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PubMed1991

The incidence of narcotic-induced emesis.

Epidemiologic studies of the incidence of emesis induced by narcotic analgesics are lacking. The histories of 260 cancer patients receiving oral narcotic analgesics prescribed at the Pain Clinic of our Institute from December 1988 to December 1989 were reviewed. Of the 260 patients, 120 were women, median age 61 (range 30-90) yr and 140 were men, median age 62 (range 30-82) yr. Nausea and vomiting associated with assumption of the various narcotics were buprenorphine 8.3% and 22.7%, morphine 18.3% and 28%, codeine 16.2% and 29.7%, and oxycodone 10% and 40%, respectively. Since the use of narcotic analgesics can effectively relieve pain and improve quality of life in cancer patients, it is important to be aware of the incidence of narcotic-induced emesis in order to use appropriate prophylactic antiemetic therapy.

Adult↗

PubMed1994

The dose-response relationship of controlled-release codeine (Codeine Contin) in chronic cancer pain.

The improved pain control provided by regular dosing of opioid analgesics in patients with severe cancer pain has been well established. However, the treatment of mild-to-moderate cancer pain is often limited to "as needed" dosing with fixed combinations of codeine or oxycodone plus a nonopioid analgesic, which do not allow optimal titration of the individual components. This randomized double-blind study was designed to evaluate the efficacy of controlled-release codeine (Codeine Contin) in patients with cancer pain, and to estimate its dose equivalence to a standard combination of acetaminophen plus codeine. Twenty-four patients with at least moderate cancer pain were randomized to Codeine Contin 100, 200, or 300 mg every 12 hr or acetaminophen plus codeine (600 mg/60 mg) every 6 hr. On days 1 and 4 of dosing, pain intensity and pain relief were assessed hourly for 12 hr. The sum of pain intensity differences (SPID) from baseline and the total pain relief (TOTPAR) scores demonstrated a dose-response relationship for Codeine Contin on days 1 and 4 that was statistically significant on day 1 and suggested greater analgesic efficacy on day 4, compared with day 1. Codeine Contin 150 mg every 12 hr was estimated to be equianalgesic to acetaminophen plus codeine (600 mg/60 mg) given every 6 hr. Because a similar equivalence was also demonstrated from analysis of adverse event data, it is concluded that Codeine Contin 150 mg produces analgesia and a side-effect profile similar to a 40% lower dose of codeine provided by the combination.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1996

Chronic opioid therapy for nonmalignant pain in patients with a history of substance abuse: report of 20 cases.

A history of substance abuse is considered by many to be a contraindication to chronic opioid therapy for nonmalignant pain. Twenty patients with a history of chronic nonmalignant pain and substance abuse treated with chronic opioid therapy for a period of more than 1 year were retrospectively evaluated to determine the factors associated with prescription abuse. The prevalence of six aberrant behavioral patterns was assessed to see if these correlated with a history of prescription abuse, as reported by the patient's pain clinic physician. Those who did not abuse opioid therapy were more likely to have a history of alcohol abuse alone or a remote history of polysubstance abuse. They were also more likely to be active members of Alcoholics Anonymous and to have a stable family or other similar support system. In contrast, those who abused opioid therapy showed characteristic aberrant patterns of behavior in their management, which indicated a clear pattern of prescription abuse early in the course of therapy. Those patients were more likely to be recent polysubstance abusers, or have a prior history of oxycodone abuse. None of them were active members of Alcoholics Anonymous. Signing an "opioids contract" was not in and of itself a predictor of successful outcome.

Adult↗

PubMedDate not supplied

Dexmedetomidine premedication before intravenous regional anesthesia in minor outpatient hand surgery.

STUDY OBJECTIVE: To assess the efficacy and safety of intravenous (i.v.) dexmedetomidine, an alpha-2 agonist, as a premedication before i.v. regional anesthesia. DESIGN: Randomized, double-blind, placebo-controlled study with two parallel groups. SETTING: Day-case surgery unit, Department of Surgery, Turku University Hospital, Turku, Finland. PATIENTS: 30 healthy ASA physical status I outpatients scheduled for minor hand surgery with i.v. regional anesthesia. INTERVENTIONS: Patients were assigned to one of two groups to receive either dexmedetomidine 1 microgram/kg i.v. (n = 15) or saline placebo i.v. (n = 15) 10 minutes before exsanguination and inflation of a tourniquet. Regional blockade was induced with 0.5% lidocaine 3 mg/kg (maximum 200 mg). Additional fentanyl 1 microgram/kg intraoperatively and oxycodone 0.05 mg/kg postoperatively were administered for analgesia if needed. MEASUREMENTS AND MAIN RESULTS: Dexmedetomidine preoperatively induced 16% to 20% decreases in systolic blood pressure (p < 0.001), diastolic blood pressure (p < 0.001), and heart rate (p < 0.001), which were mainly abolished within the 4-hour postoperative follow-up period. A clinically significant decrease in arterial oxygen saturation was not observed. The subjective intensity of pain during tourniquet inflation was similar in both groups, but fewer intraoperative (p = 0.009) opioid analgesics were needed in the dexmedetomidine group. Dexmedetomidine decreased sympathoadrenal responses: plasma norepinephrine concentration decreased to one-fourth of the baseline level (p < 0.001), and one of its main metabolites, 3,4-dihydroxyphenylglycol, decreased by 27% (p < 0.001). Dexmedetomidine also prevented an increase in plasma epinephrine concentration following tourniquet inflation (p = 0.003). Dexmedetomidine induced subjective sedation (p = 0.002), but the Maddox Wing test did not show any statistically significant differences between the groups. General effectiveness was graded superior in the dexmedetomidine group (p < 0.001). CONCLUSIONS: Dexmedetomidine is an effective premedication before i.v. regional anesthesia because it reduces patient anxiety, sympathoadrenal responses, and opioid analgesic requirements.

Adrenergic alpha-Agonists↗

PubMed2005

Selective potentiation of opioid analgesia by nonsteroidal anti-inflammatory drugs.

Opioids are often used in conjunction with nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of moderate to severe pain. In this study we have examined interactions between these two classes of drugs. NSAIDs are inactive in the radiant heat tail-flick test, an assay of moderate to severe pain in which opioids are effective. In this assay, ibuprofen potentiated the analgesic actions of hydrocodone and oxycodone, shifting their ED(50) values by 2.5-fold and 4.6-fold despite its inactivity when given alone. These opioid/NSAID interactions were dependent upon both the opioid and the NSAID. Neither aspirin nor ketorolac influenced hydrocodone actions in this model and ibuprofen did not potentiate fentanyl or morphine analgesia. Together, these studies demonstrate potent interactions between selected combinations of opioids and NSAIDS and may help explain the clinical utility of combinations. However, the findings also illustrate differences between the drugs within each class.

Analgesics, Opioid↗

PubMed2006

Comparison of the in vitro efficacy of mu, delta, kappa and ORL1 receptor agonists and non-selective opioid agonists in dog brain membranes.

Morphine and related opioid agonists are frequently used in dogs for their analgesic properties, their sedative effects and as adjuncts to anesthesia. Such compounds may be effective through a combined action at mu-, delta- and kappa-opioid receptors. In this work, the in vitro relative agonist efficacy of ligands selective for mu (DAMGO)-, delta (SNC80)- and kappa (U69593)-opioid receptors as well as the opioid receptor-like receptor ORL(1) (orphaninFQ/nociceptin) which may mediate nociceptive or antinociceptive actions was determined using the [35S]GTPgammaS binding assay in membrane homogenates from the frontal cortex, thalamus and spinal cord of beagle dogs. In addition, other analgesics commonly used in the dog were investigated. For the receptor-selective compounds, maximum stimulation of [35S]GTPgammaS binding decreased in the order kappa > ORL1 > delta > mu in cortical homogenates, compared with mu > ORL1 > kappa > delta in thalamic and spinal cord homogenates. For other opioids examined, efficacy decreased in the order etorphine >> morphine > fentanyl = oxymorphine > butorphanol = oxycodone = nalbuphine. There was no significant difference in the potency of compounds to stimulate [35S]GTPgammaS binding between cortex and thalamus, with the exception of etorphine. Buprenorphine, the partial mu-opioid receptor agonist and kappa-, delta-opioid receptor antagonist, which does have analgesic efficacy in the dog, showed no agonism in any tissue but was an effective mu-opioid receptor > ORL1 receptor antagonist. The results show that the ability of agonists to stimulate [35S]GTPgammaS binding relates to the receptor distribution of opioid and ORL1 receptors in the dog.

Analysis of Variance↗

PubMed2004

Prescription opioid abuse in patients presenting for methadone maintenance treatment.

To characterize prescription opioid dependent patients in a methadone maintenance treatment (MMT) program, a detailed retrospective chart review of new admissions (1997-1999, n=178, mean age=34.5+/-0.7 years, 65% male) was conducted. At admission most patients (83%) had been using prescription opioids (+/-heroin). Four groups were identified: 24% had used prescription opioids only; 24% used prescription opioids initially and heroin later; 35% used heroin first and prescription opioids subsequently; and 17% had used heroin only (this group was significantly younger: mean age 26+/-1 years, P=0.0001). Subjects reported regular use of prescription opioids at higher than therapeutic dosages. For example, in the 'prescription opioid only' group the reported mean (+/-S.E.) number of codeine or oxycodone-containing tablets consumed daily was 23 (+/-6) tablets and 21 (+/-3) tablets, respectively. There were no significant differences found amongst the groups in measures of social stability. Those dependent on prescription opioids alone were less likely to use illicit non-opioid drugs or to be associated with injection drug use. Those that used prescription opioids only or initially were more likely to have ongoing pain problems and to be involved in psychiatric treatment. Further research is required to better elucidate the complex relationships between pain, mental health and addiction in order to develop optimal prevention and treatment strategies for prescription opioid dependence.

Adult↗

PubMed2005

Association between non-medical and prescriptive usage of opioids.

Understanding and managing prescription opioid abuse is one of the major challenges in pain management worldwide. The relationships between prescriptive usage of opioids and reported morbidity at the national level, using data from the Drug Abuse Warning Network (DAWN), were examined. When the major prescription opioids were evaluated, the association between prescriptive medical use in kilograms and reported morbidity, as measured by a ratio between the two, was similar for the intermediate-potency opioids (hydrocodone, methadone, oxycodone, and morphine). This rate was much lower for low-potency opioids (codeine, meperidine, pentazocine, and propoxyphene) and much greater for high-potency opioids (hydromorphone and fentanyl). When the drugs were adjusted by potency (relative to morphine), the rates of reported morbidity per kilogram of morphine equivalent opioid in prescriptive usage were similar among the opioids. Using the potency-adjusted total kilograms of opioid in prescriptive use for all the opioids evaluated, there was a statistically significant association (r(2)=0.9791) with the reported morbidity for prescription analgesics as a class, as measured in the DAWN system. These data suggest that non-medical use of opioids is predictable based on potency and extent of prescriptive use.

Analgesics↗

PubMed2006

Ephemeral profiles of prescription drug and formulation tampering: evolving pseudoscience on the Internet.

The magnitude of non-therapeutic use, or misuse of prescription pharmaceuticals now rivals that of illicit drug abuse. Drug and formulation tampering enables misusers to administer higher doses by intended and non-intended routes. Perceived motives appear to be a combination of interests in achieving a faster onset and enhancing psychoactive effects. Narcotic analgesics, stimulants, and depressants are widely sought, examined, and tampered with for recreational use. This review examines tampering methods reported on the Internet for selected pharmaceutical products. The Internet provides broad and varied guidance on tampering methods that are specific to drug classes and unique formulations. Instructions are available on crushing, separating, purifying and chemically altering specific formulations to allow changes in dosage, route of administration, and time course of effects. Many pharmaceutical formulations contain features that serve as "barriers" to tampering. The nature and effectiveness of formulation barriers vary widely with many being overcome by adventurous misusers. Examples of successes and failures in tampering attempts are frequently described on Internet sites that support recreational drug use. Successful tampering methods that have widespread appeal evolve into recipes and become archived on multiple websites. Examples of tampering methods include: (1) how to separate narcotic drugs (codeine, hydrocodone, oxycodone) from excipients and non-desirable actives (aspirin, acetaminophen, ibuprofen); (2) overcoming time-release formulations (beads, layers, matrices); (3) removal of active drug from high-dose formulations (patches, pills); (4) alteration of dosage forms for alternate routes of administration. The development of successful formulations that inhibit or prevent drug/formulation tampering with drugs of abuse should take into consideration the scope and practice of tampering methods available to recreational drug users on the Internet.

Chemistry, Pharmaceutical↗

PubMed2006

Development of opioid formulations with limited diversion and abuse potential.

Non-medical abuse of prescription opioid medications is not a new phenomenon, but such use has been increasing in recent years. Various methods have been used and continue to be developed in an effort to limit diversion and abuse of opioid medications. A number of these methods will be described for opioid analgesic and addiction treatment formulations using relevant historical examples (e.g. propoxyphene, pentazocine, buprenorphine) as well as examples of formulations currently being considered or under development (e.g. oxycodone plus naltrexone, sustained-release buprenorphine). The focus, though not exclusively, will be on those formulations that represent a combination of an opioid agonist with an antagonist. These methods must take into consideration the pharmacokinetic profile of the agonist and antagonist, the expected primary route of abuse of the medication and the medication combination, the dose of medication that is likely to be abused, the availability of alternative drugs of abuse, and the population of potential abusers that is being targeted with the revised formulation.

Buprenorphine↗

PubMed2005

Interaction of mu-opioid receptor agonists and antagonists with the analgesic effect of buprenorphine in mice.

Buprenorphine is a potent opioid analgesic with partial agonistic properties at mu-opioid receptors. This study investigated the interaction potential with several full mu-agonists in the tail-flick test in mice. We further examined the reversibility of buprenorphine antinociception by different mu-opioid receptor antagonists. Combination of buprenorphine with morphine, oxycodone, hydromorphone and fentanyl in the analgesic dose range resulted in additive or synergistic effects. When given after the decline of the acute buprenorphine effect, both morphine and fentanyl also showed full efficacy. A moderate antagonistic effect according to the partial mu-agonistic properties of buprenorphine was only seen when high doses exceeding the therapeutic dose ranges were combined. Under these conditions antinociception of morphine was reduced to the effect of buprenorphine alone. Prophylactic administration of naloxone (10 mg/kg i.v.), naltrexone (1 mg/kg i.v.) and clocinnamox (5 mg/kg s.c.) fully and persistently blocked the antinociception of a high dose of buprenorphine. An established effect of buprenorphine was less sensitive, although repeated administration of naloxone induced complete antagonism, as did the irreversible antagonist clocinnamox under prophylactic and curative treatment conditions. Our results suggest that the antinociceptive effect of buprenorphine is mainly, if not exclusively, mediated by activation of mu-opioid receptors. They confirm clinical experience that in the analgesic dose range a switch between buprenorphine and full mu-agonists is possible without loss of analgesic efficacy and without a refractory period between the termination of buprenorphine analgesia and the onset of action of the new mu-opioid treatment. Antinociception of buprenorphine is sensitive towards mu-opioid receptor antagonists and incomplete inhibition can be improved by increasing the dose or repetitive dosing.

Analgesics, Opioid↗

PubMed2005

Efficacy of mu-opioid agonists in the treatment of evoked neuropathic pain: Systematic review of randomized controlled trials.

UNLABELLED: Several reviews of randomized controlled trials (RCTs) have shown the efficacy of mu-opioids in reducing spontaneous neuropathic pain (NP). However, relatively little is known about their specific efficacy for evoked pain, which is a significant problem for many patients with NP. The present systematic review assesses the efficacy of opioid agonists for the treatment of evoked NP based upon published RCTs. We searched articles in any language using the MEDLINE database (1966 to December 2004), the Cochrane Central Register of Controlled Trials (4th quarter, 2004) and the reference lists of retrieved papers, employing search terms for RCTs, opioids and NP. Only RCTs in which opioid agonists were given to treat NP of any etiology, and evoked pain was assessed were included. Data were extracted by two independent investigators. Nine articles met inclusion criteria and were classified as short-term (less than 24h; n=7) or intermediate-term trials (4 weeks; n=2). Although the scarcity of retrieved data precluded formal meta-analysis of short-term trials, we found that the intensity of dynamic mechanical allodynia was significantly attenuated by opioids relative to placebo in all studies. In contrast, no consistent effects on the magnitude of static allodynia, the threshold for mechanical allodynia or the threshold or magnitude of heat allodynia were found. The threshold and magnitude of cold-induced allodynia generally responded positively to opioid treatments in patients with peripheral pain syndromes, but not central pain syndromes. Evoked pain was studied in only two intermediate-term trials, in both of which oxycodone was significantly superior to placebo. The results of the two trials were combinable for a meta-analysis that showed an overall 24 points difference in endpoint pain intensities between patients given opioids and those treated with placebo (95% CI -33 to -15; p<0.00001). IN CONCLUSION: short-term studies show that opioids can reduce the intensity of dynamic mechanical allodynia and perhaps of cold allodynia in peripheral NP. Insufficient evidence precludes drawing conclusions regarding the effect of opioids on other forms of evoked NP. A meta-analysis of intermediate-term studies demonstrates the efficacy of opioids over placebo for evoked NP. These findings are clinically relevant because dynamic mechanical allodynia and cold allodynia are the most prevalent types of evoked pain in NP.

Analgesics, Opioid↗

PubMed2004

Relationship between 4,5-epoxymorphinan structure and in vitro modulation of cell proliferation.

Morphine belongs to the class of compounds known as 4,5-epoxymorphinans, which can alter immune function directly via receptors expressed by immune cells. However, the opioid characteristics of these receptors are not clear. Therefore, the aim of this study was to investigate the in vitro immunomodulatory effects of 24 structurally related 4,5-epoxymorphinans to allow further characterisation of the receptor that mediates the immunomodulation and to ascertain if there is any structure-effect relationship. The immunomodulation of 4,5-epoxymorphinans using isolated mouse splenocytes stimulated with concanavalin A resulted in five types of responses: an inverted bell shaped curve (oxycodone, inhibitory EC(50)=1.6 nM), an inhibitory concentration response curve (buprenorphine, inhibitory EC(50)=12.6 microM), an inverted bell-shaped curve with induction (morphine, induction EC(50)=1.7 microM), an induction concentration response curve (oxymorphone, induction EC(50)=20 nM), and the lack of any response (e.g. noroxycodone). Non-stereoselectivity, naloxone-insensitivity, naloxone-sensitivity and non-classical opioid rank order of effect were all observed. A structure-effect relationship was developed and significant evidence for non-classical opioid receptor function on immune cells was concluded.

Animals↗

PubMed2005

Proficiency testing (external quality assessment) of drug detection in oral fluid.

Eighteen external quality assessment (proficiency testing) samples were prepared from client specimens collected with the Intercept oral fluid collection device and by spiking drug-free oral fluid. Samples were circulated in pairs at quarterly intervals to 13 UK and USA based laboratories for analysis by a panel of OraSure micro-plate Intercept enzyme immunoassay kits and hyphenated mass spectrophotometric techniques. During the survey, there was a single case of non-specificity in a false report for methadone. The major errors were of lack of sensitivity relative to the concentration thresholds specified for the immunoassays. The sensitivity for overall "present"/"not found" reports calculated as true positives/(true positives+false negatives) were for the amphetamine specific assay 50%, methyl-amphetamines 93%, barbiturates 64%, cannabinoids 73%, cocaine and metabolites 100%, benzodiazepines 69%, methadone 95%, opiates 79% (opiates excluding oxycodone 93%), phencyclidine 93% and human gamma-globulin 97%. A small number of the sensitivity errors were attributable to errors in chromatographic confirmation techniques.

Clinical Laboratory Techniques↗

PubMed2006

Incisional and epidural analgesia after caesarean delivery: a prospective, placebo-controlled, randomised clinical study.

BACKGROUND: This study evaluated efficacy, safety and patient satisfaction with incisional analgesia with a subfascial catheter compared to epidural analgesia for pain relief following caesarean section. METHODS: Forty patients were randomised after elective caesarean section to receive either intermittent 10-mL boluses of 0.125% levobupivacaine into the epidural space and physiologic saline into the surgical wound or intermittent 10-mL boluses of 0.25% levobupivacaine into the wound and epidural saline with a repeated 10-dose regimen. Analgesic efficacy was evaluated by numerical pain scores (0-10, 0=no pain, 10=worst pain) and based on the consumption of supplemental opioid. Side effects, patient satisfaction and plasma concentrations of levobupivacaine were recorded. RESULTS: In the epidural group average pain scores were lower (1.8 vs. 3, P=0.006) and the consumption of local anaesthetic (29 mL vs. 38 mL, P=0.01) was smaller during the first four postoperative hours, after which both groups had pain scores of 3 or less at rest. All parturients were able to walk after the 24-h study period. The total consumption of rescue opioid oxycodone (32 vs. 37 mg, P=0.6) during the whole 72-h study period was low in both study groups. Side effects were mild and rare. Satisfaction scores were equally high in the two groups. Peak plasma concentrations of levobupivacaine were below the toxic range. CONCLUSION: Incisional local analgesia via a subfascial catheter provided satisfactory pain relief with patient satisfaction comparable to that seen with epidural analgesia. This technique may be a good alternative to the more invasive epidural technique following caesarean section as a component of multimodal pain management.

Adult↗

PubMed2005

Simultaneous analysis of thebaine, 6-MAM and six abused opiates in postmortem fluids and tissues using Zymark automated solid-phase extraction and gas chromatography-mass spectrometry.

Opiates are some of the most widely prescribed drugs in America and are often abused. Demonstrating the presence or absence of opiate compounds in postmortem fluids and/or tissues derived from fatal civil aviation accidents can have serious legal consequences and may help determine the cause of impairment and/or death. However, the consumption of poppy seed products can result in a positive opiate drug test. We have developed a simple method for the simultaneous determination of eight opiate compounds from one extraction. These compounds are hydrocodone, dihydrocodeine, codeine, oxycodone, hydromorphone, 6-monoacetylmorphine, morphine, and thebaine. The inclusion of thebaine is notable as it is an indicator of poppy seed consumption and may help explain morphine/codeine positives in cases where no opiate use was indicated. This method incorporates a Zymark RapidTracetrade mark automated solid-phase extraction system, gas chromatography/mass spectrometry, and trimethyl silane (TMS) and oxime-TMS derivatives. The limits of detection ranged from 0.78 to 12.5 ng/mL. The linear dynamic range for most analytes was 6.25-1600 ng/mL. The extraction efficiencies ranged from 70 to 103%. We applied this method to eight separate aviation fatalities where opiate compounds had previously been detected.

Autoanalysis↗

PubMed2005

A double-blind prospective comparison of rofecoxib vs ketorolac in reducing postoperative pain after arthroscopic knee surgery.

STUDY OBJECTIVE: The aim of this study was to compare the analgesic efficacy of premedication with rofecoxib vs intravenous (IV) ketorolac in reducing postoperative pain after arthroscopic knee surgery. STUDY DESIGN: This is a prospective, randomized, double-blinded study. SETTING: This study was set at a university hospital. SUBJECTS: The subjects include 54 patients with American Society of Anesthesiologists physical statuses I, II, and III undergoing knee arthroscopy. INTERVENTIONS: Group 1 received 50 mg oral rofecoxib preoperatively with IV placebo injection, which was administered 20 minutes before the end of the operation. Group 2 received a preoperative placebo and 30 mg IV ketorolac 20 minutes before the end of surgery. MEASUREMENTS: The primary outcome measure was the proportion of patients reporting pain in the postoperative anesthesia care unit, 6 hours and 24 hours after discharge. Additional end points included the use of 5:325 mg oxycodone-acetaminophen (O/A) tablets, pain scores, patient's satisfaction survey, and comparison of side effects. Data were analyzed using independent samples t tests for continuous variables or chi2 tests for categorical variables. P < .05 was considered significant. RESULTS: The 2 groups were comparable with regard to patient characteristics, intraoperative medication use, and duration of surgery. There was no difference either in pain scores or O/A use in the postoperative anesthesia care unit. At 24 hours after discharge, significantly more patients in the ketorolac group (91%) reported pain than the rofecoxib group (63%) (P = .02). Sixty-one percent of patients in the ketorolac group used O/A during the first 24 hours vs 38% in the rofecoxib group. The difference, however, was not statistically significant. CONCLUSION: Preoperative rofecoxib is as effective as ketorolac for the treatment of pain after knee arthroscopy. Higher frequency of pain reporting at 24 hours by patients in ketorolac group is explained by the longer analgesic effect of rofecoxib. Future studies should directly compare gastrointestinal injury of these drugs, as well as cost-effectiveness of rofecoxib vs ketorolac.

Adult↗

PubMed2003

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

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

Analgesics, Opioid↗