 to 0.05, 2% absolute improvement, 95% CI -5% to 1% equivalent to improving HADS anxiety on a 0 to 21 scale from 5.8 to 5.4; moderate quality evidence). Five studies measured the effect of exercise on health-related quality of life using the 36-item Short Form (SF-36) with statistically significant benefits for social function, increasing it by an absolute percent of 7.9% (95% CI 4.1% to 11.6%), equivalent to increasing SF-36 social function on a 0 to 100 scale from 73.6 to 81.5, although the evidence was low quality. Evidence was downgraded due to heterogeneity of measures, limitations with blinding and lack of detail regarding interventions. For 20/21 studies, there was a high risk of bias with blinding as participants self-reported and were not blinded to their participation in an exercise intervention.Twelve studies (with 6 to 29 participants) met inclusion criteria for qualitative synthesis. Their methodological rigour and quality was generally good. From the patients' perspectives, ways to improve the delivery of exercise interventions included: provide better information and advice about the safety and value of exercise; provide exercise tailored to individual's preferences, abilities and needs; challenge inappropriate health beliefs and provide better support.An integrative review, which compared the findings from quantitative trials with low risk of bias and the implications derived from the high-quality studies in the qualitative synthesis, confirmed the importance of these implications.

AUTHORS' CONCLUSIONS:

Chronic hip and knee pain affects all domains of people's lives. People's beliefs about chronic pain shape their attitudes and behaviours about how to manage their pain. People are confused about the cause of their pain, and bewildered by its variability and randomness. Without adequate information and advice from healthcare professionals, people do not know what they should and should not do, and, as a consequence, avoid activity for fear of causing harm. Participation in exercise programmes may slightly improve physical function, depression and pain. It may slightly improve self-efficacy and social function, although there is probably little or no difference in anxiety. Providing reassurance and clear advice about the value of exercise in controlling symptoms, and opportunities to participate in exercise programmes that people regard as enjoyable and relevant, may encourage greater exercise participation, which brings a range of health benefits to a large population of people.

Author/s:

Hurley, Michael, Dickson, Kelly, Hallett, Rachel, Grant, Robert, Hauari, Hanan, Walsh, Nicola, Stansfield, Claire, Oliver, Sandy

Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients With Chronic Back Pain or Hip or Knee Osteoarthritis Pain The SPACE Randomized Clinical Trial

Tracy Ashby — Mon, 07 Jan 2019 06:00:00 +0000

Date Added:

January 21, 2021

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

March 6, 2018

Issue:

Volume:

319

Pages:

872-882

URL:

Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients With Chronic Back Pain or Hip or Knee Osteoarthritis Pain The SPACE Randomized Clinical Trial

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jama.2018.0899

Keywords

PMID (1):

29509867

MeSH

Analgesics

analgesics, opioid

analgesics, non-narcotic

chronic pain

osteoarthritis, knee

In this RCT, comparing non-opioids to opioids for management of chronic pain in the lower back or knee due to OA the researchers found that non-opioid medications were more effective for relieving pain with fewer side effects.

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Importance Limited evidence is available regarding long-term outcomes of opioids compared with nonopioid medications for chronic pain.

Objective To compare opioid vs nonopioid medications over 12 months on pain-related function, pain intensity, and adverse effects.

Design, Setting, and Participants Pragmatic, 12-month, randomized trial with masked outcome assessment. Patients were recruited from Veterans Affairs primary care clinics from June 2013 through December 2015; follow-up was completed December 2016. Eligible patients had moderate to severe chronic back pain or hip or knee osteoarthritis pain despite analgesic use. Of 265 patients enrolled, 25 withdrew prior to randomization and 240 were randomized.

Interventions Both interventions (opioid and nonopioid medication therapy) followed a treat-to-target strategy aiming for improved pain and function. Each intervention had its own prescribing strategy that included multiple medication options in 3 steps. In the opioid group, the first step was immediate-release morphine, oxycodone, or hydrocodone/acetaminophen. For the nonopioid group, the first step was acetaminophen (paracetamol) or a nonsteroidal anti-inflammatory drug. Medications were changed, added, or adjusted within the assigned treatment group according to individual patient response.

Main Outcomes and Measures The primary outcome was pain-related function (Brief Pain Inventory [BPI] interference scale) over 12 months and the main secondary outcome was pain intensity (BPI severity scale). For both BPI scales (range, 0-10; higher scores = worse function or pain intensity), a 1-point improvement was clinically important. The primary adverse outcome was medication-related symptoms (patient-reported checklist; range, 0-19).

Results Among 240 randomized patients (mean age, 58.3 years; women, 32 [13.0%]), 234 (97.5%) completed the trial. Groups did not significantly differ on pain-related function over 12 months (overall P = .58); mean 12-month BPI interference was 3.4 for the opioid group and 3.3 for the nonopioid group (difference, 0.1 [95% CI, −0.5 to 0.7]). Pain intensity was significantly better in the nonopioid group over 12 months (overall P = .03); mean 12-month BPI severity was 4.0 for the opioid group and 3.5 for the nonopioid group (difference, 0.5 [95% CI, 0.0 to 1.0]). Adverse medication-related symptoms were significantly more common in the opioid group over 12 months (overall P = .03); mean medication-related symptoms at 12 months were 1.8 in the opioid group and 0.9 in the nonopioid group (difference, 0.9 [95% CI, 0.3 to 1.5]).

Conclusions and Relevance Treatment with opioids was not superior to treatment with nonopioid medications for improving pain-related function over 12 months. Results do not support initiation of opioid therapy for moderate to severe chronic back pain or hip or knee osteoarthritis pain.

Trial Registration clinicaltrials.gov Identifier: NCT01583985

Author/s:

Krebs, Erin E., Gravely, Amy, Nugent, Sean, Jensen, Agnes C., DeRonne, Beth, Goldsmith, Elizabeth S., Kroenke, Kurt, Bair, Matthew J, Noorbaloochi, Siamak