Pain and Addiction PubMed Abstracts

The prevalence and significance of cannabis use in patients prescribed chronic opioid therapy: a review of the extant literature.

Pain Med. 2009 Nov;10(8):1434-41

Authors: Reisfield GM, Wasan AD, Jamison RN

BACKGROUND: Cannabis is the most widely consumed illicit drug in the United States. Its use, particularly in early initiates, is associated with subsequent development of other drug and alcohol use disorders. OBJECTIVE: The authors examined the prevalence of cannabis use and the association between cannabis use and aberrant opioid-related behaviors in patients prescribed chronic opioid therapy for persistent pain. METHODS: PubMed was queried for studies of chronic opioid therapy in which aberrant opioid-related behaviors were quantitatively examined and in which cannabis use data (as determined by cannabinoid-positive urine drug tests) were extricable from that of other substances of abuse. RESULTS: The prevalence of cannabis use among patients prescribed chronic opioid therapy in these studies ranged from 6.2% to 39%, compared with 5.8% in the general United States population. Furthermore, cannabis use in chronic opioid patients shows statistically significant associations with present and future aberrant opioid-related behaviors. CONCLUSION: Cannabis use is prevalent in patients prescribed chronic opioid therapy and is associated with opioid misuse. Further research is necessary to clarify the strength and the nature of the association between cannabis use and opioid misuse, and to address additional questions about the consequences of cannabis use in the context of chronic opioid therapy.

PMID: 19793342 [PubMed - indexed for MEDLINE]

Addiction and Pain: Cannabinoid and Opioid Interactions.

Curr Drug Targets. 2010 Feb 19;

Authors: Tucci S

PMID: 20196743 [PubMed - as supplied by publisher]

Effect of metabolic blockade on the psychoactive effects of dextromethorphan.

Hum Psychopharmacol. 2010 Jan;25(1):71-9

Authors: Zawertailo LA, Tyndale RF, Busto U, Sellers EM

OBJECTIVE: Variation in the activity of cytochrome P450 2D6 (CYP2D6) affects the pharmacokinetics and effectiveness of dextromethorphan (DM), because it controls the production of dextrorphan, an active metabolite, with higher affinity for the NMDA receptor than the parent compound. This study examined whether pharmacological inhibition of CYP2D6 activity with quinidine would mimic the genetic mutation and thus also alter the psychoactive effects of DM. METHODS: In a single-blind, within-subjects study, eight healthy volunteers (all homozygous for the wild type allele for CYP2D6) received placebo and varying doses of DM, both with and without quinidine pre-treatment. Pharmacokinetic and pharmacodynamic measures were assessed at baseline and every hour post-drug for 6 h. RESULTS: Compared to the no quinidine condition, quinidine pre-treatment decreased the area under the dose-response curve on subjective measures of positively reinforcing effects (e.g., euphoria, p < 0.04; drug liking, p < 0.05), and was significantly greater for measures of dysphoria (e.g., unpleasantness, p < 0.02). These changes corresponded to increased DM and decreased dextrorphan plasma concentrations. CONCLUSIONS: Compared to DM alone, quinidine pre-treatment inhibited DM metabolism and changed its subjective effects, demonstrating that the psychoactive properties of DM are a function of drug metabolism. These results demonstrate the relationship between CYP2D6 activity, plasma drug levels, and psychoactive drug effects, and have implications for both the abuse liability and therapeutic utility of DM.

PMID: 20041473 [PubMed - indexed for MEDLINE]

Opioid pharmaceuticals and addiction: The issues, and research directions seeking solutions.

Drug Alcohol Depend. 2010 Feb 24;

Authors: Walwyn WM, Miotto KA, Evans CJ

There are few pharmaceuticals superior to opiates for the treatment of pain. However, with concerns of addiction, withdrawal and questionable efficacy for all types of pain, these compounds are far from a magical panacea for pain-relief. As it is unlikely that other classes of compounds will supersede the opioids in the very near future, it is important to both optimize current opioid therapies and curb the astounding diversion of opioids from their intended analgesic use to non-medical abuse. In optimizing opioid therapeutics it is necessary to enhance the clinical awareness of the benefits of treating pain and combine this with aggressive strategies to reduce diversion for non-medical use. At the heart of the issue of opioid misuse is the role of opioid systems in the reward circuitry, and the adaptive processes associated with repetitive opioid use that manifest during withdrawal. Emerging pharmacological insights of opioid receptors will be reviewed that provide future hope for developing opioid-based analgesics with reduced addictive properties and perhaps, reduced opponent processes. In addition, with the increased understanding of nociceptive circuitry and the molecules involved in transmitting pain, new therapeutic targets have become evident that may result in effective analgesics either alone or in combination with current opioid therapies.

PMID: 20188495 [PubMed - as supplied by publisher]

Chronic pain and cigarette smoking and nicotine dependence among a representative sample of adults.

Nicotine Tob Res. 2009 Dec;11(12):1407-14

Authors: Zvolensky MJ, McMillan K, Gonzalez A, Asmundson GJ

INTRODUCTION: Individuals with chronic pain problems are at an increased risk for certain types of substance abuse and dependence. Recent work suggests that there is a significant association between chronic pain and cigarette smoking; however, it is unclear as to whether pain-smoking effects are evident above and beyond sociodemographic factors and cooccurring substance use disorders. The present investigation examined the relation between lifetime and current (past year) chronic pain and cigarette smoking status and nicotine dependence. METHODS: This investigation comprised a large representative sample of English-speaking adults (n = 9,282) residing in the United States. Data were collected primarily through face-to-face interviews conducted between February 2001 and April 2003. RESULTS: After adjusting for sociodemographic variables and the presence of a lifetime substance use disorder, individuals with a lifetime history of chronic neck or back pain were significantly more likely to be current smokers and to be diagnosed with lifetime as well as current nicotine dependence. Although there was no significant incremental relation between current chronic neck and back pain and being a current smoker, there was a significant association with lifetime and current nicotine dependence. Similar relations were evident among those with and without medically unexplained chronic pain in regard to smoking status and lifetime and current nicotine dependence. DISCUSSION: Findings are discussed in terms of better understanding the chronic pain-smoking association.

PMID: 19828432 [PubMed - indexed for MEDLINE]

Gabapentin improves cold-pressor pain responses in methadone-maintained patients.

Drug Alcohol Depend. 2010 Feb 15;

Authors: Compton P, Kehoe P, Sinha K, Torrington MA, Ling W

Individuals on methadone maintenance for the treatment of addiction (MM) are demonstrated to be hyperalgesic to cold-pressor pain in comparison to matched controls and ex-opioid addicts, a finding described as clinical evidence of opioid-induced hyperalgesia (OIH). Interestingly, opioids induce hyperalgesia via many of the same neuro-inflammatory and central sensitization processes that occur with the development of neuropathic pain. Evaluated in this study was the efficacy of a key pharmacotherapy for neuropathic pain, gabapentin (GPN), to reverse OIH in MM patients. Utilizing a clinical trial design and double blind conditions, changes in cold-pressor pain threshold and tolerance following a 5-week trial of GPN (titrated to 2400mg/day) were evaluated at peak and trough methadone plasma levels in a well-characterized MM sample. Drug abstinence was encouraged via an escalating payment schedule, and compliance monitored via pill counts and GPN plasma levels; entered into the analyses were only those subjects compliant and abstinent throughout the study (approximately 45%). Utilizing change scores from baseline, significant improvements in cold-pressor pain threshold and pain tolerance were observed at both peak and trough methadone levels (p<0.05). Notably, drop-out rates due to medication side effects were low (2%) and the medication was well-tolerated. These results support that GPN, as prescribed for the treatment of neuropathic pain, is effective in decreasing OIH in patients who are abstinent and stable in methadone treatment.

PMID: 20163921 [PubMed - as supplied by publisher]

Conducting clinical research with prescription opioid dependence: defining the population.

Am J Addict. 2010 Mar 1;19(2):141-6

Authors: Weiss RD, Potter JS, Copersino ML, Prather K, Jacobs P, Provost S, Chim D, Selzer J, Ling W

Most treatment studies of opioid-dependent populations have focused predominantly on heroin users, despite a recent increase in those dependent upon prescription opioids. A key methodological challenge involved in studying the latter group involves defining the population. Specifically, researchers must decide whether to include (1) concurrent heroin users and (2) individuals with pain. The multi-site Prescription Opioid Addiction Treatment Study is examining treatments for this population. This paper describes various inclusion criteria considered by the study team related to heroin use and pain. The goal was to recruit a distinct but generalizable population of individuals dependent upon prescription opioids. (Am J Addict 2010;00:1-6).

PMID: 20163386 [PubMed - in process]

Sweet preferences and analgesia during childhood: effects of family history of alcoholism and depression.

Addiction. 2010 Feb 9;

Authors: Mennella JA, Pepino MY, Lehmann-Castor SM, Yourshaw LM

ABSTRACT Aim To determine whether depression and family history of alcoholism are associated with heightened sweet preferences in children, before they have experienced alcohol or tobacco and at a time during the life-span when sweets are particularly salient. Design Between- and within-subject experimental study. Participants Children, 5-12 years old (n = 300), formed four groups based on family history of alcohol dependence up to second-degree relatives [positive (FHP) versus negative (FHN)] and depressive symptoms as determined by the Pictorial Depression Scale [depressed (PDEP) versus non-depressed (NDEP)]. Measurements Children were tested individually to measure sucrose preferences, sweet food liking and, for a subset of the children, the analgesic properties of sucrose versus water during the cold pressor test. Findings The co-occurrence of having a family history of alcoholism and self-reports of depressive symptomatology was associated significantly with a preference for a more concentrated sucrose solution, while depressive symptomatology alone was associated with greater liking for sweet-tasting foods and candies and increased pain sensitivity. Depression antagonized the analgesic properties of sucrose. Conclusions While children as a group innately like sweets and feel better after eating them, the present study reveals significant contributions of family history of alcoholism and depression to this effect. Whether the heightened sweet preference and the use of sweets to alleviate depression are markers for developing alcohol-related problems or responses that are protective are important areas for future research.

PMID: 20148789 [PubMed - as supplied by publisher]

Practice Strategies to Improve Compliance and Patient Self-Management.

J Manag Care Pharm. 2010 Feb;16(1 Supp B):26-27

Authors: Ruetsch C

Background: Failure in treating opioid dependence is costly to the patient, the employer, managed care organizations, and the overall health care system. Opioid dependent patients tend to be less productive at work and in society and utilize a great many health care resources. Optimizing outcomes is essential. Objective: To introduce the benefit of integrated strategies and patient support in the treatment of opioid dependence. Summary: Health Analytics is currently studying the benefit of HereToHelp, a behavioral support program in which registered nurses or addiction treatment counselors with specialized training in addiction education provide information and encouragement to patients receiving pharmacologic treatment for opioid dependence. A total of 470 physicians in 41 states have been enlisted to participate in this patient support study. The study hypothesis is that patients who receive behavioral support and encouragement will be more compliant with their opioid replacement therapy, leading to better outcomes. Additional treatment strategies are also being developed to minimize the risk of abuse and diversion. Prodrugs and vaccines are also being investigated. Conlusion: A coordinated team approach is essential in treating pain patients and opioid-dependent patients. Offering behavior modification in addition to pharmacotherapy and utilizing strategies such as prescription monitoring programs, pain contracts, and screening are all vital components necessary for positive outcomes.

PMID: 20146552 [PubMed - as supplied by publisher]

Introduction: Landscape of Opioid Dependence.

J Manag Care Pharm. 2010 Feb;16(1 Supp B):4-8

Authors: Jan SA

Background: The use of opioids for chronic noncancer pain increased 222% from 1992 to 2002. Opioid dependence has also increased significantly, leading to a burden on patients, employers, insurers, society, and the entire health care system. It is imperative that opioid dependence is addressed and treated properly, in order to return patients to being productive participants in the workplace and society. Objective: To provide an overview of addiction, abuse, and dependence and identify risk factors for addiction. Summary: Studies have shown that intensive use of opioids is associated with increased utilization of costly health care services, prolonged disability, and continued use of opioids, leading to abuse and dependence in many patients. While identifying patients at risk for developing opioid dependence is difficult, there are many risk stratification tools now available to practitioners, including the Opioid Risk Tool (ORT) or Screener and Opioid Assessment for Patients with Pain (SOAPP). Understanding the differences between dependence, addiction, and tolerance is essential to managing patients on opioids. Conclusion: It is imperative that patients be properly managed when being treated for pain. Physicians and employers have to be able to identify patients at risk for opioid abuse or exhibiting symptoms of opioid abuse and know how to address their needs.

PMID: 20146548 [PubMed - as supplied by publisher]

The atypical alpha-conotoxin LtIA from Conus litteratus targets a novel microsite of the alpha3beta2 nicotinic receptor.

J Biol Chem. 2010 Feb 9;

Authors: Luo S, Bharati Akondi K, Zhangsun D, Wu Y, Zhu X, Hu Y, Christensen S, Dowell C, Daly NL, Craik DJ, Wang CI, Lewis RJ, Alewood PF, McIntosh JM

Different nicotinic acetylcholine receptor (nAChR) subtypes are implicated in learning, pain sensation, and disease states including Parkinson's and nicotine addiction. Alpha-Conotoxins are among the most selective nAChR ligands. Mechanistic insights into the structure, function and receptor interaction of alpha-conotoxins may serve as a platform for development of new therapies. Previously characterized alpha-conotoxins have a highly conserved Ser-Xaa-Pro motif that is crucial for potent nAChR interaction. The current study characterized the novel alpha-conotoxin LtIA, which lacks this highly conserved motif but potently blocked alpha3beta2 nAChRs with a 9.8 nM IC50. The off-rate of LtIA was rapid relative to Ser-Xaa-Pro-containing alpha-conotoxin MII. Nevertheless, pre-block of alpha3beta2 nAChRs with LtIA prevented the slowly reversible block associated with MII, suggesting overlap in their binding sites. nAChR beta subunit ligand-binding interface mutations were used to examine the >1000-fold selectivity difference of LtIA for alpha3beta2 vs. alpha3beta4 nAChRs. Unlike MII, LtIA had a >900-fold increased IC50 on alpha3beta2(F119Q) versus wildtype nAChRs, whereas T59K and V111I beta2 mutants had little effect. Molecular docking simulations suggested that LtIA had a surprisingly shallow binding site on the alpha3beta2 nAChR that includes beta2 K79. The K79A mutant disrupted LtIA binding, but was without effect on an LtIA analog where the Ser-Xaa-Pro motif is present, consistent with distinct binding modes.

PMID: 20145249 [PubMed - as supplied by publisher]

Responses to open peer commentaries on "The Subjective Brain, Identity, and Neuroethics".

Am J Bioeth. 2009 Sep;9(9):W1-4

Authors: Gillett GR

PMID: 19998175 [PubMed - indexed for MEDLINE]

Methadone and buprenorphine toxicity in children.

Am J Addict. 2010 Jan 1;19(1):89-95

Authors: Boyer EW, McCance-Katz EF, Marcus S

Recent years have seen very large increases in the prescribing of methadone and buprenorphine formulations for treatment of opioid addiction as well as the increasing utilization of methadone for the treatment of chronic pain. Coincident with the rise in the prescribing of these drugs has been a substantial increase in pediatric opioid toxicities and adverse events. This review will address the current state of methadone- and buprenorphine-related adverse events in children in the United States. We will also discuss treatment of opioid toxicity in pediatric populations and make recommendations aimed at reducing these occurrences. (Am J Addict 2009;19:89-95).

PMID: 20132125 [PubMed - in process]

Indicators of buprenorphine and methadone use and abuse: what do we know?

Am J Addict. 2010 Jan 1;19(1):73-88

Authors: Maxwell JC, McCance-Katz EF

Abuse of prescription opioids is a growing problem. The number of methadone pain pills distributed now exceeds liquid methadone used in opioid treatment, and the increases in buprenorphine indicators provide evidence of the need to monitor and intervene to decrease the abuse of this drug. The need for additional and improved data to track trends is discussed, along with findings as to the characteristics of the users and combinations of drugs. Data on toxicities related to methadone or buprenorphine, particularly in combination with other prescribed drugs, are presented and clinical implications and considerations are offered. These findings underscore the need for physicians to be aware of potential toxicities and to educate their patients regarding these issues. (Am J Addict 2009;19:73-88).

PMID: 20132124 [PubMed - in process]

Opioid contracts and random drug testing for people with chronic pain - think twice.

J Law Med Ethics. 2009 Dec;37(4):841-5

Authors: Collen M

The use of opioid contracts, which often require patients to submit to random drug screens, have become widespread amongst physicians using opioids to treat chronic pain. The main purpose of the contract is to improve care through better adherence to opioid therapy but there is little evidence as to its efficacy. The author suggests the use of opioid contracts and random drug testing destroys patients' trust which impacts health outcomes, and that physicians' motivation for their use are concerns about prosecution, medication abuse and misuse, and addiction. Statistics are provided to counter fears, and evidence is offered suggesting opioid contracts are unenforceable and lack efficacy; random drug testing is often inconclusive, and a patient's trust improves adherence to treatment.

PMID: 20122120 [PubMed - in process]

A comparison of drug overdose deaths involving methadone and other opioid analgesics in West Virginia.

Addiction. 2009 Sep;104(9):1541-8

Authors: Paulozzi LJ, Logan JE, Hall AJ, McKinstry E, Kaplan JA, Crosby AE

AIMS: To describe all people dying from unintentional overdoses of methadone or other opioid analgesics (OOA) in West Virginia in 2006. DESIGN: We analyzed medical examiner data supplemented by data from the state prescription drug monitoring program. We compared people whose deaths involved methadone with those whose deaths involved OOA. FINDINGS: The methadone group included 87 decedents, and the OOA group included 163 decedents. Most were male. Decedents in the methadone group were significantly younger than those in the OOA group: more than a quarter were 18-24 years of age. For both groups, approximately 50% had a history of pain, and 80% had a history of substance abuse. There was no intergroup difference in the prevalence of benzodiazepines at post-mortem. Methadone was significantly less likely to have ever been prescribed than OOA. Among those with prescriptions, the proportion prescribed within 30 days of death was significantly greater for methadone than for hydrocodone, but not for oxycodone. Ten (11.5%) of the methadone decedents were enrolled in an opiate treatment program (OTP) at the time of death. CONCLUSIONS: The high prevalence of a substance abuse history and lack of prescriptions suggest that most of the deaths in both groups are related to substance abuse. There was no indication of a harmful effect from methadone's metabolic interaction with benzodiazepines, but provider or patient unfamiliarity with methadone may have been a risk factor. Prescribing methadone, especially to young males, requires extra care. Providers, OTPs and coroners/medical examiners should use state prescription drug monitoring programs to monitor the use of controlled substances by their patients.

PMID: 19686524 [PubMed - indexed for MEDLINE]

Oral manifestations of "meth mouth": a case report.

J Contemp Dent Pract. 2010;11(1):E073-80

Authors: Turkyilmaz I

AIM: The aim of the documentation of this clinical case is to make clinicians aware of "meth mouth" and the medical risks associated with this serious condition. BACKGROUND: Methamphetamine is a very addictive, powerful stimulant that increases wakefulness and physical activity and can produce other effects such as cardiac dysrhythmias, hypertension, hallucinations, and violent behavior. Dental patients abusing methamphetamine can present with poor oral hygiene, xerostomia, rampant caries ("meth mouth"), and excessive tooth wear. Oral rehabilitation of patients using methamphetamine can be challenging. CASE DESCRIPTION: A 30-year-old Caucasian woman presented with dental pain, bad breath, and self-reported poor esthetics. A comprehensive examination including her medical history, panoramic radiograph, and intraoral examination revealed 19 carious lesions, which is not very common for a healthy adult. She reported her use of methamphetamine for five years and had not experienced any major carious episodes before she started using the drug. SUMMARY: The patient's medical and dental histories along with radiographic and clinical findings lead to a diagnosis of "meth mouth." Although three different dental treatment modalities (either conventional or implant-supported) have been offered to the patient since August 2007, the patient has yet to initiate any treatment. CLINICAL SIGNIFICANCE: This clinical case showing oral manifestations of meth mouth was presented to help dental practitioners recognize and manage patients who may be abusing methamphetamines. Dental practitioners also may be skeptical about the reliability of appointment keeping by these patients, as they frequently miss their appointments without reasonable justification.

PMID: 20098969 [PubMed - in process]

Acute myocardial infarction in a young patient with bicuspid aortic valve.

Turk Kardiyol Dern Ars. 2009 Oct;37(7):490-2

Authors: Demir M

Bicuspid aortic valve is one of the most common congenital heart valve disorders. We present the development of acute myocardial infarction (AMI) in an 18-year-old male patient with unrecognized bicuspid aortic valve and moderate aortic regurgitation. He presented with chest pain. The electrocardiogram showed ST-segment elevation in leads V2 to V6. Creatine kinase-MB level was elevated to 97 U/l and troponin I was very high (45,000 ng/ml). The diagnosis was made as anterior wall AMI. Following treatment with intravenous rt-PA, ST-segment elevation completely returned to normal. Transthoracic echocardiography showed a bicuspid aortic valve, moderate aortic regurgitation, and apical wall hypokinesia; left ventricular global systolic function was normal. The patient had no risk factors for coronary atherosclerosis, nor a history of substance addiction or a family history of coronary artery disease. Protein C, protein S and homocysteine levels were normal. He refused any further intervention. Two weeks after discharge, he presented again with chest pain. Electrocardiography, cardiac markers, and coronary arteriography were normal. He was discharged on appropriate medical treatment. The presented case is the first report of AMI in a patient with bicuspid aortic valve.

PMID: 20098045 [PubMed - in process]

[Every life counts : Suicide by anesthetists.]

Anaesthesist. 2010 Jan 23;

Authors: Mäulen B

This article has its roots in the consternation of head anesthetists over the loss of colleagues. Anesthesia, intensive care medicine, emergency medicine and pain therapy has lost too many first class colleagues through suicide, addiction, severe depression and other causes. It is time to direct attention not exclusively to patients but also to apply an important occupational principle in the rescue service and intensive care medicine to the profession of anesthetists: Every life counts! The following article supplies information on the frequency, methods and possible reasons for suicide by physicians and suggestions for the prevention of suicide as well as treatment of physicians who are at risk ofsuicide will be presented.

PMID: 20094691 [PubMed - as supplied by publisher]

Long-term opioid management for chronic noncancer pain.

Cochrane Database Syst Rev. 2010;(1):CD006605

Authors: Noble M, Treadwell JR, Tregear SJ, Coates VH, Wiffen PJ, Akafomo C, Schoelles KM

BACKGROUND: Opioid therapy for chronic noncancer pain (CNCP) is controversial due to concerns regarding long-term effectiveness and safety, particularly the risk of tolerance, dependence, or abuse. OBJECTIVES: To assess safety, efficacy, and effectiveness of opioids taken long-term for CNCP. SEARCH STRATEGY: We searched 10 bibliographic databases up to May 2009. SELECTION CRITERIA: We searched for studies that: collected efficacy data on participants after at least 6 months of treatment; were full-text articles; did not include redundant data; were prospective; enrolled at least 10 participants; reported data of participants who had CNCP. Randomized controlled trials (RCTs) and pre-post case-series studies were included. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted safety and effectiveness data and settled discrepancies by consensus. We used random-effects meta-analysis' to summarize data where appropriate, used the I(2) statistic to quantify heterogeneity, and, where appropriate, explored heterogeneity using meta-regression. Several sensitivity analyses were performed to test the robustness of the results. MAIN RESULTS: We reviewed 26 studies with 27 treatment groups that enrolled a total of 4893 participants. Twenty five of the studies were case series or uncontrolled long-term trial continuations, the other was an RCT comparing two opioids. Opioids were administered orally (number of study treatments groups [abbreviated as "k"] = 12, n = 3040), transdermally (k = 5, n = 1628), or intrathecally (k = 10, n = 231). Many participants discontinued due to adverse effects (oral: 22.9% [95% confidence interval (CI): 15.3% to 32.8%]; transdermal: 12.1% [95% CI: 4.9% to 27.0%]; intrathecal: 8.9% [95% CI: 4.0% to 26.1%]); or insufficient pain relief (oral: 10.3% [95% CI: 7.6% to 13.9%]; intrathecal: 7.6% [95% CI: 3.7% to 14.8%]; transdermal: 5.8% [95% CI: 4.2% to 7.9%]). Signs of opioid addiction were reported in 0.27% of participants in the studies that reported that outcome. All three modes of administration were associated with clinically significant reductions in pain, but the amount of pain relief varied among studies. Findings regarding quality of life and functional status were inconclusive due to an insufficient quantity of evidence for oral administration studies and inconclusive statistical findings for transdermal and intrathecal administration studies. AUTHORS' CONCLUSIONS: Many patients discontinue long-term opioid therapy (especially oral opioids) due to adverse events or insufficient pain relief; however, weak evidence suggests that patients who are able to continue opioids long-term experience clinically significant pain relief. Whether quality of life or functioning improves is inconclusive. Many minor adverse events (like nausea and headache) occurred, but serious adverse events, including iatrogenic opioid addiction, were rare.

PMID: 20091598 [PubMed - in process]