Search

Fibromyalgia is a syndrome characterized by chronic generalized pain in addition to different symptoms such as fatigue, sleep disturbances, stiffness, cognitive impairment, and psychological distress. Multidisciplinary treatment combining pharmacological and nonpharmacological therapies is advised.Publications describing randomized controlled trials and long-term extension studies evaluating drug treatment for fibromyalgia were searched in PubMed and Scopus and included in this review.Different drugs are recommended for the treatment of fibromyalgia by different published guidelines, although only three of them have been approved for this indication by the US FDA, and none have been approved by the European Medicines Agency. According to the available evidence, pregabalin, duloxetine and milnacipran should be the drugs of choice for the treatment of this disease, followed by amitriptyline and cyclobenzaprine. Other drugs with at least one positive clinical trial include some selective serotonin reuptake inhibitors, moclobemide, pirlindole, gabapentin, tramadol, tropisetron, sodium oxybate and nabilone. None of the currently available drugs are fully effective against the whole spectrum of fibromyalgia symptoms, namely pain, fatigue, sleep disturbances and depression, among the most relevant symptoms. Combination therapy is an option that needs to be more thoroughly investigated in clinical trials.

Aim The aim of this study was to characterize urethral neuromuscular function before and 2 weeks after medication therapy. Methods Premenopausal women without lower urinary tract symptoms were randomly allocated to 1 of the 6 medications for 2 weeks (pseudoephedrine ER of 120 mg, imipramine of 25 mg, cyclobenzaprine of 10 mg, tamsulosin of 0.4 mg, solifenacin of 5 mg, or placebo). At baseline and after medication, participants underwent testing: quantitative concentric needle electromyography (CNE) of the urethral sphincter using automated multimotor unit action potential software, current perception threshold (CPT) testing to measure periurethral sensation, and standard urodynamic pressure flow studies (PFS). Nonparametric tests were used to compare pre-post differences. Results Fifty-six women had baseline testing, 48 (85.7%) completed follow-up CNE, and 49 (87.5%) completed follow-up CPT and PFS testing. Demographics showed no significant differences among medication groups with respect to age (mean, 34.3; SD, 10.1), body mass index (mean, 31.8; SD, 7.5), parity (median, 1; range, 0-7), or race (14% Caucasian, 80% African American). The PFS parameters were not significantly different within medication groups. No significant pre-post changes in CNE values were noted; however, trends in amplitudes were in a direction consistent with the expected physiologic effect of the medications. With CPT testing, a trend toward increased urethral sensation at the 5-Hz stimulation level was observed after treatment with pseudoephedrine (0.15-0.09 mA at 5 Hz, P = 0.03). Conclusions In women without lower urinary tract symptoms, pseudoephedrine improved urethral sensation but not urethral neuromuscular function on CNE or PFS. Imipramine, cyclobenzaprine, tamsulosin, solifenacin, and placebo did not change urethral sensation or neuromuscular function.

A 35-year-old female patient was brought into the emergency department by EMS one weekend morning after being found down by her parents, with a chief complaint of altered mental status, confusion, and somnolence. Upon arrival the patient was drowsy but arousable and able to converse. She admitted to taking a handful of her muscle relaxant medicine (cyclobenzaprine) with some alcohol that prior evening when she had an argument with her boyfriend. Her past medical history included depression, for which she took escitalopram 10 mg daily. The muscle relaxant was given to her recently for an acute muscle spasm of her lower back. She denied any other drugs or medications.

This health technology assessment evaluated the efficacy of pharmacological treatment in patients with oro-facial pain. Randomised controlled trials were included if they reported pharmacological treatment in patients ≥18 years with chronic (≥3 months) oro-facial pain. Patients were divided into subgroups: TMD-muscle [temporomandibular disorders (TMD) mainly associated with myalgia]; TMD-joint (TMD mainly associated with temporomandibular joint pain); and burning mouth syndrome (BMS). The primary outcome was pain intensity reduction after pharmacological treatment. The scientific quality of the evidence was rated according to GRADE. An electronic search in PubMed, Cochrane Library, and EMBASE from database inception to 1 March 2017 combined with a handsearch identified 1552 articles. After screening of abstracts, 178 articles were reviewed in full text and 57 studies met the inclusion criteria. After risk of bias assessment, 41 articles remained: 15 studies on 790 patients classified as TMD-joint, nine on 375 patients classified as TMD-muscle and 17 on 868 patients with BMS. Of these, eight studies on TMD-muscle, and five on BMS were included in separate network meta-analysis. The narrative synthesis suggests that NSAIDs as well as corticosteroid and hyaluronate injections are effective treatments for TMD-joint pain. The network meta-analysis showed that clonazepam and capsaicin reduced pain intensity in BMS, and the muscle relaxant cyclobenzaprine, for the TMD-muscle group. In conclusion, based on a limited number of studies, evidence provided with network meta-analysis showed that clonazepam and capsaicin are effective in treatment of BMS and that the muscle relaxant cyclobenzaprine has a positive treatment effect for TMD-muscle pain.

Fibromyalgia (FM) primarily affects women, and it is increasingly recognized by health care providers as more patients seek assistance for their chronic pain conditions. FM patients suffer from reduced quality of life, daily functioning and productivity. A single FM patient can cost society tens of thousands of dollars each year, with the overall expense increasing alongside disease severity. Indirect costs account for the majority of total expenditures and involve losses in productivity, reduced work hours, absenteeism, disability, unemployment, early retirement, informal care and other out-of-pocket costs. Health care utilization increases in concert with the severity of illness. Moreover, FM patients often have several comorbid illnesses (e.g. depression, anxiety and sleep disturbances), resulting in extreme escalation of overall health care expenditures. Medications with the best efficacy in the treatment of FM include the tricyclic antidepressants amitriptyline and nortriptyline, cyclobenzaprine (a skeletal muscle relaxant), tramadol, duloxetine, milnacipran, pregabalin and gabapentin. Corticosteroids, nonsteroidal anti-inflammatory drugs, benzodiazepines and opioid analgesics, with the exception of tramadol, are not considered efficacious. Medication selection should be individualized and influenced by the severity of illness and the presence of comorbidities and functional disabilities.

Data sourcesElectronic searches of PubMed, the Cochrane Library, Embase, the National Health Service Economic Evaluation Database and HTA until March 2017. Also handsearched referenced in the original articles. Grey literature was not included.Study selectionRandomised controlled trials with more than ten participants with oro-facial pain duration of more than three months were sub grouped into: TMD-muscle pain (TMD-m), TMD-joint pain (TMD-j), burning mouth syndrome (BMS) and other oro-facial pain. Studies include any pharmacological treatment against another pharmacological, non-pharmacological treatment, placebo or no treatment. The primary outcome was change in pain intensity and the secondary outcome was the effect on quality of life.Data extraction and synthesisThree authors formed three review pairs that independently checked for inclusion. Four pairs of reviewers independently evaluated the risk of bias using the Swedish Agency for Health Technology Assessment and Assessment of Social Services tool. Two authors independently extracted data that were later assessed according to a modified GRADE system.ResultsForty-one studies, rated medium to low risk of bias, were included in qualitative analysis on patients with TMD-j pain (15 studies, n = 790), TMD-m pain (nine studies, n = 375), BMS (17 studies n = 868). For the TMD-j group five studies support NSAIDs and nine corticosteroid and hyaluronate injections. Eight of the nine TMD-m studies were included in a network meta-analysis (NMA), they support cyclobenzaprine, botulinum toxin injections and topical treatment with Ping-On ointment. Five of the 17 BMS studies included in a NMA support topical capsaicin and clonazepam. Of the remaining 12, five showed no effect while the remaining support alpha lipoic acid, gabapentin, clonazepam, amisulpride and SSRIs.ConclusionsBased on the results of the NMA the authors concluded that clonazepam and capsaicin are effective for BMS while cyclobenzaprine, a muscle relaxant, has a positive treatment effect on TMJ-m. Evidence from the narrative synthesis suggests NSAIDs, corticosteroid and hyaluronate injections are effective for TMD-j pain.

Background The use of compounded topical pain creams has increased dramatically, yet their effectiveness has not been well evaluated. Objective To determine the efficacy of compounded creams for chronic pain. Design Randomized controlled trials of 3 interventions. (ClinicalTrials.gov: NCT02497066). Setting Military treatment facility. Participants 399 patients with localized pain classified by each patient's treating physician as neuropathic (n = 133), nociceptive (n = 133), or mixed (n = 133). Intervention Pain creams compounded for neuropathic pain (ketamine, gabapentin, clonidine, and lidocaine), nociceptive pain (ketoprofen, baclofen, cyclobenzaprine, and lidocaine), or mixed pain (ketamine, gabapentin, diclofenac, baclofen, cyclobenzaprine, and lidocaine), or placebo. Measurements The primary outcome measure was average pain score 1 month after treatment. A positive categorical response was a reduction in pain score of 2 or more points coupled with a score above 3 on a 5-point satisfaction scale. Secondary outcomes included Short Form-36 Health Survey scores, satisfaction, and categorical response. Participants with a positive outcome were followed through 3 months. Results For the primary outcome, no differences were found in the mean reduction in average pain scores between the treatment and control groups for patients with neuropathic pain (-0.1 points [95% CI, -0.8 to 0.5 points]), nociceptive pain (-0.3 points [CI, -0.9 to 0.2 points]), or mixed pain (-0.3 points [CI, -0.9 to 0.2 points]), or for all patients (-0.3 points [CI, -0.6 to 0.1 points]). At 1 month, 72 participants (36%) in the treatment groups and 54 (28%) in the control group had a positive outcome (risk difference, 8% [CI, -1% to 17%]). Limitations Generalizability is limited by heterogeneity among pain conditions and formulations of the study interventions. Randomized follow-up was only 1 month. Conclusion Compounded pain creams were not better than placebo creams, and their higher costs compared with approved compounds should curtail routine use. Primary funding source Centers for Rehabilitation Sciences Research, Defense Health Agency, U.S. Department of Defense.

Introduction Sexual dysfunction is a well-known side effect of antidepressants. Painful ejaculation is a rare side effect that has been reported with the use of some psychiatric drugs such as triclyclic antidepressants. Cyclobenzaprine is a muscle relaxant that is structurally similar to tricyclic antidepressants. It is the most commonly prescribed muscle relaxant in the United States and accounts for 18% of all prescriptions written for chronic back pain. Methods A 55-year-old man was referred to our pain medicine clinic for evaluation and treatment of pain with ejaculation. Main outcome Measure The main outcome measure was to review the current published literature and case reports on painful ejaculation from medication use, in particular tricyclic antidepressants. Results After discontinuation of cyclobenzaprine, our patient's sexual dysfunction resolved. This result was consistent with the literature reviewed on the topic. Conclusion Painful ejaculation is likely an underreported side effect of tricyclic antidepressants and cyclobenzaprine use. Fortunately, these symptoms are reversible and discontinuation of these medications is typically an effective cure.

Fibromyalgia is a chronic disorder characterized by widespread pain and tenderness, often accompanied by fatigue, memory problems, and sleep disturbances. Therapy includes both nonpharmacological (education, cognitive behavioral therapy, and exercise) and pharmacological treatment (including medicines as pregabalin, duloxetine, milnacipran, amitriptyline, serotonin selective reuptake inhibitors, and cyclobenzaprine). A number of surveys have reported that cannabis products are frequently used in patients with fibromyalgia. Results showed that most of the patients who tried medical marijuana found it to be effective or very effective for the therapy of some symptoms of this condition. Significant relief of pain and stiffness has been reported after cannabis self-administration. The efficacy and tolerability of oral nabilone for the treatment of pain and sleep difficulty have been established in some noncontrolled studies and two randomized-controlled clinical trials. Nabilone significantly reduced pain and improved quality of life in comparison to placebo. Nabilone was more effective than amitriptyline in improving sleep in fibromyalgia. More studies are needed to evaluate the efficacy and safety of cannabinoids in fibromyalgia.

Fibromyalgia is a chronic disorder with a broad spectrum of clinical manifestations such as muscular weakness and pain, fatigue and sleep disturbances. In this case we describe a female patient, frequent tea consumer with a classic presentation of fibromyalgia, initially treated with paracetamol+caffeine, due to poor control of symptoms cyclobenzaprine was prescribed, after a few months the symptoms got worse and duloxetine was added to the pharmacotherapy, few days later her muscle pain and weakness worsened, this could be explained by either the acrylamide from tea that mimics the fibromyalgia symptoms or food-drug interactions. Palpitations, insomnia, restless legs syndrome and anxiety associated to a mild serotoninergic syndrome could be due to drug-drug interactions. The novelty of this article is the presence of neurotoxic acrylamide in tea and the interactions it may have, not only with disease but with conventional pharmacotherapy also. It is of relevance to raise awareness about the possible toxic compounds found in food.

Clinical QuestionDoes the addition of cyclobenzaprine or oxycodone with acetaminophen to naproxen result in improved functional outcomes at one week when compared to placebo in patients with acute low back pain?Article ChosenFriedman B, Dym A, Davitt, M, et al. Naproxen with cyclobenzaprine, oxycodone/acetaminophen, or placebo for treating acute low back pain: a randomized clinical trial. JAMA 2015:20;314(15):1572-80.Study ObjectiveThe primary objective of this study was to compare functional outcomes at one week and three months after emergency department (ED) presentation for acute low back pain among patients prescribed naproxen plus one of the following: (1) oxycodone/acetaminophen; (2) cyclobenzaprine; or (3) placebo.

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.

A common treatment for chronic pain is prescription of analgesics, but their long-term use entails risk of morbidity, addiction and misuse. One way to reduce the risk of abuse is prescribing of analgesics in a topical form. Physicians are urged to perform urine drug testing to ensure that patients are compliant with their medication regimens. However, there is little data on the efficiency of transdermal delivery for many analgesic drugs, and no data on expected urine drug levels. This study includes data from over 29,000 specimens tested for gabapentin, ketamine, cyclobenzaprine or amitriptyline used orally or topically. Gabapentin and amitriptyline concentrations were more likely to be below the limits of detection (25-40 ng/mL) in the urine of patients using them topically as compared with patients using them orally. Levels in gabapentin-positive topical specimens were much lower than in gabapentin-positive oral specimens (261 ng/mL vs >10,000 ng/mL). In contrast, ketamine and cyclobenzaprine were more readily detectable in the urine of topical users. Ketamine topical specimens were positive 12% more often than oral specimens, and mean topical specimen levels were 68-100% those of oral specimens. Cyclobenzaprine specimens were equally likely to be positive whether the dose was oral or topical, although mean levels after topical dosing were approximately 13-21% those after oral dosing. These findings are consistent with the reported percutaneous absorption efficiencies of gabapentin and ketamine, and are likely to be related to the absorption efficiencies of cyclobenzaprine and amitriptyline.

Fibromyalgia (FM) affects up to 6% of U.S. adults, resulting in a significant burden on the health care system and poor quality of life for patients. Duloxetine, pregabalin, and milnacipran are approved for management of FM; however, consensus is lacking regarding optimal therapy. Patients with FM taking approved medications often do not experience meaningful symptom relief, and many experience intolerable adverse events.To assess treatment patterns associated with available and commonly used medications for the management of FM using U.S. health insurance claims.This retrospective analysis used the MarketScan claims database to identify adults with a first diagnosis of FM (ICD-9-CM code 729.1) between 2009 and 2011 with continuous health plan enrollment for 12 months pre- and post-index. Medications of interest were pregabalin, gabapentin, duloxetine, milnacipran, cyclobenzaprine, and tramadol. These are 6 of the 8 medications recommended by the American College of Rheumatology (ACR) for treating FM; the other 2 (amitriptyline and venlafaxine) were only included in some initial assessments. The Charlson Comorbidity Index (CCI) was used to assess overall comorbidity burden. Endpoints included proportion of patients treated within 1 year after first diagnosis; initial treatment pattern; adherence over the first-year follow-up period for the medications of interest; and discontinuation, switching, and combination therapy patterns among pain medications of interest at different time points. Proportion of days covered (PDC; defined as number of days in the period when the patient had drug supply divided by the number of days in the period) was used to define adherence, which was categorized as low (PDC50%), medium (PDC 50% to80%), or high (PDC ≥ 80%). The time to discontinuation (defined as the first drug supply gap ≥ 90 days) was estimated using Kaplan-Meier analysis.Overall, 240,144 patients met the inclusion criteria. Patients were predominantly women (68%), had preferred provider organization insurance coverage (68%), and had a CCI score1 at baseline (69%). Only 31% (n = 74,738) initiated a treatment with a prescription medication listed in the ACR guidelines, and many patients received less than the recommended dose. Most (n = 70,919) patients initially received monotherapy with one of the 8 prescription medications. Of those who started with ≥ 2 medications (n = 3,819), cyclobenzaprine plus tramadol was the most frequent combination. Adherence was suboptimal for all 6 medications of interest. Duloxetine had the highest mean PDC (59%); for all other agents, mean PDC was50%. With the exception of duloxetine, discontinuation rates at 6 months were50% for all agents. Alterations in therapy were common. Among patients who discontinued their initial treatment of duloxetine, pregabalin, or milnacipran, approximately one-third had switched treatments within 90 days after their first prescription. For those who maintained their initial treatment agent, approximately 50% of patients added a second pain medication within 1 year of treatment initiation.The evidence suggests that patients with FM often do not receive 1 of the prescription medications recommended by ACR guidelines, and those who do are commonly prescribed lower-than-recommended doses, potentially resulting in poor effectiveness and tolerability. Discontinuation, switching, and addition of new pain medications are common, which may indicate low levels of satisfaction with initial treatment. New therapies with improved effectiveness and better tolerability are urgently needed for patients with FM.

Introduction Pharmacologic treatment of radicular pain with oral medications is limited by adverse effects and concern for dependence. While topical formulations have been explored in pain research, there is no published literature evaluating the efficacy in radicular pain. We present the first three cases of radicular pain successfully treated with a topical formulation of diclofenac, ibuprofen, baclofen, cyclobenzaprine, bupivacaine, gabapentin, and pentoxifylline (T7). Case Presentation Case series evaluating T7 for treatment of radicular pain in a single, outpatient pain center. Pain was rated on the numeric rating scale (NRS) on initial evaluation and follow up after a trial of T7. One to two grams of T7 was applied to the affected area 3 - 4 times daily in addition to the patient’s baseline pharmacologic management. Three patients with median age of 50 (range, 39 to 65) and diagnosis of cervical and/or lumbosacral radicular pain participated. Two of the three had chronic radicular pain despite use of analgesic agents, spinal injections and failed spinal surgery syndrome. Each reported subjective improvement in radicular pain, function and sleep. There was an average decrease in NRS score consistent with 30% - 40% global improvement in symptoms, clinically significant based on the minimal clinically important difference for radicular pain. T7 was well tolerated without adverse reactions. Surgery was prevented or delayed in all cases. Conclusions This is the first report of the successful treatment of radicular pain with a topical agent. This highlights the need for randomized, prospective study of both single and compounded topical agents for treatment of radicular pain.

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.

A sensitive, specific, and rapid high-pressure liquid chromatography/mass spectrometry/mass spectrometry method was developed for the quantitation of 11 tricyclic antidepressants and/or their metabolites; fluoxetine and norfluoxetine; cyclobenzaprine; and trazodone in urine. Samples were alkalinized with 0.2 N NaOH and extracted into 2 ml of hexane: ethyl acetate (1:1), evaporated to dryness, and reconstituted with 100 μl of 20 mM ammonium formate: methanol (20:80). The chromatographic separation was performed using an Allure Biphenyl 100 × 3.2 mm, 5-μ column with a mobile phase consisting of 20 mM ammonium formate: methanol (20:80 v/v) at a flow rate of 0.5 ml/min. The detection was accomplished by multiple-reaction monitoring via electrospray ionization source operating in the positive ionization mode. The calibration curve was linear over the investigated concentration range, 25-2,000 ng/ml, for each analyte using 1.0 ml of urine. The lower limit of quantitation for each analyte was 25 ng/ml. The intra- and inter-day precisions had coefficient of variation less than 15% and the accuracy was within the range from 88% to 109%. The method proved adequate for the tricyclic antidepressants analysis of urine for emergency clinical toxicology and pain management compliance testing.

Objective: Tinnitus is defined as an intrinsic sound sensation that cannot be attributed to an external sound source. Currently there are no standardized drug therapies for the treatment of tinnitus. Based on the analogy between pain and tinnitus it is suggested that among all antidepressant families that have been used for tinnitus, particular interest should be paid to the tricyclic group of drugs as they have an analgesic effect. The aim of the present study was to investigate the effect of a tricyclic pharmacological agent, namely cyclobenzaprine for the relief of tinnitus complaints. Subjects and methods: 65 patients, who received the drug treatment, were compared to 30 patients on a waiting list, who received no treatment. Results: Analysis shows that cyclobenzaprine offers some benefit to patients with tinnitus on both tinnitus intensity and tinnitus distress, while a waiting list control group does not demonstrate any improvement: 24% of the tinnitus patients showed a clear response to cyclobenzaprine with a reduction of 53% on tinnitus intensity and 25% had a clear response to cyclobenzaprine with a reduction of 55% on tinnitus distress. It was further demonstrated that particular subgroups, namely pure tone tinnitus patients and unilateral tinnitus patients, respond better to cyclobenzaprine. Conclusion: Our results indicate that cyclobenzaprine is a promising drug to treat tinnitus particularly in certain subgroups. As there is a good risk-benefit ratio and there are currently no well-established, specific treatments for tinnitus, cyclobenzaprine might be worthwhile to further investigate.

A sensitive, rapid and simple liquid chromatography–electrospray ionization mass spectrometry (LC-ESI-MS/MS) method was developed for the quantitative determination of cyclobenzaprine in human plasma, to study the pharmacokinetic behavior of cyclobenzaprine capsule in healthy Chinese volunteers. With escitalopram as the internal standard (IS), sample pretreatment involved a one-step liquid–liquid extraction using saturated sodium carbonate solution and hexane–diethyl ether (3:1, v/v). The separation was performed on an Ultimate XB-CN column (150 × 2.1 mm, 5 µm). Isocratic elution was applied using acetonitrile–water (40:60, v/v) containing 10 m M ammonium acetate and 0.1% formic acid. The detection was carried out on a triple-quadrupole tandem mass spectrometer in multiple reaction monitoring mode via electrospray ionization. The ion-pairs including m/z 276.2–216.2 for cyclobenzaprine and m/z 325.2–109.1 for IS were used for monitoring. Linear calibration curves were obtained over the range of 0.049–29.81 ng/mL with the lower limit of quantification at 0.049 ng/mL. The intra- and inter-day precision showed ≤6.5% relative standard deviation. The established method laid the groundwork for follow-up studies and provided basis for the clinical administration of cyclobenzaprine. Copyright © 2011 John Wiley & Sons, Ltd.

Background Pain, swelling and trismus are undesirable effects of extraction of impacted mandibular third molars. The authors conducted a study to evaluate the effectiveness of the muscle relaxant cyclobenzaprine when used as a supplement to cryotherapeutic, antibiotic and steroidal anti-inflammatory treatment with the aim of reducing undesirable consequences after third-molar extraction. Methods The authors conducted a prospective, randomized, double-masked, placebo-controlled clinical trial involving 50 participants aged 18 to 29 years randomly assigned to receive cyclobenzaprine or the placebo. The authors used a split-mouth design, so each participant acted as his or her own control. For each participant, the authors extracted one impacted mandibular third molar on each side of the mouth at different times. Participants received 10 milligrams of cyclobenzaprine or a placebo once per day the day before surgery, the day of surgery and the first day after surgery. The authors assessed the participants' postoperative pain by means of a visual analog scale at four, six, eight, 12, 24 and 48 hours. They measured the participants' swelling and maximal interincisor distance at 48 hours and seven days. Results The authors assessed both sides of each participant's mouth for differences in pain, swelling and trismus. They found no statistically significant differences between sides of the mouth regarding these three variables. Conclusions The results of this trial indicate that the influence of cyclobenzaprine over pain, swelling and trismus does not justify prescribing additional medication for patients undergoing third-molar extraction. Clinical Implications The muscle relaxant cyclobenzaprine was ineffective in reducing pain, swelling and trismus after third-molar extraction.

Objective.To determine the effects of bedtime very low dose (VLD) cyclobenzaprine (CBP) on symptoms and sleep physiology of patients with fibromyalgia (FM), unrefreshing sleep, and the α-nonREM sleep electroencephalographic (EEG) anomaly at screening.Methods.Of 37 patients with FM in the screened population, 36 were randomized and treated in this 8-week, double-blind, placebo-controlled, dose-escalating study of VLD CBP 1–4 mg at bedtime. We evaluated changes in subjective symptoms including pain, tenderness, fatigue, mood [Hospital Anxiety and Depression Scale (HAD)], and objective EEG sleep physiology (at screening, baseline, and Weeks 2, 4, and 8).Results.In the VLD CBP-treated group (n = 18) over 8 weeks, musculoskeletal pain and fatigue decreased, tenderness improved; total HAD score and the HAD depression subscore decreased; patient-rated and clinician-rated fatigue improved. In the placebo-treated group (n = 18), none of these outcome measures changed significantly. Compared to placebo at 8 weeks, VLD CBP significantly improved pain, tenderness, and the HAD Depression subscore. Analysis of cyclic alternating pattern (CAP) sleep EEG revealed that significantly more subjects in the VLD CBP group than the placebo group had increased nights of restorative sleep in which CAPA2+A3/CAPA1+A2+A3= CAPA2+A3(Norm)≤ 33%. For VLD CBP-treated subjects, the increase in nights with CAPA2+A3(Norm)≤ 33% was correlated to improvements in fatigue, total HAD score, and HAD depression score.Conclusion.Bedtime VLD CBP treatment improved core FM symptoms. Nights with CAPA2+A3(Norm)≤ 33% may provide a biomarker for assessing treatment effects on nonrestorative sleep and associated fatigue and mood symptoms in persons with FM.

Objectives: Many treatments have been proposed for myofascial pain syndrome. The objective of this study was to compare the analgesic effect of acupuncture to trigger point injection combined with cyclobenzaprine chlorhydrate and sodium dipyrone. Methods: A randomized study was performed in 30 patients divided into 2 groups: G1 received trigger point injection with 0.25% bupivacaine twice weekly, and both cyclobenzaprine chlorhydrate 10 mg/day and sodium dipyrone 500 mg every 8 hours; G2 received classical and trigger point acupuncture twice weekly. All patients were instructed in physical exercise. The following parameters were evaluated: pain intensity rated on a numerical scale, number of trigger points, and quality of life before and 4 weeks after treatment. Results: The pain scores and the number of trigger points reduced significantly in both groups, with no significant difference between groups. Significant improvement in the quality of life scores was observed for some of the functional domains in the 2 groups, whereas there was no improvement of the general health status domain in either group or of the emotional domain in G1. Conclusion: Acupuncture, when compared with trigger point injection, combined with cyclobenzaprine chlorhydrate and sodium dipyrone provided similar pain relief and improvement in quality of life measures at 4 weeks. ▪