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Markers of abuse liability of short- vs long-acting opioids in chronic pain patients: a randomized cross-over trial.

ABSTRACT: Abuse liability is thought to possibly be lower in long- than in short-acting opioids because lower peak serum levels may be less likely to induce psychoactive effects.We compared patient responses to extended-release morphine, hydrocodone plus acetaminophen, and placebo in a randomized, double-blind crossover study using markers of abuse liability. Patients indicated their craving for drugs on 5 visual analog scales (VASs), completed the Addiction Research Center Inventory, and underwent cue reactivity testing. To perform the latter, subjects watched a video intended to produce a positive or a negative affect, after which a vial of medication was or was not presented (the cue) and then indicated their craving for drugs on 5 different VASs (the reactivity).Differences in Addiction Research Inventory scores were statistically significant but clinically unimportant. Neuropsychological test results were mixed and unrelated to the medications studied. Cue reactivity did not differ among conditions but was uniformly high.Using several markers of abuse liability, long-acting opioids do not have lower abuse potential than do short-acting opioids or placebo. Although cue reactivity did not differ among the conditions, uniformly high results in these patients suggest that it may have some value as a component of abuse liability testing.

SUBMITTER: Wilsey BL

PROVIDER: S-EPMC2757543 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Markers of abuse liability of short- vs long-acting opioids in chronic pain patients: a randomized cross-over trial.

Wilsey Barth L BL Fishman Scott S Li Chin-Shang CS Storment Jeanna J Albanese Anthony A

Pharmacology, biochemistry, and behavior 20090804 1

<h4>Background</h4>Abuse liability is thought to possibly be lower in long- than in short-acting opioids because lower peak serum levels may be less likely to induce psychoactive effects.<h4>Methods</h4>We compared patient responses to extended-release morphine, hydrocodone plus acetaminophen, and placebo in a randomized, double-blind crossover study using markers of abuse liability. Patients indicated their craving for drugs on 5 visual analog scales (VASs), completed the Addiction Research Cen ...[more]

PMID: 19660492

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Project description:BackgroundOpioids are frequently prescribed for the management of patients with chronic non-cancer pain (CNCP). Previous meta-analyses of efficacy and harms have combined treatment effects across all opioids; however, specific opioids, pharmacokinetic properties (ie, long acting vs short acting), or the type of formulation (ie, immediate vs extended release) may be a source of heterogeneity for pooled effects.MethodsWe will conduct a network meta-analysis (NMA) of randomized controlled trials evaluating opioids for CNCP. We will acquire eligible studies through systematic searches of EMBASE, MEDLINE, CINAHL, AMED, PsycINFO, and the Cochrane Central Registry of Controlled Trials (CENTRAL). Eligible studies will have randomly allocated adult CNCP patients to an oral or transdermal opioid versus another type of opioid (or formulation) or placebo, and follow patients for ≥ 4 weeks. We will collect outcome data for pain intensity, physical function, nausea, vomiting, and constipation. Pairs of reviewers will, independently and in duplicate, abstract data from eligible trials and assess risk of bias using a modified Cochrane tool. We will assess coherence of our networks through both a global test, and by comparing direct and indirect evidence for each comparison with node-splitting.ResultsUsing a frequentist approach, we will conduct random effects multiple treatment meta-analysis to establish treatment effects of individual opioids for each outcome. The certainty of evidence for pooled treatment effects will be assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. We will categorize interventions from most to least effective based on the effect estimates obtained from NMAs and their associated certainty of evidence, as follows: superior to both placebo and alternatives; superior to placebo, but inferior to alternatives; and no better than placebo.ConclusionThis NMA will determine the relative effectiveness and adverse effects of individual opioids among patients with CNCP. Our results will help inform the appropriateness of assuming similar beneficial and adverse effects of varying opioid formulations.Systematic review registrationThis systematic review is registered with Prospective Register of Systematic Reviews, an international prospective register of systematic reviews (registration no.: CRD42018110331), available at https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=110331.

Project description:ImportanceLong-acting opioids increase the risk of unintentional overdose deaths but also may increase mortality from cardiorespiratory and other causes.ObjectiveTo compare all-cause mortality for patients with chronic noncancer pain who were prescribed either long-acting opioids or alternative medications for moderate to severe chronic pain.Design, setting, and participantsRetrospective cohort study between 1999 and 2012 of Tennessee Medicaid patients with chronic noncancer pain and no evidence of palliative or end-of-life care.ExposuresPropensity score-matched new episodes of prescribed therapy for long-acting opioids or either analgesic anticonvulsants or low-dose cyclic antidepressants (control medications).Main outcomes and measuresTotal and cause-specific mortality as determined from death certificates. Adjusted hazard ratios (HRs) and risk differences (difference in incidence of death) were calculated for long-acting opioid therapy vs control medication.ResultsThere were 22,912 new episodes of prescribed therapy for both long-acting opioids and control medications (mean [SD] age, 48 [11] years; 60% women). The long-acting opioid group was followed up for a mean 176 days and had 185 deaths and the control treatment group was followed up for a mean 128 days and had 87 deaths. The HR for total mortality was 1.64 (95% CI, 1.26-2.12) with a risk difference of 68.5 excess deaths (95% CI, 28.2-120.7) per 10,000 person-years. Increased risk was due to out-of-hospital deaths (154 long-acting opioid, 60 control deaths; HR, 1.90; 95% CI, 1.40-2.58; risk difference, 67.1; 95% CI, 30.1-117.3) excess deaths per 10,000 person-years. For out-of-hospital deaths other than unintentional overdose (120 long-acting opioid, 53 control deaths), the HR was 1.72 (95% CI, 1.24-2.39) with a risk difference of 47.4 excess deaths (95% CI, 15.7-91.4) per 10,000 person-years. The HR for cardiovascular deaths (79 long-acting opioid, 36 control deaths) was 1.65 (95% CI, 1.10-2.46) with a risk difference of 28.9 excess deaths (95% CI, 4.6-65.3) per 10,000 person-years. The HR during the first 30 days of therapy (53 long-acting opioid, 13 control deaths) was 4.16 (95% CI, 2.27-7.63) with a risk difference of 200 excess deaths (95% CI, 80-420) per 10,000 person-years.Conclusions and relevancePrescription of long-acting opioids for chronic noncancer pain, compared with anticonvulsants or cyclic antidepressants, was associated with a significantly increased risk of all-cause mortality, including deaths from causes other than overdose, with a modest absolute risk difference. These findings should be considered when evaluating harms and benefits of treatment.

Project description:ImportanceCardiovascular events and mortality are the principal causes of excess mortality and health care costs for people with type 2 diabetes. No large studies have specifically compared long-acting insulin alone with long-acting plus short-acting insulin with regard to cardiovascular outcomes.ObjectiveTo compare cardiovascular events and mortality in adults with type 2 diabetes receiving long-acting insulin who do or do not add short-acting insulin.Design, setting, and participantsThis retrospective cohort study emulated a randomized experiment in which adults with type 2 diabetes who experienced a qualifying glycated hemoglobin A1c (HbA1c) level of 6.8% to 8.5% with long-acting insulin were randomized to continuing treatment with long-acting insulin (LA group) or adding short-acting insulin within 1 year of the qualifying HbA1c level (LA plus SA group). Retrospective data in 4 integrated health care delivery systems from the Health Care Systems Research Network from January 1, 2005, to December 31, 2013, were used. Analysis used inverse probability weighting estimation with Super Learner for propensity score estimation. Analyses took place from April 1, 2018, to June 30, 2019.ExposuresLong-acting insulin alone or with added short-acting insulin within 1 year from the qualifying HbA1c level.Main outcomes and measuresMortality, cardiovascular mortality, acute myocardial infarction, stroke, and hospitalization for heart failure.ResultsAmong 57 278 individuals (39 279 with data on cardiovascular mortality) with a mean (SD) age of 60.6 (11.5) years, 53.6% men, 43.5% non-Hispanic White individuals, and 4 years of follow-up (median follow-up of 11 [interquartile range, 5-20] calendar quarters), the LA plus SA group was associated with increased all-cause mortality compared with the LA group (hazard ratio, 1.27; 95% CI, 1.05-1.49) and a decreased risk of acute myocardial infarction (hazard ratio, 0.89; 95% CI, 0.81-0.97). Treatment with long-acting plus short-acting insulin was not associated with increased risks of congestive heart failure, stroke, or cardiovascular mortality.Conclusions and relevanceFindings of this retrospective cohort study suggested an increased risk of all-cause mortality and a decreased risk of acute myocardial infarction for the LA plus SA group compared with the LA group. Given the lack of an increase in major cardiovascular events or cardiovascular mortality, the increased all-cause mortality with long-acting plus short-acting insulin may be explained by noncardiovascular events or unmeasured confounding.

Dataset Information

Markers of abuse liability of short- vs long-acting opioids in chronic pain patients: a randomized cross-over trial.

Publications

Markers of abuse liability of short- vs long-acting opioids in chronic pain patients: a randomized cross-over trial.

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