Polysubstance Use in Adults With Opioid Use Disorder Receiving Buprenorphine Maintenance.

INTRODUCTION: Studying polysubstance use is a public health recommendation. In the United Arab Emirates, more than 80% of adults with opioid use disorder (OUD) use 2 or more nonopioid substances. This secondary analysis contrasts the characteristics of polysubstance users (OUD + ≥1 nonopioid) with OUD, explores the correlates and predictors of nonfatal overdose, and examines the impact of polysubstance use on OUD treatment outcomes using buprenorphine (BUP). METHODS: This analysis uses data from a 16-week outpatient randomized controlled trial of 141 adults with OUD allocated to BUP + incentivized adherence and abstinence monitoring (n = 70) and BUP in usual care (control, n = 71). Outcomes were nonfatal overdose events over the preceding 12 months, positive drug screens, and treatment retention. Participant characteristics were contrasted, and bivariate statistical tests were conducted for simple associations followed by logistic regression. RESULTS: Polysubstance use was reported by 117 participants (82.9%), the majority of whom used pregabalin 72.1% (n = 75). Compared with OUD, polysubstance users observed higher arrests (median, 1.0 [interquartile range, 0.0-3.0] vs 0.5 [interquartile range, 0.0-2.0]; P = 0.04]) and nonfatal overdose events (n = 33 [31.8%] vs 2 [10.8%], P = 0.003). Carisoprodol and injecting drug use independently predicted nonfatal overdose (adjusted odds ratio, 4.519 [95% confidence interval, 1.81-11.22] and 2.74 [95% confidence interval, 1.15-6.51], respectively). No significant difference was observed in opioid use and retention in treatment outcomes between groups. CONCLUSION: Carisoprodol and injecting drug use increase the likelihood of nonfatal overdose in adults with OUD. Polysubstance use does not impact response to BUP treatment compared with OUD.

Impact of Schedule IV controlled substance classification on carisoprodol utilization in the United States: An interrupted time series analysis.

BACKGROUND: In January 2012, the Drug Enforcement Agency (DEA) classified carisoprodol as a Schedule IV controlled substance at the US federal level. We aimed to examine the effect of this policy on the use of carisoprodol in a commercially-insured population. METHODS: This interrupted time series study included individuals with musculoskeletal disorders in the IBM MarketScan Commercial Database between December 2009 and February 2014. We used comparative segmented linear regression to assess changes in the proportions of patients who filled/newly filled carisoprodol each month. RESULTS: A total of 13.3 million patients were included. 29 states with no scheduling prior to the DEA classification had lower baseline prevalence of carisoprodol use compared to 17 states that had scheduled carisoprodol individually before 2010 (11.0 vs. 21.1 patients with fills per 1000 patients). The federal scheduling was associated with an immediate decline (-1.12 per 1000 patients, p < 0.01) and decreasing trend in prevalence (-0.07 per 1000 patients per month, p = 0.02). This effect was not modified by existing state-level scheduling status. During the first, second, third, and fourth 6-month periods after federal scheduling, the relative difference between observed and predicted prevalence was 7.8%, 10.5%, 13.4%, and 19.8%. Similar patterns were observed for carisoprodol initiation. Overall, declining use was more pronounced among younger age groups and patients with injury. CONCLUSIONS: Schedule IV controlled substance classification at the federal level was associated with a moderate reduction in the dispensing of carisoprodol regardless of whether scheduling was already present at the state level.

Combination pharmacotherapy for the treatment of fibromyalgia in adults.

BACKGROUND: Fibromyalgia is a chronic widespread pain condition affecting millions of people worldwide. Current pharmacotherapies are often ineffective and poorly tolerated. Combining different agents could provide superior pain relief and possibly also fewer side effects. OBJECTIVES: To assess the efficacy, safety, and tolerability of combination pharmacotherapy compared to monotherapy or placebo, or both, for the treatment of fibromyalgia pain in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, and Embase to September 2017. We also searched reference lists of other reviews and trials registries. SELECTION CRITERIA: Double-blind, randomised controlled trials comparing combinations of two or more drugs to placebo or other comparators, or both, for the treatment of fibromyalgia pain. DATA COLLECTION AND ANALYSIS: From all studies, we extracted data on: participant-reported pain relief of 30% or 50% or greater; patient global impression of clinical change (PGIC) much or very much improved or very much improved; any other pain-related outcome of improvement; withdrawals (lack of efficacy, adverse events), participants experiencing any adverse event, serious adverse events, and specific adverse events (e.g. somnolence and dizziness). The primary comparison was between combination and one or all single-agent comparators. We also assessed the evidence using GRADE and created a 'Summary of findings' table. MAIN RESULTS: We identified 16 studies with 1474 participants. Three studies combined a non-steroidal anti-inflammatory drug (NSAID) with a benzodiazepine (306 participants); two combined amitriptyline with fluoxetine (89 participants); two combined amitriptyline with a different agent (92 participants); two combined melatonin with an antidepressant (164 participants); one combined carisoprodol, paracetamol (acetaminophen), and caffeine (58 participants); one combined tramadol and paracetamol (acetaminophen) (315 participants); one combined malic acid and magnesium (24 participants); one combined a monoamine oxidase inhibitor with 5-hydroxytryptophan (200 participants); and one combined pregabalin with duloxetine (41 participants). Six studies compared the combination of multiple agents with each component alone and with inactive placebo; three studies compared combination pharmacotherapy with each individual component but did not include an inactive placebo group; two studies compared the combination of two agents with only one of the agents alone; and three studies compared the combination of two or more agents only with inactive placebo.Heterogeneity among studies in terms of class of agents evaluated, specific combinations used, outcomes reported, and doses given prevented any meta-analysis. None of the combinations of drugs found provided sufficient data for analysis compared with placebo or other comparators for our preferred outcomes. We therefore provide a narrative description of results. There was no or inadequate evidence in any comparison for primary and secondary outcomes. Two studies only reported any primary outcomes of interest (patient-reported pain relief of 30%, or 50%, or greater). For each 'Risk of bias' item, only half or fewer of studies had unequivocal low risk of bias. Small size and selective reporting were common as high risk of bias.Our GRADE assessment was therefore very low for primary outcomes of pain relief of 30% or 50% or greater, PGIC much or very much improved or very much improved, any pain-related outcome, participants experiencing any adverse event, any serious adverse event, or withdrawing because of an adverse event.Three studies found some evidence that combination pharmacotherapy reduced pain compared to monotherapy; these trials tested three different combinations: melatonin and amitriptyline, fluoxetine and amitriptyline, and pregabalin and duloxetine. Adverse events experienced by participants were not serious, and where they were reported (in 12 out of 16 studies), all participants experienced them, regardless of treatment. Common adverse events were nausea, dizziness, somnolence, and headache. AUTHORS' CONCLUSIONS: There are few, large, high-quality trials comparing combination pharmacotherapy with monotherapy for fibromyalgia, consequently limiting evidence to support or refute the use of combination pharmacotherapy for fibromyalgia.

A prospective evaluation of psychotherapeutic and illicit drug use in patients presenting with chronic pain at the time of initial evaluation.

BACKGROUND: Reports of chronic pain and associated opioid use, abuse, and fatalities continue to increase at an alarming rate, not only in the United States but also across the globe. In light of the many resultant fatalities, multiple authors and authorities have cautioned against the excessive use of opioids. Consequently, the Food and Drug Administration, Drug Enforcement Administration, and multiple state authorities have been proposing and implementing a plethora of regulations to curb opioid overuse and abuse. In the majority of cases, pain physicians have been portrayed as the perpetrators responsible for escalating use and abuse and resultant fatalities. OBJECTIVES: To assess the patterns of psychotherapeutic drug use and illicit drug use at the time of initial evaluation. STUDY DESIGN: A prospective evaluation. SETTING: A private, specialty referral interventional pain management clinic in the United States. METHODS: Participants were all new patients presenting to interventional pain management evaluated by one physician. Inclusion criteria was patients over 18 years of age with chronic spinal pain of at least one year duration. RESULTS: The results of this evaluation indicate that 94% of patients were on long-term opioids prior to presenting to interventional pain management. Illicit drug use is also common, although it has declined significantly. While a large proportion of individuals (45.7%) have used illicit drugs at some point in the past, current illicit drug use is present in only 7.9% of patients, both past and current use are similar to that of the general population. More importantly, a significant proportion of patients have been on opioids (high doses of more than 40 mg equivalents of morphine 48.8%) on a long-term basis, initiated and maintained by primary care physicians, prior to presenting to interventional pain management. Further, 35% were on benzodiazepines, and 9.2% on carisoprodol prior to presenting to interventional pain management. LIMITATIONS: The limitations of this evaluation include that it is a prospective, single center evaluation by one physician that is partially dependent on subjective recall of the patient. CONCLUSION: This study shows an overwhelming majority of patients were initiated and maintained with opioids in managing chronic noncancer pain. They were frequently on high doses over a long period of time with multiple drug combinations prescribed by primary care physicians.

Carisoprodol: update on abuse potential and legal status.

Carisoprodol is a centrally acting skeletal muscle relaxant of which meprobamate, a controlled substance, is the primary active metabolite. The abuse of carisoprodol has increased dramatically in the last several years. A withdrawal syndrome occurs in some patients who abruptly cease carisoprodol intake. The symptoms of this syndrome are similar to those seen with meprobamate withdrawal, suggesting that they may result from withdrawal from meprobamate accumulated with intake of excessive carisoprodol; however, carisoprodol is capable of modulating GABAA function, which may contribute to its abuse potential.There has been considerable debate about whether carisoprodol should be considered a controlled substance. Carisoprodol was removed from the market in Norway on May 1, 2008, but may still be used by specially approved patients. Carisoprodol was classified as a controlled substance in several US states, and effective January 11, 2012, became a schedule IV controlled substance at the US federal level. This article updates the literature on abuse potential and examines recent developments regarding the legal status of carisoprodol.

Observations of medication compliance by measurement of urinary drug concentrations in a pain management population.

BACKGROUND: One of the major concerns of physicians treating pain patients with opioids is to determine whether the patients are compliant, and this is commonly determined by urine drug testing. There is limited information on which drugs these patients are most compliant with. There is also limited information as to how compliance is defined in terms of cutoffs. OBJECTIVE: To compare reported patient medication use with the presence of the drug in the patients' urine with defined cutoffs. METHOD: A retrospective study of the medications listed by the physicians' offices and the confirmed drug test findings. A Millennium Laboratories database of 20, 457 patient results was examined for the presence of the listed medications and was matched for the presence of the drugs above the analytical cutoffs. RESULTS: For oxycodone and hydrocodone, the authors observed 23 and 24 percent noncompliance, respectively. For carisoprodol, they observed 33 percent noncompliance. For morphine, they observed 14 percent noncompliance. For methadone, they observed 9 percent noncompliance. CONCLUSIONS: Noncompliance is prevalent in this patient population and varies with the prescribed drug.

Carisoprodol withdrawal after internet purchase.

INTRODUCTION: Carisoprodol is a centrally acting muscle relaxant used in the treatment of various musculoskeletal disorders whose main metabolite, meprobamate, is a controlled substance in the United States due to its sedative properties and potential for abuse. CASE DESCRIPTION: We report a case of a 51-year-old man with cognitive impairment and tremor who developed worsening tremor, anxiety, myoclonus, ataxia, and psychosis on abrupt cessation of carisoprodol. At hospital discharge, his cognitive function significantly improved compared with when he was on carisoprodol. CONCLUSION: Carisoprodol withdrawal is an important and under-recognized syndrome that should be considered in patients presenting with neurologic symptoms who are taking the medication. Carisoprodol withdrawal can be successfully treated with the use of benzodiazepines, although further studies are needed to identify the most appropriate treatment protocol.

Carisoprodol: abuse potential and withdrawal syndrome.

Carisoprodol (N-isopropyl-2 methyl-2-propyl-1,3-propanediol dicarbamate; N-isopropylmeprobamate) is a centrally acting skeletal muscle relaxant whose primary active metabolite is meprobamate, a substance with well established abuse potential similar to that of benzodiazepines. A number of reports show that carisoprodol has been abused for its sedative and relaxant effects, to augment or alter the effects of other drugs, and by the intentional combination of carisoprodol and other noncontrolled medications because of the relative ease (as compared to controlled substances) of obtaining prescriptions. The diversion and abuse of carisoprodol and its adverse health effects appear to have dramatically increased over the last several years. Clinicians have begun to see a withdrawal syndrome consisting of insomnia, vomiting, tremors, muscle twitching, anxiety, and ataxia in patients who abruptly cease intake of large doses of carisoprodol. Hallucinations and delusions may also occur. The withdrawal symptoms are very similar to those previously described for meprobamate withdrawal, suggesting that what may actually be occurring is withdrawal from meprobamate accumulated as a result of intake of excessive amounts of carisoprodol. However carisoprodol itself is capable of modulating GABA(A) function, and this may contribute both to the drugs abuse potential and to the occurrence of a withdrawal syndrome with abrupt cessation of intake. Carisoprodol has been classified as a controlled substance in several states in the US and restrictions on the use of the drug have been imposed in some European countries. Carisoprodol is metabolized to a controlled substance, has clear evidence of abuse potential and increasing incidence of abuse, and has shown evidence of a withdrawal syndrome with abrupt cessation from intake. This article will discuss the abuse potential of carisoprodol and the associated withdrawal syndrome, and consider implications for future use of the drug.

Randomized, double-blind trial of carisoprodol 250 mg compared with placebo and carisoprodol 350 mg for the treatment of low back spasm.

BACKGROUND: Carisoprodol, a centrally active skeletal muscle relaxant, is widely used for the treatment of acute, painful musculoskeletal disorders. When administered at a dose of 350 mg four times daily, carisoprodol demonstrated significant clinical benefit in its early clinical development trials; however, some unfavorable side effects, such as drowsiness and dizziness, were reported. Recently, research was conducted to determine if a lower dose of carisoprodol would retain efficacy but improve tolerability compared to the higher 350-mg dose. OBJECTIVE: The purpose of this multicenter study was to compare the efficacy and safety of carisoprodol 250-mg tablets four times daily to 350-mg tablets four times daily and to placebo in patients with acute, painful musculoskeletal spasm of the lower back. RESEARCH DESIGN AND METHODS: In this 1-week double-blind, placebo-controlled, parallel-group multicenter trial, patients 18 to 65 years of age with moderate to severe back spasm were randomly assigned to treatment with carisoprodol 250-mg tablets (n = 264), 350-mg tablets (n = 273), or matching placebo tablets (n = 269) three times daily and at bedtime. MAIN OUTCOME MEASURES: The coprimary efficacy variables were patient-rated relief from starting backache and patient-rated global impression of change assessed on treatment day 3. RESULTS: The carisoprodol 250-mg regimen was significantly more effective than placebo as assessed by both patient-rated relief from starting backache (p = 0.0001) and patient-rated global impression of change (p = 0.0046). There were no significant differences between the 250-mg and 350-mg dosages for the coprimary efficacy endpoints, and patients improved with or without sedation. Fewer than 1% of patients in the carisoprodol 250-mg group discontinued prematurely because of treatment-emergent adverse events, and no patient discontinued because of drowsiness. CONCLUSIONS: When administered three times daily and at bedtime, carisoprodol 250 mg was as effective as 350 mg three times daily and at bedtime with a lower incidence of adverse events and fewer discontinuations of therapy due to adverse events. Patients improved whether or not they reported sedation as an adverse event.

Prescription pattern of codeine for non-malignant pain: a pharmacoepidemiological study from the Norwegian Prescription Database.

BACKGROUND: Opioid prescription for pain relief is increasing. Codeine is the dominating opioid in several European countries, with Norway being among the highest codeine users. AIM: To determine whether codeine is primarily used for acute pain or whether there is a prescription pattern indicating problematic opioid use. METHODS: All pharmacies in Norway are obliged to submit data electronically to the Norwegian Prescription Database at the Norwegian Institute of Public Health on all dispensed prescriptions. Because all prescriptions are identified with a unique person identifier, it is possible to identify all prescriptions to one subject. All subjects who had prescription(s) of codeine dispensed to them in 2004, 2005 or 2006 are included in the study. RESULTS: 385 190 Norwegian persons had at least one prescription of codeine dispensed to them due to non-cancer pain in 2005, corresponding to a 1-year periodic prevalence of 8.3%. 223 778 (58%) received only one prescription in 2005, 121 025 (31%) received more than one prescription but <120 defined daily doses (DDDs), 30 939 (8%) received between 120 and 365 DDDs, 7661 (2%) between 365 and 730 DDDs, while only 1787 (0.5%) exceeded the maximum recommended dose of 730 DDDs. In the latter group, co-medication with benzodiazepines (65%) and carisoprodol (45%) was prevalent. CONCLUSION: About one in 10 adult persons in Norway were dispensed codeine in 2005. A majority (58%) received codeine only once, most likely for acute pain, whereas a small minority (0.5%) had a prescription pattern indicating problematic opioid use.

High-dose carisoprodol during pregnancy and lactation.

OBJECTIVE: To report a case of use of high-dose carisoprodol during pregnancy and breast-feeding. CASE SUMMARY: A 28-year-old woman with severe back muscle spasm took carisoprodol 2800 mg/day before and throughout an uncomplicated pregnancy and while exclusively breast-feeding her infant during the first month after birth. Serum drug concentrations of carisoprodol and the active metabolite meprobamate were measured in the mother and infant. Concentrations of these agents also were measured in breast milk. Developmental toxicity was not observed in the near-term infant, whose birth weight was at the 10th percentile for gestational age. Only slight sedation was noted in the infant during breast-feeding, and no signs or symptoms of withdrawal were noted when nursing was stopped. DISCUSSION: Carisoprodol and meprobamate are excreted into breast milk. Although the published human pregnancy data are limited to 15 cases, carisoprodol does not appear to cause developmental toxicity (growth restriction, structural anomalies, functional/neurobehavioral deficits, or death), even when the mother is taking high doses. No signs or symptoms of withdrawal were noted in our infant or in a previously published case when breast-feeding was stopped. Long-term follow-up has not been conducted in exposed infants, and the possibility of functional/neurobehavioral l deficits appearing later in life cannot be excluded. CONCLUSIONS: Except for mild sedation, no other toxicity was observed in a near-term infant exposed to carisoprodol throughout gestation and during breast-feeding in the first month after birth.

Are there alternatives to the use of quinine to treat nocturnal leg cramps?

OBJECTIVE: To review the efficacy and tolerability profiles of quinine in nocturnal and dialysis-associated leg cramps and to examine potential alternative agents. DATA SOURCES: Selection and extraction: a MEDLINE/PubMed, English-language literature search from 1966 to the present using quinine, leg cramps, vitamin E, verapamil, muscle relaxants, gabapentin as search terms. DATA SYNTHESIS: Quinine, an alkaloid originally isolated from the cinchona tree, has been used for many years to treat/prevent leg cramps. In the mid-1990s, the Food and Drug Administration (FDA) banned over-the-counter availability of quinine and marketing of prescription quinine products for leg cramps. In early 2007, FDA banned all prescription quinine products other than Qualaquin. FDA acted in this manner because of a perception that quinine is not effective for this condition and that its risk potential far exceeds its efficacy potential. Efficacy trials for quinine in leg cramps have numerous design flaws that have resulted in poor quality data, producing both positive and negative findings. Two meta-analyses have reached different conclusions. Superimposed on the questionable efficacy of quinine is the well-known toxicity profile of the drug, involving the hematologic, renal, neurologic, cardiac, and endocrine systems. CONCLUSION: Are there any alternatives to quinine for leg cramps? Data are available supporting the potential efficacy of verapamil, gabapentin, carisoprodol, and orphenadrine in the general population, and vitamin E in the dialysis population. One or more of these agents should be tried before resorting to a time-limited (four- to six-week) trial of quinine for the treatment/prevention of leg cramps.

Double-blind, placebo-controlled trial of carisoprodol 250-mg tablets in the treatment of acute lower-back spasm.

PURPOSE: The objective of this placebo-controlled trial was to determine the efficacy and safety of carisoprodol (Soma, MedPointe Pharmaceuticals, Somerset, NJ, USA), a centrally acting skeletal muscle relaxant used to treat acute, painful musculoskeletal conditions, at a dosage of 250 mg three times daily and at bedtime in patients with acute, painful muscle spasm of the lower back. METHODS: This was a 7-day, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Qualified patients were randomly assigned to treatment with carisoprodol 250-mg tablets (n = 277) or matching placebo tablets (n = 285). The coprimary efficacy endpoints were patient-rated global impression of change and patient-rated relief from starting backache scored on a 5-point rating scale. The primary analysis was on study Day 3. Four secondary endpoints were also assessed: (1) the Roland-Morris Disability Questionnaire (RMDQ), (2) time to symptom improvement, (3) patient-rated medication helpfulness, and (4) physician assessment of range of motion. RESULTS: Carisoprodol was significantly more effective than placebo for patient-rated global impression of change (2.24 vs. 1.70; p < 0.0001) and patient-rated relief from starting backache (1.83 vs. 1.12; p < 0.0001). Patients experienced clinical improvement with or without sedation. Onset of moderate or marked improvement was 3 days with carisoprodol compared to 6 days with placebo (p < 0.0001). No patient discontinued treatment with carisoprodol because of drowsiness, and there were no serious adverse events or clinically significant effects on laboratory values or vital signs. CONCLUSIONS: In this study, patients with acute muscle spasm of the lower back had significantly greater and more rapid relief from starting backache, and had improved functional status, as measured by the RMDQ, during treatment with carisoprodol 250-mg tablets compared to placebo. Patients experienced clinical improvement with or without sedation.

Abuse potential of carisoprodol: a retrospective review of Idaho Medicaid pharmacy and medical claims data.

BACKGROUND: Carisoprodol is a muscle relaxant indicated as adjunctive therapy in acute, painful musculoskeletal conditions. Case reports of drug-seeking behavior and utilization of carisoprodol in combination with opioids have suggested abuse potential. OBJECTIVES: We undertook a retrospective review of claims data to identify and characterize potential indicators of abuse in long-term users of carisoprodol and to determine any continued use of the drug by former long-term users following prior authorization implementation. METHODS: The Idaho Medicaid pharmacy and medical claims database was queried from January 1 to December 31, 2005, to identify long-term users of muscle relaxants. Use of concomitant opioids and coded diagnoses relating to past drug abuse were analyzed and compared between patients who used carisoprodol and patients who used other muscle relaxants. Data from 11 of 30 surveys mailed to pharmacies filling prescriptions for long-term users of carisoprodol were also collected to determine the frequency of self-pay-continued use after Medicaid coverage of the drug was discontinued. RESULTS: Long-term users of carisoprodol (n = 340) and other skeletal muscle relaxants (SMRs) (n = 453) were identified from among 130,000 individuals in the Idaho Medicaid pharmacy and medical claims database in calendar year 2005. Patients in both groups were similar in terms of mean age (~47 years) and sex (71.5% female). Patients using carisoprodol used concomitant opioids more frequently (81.5% vs 59.8%; P < 0.01), more commonly had past diagnoses indicating other drug abuse (34.1% vs 21.4%; P < 0.01), and in 80% of reported cases, continued to pay out of pocket for carisoprodol when third-party coverage was discontinued. Taken together, these findings are consistent with published case reports suggesting the abuse potential of carisoprodol. CONCLUSIONS: The results from this review suggest that, compared with long-term users of other SMRs, carisoprodol patients utilized concomitant opioids more frequently and concomitant NSAIDs less frequently, more commonly had past diagnoses indicating other drug dependence or abuse, and continued to pay out of pocket for carisoprodol when third-party coverage was discontinued. While none of these issues alone may be direct indicators of abuse, collectively they suggest that patients who used carisoprodol long term displayed abuse potential characteristics more frequently than long-term users of other agents.

The risk of traffic accidents after prescriptions of carisoprodol.

OBJECTIVE: Carisoprodol, a drug used for acute lower back pain, may cause psychomotor impairment. We wanted to investigate if patients using carisoprodol had increased risk of being involved in a traffic accident. METHODS: Data were retrieved from three population-based registries for the period April 2004-September 2005. The Norwegian Prescription Database contained individual information on all dispensed drugs at all pharmacies outside hospitals. The Norwegian Road Accident Registry contained information on all drivers involved in motor vehicle accidents with person injury. The Norwegian Central Population Registry was used to control for emigration or death. The accident incidence among carisoprodol exposed and unexposed subjects was compared by standardized incidence ratio. RESULTS: Having a prescription for carisoprodol dispensed increased the standardized incidence ratio for being involved in an accident with person injury to 3.7 (95% CI 2.9-4.8) the first week after the date of dispensing. This was similar to diazepam (2.8; 2.2-3.6), but higher than for salbutamol (1.1; 0.6-1.8). CONCLUSIONS: Patients receiving carisoprodol seem to have an increased risk of being involved in traffic accidents involving person injury. The study gives support to earlier work published on the impairing effects of carisoprodol.

Identifying controlled substance patterns of utilization requiring evaluation using administrative claims data.

OBJECTIVES: To develop a systems approach to identify, for further evaluation, patients with potential controlled substance misuse or mismanagement using software queries applied to administrative health claims data. STUDY DESIGN: Retrospective validation of the system using insurance claims. PATIENTS AND METHODS: Data from administrative health claims databases representing nearly 7 million individuals younger than 65 years were used by multidisciplinary expert panels to develop and validate controlled substance patterns of utilization requiring evaluation (CS-PURE) criteria. RESULTS: Thirty-four CS-PURE queries were developed in SAS and applied to administrative claims records to identify patients with potential controlled substance misuse or mismanagement. From these, we identified 10 CS-PURE with the highest expert agreement that intervention was warranted. Expert panel agree, ment that CS-PURE correctly identified cases ranged from 48% to 100%, with at least 50% agreement in 9 of 10 CS-PURE. The prevalence rates for CS-PURE ranged from 0.001% to 0.252%. This translates to identifying between 5 and 1116 patients for individual CS-PURE in a 500 000-member health plan. CONCLUSIONS: We developed and empirically validated a group of queries using CS-PURE to identify patients with potential controlled substance misuse or mismanagement that would warrant further evaluation by the treating physician, a quality assurance function, or the medical director. Claims-based CS-PURE identification is generalizable to most health insurers with access to medical and pharmaceutical claims records. Although CS-PURE are not direct measures of misuse, they can direct attention to potential problems to determine if intervention is needed.

Commonly used muscle relaxant therapies for acute low back pain: a review of carisoprodol, cyclobenzaprine hydrochloride, and metaxalone.

BACKGROUND: Low back pain is a leading reason for primary care visits. Many treatment options are available, but some lack scientific support. OBJECTIVE: The aim of this review was to discuss the etiology of low back pain and the relative risks and benefits of muscle relaxants commonly prescribed for the management of back pain. METHODS: We searched Intercontinental Marketing Services data for January 2003 through January 2004 to determine the most commonly prescribed agents for the management of musculoskeletal pain. Carisoprodol, cyclobenzaprine hydrochloride, and metaxalone represented >45% of all such prescriptions. Cochrane Library, MEDLINE, and EMBASE databases were searched (time frame: 1960 through January 2004; search terms: back pain, carisoprodol, cyclobenzaprine, metaxalone, muscle relaxants, and pharmacotherapy) and reference lists of identified articles were hand-searched. RESULTS: Three trials of carisoprodol (N = 197) were located in the Cochrane Library database. Two double-blind, randomized, placebo-controlled trials evaluating the safety and efficacy of cyclobenzaprine hydrochloride (N = 1405) were identified in the literature. Three double-blind, placebo-controlled trials were identified for metaxalone (N = 428) in 2 reports. The types of adverse events seen with these agents involved the central nervous system, including drowsiness/sedation, fatigue, and dizziness. However, the efficacy of cyclobenzaprine hydrochloride was shown to be independent of its sedative effects, which were dose related. The potential for abuse with carisoprodol is of growing concern. CONCLUSIONS: Analgesic pain management for low back pain due to muscle spasm may be combined with a muscle relaxant. Cyclobenzaprine hydrochloride has the most recent and largest clinical trials demonstrating its benefit, but carisoprodol and metaxalone also appear to be effective. However, carisoprodol's usefulness is mitigated by its potential for abuse.

A randomized clinical trial comparing chiropractic adjustments to muscle relaxants for subacute low back pain.

BACKGROUND: The adult lifetime incidence for low back pain is 75% to 85% in the United States. Investigating appropriate care has proven difficult, since, in general, acute pain subsides spontaneously and chronic pain is resistant to intervention. Subacute back pain has been rarely studied. OBJECTIVE: To compare the relative efficacy of chiropractic adjustments with muscle relaxants and placebo/sham for subacute low back pain. DESIGN: A randomized, double-blind clinical trial. METHODS: Subjects (N = 192) experiencing low back pain of 2 to 6 weeks' duration were randomly allocated to 3 groups with interventions applied over 2 weeks. Interventions were either chiropractic adjustments with placebo medicine, muscle relaxants with sham adjustments, or placebo medicine with sham adjustments. Visual Analog Scale for Pain, Oswestry Disability Questionnaire, and Modified Zung Depression Scale were assessed at baseline, 2 weeks, and 4 weeks. Schober's flexibility test, acetaminophen usage, and Global Impression of Severity Scale (GIS), a physician's clinical impression used as a secondary outcome, were assessed at baseline and 2 weeks. RESULTS: Baseline values, except GIS, were similar for all groups. When all subjects completing the protocol were combined (N = 146), the data revealed pain, disability, depression, and GIS decreased significantly (P <.0001); lumbar flexibility did not change. Statistical differences across groups were seen for pain, a primary outcome, (chiropractic group improved more than control group) and GIS (chiropractic group improved more than other groups). No significant differences were seen for disability, depression, flexibility, or acetaminophen usage across groups. CONCLUSION: Chiropractic was more beneficial than placebo in reducing pain and more beneficial than either placebo or muscle relaxants in reducing GIS.