A new skeletal muscle relaxant (DS 103-282) compared to diazepam in the treatment of muscle spasm of local origin. Zopiclone as night medication in rheumatoid arthritis. Acute back pain and spasm. A controlled multicenter trial of combined analgesic and antispasm agents. The response of neuropathic pain and pain in complex regional pain syndrome I to carbamazepine and sustained-release morphine in patients pretreated with spinal cord stimulation: a double-blinded randomized study. Clinical symptomatology and computer analyzed EEG before, during and after anxiolytic therapy of alcohol withdrawal patients. Treatment of spasticity with tizanidine in multiple sclerosis.
The myotonolytic activity of a new muscle-relaxant, DS 103-282, was compared with that of diazepam in a randomized double-blind study on thirty patients suffering from acute muscular spasm due to disorders of the cervical and lumbar segments of the spine. Fifteen patients received 5 mg DS 103-282 and fifteen received 5 mg diazepam on a three times daily regime for 7 days. DS 103-282 was found to alleviate symptoms and improve mobility to a significant degree (p less than or equal to 0.05) in all parameters evaluated and was also significantly superior to diazepam in 5 of these. Onset of action was particularly rapid for DS 103-282. Both medications were well tolerated and there was no significant difference between them. On the basis of these data DS 103-282 may be considered a more powerful and faster-acting myotonolytic agent than diazepam with which it was compared in similar clinical indications. Sleep disturbances and related daytime complaints are frequent in rheumatoid arthritis (RA). The aim of the current study was therefore to evaluate the effect of a newer hypnotic on sleep structure and clinical parameters in RA. Forty outpatients were randomized to a two week treatment regimen with either 7.5 mg zopiclone or placebo at bedtime. Clinical examinations were performed before and after treatment and the degree of pain, fatigue, sleepiness, morning stiffness, and activities of daily living were assessed. Two sleep questionnaires were also completed weekly. Polysomnography was performed before the study and after 14 days of treatment. Recordings were evaluated using conventional sleep scoring as well as frequency analysis of the electroencephalography (EEG). Patients in the zopiclone group had subjective improvement of sleep, but otherwise no differences in pain score or the other clinical parameters were found. Conventional sleep assessments showed only minor changes during treatment, but frequency analysis demonstrated a shift from the lower towards the higher EEG frequencies in the active treatment group. Although the modulation of the EEG can represent a non-specific pharmacologic epiphenomenon, it might also reflect a disturbance of sleep microstructure. In conclusion, treatment with zopiclone may be of value for subjective sleep complaints in selected patients with RA, but it is doubtful whether hypnotics improve daytime symptoms in this patient group. 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. Forty-three patients with peripheral neuropathic pain, exclusively pain reduced by spinal cord stimulation (SCS), were switched into a painful state after SCS inactivation. This mode was used to assess the pain-relieving effect of carbamazepine (CMZ) and opioids in a double-blinded, placebo-controlled trial. In Phase 1, the patients were randomly allocated to receive either CMZ (600 mg/d) or placebo during an SCS-free period of 8 days. In Phase 2, after a CMZ elimination interval of 7 days, 38 patients received either sustained-release morphine (90 mg/d) or placebo for 8 days. In cases of intolerable pain, the patients were authorized to reactivate their SCS. The pain intensity was rated on a numeric analog scale. In 38 patients who completed Phase 1, significant delay in pain increase was observed in the CMZ group as compared with placebo (P = 0.038). In Phase 2, the trend observed with morphine was insignificant (P = 0.41). Two CMZ patients and one morphine patient showed complete pain relief and preferred to continue the medication. Thirty-five patients returned to SCS. We conclude that CMZ is effective in peripheral neuropathic pain. Morphine obviously requires larger individually titrated dosages than those used in this study for results to be adequately interpreted. In a double-blind study the clinical symptomatology and quantitatively analyzed EEG of 42 hospitalized chronic alcoholics (ICD 303) undergoing alcohol withdrawal were investigated before, during and after 3 weeks' treatment with 2 pharmacokinetically different benzodiazepines: the short-acting lopirazepam (a new pyridodiazepine) and the long-acting prazepam. At the end of weeks 1 and 3 the titrated optimal daily doses were 24 and 23 mg lopirazepam and 35 and 32 prazepam, respectively, thus confirming our earlier pharmaco-EEG predictions that on a mg to mg basis the former drug is slightly more CNS potent than the latter. Thereafter, the patient population was divided into 6 subgroups: 2 groups continuing on active medication, 2 groups receiving placebo, and 2 groups with no pharmacotherapy for 1 week. Clinical assessments included the CGI, the Hamilton Anxiety Score, the Zung Self-Rating Scale for Anxiety and Depression, the Zerssen Befindlichkeitsskala and the questionnaire for somatic findings and side effect and were carried out on days 0, 7, 21 and 28 as was a radioreceptor assay for benzodiazepines in plasma. Quantitative EEG investigations were carried out on days 0, 21 and 28 and included recordings before and 2 h after one single dose of 10 mg. Statistical analysis demonstrated a marked and highly significant decrease in psychopathology as well as good drug tolerance at the end of the first week of therapy and thereafter a slight continuation in improvement until the end of the 3rd week. There were, however, no statistically significant differences between the 2 active compounds, nor were there any statistically significant differences between the 6 subgroups in the 4th week. On the other hand, blood level investigations demonstrated that even after a 3-week treatment period, blood levels dropped down to a morning minimum 12 h after the last evening medication of the short-acting lopirazepam, while plasma levels of the long-acting prazepam remained high. This was also reflected in the spectral analyzed EEG, which showed, after one single dosage of both drugs, a typical anxiolytic profile which was more pronounced after lopirazepam than prazepam, while after the chronic administration (12 h after the evening medication) only prazepam showed an anxiolytic profile. The lopirazepam-treated patients exhibited on the one hand a lack of benzodiazepine-specific alterations, but showed on the other hand EEG changes possibly reflecting clinical improvement. The relevance of the findings will be discussed. Spasticity is a frequent and often disabling symptom in MS patients. Current drugs used as antispastic agents include Dantrolene Sodium, Baclofen and Diazepam. Tizanidine (5-chloro-4-(2imidazolin-2 yl amino)-2,1,3-benzothialdiazole) is a new antispasticity agent that has purported central action. A double blind placebo controlled trial was performed to study the efficacy of this drug in MS patients. Sixty-six patients entered an eight week therapeutic trial and fifty-nine completed the trial. Patients were assessed at 0, 2, 3 and 8 weeks of therapy for clinical effects. Electrophysiologic tests were performed at 0 and 8 weeks. A statistically significant benefit was noted in spastic muscle groups in the legs with concomitant significant reduction in hyperactive stretch reflexes and ankle clonus. Side effects most frequently cited included dry mouth and drowsiness. Two patients developed elevated liver function test that decreased with cessation of therapy. Other clinical details, side effects and electrophysiologic data will be presented. Tizanidine appears to reduce clinical spasticity and hyperreflexia in MS patients although no change in functional status was detected. Tizanidine may well serve as an alternate antispastic agent, alone or in combination with other agents.
Based upon the currently available evidence in patients with RA, benzodiazepines (diazepam and triazolam) do not appear to be beneficial in improving pain over 24 hours or one week. The non-benzodiazepine agent zopiclone also did not significantly reduce pain over two weeks. However, even short term muscle relaxant use (24 hours to 2 weeks) is associated with significant adverse events, predominantly drowsiness and dizziness.