A randomized,placebo‐controlled trial of levetiracetam in central pain in multiple sclerosis

Levetiracetam is an anticonvulsant which is assumed to act by modulating neurotransmitter release via binding to the vesicle protein SV2A. This could have an impact on signalling in the pain pathway. The aim of this study was to test the analgesic effect of levetiracetam in central pain in multiple sclerosis. This was a randomized, double‐blind, placebo‐controlled, cross‐over trial with levetiracetam 3000 mg/day versus placebo (6‐week treatment periods). Patients with multiple sclerosis, symptoms and signs complying with central neuropathic pain and pain symptoms for more than 6 months, as well as pain intensity of more than 4 on a 0 to 10‐point numeric rating scale were included in the study. The primary outcome measure was pain relief at the end of each treatment period as measured on a 6‐point verbal scale. Eighty‐nine patients were screened for participation and 30 patients entered the study. Twenty‐seven patients were included in the data analysis. There were no differences in the ratings of pain relief (levetiracetam 2.4 vs. placebo 2.1, p = 0.169), total pain intensity (levetiracetam 5.3 vs. placebo 5.7, p = 0.147) or any of the other outcome measures (p = 0.086–0.715) in the total sample of patients. However, there was significant reduction of pain, increased pain relief and/or more favourable pain relief with levetiracetam than with placebo in patients with lancinating or without touch‐evoked pain (p = 0.025–0.046). This study found no effect of the anticonvulsant levetiracetam in non‐selected patients with central pain in multiple sclerosis, but an effect in subgroups with specific pain symptoms was indicated.     

Shiatsu for chronic lower back pain: Randomized controlled study

BackgroundAlthough Shiatsu, a kind of complementary alternative medicine, was developed in Japan and is practiced around the world, no experimental studies on Shiatsu have been conducted. The aim of this study is to investigate the efficacy of Shiatsu therapy for chronic lower back pain.MethodWe conducted a prospective, randomized, open, blinded-endpoint design study at St. Luke’s International Hospital, Tokyo, Japan from 2015 to 2017. Patients with lower back pain for more than 12 weeks and a score of four or more on the Roland-Morris Disability Questionnaire (RMDQ) at baseline were included in this study. We excluded patients with severe conditions, such as bone metastasis, or dementia. Patients were randomly allocated to either Shiatsu therapy in addition to standard care or standard care only by computer randomization. Those allocated to Shiatsu received one-hour Shiatsu every week for four weeks. Our primary outcome was improvement of RMDQ, and secondary outcomes were improvement of Short-Form McGill Pain Questionnaire (SF-MPQ), Oswestry Disability Index (ODI) and EQ-5D after 4 weeks and 8 weeks. Bivariate analyses were applied for assessing statistical significance.ResultFifty-nine patients were included; 30 were allocated to Shiatsu, and 29 to the control group. None of the baseline characteristics were significantly different between groups. Twenty seven patients (90%) in the Shiatsu group and 24 patients (83%) in the control group completed the study. At week 4, Shiatsu group tended to show greater improvement only in EQ-5D (difference 0.068, p = 0.07), but not statistically significant, compared to control group, wheres other outcome measures were similar between the groups. At week 8, those in the Shiatsu group tended to have greater improvement in RMDQ (difference 1.7, p = 0.08) compared to the control group. The Shiatsu group showed greater improvement in present pain scale of SF-MPQ (difference 0.5, p < 0.05), ODI (difference 4.0, p < 0.01) and EQ-5D (difference 0.099, p = 0.01) compared to control group.ConclusionIn our limited sample trail, Shiatsu therapy combined with standard care for lower back pain improves some symptoms and QOL shortly after Shiatsu therapy.     

The anticonvulsant levetiracetam for the treatment of pain in polyneuropathy: A randomized,placebo‐controlled,cross‐over trial

Levetiracetam is an anticonvulsant which is assumed to act by modulating neurotransmitter release via binding to the vesicle protein SV2A. This could have an impact on signaling in the nociceptive system, and a pilot study indicated relief of neuropathic pain with levetiracetam. Objectives: The aim of this study was to test the analgesic effect of levetiracetam in painful polyneuropathy. Methods: This was a randomized, double‐blind, placebo‐controlled, cross‐over trial with levetiracetam 3000 mg/day versus placebo (6‐week treatment periods). Patients with diagnosed polyneuropathy and symptoms for more than 6 months, age between 20 and 80 years, pain intensity of more than 4 on a 0–10‐point numeric rating scale, and pain at least 4 days a week were included in the study. The primary outcome measure was pain relief at the end of each treatment period as measured on a 6‐point verbal scale. Results: Ninety‐three patients were screened for participation and 39 patients entered the study. Thirty‐five patients were included in the data analysis. There were no differences in the ratings of pain relief (levetiracetam 2.29 versus placebo 2.28, p =0.979), total pain intensity (levetiracetam 5.5 versus placebo 5.3, p =0.293) or any of the other outcome measures (p =0.147–1.00). Conclusion: This study indicates that the anticonvulsant levetiracetam has no clinically relevant effect on painful polyneuropathy.     

Postoperative analgesia and early rehabilitation after total knee replacement: A comparison of continuous low‐dose intravenous ketamine versus nefopam

The effects of nefopam and ketamine on pain control and rehabilitation after total knee replacement were compared in a prospective, double blinded study.Seventy-five patients were randomly assigned to receive a 0.2 mg kg^?1 bolus of nefopam or ketamine, followed by a 120 μg kg^?1 h^?1 continuous infusion until the end of surgery, and 60 μg kg^?1 h^?1 until the second postoperative day, or an equal volume of saline considered as placebo. Pain scores measured on a visual analog scale at rest and on mobilization, and patient-controlled intravenous morphine consumption, were assessed during 48 h. We measured the maximal knee flexion on the third postoperative day, and the delay to obtain a 90° flexion.Ketamine and nefopam reduced morphine consumption (p < 0.0001). Pain scores, were lower at rest and on mobilization in the ketamine group compared to the two other groups at all times of measurement. Pain score were lower in patients receiving nefopam compared to placebo, on arrival in the recovery room and at 2 h. Ketamine improved knee flexion on post operative day 3 (59° [33–63] vs. 50° [47–55] and 50° [44–55] in ketamine, placebo and nefopam groups, respectively, p < 0.0002) and decreased the delay to flex the knee at 90° (9.1 ± 4.2 vs. 12.3 ± 4.0 days, in ketamine and placebo groups, respectively, p = 0.01).Ketamine produces opioid-sparing, decreases pain intensity, and improves mobilization after total knee replacement. Nefopam achieves less significant results in that circumstances.     

Absence of long‐term analgesic effect from a short‐term S‐ketamine infusion on fibromyalgia pain: A randomized,prospective, double blind,active placebo‐controlled trial

To assess the analgesic efficacy of the N‐methyl‐D‐aspartate receptor antagonist S(+)‐ketamine on fibromyalgia pain, the authors performed a randomized double blind, active placebo‐controlled trial. Twenty‐four fibromyalgia patients were randomized to receive a 30‐min intravenous infusion with S(+)‐ketamine (total dose 0.5 mg/kg, n=12) or the active placebo, midazolam (5 mg, n =12). Visual Analogue Pain Scores (VAS) and ketamine plasma samples were obtained for 2.5‐h following termination of treatment; pain scores derived from the fibromyalgia impact questionnaire (FIQ) were collected weekly during an 8‐week follow‐up. Fifteen min after termination of infusion the number of patients showing a reduction in pain scores >50% was 8 vs. 3 (P<0.05), at t=180 min 6 vs. 2 (ns), at the end of week‐1 2 vs. 0 (ns) and at end of week‐8 2 vs. 2 in the ketamine and midazolam groups, respectively. Ketamine effect on VAS closely followed ketamine plasma concentrations. For VAS and FIQ scores no significant differences in treatment effects were observed in the 2.5‐h following infusion or during the 8‐week follow‐up. Side effects as measured by the Bowdle questionnaire (which scores for 13 separate psychedelic symptoms) were mild to moderate in both study groups and declined rapidly, indicating adequate blinding of treatments. Efficacy of ketamine was limited and restricted in duration to its pharmacokinetics. The authors argue that a short‐term infusion of ketamine is insufficient to induce long‐term analgesic effects in fibromyalgia patients.     

Pregabalin for relief of neuropathic pain associated with diabetic neuropathy: A randomized,double‐blind study

Seven published, randomized, placebo‐controlled clinical trials with pregabalin have shown robust efficacy for relief of neuropathic pain from DPN and PHN. An investigation of the efficacy and safety of twice daily pregabalin enrolled 395 adults with painful DPN for ≥1 year in a 12‐week, double‐blind, placebo‐controlled trial. Patients were randomized to placebo, 150, 300, or 600mg/day pregabalin (n=96, 99, 99, and 101). Primary efficacy measure was change from baseline in endpoint mean pain score from patients’ daily pain diaries. Secondary efficacy measures included pain‐related sleep‐interference scores, Patient and Clinical Global Impressions of Change (PGIC, CGIC), and the EuroQOL Health Utilities Index (EQ‐5D). Statistically significant reduction in pain was observed in patients receiving pregabalin 600mg/day, and 46% of patients treated with 600mg/day pregabalin reported ≥50% improvement in mean pain scores from baseline (vs 30% of placebo patients, p=0.036). Number needed to treat to achieve such response was 6.3. Pregabalin 600mg/day was significantly superior to placebo in improving pain‐related sleep‐interference scores (p=0.003), PGIC (p=0.021), and CGIC (p=0.009). (Neither pregabalin 150 nor 300mg/day separated from placebo on these measures, largely because of an atypically large placebo response in one country representing 42% of patients.) All pregabalin dosages were superior to placebo in improving EQ‐5D utility scores (all p≥0.0263 vs placebo). Pregabalin was well tolerated at all dosages; adverse events were generally mild to moderate. Number needed to harm (discontinuation because of adverse events) was 10.3 for pregabalin 600mg/day.     

Lack of efficacy of alpha‐lipoic acid in burning mouth syndrome: A double‐blind,randomized, placebo‐controlled study

Background: A systematic review from the Cochrane Collaboration stated that alpha‐lipoic acid (ALA) may help in the management of burning mouth syndrome (BMS). Because all of the data on ALA came from a single group, it has been stressed that its effectiveness should be reproduced in other populations. Aim: A double‐blind, randomized, placebo‐controlled study, including two test groups (Group A and Group B) and one control group (Group C), was carried out to evaluate the efficacy of systemic ALA (400mg) and ALA (400mg) plus vitamins in the treatment of BMS. Methods: Sixty‐six patients (54 females and 12 males) were included in an 8‐week trial. Symptoms were evaluated by using a visual analogue scale (VAS) and the McGill Pain Questionnaire (MPQ) at 0, 2, 4, 8 and 16 weeks. Results: Fifty‐two patients (43 females and 9 males, aged 67.3±11.9 years) completed the study. All three groups had significant reductions in the VAS score and in the mixed affective/evaluative subscale of the MPQ; the responders’ rate (at least 50% improvement in the VAS score) was about 30%. No significant differences were observed among the groups either in the response rate or in the mean latency of the therapeutic effect. Conclusions: The fairly high placebo effect observed is very similar to data obtained from patients affected by atypical facial pain. This study failed to support a role for ALA in the treatment of BMS, and further investigations are needed to identify the cause of BMS in order to develop efficacious therapies.     

PRODIGE: a randomized placebo‐controlled trial of dalteparin low‐molecular‐weight heparin thromboprophylaxis in patients with newly diagnosed malignant glioma

Summary. Background and objectives: Venous thromboembolism (VTE) occurs in 20–30% of patients with malignant glioma per year of survival. We tested the efficacy of long‐term dalteparin low‐molecular‐weight heparin (LMWH) for prevention of VTE in these patients. Patients/methods: Adults with newly diagnosed malignant glioma were randomized to receive dalteparin 5000 anti‐Xa units or placebo, both subcutaneously once daily for 6 months starting within 4 weeks of surgery. Treatment continued for up to 12 months. The primary outcome was the cumulative risk of VTE over 6 months. The target sample size was 512 patients. Events were adjudicated by a committee unaware of treatment. Results: The trial began in 2002 and closed in May 2006 because of expiration of study medication. Ninety‐nine patients were randomized to LMWH and 87 to placebo. Twenty‐two patients developed VTE in the first 6 months: nine in the LMWH group and 13 in the placebo group [hazard ratio (HR) = 0.51, 95% confidence interval (CI): 0.19–1.4, P = 0.29]. At 6 months, there were three major bleeds on LMWH and none on placebo; at 12 months, 5 (5.1%) major bleeds on LMWH and 1 (1.2%) on placebo occurred (HR = 4.2, 95% CI: 0.48–36, P = 0.22). All major bleeds were intracranial and occurred while on study medication. The 12‐month mortality rates were 47.8% for LMWH and 45.4% for placebo (HR = 1.2, 95% CI: 0.73–2.0, P = 0.48). Conclusions: Trends suggesting reduced VTE and increased intracranial bleeding were seen in the LMWH thromboprophylaxis group. The role of long‐term anticoagulant thromboprophylaxis in patients with brain tumors remains uncertain.     

Back massage intervention for relieving lower back pain in puerperal women: A randomized control trial study

This study evaluates the effectiveness of a back massage (BM) intervention in relieving lower back pain (LBP) in post‐partum women.This is a randomized controlled trial study. Sixty normal spontaneous delivery women (response rate: 96.7%), who gave birth at our hospital, participated in this study from February to May of 2012. We randomly assigned 30 women to the experimental group and 30 women to the control group. During the 1 month post‐partum period, the women in the experimental group received a BM for 5 consecutive days, whereas the women in the control group received routine care only. The LBP score was assessed according to a pain visual analog scale. After 5 days of intervention, the experimental group (n = 30) experienced significantly less LBP than did the control group (n = 30) (2.97 ± 1.71 vs. 4.43 ± 1.77, t = 3.26, P = 0.002). BM therapy can effectively reduce LBP during the first post‐partum month. Additional studies are required to confirm the effects of BM therapy during extended post‐partum periods.     

Efficacy of pulsed electromagnetic therapy for chronic lower back pain: a randomized, double-blind, placebo-controlled study

This randomized, double-blind, placebo-controlled clinical trial studied the effectiveness of pulsed electromagnetic therapy (PEMT) in patients with chronic lower back pain. Active PEMT (n = 17) or placebo treatment (n = 19) was performed three times a week for 3 weeks. Patients were assessed using a numerical rating scale (NRS) and revised Oswestry disability scores for 4 weeks after therapy. PEMT produced significant pain reduction throughout the observation period compared with baseline values. The percentage change in the NRS score from baseline was significantly greater in the PEMT group than the placebo group at all three time-points measured. The mean revised Oswestry disability percentage after 4 weeks was significantly improved from the baseline value in the PEMT group, whereas there were no significant differences in the placebo group. In conclusion, PEMT reduced pain and disability and appears to be a potentially useful therapeutic tool for the conservative management of chronic lower back pain.