Cyclobenzaprine hydrochloride effect on skeletal muscle spasm in the lumbar region and neck: two double-blind controlled clinical and laboratory studies. Cyclobenzaprine and naproxen versus naproxen alone in the treatment of acute low back pain and muscle spasm. [Results of a double-blind study of diclofenac + vitamin B1, B6, B12 versus diclofenac in patients with acute pain of the lumbar vertebrae. A multicenter study]. Comparison of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia. A randomized, double-blind clinical trial. The effectiveness of adding pharmacologic treatment with clonazepam or cyclobenzaprine to patient education and self-care for the treatment of jaw pain upon awakening: a randomized clinical trial. Acute back pain and spasm. A controlled multicenter trial of combined analgesic and antispasm agents. [Prospective study of the analgesic action of clomipramine versus placebo in refractory lumbosciatica (68 cases)]. A pilot study examining topical amitriptyline, ketamine, and a combination of both in the treatment of neuropathic pain. Efficacy and safety of pregabalin 600 mg/d for treating painful diabetic peripheral neuropathy: a double-blind placebo-controlled trial.
A new drug, Cyclobenzaprine hydrochloride (Flexeril), was compared with diazepam (Valium) and placebo in double-blind trials for efficacy in treating spasms and pain in the neck and low back. Complex recording methods involving clinical evaluations (graded), patient self-ratings, goniometry, motion analysis by computer, electromyography of controlled motions and detailed statistical analysis were used. Clinical improvement over two weeks was statistically significant in all treatment groups with a statistically significant preference for Cyclobenzaprine hydrochloride. The most striking improvements recorded were in the electromyographic findings, which showed statistically significant changes for the Cyclobenzaprine group. Clinical muscle spasms are not accompanied by increased myoelectric activity; the reverse is true. With improvement, myoelectric activity in back muscles is augmented during prescribed stressful movements as measured by electromyography and computer analysis combined with complex electrogoniometry. Two groups of 20 patients each, with mild to moderate acute low back pain with associated muscle spasm of ten days' duration or less, were treated with a combination of cyclobenzaprine and naproxen or naproxen alone in a randomized, 14-day open-label trial. Cyclobenzaprine was added to the naproxen regimen as an adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful, musculoskeletal conditions. The clinical characteristics of each study group, including the number of worker's compensation patients, were comparable. Combination therapy was associated with less objective muscle spasm and tenderness and greater motion of the lumbosacral spine (P less than 0.05). There were trends toward faster resolution of functional deficits and pain with combined therapy. Combination therapy was associated with more side effects, due primarily to drowsiness from the cyclobenzaprine. The results of this study demonstrated that patients with muscle spasm associated with acute low back strain benefited from the use of combination therapy consisting of a nonsteroidal anti-inflammatory agent (naproxen) and a muscle relaxant (cyclobenzaprine). Several clinical trials have shown that the duration of treatment of painful vertebral syndromes can be shortened by using a combination of vitamins B1, B6, B12 and diclofenac instead of diclofenac. In addition, a more efficient pain relief could be achieved by the combination therapy. In order to confirm these results, we compared the clinical efficacy of diclofenac (25 mg) and a combination preparation with diclofenac (25 mg) plus vitamins B1 (thiamine nitrate 50 mg), B6 (pyridoxine hydrochloride 50 mg) and B12 (cyanocobalamin 0.25 mg) in a multicentric randomized double-blind study including 418 patients. All patients received 3 x 2 capsules daily for a maximum of 2 weeks. In case of total pain relief, therapy should be discontinued after one week. Data of 376 patients could be evaluated. 53 out of 184 patients receiving the combination and 48 out of 192 patients treated with diclofenac alone could stop therapy due to sufficient pain relief after one week. The evaluation of the "Hoppe Pain Questionnaire" and the data concerning pain intensity also revealed better results for the combination preparation. The differences in favour of the B-vitamin-diclofenac-combination were statistically significant in patients with severe pain at the beginning of therapy. Considering undesirable side-effects (symptoms in 70 out of 418 patients) there were no significant differences between the two medications. This clinical trial provides further evidence that the combination therapy with diclofenac plus B-vitamins is more effective than diclofenac alone for the treatment of painful vertebral syndromes. To compare the relative efficacy and tolerability of amitriptyline, cyclobenzaprine, and placebo in the treatment of fibromyalgia, and to identify predictors of response to amitriptyline and cyclobenzaprine.
                Two hundred eight patients who fulfilled the American College of Rheumatology criteria for the classification of fibromyalgia were entered into a 6-month prospective, double-blind, multicenter trial and were randomized to 1 of 3 treatment groups: amitriptyline, cyclobenzaprine, or placebo.
                After 1 month, 21%, 12%, and 0% of the amitriptyline, cyclobenzaprine, and placebo patients, respectively, had significant clinical improvement (amitriptyline versus placebo P = 0.002, cyclobenzaprine versus placebo P = 0.02, amitriptyline versus cyclobenzaprine P not significant). These percentages increased to 36%, 33%, and 19%, respectively, at the 6-month assessment (P not significant). The nature and frequency of side effects reported by patients treated with amitriptyline and those reported by patients treated with cyclobenzaprine were similar. A normal Minnesota Multiphasic Personality Inventory (MMPI) profile at baseline was predictive of clinical improvement at the 1-month evaluation (odds ratio 3.3, 95% confidence interval 1.2-9.0). However, neither the MMPI profile nor any of the demographic, clinical, or functional parameters evaluated at baseline predicted long-term response.
                Our data confirm the short-term efficacy of amitriptyline and cyclobenzaprine in a small percentage of patients with fibromyalgia. Long-term efficacy could not be demonstrated because of a higher-than-expected placebo response. Predictors of response to these drugs could not be determined. To compare the relative effectiveness of a benzodiazepine (clonazepam), a muscle relaxant (cyclobenzaprine), and a placebo for the treatment of jaw pain upon awakening, when each is combined with the recommended nonpharmacological components of initial medical management.
                Forty-one subjects were recruited with a diagnosis of myofascial pain based on the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). All subjects were given education about TMD and a self-care program. Subjects were randomized into 1 of 3 groups: clonazepam (0.5 mg/night), cyclobenzaprine (10 mg/night), or placebo. The primary outcome measure was the subjects' average intensity of jaw pain upon awakening over the prior week. This was recorded with a visual analog scale at pretreatment and at the completion of the 3-week trial. A secondary outcome measure was sleep quality based on the Pittsburg Sleep Quality Index.
                Within-group changes showed a statistically significant (P < .001) decrease in jaw pain upon awakening for all 3 groups. Between-group differences demonstrated a statistically significant difference (P < .016) between cyclobenzaprine and placebo, and between cyclobenzaprine and clonazepam. There was no significant effect on sleep quality in any group.
                This study suggests that cyclobenzaprine is statistically superior to either placebo or clonazepam when added to self-care and education for the management of jaw pain upon awakening. Based on the subjects' report of sleep quality, these medications failed to significantly improve sleep in the short term. A double-blind, 18-center, balanced trial of diflunisal vs. cyclobenzaprine HCl vs. these two drugs combined vs. placebo produced complete results from 175 patients. They had sought treatment at the cooperating centers for acute painful spasms of the back within a day or two of trauma or strain. Global results over the 7 to 10 days of observations revealed a clinically and statistically significant superiority of the combined therapy by Day 4 (P = 0.006) and almost all patients recovered within a week to 10 days. A combination therapy with an effective safe analgesic and a true muscle relaxant for less than a week appears to be an excellent relief measure for acute back problems. The authors sought to determine the analgesic activity of clomipramine (CMP) versus placebo, efficacy and side-effects according to the time of administration, long term clinical results and the relationship between plasma levels and analgesic effect. This double-blind randomised trial involved the infusion of 250 ml of glucose solution morning and evening versus placebo. CMP was administered at progressive doses for 8 days (maximum dosage 75 mg), either in the morning at 8 a.m. or in the evening at 6 p.m. Sixty eight patients accepted to be treated, all suffering from low back pain with or without sciatica. Maintenance treatment at the dose of 75 mg/day was then administered. CMP had a statistically significant analgesic action independent (rapidity of action) of its antidepressant activity. CMP was more effective and better tolerated (sedative and tranquilizer effect) in the evening. Long term results were poor (75% of cases). There was no link between plasma levels and clinical response. The authors noted that the analgesic activity of CMP was rapid, but for a duration limited to the short term and that this efficacy compared with the quite good results obtained with the placebo could be explained by a possible methodological bias (patients hospitalised and treated by intravenous infusions). The finding that CMP was better tolerated in the evening, without any loss of efficacy, is a positive feature (chronotherapeutic trial). Poor long term results could be partially explained by side-effects (66%). There was no relationship between analgesic effect and plasma levels. The involvement of ongoing peripheral activity in the generation of nociceptive input in neuropathic pain suggests that topical drug delivery may be useful as a treatment strategy. This is a pilot study providing initial information regarding the use of novel topical preparations containing amitriptyline (AMI), ketamine (KET), and a combination of both in the treatment of neuropathic pain.
                The study design included a 2 day randomized, double blind, placebo controlled, 4 way cross-over trial of all treatments, followed by an open label treatment phase using the combination cream for 7 days. Twenty volunteers with chronic neuropathic pain were randomly assigned to treatment order and applied 5 mls of each topical treatment (1% AMI, 0.5% KET, combination AMI 1%/KET 0.5%, and placebo) for 2 days. Measures of pain at the end of each block included the short form McGill Pain Questionnaire (MPQ) and visual analog scales (VAS) for present pain intensity and pain relief. Eleven subjects who judged subjective improvement from any treatment in the initial trial entered the open-label trial and used the combination cream for 7 days. Pain levels were recorded daily using the same measures. Blood levels for amitriptyline and ketamine were performed at 7 days to determine whether systemic absorption had occurred.
                There was no statistically significant difference from placebo after 2 days for any treatment during the double blind component of the trial. In the 11 subjects who used the combination cream, there was a statistically significant effect, with subjects reporting significantly greater analgesia by days 3 to 7 according to measures of pain and pain relief. Blood levels revealed that there was no significant systemic absorption of amitriptyline or ketamine. Only 2 subjects experienced side effects; these were minor and did not lead to discontinuation of the cream.
                This pilot study demonstrated a lack of effect for all treatments in the 2 day double blind placebo controlled trial, followed by analgesia in an open label trial in a subgroup of subjects who chose to use the combination cream for 7 days. Blood analysis revealed no significant systemic absorption of either agent after 7 days of treatment, and creams were well tolerated. A larger scale randomized trial over a longer interval is warranted to examine further effects observed in the open label trial. Recent consensus guidelines recommend pregabalin as a first-tier treatment for painful diabetic peripheral neuropathy (DPN). We evaluated the efficacy of pregabalin 600 mg/d (300 mg dosed BID) versus placebo for relieving DPN-associated neuropathic pain, and assessed its safety using objective measures of nerve conduction (NC).
                In this randomized, double-blind, placebo-controlled trial, the primary efficacy measure was endpoint mean pain score (MPS) from daily pain diaries (11-point scale). NC velocity and sensory and motor amplitudes were assessed at baseline, endpoint, and end of follow-up (2 weeks post-treatment). At each timepoint, the median-motor, median-sensory, ulnar-sensory, and peroneal-motor nerves were evaluated. Secondary efficacy measures included weekly MPS and proportion of responders (patients achieving >or=50% reduction in MPS from baseline to endpoint). After 1-weeks' dosage escalation, pregabalin-treated patients received 300 mg BID for 12 weeks.
                Eighty-two patients received pregabalin and 85 placebo. Mean durations were 10 years for diabetes and approximately 5 years for painful DPN. Pregabalin-treated patients had lower MPS than controls (mean difference, -1.28; p <.001). For all four nerves, 95% CIs for median differences in amplitude and velocity from baseline to endpoint and baseline to follow-up included 0 (ie, no significant difference vs. placebo). Significant pain improvement among pregabalin-treated patients was evident at week 1 and sustained at every weekly timepoint. More pregabalin-treated patients (49%) than controls (23%) were responders (p <.001).
                Pregabalin 600 mg/d (300 mg BID) effectively reduced pain, was well tolerated, and had no statistically significant or clinically meaningful effect on NC in patients with painful DPN.
There was insufficient evidence to support the use of cyclobenzaprine in the treatment of MP. We identified only two small studies in which a total of 35 participants were given cyclobenzaprine, and it was not possible to estimate risks for benefits or harms. Further high quality RCTs of cyclobenzaprine for treating MP need to be conducted before firm conclusions on its effectiveness and safety can be made. Experts in this area should elect cut-off points for participants to identify whether a patient has achieved a clinically relevant reduction of pain (primary outcome), so that their results can be combined easily into future versions of this review.