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Objective To examine the prevalence and duration of skeletal muscle relaxant (SMR) treatment among commercially insured adults in the United States. Methods We used the MarketScan Research Database to identify a cohort of adults 18 to 64 years who had ≥2-year continuous enrollment between 2005 and 2018. We estimated the prevalence of SMR treatment using a repeated cross-sectional design and derived treatment duration using the Kaplan-Meier method. Analyses were stratified by age group, sex, geographic region, individual SMR agent, and musculoskeletal disorder. Results 48.7 million individuals were included. Treatment prevalence ranged from 61.5 to 68.3 per 1,000. About one-third of users did not have a preceding musculoskeletal disorder diagnosis. Cyclobenzaprine was the dominant agent accounting for >50% of prescriptions. The considerable growth in the use of baclofen, tizanidine, and methocarbamol paralleled with a decline in carisoprodol and metaxalone use. The prevalence was highest in the South while lowest in the Northeast. The median treatment duration was 14 days with 4.0%, 1.9%, and 1.0% of individuals using SMRs for more than 90, 180, and 365 days, respectively. Compared with cyclobenzaprine, patients initiating baclofen, tizanidine, and carisoprodol had longer treatment duration. Conclusions SMRs are widely used in the United States. Their use slightly increased in recent years, but trends varied among individual agents, patient groups, and geographic regions. Despite limited evidence to support efficacy, a sizable number of U.S. adults used SMRs for long-term and off-label conditions. Further study is needed to understand determinants of treatment as well as outcomes associated with such use.

A collaborative study was conducted to investigate discrepancies in recoveries of two commonly prescribed compounds, amitriptyline and cyclobenzaprine, in patient urine samples when hydrolyzed with different enzymes from different sources. A 2- to 10-fold increase in analyte recoveries was seen for patient samples hydrolyzed using a recombinant β-glucuronidase (IMCSzyme™) over samples hydrolyzed with β-glucuronidase from Haliotis rufescens We report outcomes from four commercially available β-glucuronidase enzymes (IMCSzyme™, Patella vulgata, Helix pomatia and H. rufescens) on patient samples that tested positive for amitriptyline and cyclobenzaprine. Our results confirm reduced hydrolysis of glucuronides by β-glucuronidases isolated from mollusks, but near complete conversion when using the recombinant enzyme. Our premise is that systematic differences in hydrolysis efficiencies due to varying substrate affinity among enzyme subtypes potentially impacts accuracy and reliability of measurements.

Objective. This study was designed to describe burden of illness and treatment patterns, and to examine the patient, physician, and care factors associated with the treatment choices of individuals receiving new prescriptions for fibromyalgia (FM). Design. This is a baseline assessment of the Real-World Examination of Fibromyalgia: Longitudinal Evaluation of Costs and Treatments (REFLECTIONS), a prospective observational study. Baseline data (including a physician survey, a patient visit form, and computer-assisted telephone interviews) were collected from July 2008 through May 2010 in 58 care settings in the United States, including Puerto Rico. Results. Patients (N = 1,700) were mostly female (94.6%) and white (82.9%). Mean age was 50.4 years and mean duration of illness was 5.6 years. Mean Fibromyalgia Impact Questionnaire total score was 54.4 (range 0–80), and Brief Pain Inventory average pain severity level was 5.5 (range 0–10). Patients reported high annual health care use and numerous work limitations related to FM. Patients were taking 182 unique types of medications prescribed for FM, including duloxetine (26.8%), nonsteroidal anti-inflammatory drugs (26.6%), pregabalin (24.5%), opioids (24.2%), tramadol (15.3%), benzodiazepines (15.2%), cyclobenzaprine (12.9%), milnacipran (8.9%), and others. Most patients took more than one medication concurrently (77.8%). Type of current medications used was most strongly associated with medication history and physician specialty. Conclusions. Burden of illness was high for patients with FM, and treatment patterns were highly variable. Importantly, the treatments with the most evidence to support their use were not always the most frequently chosen.

Dear Editor: We report a case of serotonin syndrome in a patient taking five agents that have known or reported serotonergic association. Symptoms began a year prior and were missed by multiple clinicians despite the addition of more serotonergic agents. We would like to discuss the importance of medication review, physical examination, and awareness of serotonin syndrome. A 41-year-old 84-kg woman presented to our chronic pain management clinic for removal of a lumbar spinal stimulator. Her past medical history included lumbar spondylosis with radiculopathy, cervical spondylosis with radiculopathy, anxiety, depression, osteoarthritis of the shoulders, and seasonal allergic rhinitis. Her surgical history included the placement of a spinal cord stimulator 3 years prior, multiple lumbar facet joint injections, a lumbar nerve radiofrequency ablation, a cervical epidural steroid injection, and two cesarean sections. Her medication list at the time of presentation was amitriptyline 50 mg daily, carisoprodol 350 mg three times daily, cetirizine 10 mg daily, cyclobenzaprine 5–10 mg at bedtime, duloxetine 120 mg at bedtime, gabapentin 800 mg three times daily, and tramadol 50 mg four times daily. She had been treated by a chronic pain specialist up to 3 years prior to her presentation with us. She received multiple injections and eventually a spinal cord stimulator for her lumbar back pain. She reported taking duloxetine for several years at 60 mg daily. She also reported taking a combination of duloxetine, celecoxib, pregabalin, and over-the-counter analgesics during that time …

Patients taking tricyclic antidepressants (TCA) can experience toxicity or severe side effects. As a rapid and less technically demanding alternative to quantitative serum analysis, most laboratories offer qualitative immunoassays to assist in the evaluation of a suspected TCA overdose. However, the relationship between quantitative serum and qualitative urine levels of TCA-related compounds and their metabolites has not been comprehensively studied. Serum high-performance liquid chromatography results were compared to the qualitative urine results using the Syva Rapid Test and the Biosite Triage. Serum concentrations of amitriptyline, desipramine, doxepin, imipramine, and nortriptyline ranging from subtherapeutic to toxic triggered a positive response on both urine immunoassay devices. On the other hand, neither immunoassay uniformly detected clomipramine, even at serum levels greater than the therapeutic range. False positives due to cyclobenzaprine were more common with the Biosite assay. For virtually all positive urine TCA findings, it was not possible to determine whether the positive results corresponded to subtherapeutic, therapeutic, supratherapeutic, or toxic serum concentrations. Because urine immunoassays are the only option for many laboratories analyzing specimens for TCAs (especially in an emergency setting), clinicians must understand the limitations and interpret results in conjunction with clinical findings and/or quantitation of serum levels.

Cyclobenzaprine and its major metabolite, norcyclobenzaprine, differ from amitriptyline and nortriptyline only by the presence of a double bond in the cycloheptane ring. Three patients developed sufficient levels of cyclobenzaprine and norcyclobenzaprine because of either rapid or long-term ingestion of cyclobenzaprine to cause positive interferences in both a Syva EMIT assay and a high-performance liquid chromatographic (HPLC) assay for identification and quantitation of tricyclic antidepressants in serum. Cyclobenzaprine coeluted with amitriptyline, and norcyclobenzaprine eluted slightly earlier than, but was poorly resolved from, nortriptyline in this HPLC assay. We found that cyclobenzaprine could be distinguished from amitriptyline and that norcyclobenzaprine could be distinguished from nortriptyline on the basis of gas chromatographic retention times upon gas chromatographic-mass spectrometric analyses after derivatization with trifluoroacetic anhydride. The compounds were also distinguishable by mass spectrometric criteria.

A critical examination of the literature on centrally acting, orally administered skeletal muscle relaxants (SMRs) is presented. The available comparative clinical studies are reviewed, and the pharmacology, metabolism and adverse effects of the oral SMRs are discussed briefly. The drugs covered are carisoprodol, chlorphenesin carbamate, chlorzoxazone, cyclobenzaprine hydrochloride, diazepam, metaxalone, methocarbamol, and orphenadrine citrate. The mechanism of action of these agents is not well defined, and their effects are measured mainly by subjective responses. Thus, acceptable evidence of efficacy is difficult to obtain, especially if clinical studies continue to be designed inadequately. There are inadequate data to support the superiority of any one drug. Further, unique clinical efficacy of any oral SMR in comparison to nonspecific sedation has not been established. Based on subjective responses, all agents, except diazepam, have been shown to be superior to placebo in acute disorders; cyclobenzaprine has not been evaluated in acute conditions. SMRs are less effective in chronic disorders. Combination muscle relaxant-analgesic products appear to be superior to their individual components, but the relative efficacy of these combination products in comparison to combined use of individual sedative and analgesic agents is unknown.

We evaluated a technique for detecting cyclobenzaprine interference with liquid-chromatographic assays for tricyclic antidepressants. The technique involves dual-wavelength absorbance monitoring of the column effluent at 214 and 254 nm. Ratios of analyte peak heights at each wavelength are used to check for the presence of co-eluting interferences. With this technique, one can detect interference with an amitriptyline assay caused by 10 micrograms of cyclobenzaprine per liter.