The effects of long‐term opioid treatment on the immune system in chronic non‐cancer pain patients: A systematic review

Abstract Introduction In individuals with chronic pain, sleep disturbances have been suggested to increase suffering, perception of pain, and to negatively affect long-term prognosis. This systematic review and meta-analysis aims to determine the pooled prevalence of sleep disturbances in chronic non-cancer pain patients with no other sleep disorders, using the patient-rated questionnaires Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI). Methods Multiple databases were searched for studies reporting the prevalence of sleep disturbances in chronic pain patients. Chronic pain was defined as pain >3 months. Comorbid sleep disorders such as sleep disordered breathing and restless leg syndrome were excluded. Sleep disturbances were defined using the PSQI cutoff of > 5 (poor sleep quality) and ISI ≥ 8 (subthreshold to clinical insomnia). The meta-analysis was conducted to examine the pooled prevalence of PSQI and ISI data using the inverse-variance random-effects model and to examine mean differences in PSQI scores. Results The systematic search resulted in 25,486 articles and 20 were included for analysis. In 12 studies using PSQI, the pooled prevalence of sleep disturbance was 75.3% among 3,597 chronic pain patients (mean age 53 ± 12 years; 74% female). In eight studies using ISI, the pooled prevalence was 72.9% among 2,578 chronic pain patients (mean age 63 ± 12 years; 57% female). The meta-analysis showed a significant mean difference of 2.75 (p < 0.001) in the global PSQI score between the chronic pain group versus the non-chronic pain group. The meta-analysis also showed a significant mean difference in the scores of four of seven PSQI components: sleep latency, sleep efficiency, sleep duration, and sleep disturbances (p < 0.05). Conclusion In chronic pain patients, the pooled prevalence of sleep disturbances as measured by PSQI (75.3%) and ISI (72.9%) studies was much higher than those reported for the general population. The relatively high prevalence of sleep disturbances in chronic pain patients emphasizes the importance of further characterizing the relationship between sleep and chronic pain. Support (if any):

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A Systematic Review of Randomized Trials of Long-Term Opioid Management for Chronic Non-Cancer Pain

January 2018 - Pain Physician ◽

10.36076/ppj.2011/14/91 ◽

2011 ◽

Vol 3;14 (2;3) ◽

pp. 91-121

Author(s):

Laxmaiah Manchikanti

Keyword(s):

Systematic Review ◽

Cancer Pain ◽

Systematic Reviews ◽

Randomized Trials ◽

Opioid Therapy ◽

Functional Improvement ◽

Controlled Trials ◽

Chronic Opioid Therapy ◽

Level Of Evidence

Background: Even though opioids have been used for pain for thousands of years, opioid therapy for chronic non-cancer pain is controversial due to concerns regarding the long-term effectiveness and safety, particularly the risk of tolerance, dependance, or abuse. While the debate continues, the use of chronic opioid therapy for chronic non-cancer pain has increased exponentially. Even though evidence is limited, multiple expert panels have concluded that chronic opioid therapy can be effective therapy for carefully selected and monitored patients with chronic non-cancer pain. Study Design: A systematic review of randomized trials of opioid management for chronic noncancer pain. Objective: The objective of this systematic review is to evaluate the clinical efficacy of opioids in the treatment of chronic non-cancer pain. Methods: A comprehensive evaluation of the literature relating to opioids in chronic non-cancer pain was performed. The literature was evaluated according to Cochrane review criteria for randomized controlled trials (RCTs) and Jadad criteria. A literature search was conducted by using PubMed, EMBASE, Cochrane library, ECRI Institute Library, U.S. Food and Drug Administration (FDA) website, U.S. National Guideline Clearinghouse (NGC), Database of Abstracts of Reviews of Effectiveness (DARE), clinical trials, systematic reviews and cross references from systematic reviews. The level of evidence was classified as good, fair, or poor based on the quality of evidence developed by the United States Preventive Services Task Force (USPSTF) and used by other systematic reviews and guidelines. Outcome Measures: Pain relief was the primary outcome measure. Other outcome measures were functional improvement, withdrawals, and adverse effects. Results: Based on the USPSTF criteria, the indicated level of evidence was fair for Tramadol in managing osteoarthritis. For all the drugs assessed, including Tramadol, for all other conditions, the evidence was poor based on either weak positive evidence, indeterminate evidence, or negative evidence. Limitations: A paucity of literature, specifically with follow-up beyond 12 weeks for all types of opioids with controlled trials for various chronic non-cancer pain conditions. Conclusions: This systematic review illustrated fair evidence for Tramadol in managing osteoarthritis with poor evidence for all other drugs and conditions. Thus, recommendations must be based on non-randomized studies. Key words: Chronic non-cancer pain, opioids, opioid efficacy, opioid effectiveness, significant pain relief, functional improvement, adverse effects, morphine, hydrocodone, hydromorphone, fentanyl, tramadol, buprenorphine, methadone, tapentadol, oxycodone, oxymorphone, systematic reviews, randomized trials

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A Systematic Review of Randomized Trials on the Effectiveness of Opioids for Cancer Pain

January 2018 - Pain Physician ◽

10.36076/ppj.2012/15/es39 ◽

2012 ◽

Vol 3S;15 (3S;7) ◽

pp. ES39-ES58 ◽

Cited By ~ 1

Author(s):

Lakshmi Koyyalagunta

Keyword(s):

United States ◽

Systematic Review ◽

Side Effects ◽

Pain Relief ◽

Cancer Pain ◽

Outcome Measures ◽

Randomized Trials ◽

Transdermal Fentanyl

Background: In all recommended guidelines put forth for the treatment of cancer pain, opioids continue to be an important part of a physician’s armamentarium. Though opioids are used regularly for cancer pain, there is a paucity of literature proving efficacy for long-term use. Cancer is no longer considered a “terminal disease”; 50% to 65% of patients survive for at least 2 years, and there are about 12 million cancer survivors in the United States. There is a concern about side effects, tolerance, abuse and addiction with long-term opioid use and a need to evaluate the effectiveness of opioids for cancer pain. Objective: The objective of this systematic review was to look at the effectiveness of opioids for cancer pain. Study Design: A systematic review of randomized trials of opioids for cancer pain. Methods: A comprehensive review of the current literature for randomized controlled trials (RCTs) of opioids for cancer pain was done. The literature search was done using PubMed, EMBASE, Cochrane library, clinical trials, national clearing house, Web of Science, previous narrative systematic reviews, and cross references. The studies were assessed using the modified Cochrane and Jadad criteria. Analysis of evidence was done utilizing the modified quality of evidence developed by United States Preventive Services Task Force (USPSTF). Outcome Measures: Pain relief was the primary outcome measure. Secondary outcome measures are quality of life (QoL) and side effects including tolerance and addiction. Results: The level of evidence for pain relief based on the USPSTF criteria was fair for transdermal fentanyl and poor for morphine, tramadol, oxycodone, methadone, and codeine. Limitations: Randomized trials in a cancer setting are difficult to perform and justify. There is a paucity of long-term trials and this review included a follow-up period of only 4 weeks. Conclusion: This systematic review of RCTs of opioids for cancer pain showed fair evidence for the efficacy of transdermal fentanyl and poor evidence for morphine, tramadol, oxycodone, methadone, and codeine. Key words: Opioids, pain relief, cancer pain, morphine, hydromorphone, methadone, fentanyl, oxymorphone, hydrocodone, oxycodone, buprenorphine.

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Evaluation of the side effects related to long term opioid treatment in cancer pain children

Pain ◽

10.1016/0304-3959(90)92153-h ◽

1990 ◽

Vol 41 ◽

pp. S8 ◽

Cited By ~ 1

Author(s):

E. Pichard-Leandri ◽

Ph. Poulain ◽

A. Gauvain-Piquard

Keyword(s):

Side Effects ◽

Cancer Pain ◽

Opioid Treatment

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Factors associated with the development of depression in chronic non-cancer pain patients following the onset of opioid treatment for pain

Journal of Affective Disorders ◽

10.1016/j.jad.2015.05.049 ◽

2015 ◽

Vol 184 ◽

pp. 72-80 ◽

Cited By ~ 20

Author(s):

Kimberley Smith ◽

Richard P. Mattick ◽

Raimondo Bruno ◽

Suzanne Nielsen ◽

Milton Cohen ◽

...

Keyword(s):

Cancer Pain ◽

Opioid Treatment ◽

Factors Associated ◽

Pain Patients

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Predictive Value of Intrathecal Narcotic Trials for Long-Term Therapy with Implantable Drug Administration Systems in Chronic Non-Cancer Pain Patients

Pain Practice ◽

10.1046/j.1533-2500.2002.02040.x ◽

2002 ◽

Vol 2 (4) ◽

pp. 315-325 ◽

Cited By ~ 20

Author(s):

Eric Dominguez ◽

Bolkar Sahinler ◽

Deeni Bassam ◽

Miles Day ◽

Leland Lou ◽

...

Keyword(s):

Cancer Pain ◽

Drug Administration ◽

Predictive Value ◽

Term Therapy ◽

Long Term Therapy ◽

Pain Patients

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Systematic review of the role of alternative application routes for opioid treatment for moderate to severe cancer pain: An EPCRC opioid guidelines project

Palliative Medicine ◽

10.1177/0269216310383739 ◽

2011 ◽

Vol 25 (5) ◽

pp. 578-596 ◽

Cited By ~ 39

Author(s):

Lukas Radbruch ◽

Peter Trottenberg ◽

Frank Elsner ◽

Stein Kaasa ◽

Augusto Caraceni

Keyword(s):

Systematic Review ◽

Cancer Pain ◽

Opioid Treatment

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Metamizole/dipyrone for the relief of cancer pain: A systematic review and evidence-based recommendations for clinical practice

Palliative Medicine ◽

10.1177/0269216316655746 ◽

2016 ◽

Vol 31 (1) ◽

pp. 26-34 ◽

Cited By ~ 28

Author(s):

Jan Gaertner ◽

Ulrike M Stamer ◽

Constanze Remi ◽

Raymond Voltz ◽

Claudia Bausewein ◽

...

Keyword(s):

Systematic Review ◽

Cancer Pain ◽

Pain Intensity ◽

Oral Morphine ◽

Cochrane Library ◽

Evidence Based ◽

Low Doses ◽

Inflammatory Drugs ◽

Anti Inflammatory

Background: Dipyrone (metamizole) is one of the most widely used non-opioid analgesics for the treatment of cancer pain. Aim: Because evidence-based recommendations are not yet available, a systematic review was conducted for the German Guideline Program in Oncology to provide recommendations for the use of dipyrone in cancer pain. Design: First, a systematic review for clinical trials assessing dipyrone in adult patients with cancer pain was conducted. Endpoints were pain intensity, opioid-sparing effects, safety, and quality of life. Data sources: The search was performed in MedLine, Embase (via Ovid), and the Cochrane Library (1948–2013) and additional hand search was conducted. Finally, recommendations were developed and agreed in a formal structured consensus process by 53 representatives of scientific medical societies and 49 experts. Results: Of 177 retrieved studies, 4 could be included (3 randomized controlled trials and 1 cohort study, n = 252 patients): dipyrone significantly decreased pain intensity compared to placebo, even if low doses (1.5–2 g/day) were used. Higher doses (3 × 2 g/day) were more effective than low doses (3 × 1 g/day), but equally effective as 60 mg oral morphine/day. Pain reduction of dipyrone and non-steroidal anti-inflammatory drugs did not differ significantly. Compared to placebo, non-steroidal anti-inflammatory drugs, and morphine, the incidence of adverse effects was not increased. Conclusion: Dipyrone can be recommended for the treatment of cancer pain as an alternative to other non-opioids either alone or in combination with opioids. It can be preferred over non-steroidal anti-inflammatory drugs due to the presumably favorable side effect profile in long-term use, but comparative studies are not available for long-term use.

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Systematic Review of Intrathecal Infusion Systems for Long-Term Management of Chronic Non-Cancer Pain

January 2018 - Pain Physician ◽

10.36076/ppj.2009/12/349 ◽

2009 ◽

Vol 2;12 (2;3) ◽

pp. 349-360

Author(s):

Vikram B. Patel

Keyword(s):

Systematic Review ◽

Cancer Pain ◽

Task Force ◽

Intractable Pain ◽

Level Of Evidence ◽

Level Ii ◽

Infusion Systems ◽

Infusion Devices ◽

Intrathecal Infusion

Background: Disability, societal, and health impact of chronic intractable pain secondary to various failed therapies is a major issue. As advanced therapy, implantable therapies, which include intrathecal devices and spinal cord stimulation systems, are frequently used in managing chronic intractable pain. Thus, continuous infusion of intrathecal medication is one of the methods used for the control of chronic, refractory, cancer, and non-cancer pain. However, despite the high costs of chronic non-cancer pain, it has been claimed that there is a lack of evidence for intrathecal infusion systems and the cost effectiveness of these systems has been questioned in improving pain and function. Study Design: A systematic review of intrathecal infusion devices for chronic non-cancer pain. Objective: To determine the efficacy, utilization, safety, and complications associated with the use of intrathecal infusion devices for long-term management of chronic non-cancer pain. Methods: Literature search was performed through EMBASE, Medline, Cochrane databases, and systematic reviews identified from 1966 to December 2008. Studies were then reviewed and assessed using the Agency for Healthcare Research and Quality (AHRQ) criteria for observational studies and the Cochrane Musculoskeletal Review Group criteria for randomized trials. The level of evidence was determined using 5 levels of evidence, ranging from Level I to III with 3 subcategories in Level II, based on the quality of evidence developed by the U.S. Preventive Services Task Force (USPSTF). Outcome Measures: The primary outcome measure was pain relief (short-term relief ≤ one-year and long-term > one-year). Secondary outcome measures of improvement in functional status, psychological status, return to work, and reduction in opioid intake were also utilized. Results: The level of evidence for intrathecal infusion systems indicated either Level II-3 or Level III (limited) based on U.S. Preventive Services Task Force (USPSTF) criteria. Limitations: The limitations of this study include the paucity of literature, lack of quality evidence, and lack of randomized trials. Conclusion: This systematic review illustrates Level II-3 or Level III (limited) evidence for intrathecal infusion systems for long-term relief in chronic non-cancer pain. Key words: Intrathecal infusion, intraspinal infusion, programmable infusion systems, spinal infusion, intra-spinal infusion devices, baclofen infusion, intrathecal opiates

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