Capsaicin 8% Patch in Painful Diabetic Peripheral Neuropathy: A Randomized,Double-Blind,Placebo-Controlled Study

This 12-week study evaluated the efficacy and safety of capsaicin 8% patch versus placebo patch in painful diabetic peripheral neuropathy (PDPN). Patients aged 18 years or older with PDPN were randomized (1:1) to one 30-minute treatment (capsaicin 8% patch or placebo patch) to painful areas of the feet. Overall, 369 patients were randomized (capsaicin 8% patch, n = 186; placebo patch, n = 183). Percentage reduction in average daily pain score from baseline to between weeks 2 through 8 (the primary end point) was statistically significant for capsaicin 8% patch versus placebo (?27.4% vs ?20.9%; P = .025); improvements in pain were observed from week 2 onward. Versus placebo, patients treated with capsaicin 8% patch had a shorter median time to treatment response (19 vs 72 days) and modest improvements in sleep interference scores from baseline to between weeks 2 through 8 (P = .030) and weeks 2 through 12 (P = .020). Apart from application site reactions, treatment-emergent adverse events were similar between groups. No indications of deterioration in sensory perception of sharp, cold, warm, or vibration stimuli were observed. In patients with PDPN, capsaicin 8% patch treatment provided modest pain relief and sleep quality improvements versus a placebo patch, similar in magnitude to other treatments with known efficacy, but without systemic side effects or sensory deterioration.

Levetiracetam in the treatment of neuropathic pain: three case studies

CASE REPORTS: A 55-year-old woman presented with numbness and pain in both lower extremities. The pain was of sudden onset and of 4 months' duration. A nerve conduction study demonstrated a bilateral sensorimotor peripheral neuropathy with axonal and demyelinating features of a mild degree. Initial treatment with oral thiamine and topiramate had little efficacy and caused unacceptable side effects. A switch to 1500 mg bid levetiracetam plus nortriptyline resulted in a 60% improvement in pain symptoms. A 75-year-old man presented with numbness in both feet of 5 years' duration. The sensation of numbness had progressed to persistent pain, resulting in sleep disruption. The patient's use of oral thiamine did not lead to pain relief, but the addition of 500 mg levetiracetam once in the evening led to a complete resolution of his pain and to sleep improvement. A 67-year-old obese male was referred from a podiatrist with progressive dysfunction in both lower extremities that developed over a 1-year period. Walking more than a few steps resulted in sharp, shooting pain that at night disrupted sleep. A nerve conduction study demonstrated a severe bilateral sensorimotor peripheral neuropathy with axonal and demyelinating features. Treatment with 1000 mg levetiracetam bid resulted in complete absence of pain. CONCLUSIONS: In these 3 case studies, levetiracetam was demonstrated to be an effective therapy in the treatment of neuropathic pain. It has the benefits of a low incidence of adverse events and an improvement in patients' sleep.     

Efficacy of desipramine in painful diabetic neuropathy: a placebo-controlled trial

Although amitriptyline relieves pain in many patients with painful diabetic neuropathy, side effects often preclude effective treatment. Desipramine has the least anticholinergic and sedative effects of the first generation tricyclic antidepressants. We compared a 6 week course of desipramine (mean dose, 201 mg/day) to active placebo in 20 patients with painful diabetic neuropathy in a double-blind crossover trial. Pain relief with desipramine was statistically significant in weeks 5 and 6. Eleven patients reported at least moderate relief with desipramine, compared to 2 with placebo. Pain relief tended to be greater in depressed patients, but relief was also observed in patients who did not show an antidepressant effect. We conclude that desipramine relieves pain in many patients with painful diabetic neuropathy, offering an alternative for patients unable to tolerate amitriptyline. Blockade of norepinephrine reuptake, an action shared by desipramine, amitriptyline, and other antidepressants proven effective in neuropathic pain, may mediate this analgesic effect.     

Relief of painful diabetic peripheral neuropathy with pregabalin: a randomized, placebo-controlled trial.

This was a 6-week, randomized, double-blind, multicenter study evaluating the efficacy of pregabalin in the treatment of painful diabetic neuropathy. Two hundred forty-six men and women with painful diabetic neuropathy received pregabalin (150 or 600 mg/day by mouth) or placebo. The primary efficacy variable was mean pain score at the end of treatment. Efficacy results indicate that pregabalin 600 mg/day significantly decreased mean pain score to 4.3 (vs 5.6 for placebo, P = .0002) and increased the proportion of patients who had a > or =50% decrease from baseline pain (39% vs 15% for placebo, P = .002). Pregabalin also significantly reduced sleep interference, past week and present pain intensity, sensory and affective pain scores, and bodily pain and decreased by > or =50% the number of patients describing their pain as gnawing, sickening, fearful, and punishing-cruel. More patients receiving pregabalin 600 mg/day than placebo showed improvement, as rated on the Clinical and Patient Global Impression of Change scales, 73% vs 45% and 85% vs 47%, respectively. Pregabalin 150 mg/day was essentially no different from placebo. Dizziness was the most common side effect. These study results show pregabalin 600 mg/day to be safe and effective in reducing the pain and other associated symptoms of painful diabetic neuropathy. PERSPECTIVE: Painful diabetic peripheral neuropathy is a challenging neuropathic pain syndrome. This randomized controlled trial demonstrates that pregabalin, a new drug that interacts with the alpha2-delta protein subunit of the voltage-gated calcium channel, is an efficacious and safe treatment for the pain of this condition.     

Morphine, nortriptyline and their combination vs. placebo in patients with chronic lumbar root pain

Although lumbar radicular pain is the most common chronic neuropathic pain syndrome, there have been few randomized studies of drug treatments. We compared the efficacy of morphine (15-90 mg), nortriptyline (25-100 mg), their combination, and a benztropine "active placebo" (0.25-1 mg) in patients with chronic sciatica. Each period consisted of 5 weeks of dose escalation, 2 weeks of maintenance at the highest tolerated doses, and 2 weeks of dose tapering. The primary outcome was the mean daily leg pain score on a 0-10 scale during the maintenance period. Secondary outcomes included a 6-point ordinal global pain relief scale, the Beck Depression Inventory (BDI), the Oswestry Back Pain Disability Index (ODI) and the SF-36. In the 28 out of 61 patients who completed the study, none of the treatments produced significant reductions in average leg pain or other leg or back pain scores. Pain reduction, relative to placebo treatment was, 14% for nortriptyline (95% CI=[-2%, 30%]), 7% for morphine (95% CI=[-8%, 22%]), and 7% for the combination treatment (95% CI=[-4%, 18%]). Mean doses were: nortriptyline alone, 84+/-24.44 (SD) mg/day; morphine alone, 62+/-29 mg/day; and combination, morphine, 49+/-27 mg/day plus nortriptyline, 55 mg+/-33.18 mg/day. Over half of the study completers reported some adverse effect with morphine, nortriptyline or their combination. Within the limitations of the modest sample size and high dropout rate, these results suggest that nortriptyline, morphine and their combination may have limited effectiveness in the treatment of chronic sciatica.     

A randomized, double-blind, crossover study of the use of transcutaneous spinal electroanalgesia in patients with pain from chronic critical limb ischemia

Transcutaneous spinal electroanalgesia (TSE) uses two electrodes placed over the skin of the dorsal spine to deliver pulses of short wavelength, high frequency, and relatively high voltage to the spinal cord without causing paresthesia. TSE has been used to treat pain and may improve limb blood flow. This randomized, double-blind, crossover study assessed the effect of TSE on microcirculation, pain, and activity in 8 patients (3 men, 5 women, median age 66.5 years, range 62-76 years) with chronic critical limb ischemia (CLI). After a one-week baseline period, patients used an active or inactive TSE machine for one hour daily for one week. Following a week of no stimulation, patients repeated the week of treatment with an identical matched machine. Daily use of TSE for one week did not improve microcirculatory perfusion (transcutaneous oxygenation), pain (verbal rating scale, McGill Pain Questionnaire), physical function (Functional Limitations Profile), mood (Beck Depression Inventory, Beck Anxiety Inventory), or sleep. There was no patient preference for the active TSE machines. This study showed that TSE administered daily for one week did not improve microcirculation, pain, or activity in patients with chronic CLI.     

前列腺素联合甲钴胺治疗糖尿病周围神经病变的临床疗效

目的观察前列腺素E1联合甲钴胺治疗糖尿病周围神经病变的临床疗效及其安全性。方法 96例糖尿病周围神经病变患者分为治疗组(n=55)及对照组(n=41),两组均给予胰岛素控制血糖,控制血压等基础治疗,治疗组同时给予前列腺E110μg/d静脉滴注及甲钴胺500μg/d肌肉注射治疗共4周,4周后改为甲钴胺500μg,3次/d口服继续治疗8周,于治疗前及治疗后分别测定双下肢运动神经传导速度、感觉神经传导速度及临床症状变化。结果治疗后患者周围神经病变如麻木、疼痛、感觉异常均有明显改善,神经传导速度有不同程度的提高,未出现明显不良反应。结论前列腺素E1及甲钴胺的联合应用对于糖尿病周围神经病变的疗效确切,临床治疗安全、可靠。     

Lack of effect of clonidine and pentoxifylline in short-term therapy of diabetic peripheral neuropathy

The goal of this study was to confirm or rule out anecdotal reports of beneficial effects of clonidine and pentoxifylline in the treatment of painful diabetic peripheral neuropathy. Clonidine was administered to 16 subjects at two dosage levels (0.1 and 0.2 mg/day) and was compared to placebo in a crossover design, with each phase lasting 4 wk. Either pentoxifylline (400 mg 3 times/day) or placebo was given to 21 subjects in a 12-wk trial. Discomfort was characterized and rated with a subjective pain score (range 0-20). There was a significant decrease in pain score from baseline with both active drugs (P less than 0.05), but this was no better than the response to placebo (P less than 0.30 for clonidine and P less than 0.95 for pentoxifylline). This study does not demonstrate a short-term benefit of either clonidine or pentoxifylline in the treatment of peripheral neuropathy.     

Randomized, placebo-controlled, parallel group versus crossover study designs for the study of dementia in Parkinson's disease

In studies of dementia, crossover designs are controversial, reflecting concerns about temporal stability of disease, confounding of treatment effects with period by treatment interactions and/or carryover effects. Carryover effects are differences in the lingering effect of treatments (placebo) into subsequent periods. In the context of a trial to study the effect of donepezil on dementia in patients with Parkinson's disease, we examine two-sequence crossover studies with two or four periods, and a four-sequence design with two periods. We quantify bias in estimated treatment effects due to carryover effects and explore the use of biased estimators in hypothesis testing. For hypothesis testing, type I error rates are valid if (1) repeated administration of treatment alters the outcome only for effective treatments and (2) carryover effects due to placebo following treatment periods are nonzero only for effective treatments. For crossover and parallel group designs, sample sizes are adjusted for reduced statistical power due to carryover effects and temporal changes in variance. For the proposed clinical study, we estimate that a single-period parallel group design with baselines would require 104 patients and take about 23 months to complete. A two-sequence, four-period parallel group design with baselines would require about 80 patients and about 20 months to complete. We conservatively assume a carryover effect of 50% of the treatment effect for a two-sequence four-period crossover design. The estimated treatment effect for this model may underestimate the true treatment effect by up to 13%. The sample size/study length requirements are 28 patients or 12.4 months, respectively, a substantial saving over either parallel group design. The cost of allowing for carryover in the sample size calculation is about 1.2 months of study time.     

万珂引起周围神经病变患者的安全管理

目的 使用前客观的评估有无周围神经病变。其次,建议监测MM患者神经病变的症状,如烧灼感、感觉过敏、感觉减退、感觉异常、不适感或神经疼痛,如患者出现症状加重,本品的剂量和治疗方案则需要进行调整。从而安全有效的使用万珂。方法 本品的推荐剂量为单次注射1.3mg/m2,每周注射两次。连续注射两周(即在第1,4,8和11天注射)后停药10天(即从第12至21天)3周为一个疗程,两次给药至少间隔72小时。对于超过8个疗程的维持治疗,可按标准方案给药,也可以按每周1次、连续给药4周的维持方案(第1、8、15和22天),随后是13天的休息期(第23至35天)。结论：增加用药前的评估和用药中的监测,可减少周围神经病变的发生率,提高疗效,增强患者的信心和生活质量,安全有效的控制周围神经病变的发生。     

Effect of acupuncture administered in a group setting on pain and subjective peripheral neuropathy in persons with human immunodeficiency virus disease

OBJECTIVES: The present study was performed to determine the effect of 5 weeks of acupuncture treatment in a group setting on pain and symptoms of peripheral neuropathy in human immunodeficiency virus (HIV)infected individuals. DESIGN: Twenty-one (21) subjects completed the study that consisted of a pretreatment and post-treatment case series design. The subjects completed the Pain Rating Scale and the Subjective Peripheral Neuropathy Screen (SPNS) before and after 5 weeks of acupuncture. The acupuncture treatments occurred two evenings per week. Each of the 10 sessions consisted of participants receiving 10-15 needle insertions in acupoints that addressed the individual's changing pattern of pain, sleep problems, or other health issues. The treatment utilized only main or common points located below the elbows and knees, and on the head, neck, and ears. Only reactive points were used in the acupuncture treatments. Needles were left in situ for 30-45 minutes. RESULTS: Comparison of the pretreatment and post-treatment Pain Rating Scale results indicated a significant reduction in present pain (p = 0.0002), least and most pain in the last 24 hours (p < 0.0001 and p = 0.0004, respectively) and the total pain summary score (p < 0.0001). Symptoms reported in the SPNS were reduced during the 5 weeks of acupuncture. Scores for pain/aching/burning, pins and needles, and numbness in the hands and feet were reduced (all significant at less than p = 0.0065), as well as the total summary score (p = 0.0001). CONCLUSION: The results of this study indicate that subjective pain and symptoms of peripheral neuropathy were reduced during the period of individual acupuncture therapy delivered in a group setting. While the study design did not allow for control of nonspecific placebo factors, the data support the hypothesis that acupuncture in a group setting can reduce pain and neuropathic symptoms in HIV-infected individuals.     

Lacosamide in painful diabetic peripheral neuropathy: a phase 2 double-blind placebo-controlled study

BACKGROUND: Peripheral diabetic neuropathy affects between 20% and 45% of patients with diabetes. OBJECTIVE: To ascertain the effect of lacosamide on pain associated with peripheral diabetic neuropathy. METHODS: One hundred nineteen patients with a 1 to 5-year history of pain attributed to diabetic neuropathy and a score of > or =4 on the Likert pain scale entered the multicenter, randomized, double-blind, placebo-controlled trial. Lacosamide (N=60) titrated from 100 to 400 mg/d or maximum tolerated dose and placebo (N=59) were the trial interventions. Primary efficacy criterion was change in pain score on the 11-point Likert pain scale. Secondary assessments included Short-Form McGill Pain and Short-Form-36 Quality of Life Questionnaires, sleep/activity interference, pain intensity, Patient and Clinical Global Impression of Change, and Profile of Mood. Patients receiving at least 1 dose of medication underwent safety evaluation. RESULTS: Ninety-four patients (lacosamide 46; placebo 48) completed the trial. Lacosamide had significantly (P=0.039) better pain relief versus placebo (primary outcome). Improvements were also seen in secondary outcome measures. Adverse events occurred in 52 lacosamide and 44 placebo patients. Common adverse events, occurring in > or =5% of patients, were headache (lacosamide 18%, placebo 22%), dizziness (lacosamide 15%, placebo 8%), and nausea (lacosamide 12%, placebo 7%). Five lacosamide and 3 placebo patients withdrew for adverse events. DISCUSSION: Lacosamide seems to attenuate pain in diabetic neuropathy in doses up to 400 mg/d and improves quality of life issues.     

Percutaneous electrical nerve stimulation: a novel analgesic therapy for diabetic neuropathic pain

OBJECTIVE: To evaluate the use of percutaneous electrical nerve stimulation (PENS) in the management of patients with painful diabetic peripheral neuropathy. RESEARCH DESIGN AND METHODS: A total of 50 adult patients with type 2 diabetes and peripheral neuropathic pain of >6 months duration involving the lower extremities were randomly assigned to receive active PENS (needles with electrical stimulation at an alternating frequency of 15 and 30 Hz) and sham (needles only) treatments for 3 weeks. Each series of treatments was administered for 30 min three times a week according to a standardized protocol. After a 1-week washout period, all patients were subsequently switched to the other modality. A 10-cm visual analog scale (VAS) was used to assess pain, physical activity, and quality of sleep before each session. The changes in VAS scores and daily requirements for oral analgesic medication were determined during each 3-week treatment period. Patients completed the MOS 36-Item Short-Form Health Survey (SF-36), the Beck Depression Inventory (BDI), and the Profile of Mood States (POMS) before and after completion of each treatment modality. At the end of the crossover study, a patient preference questionnaire was used to compare the effectiveness of the two modalities. RESULTS: Compared with the pain VAS scores before active (6.2 +/- 1.0) and sham (6.4 +/- 0.9) treatments, pain scores after treatment were reduced to 2.5 +/- 0.8 and 6.3 +/- 1.1, respectively. With active PENS treatment, the VAS activity and sleep scores were significantly improved from 5.2 +/- 1.0 and 5.8 +/- 1.3 to 7.9 +/- 1.0 and 8.3 +/- 0.7, respectively. The VAS scores for pain, activity, and sleep were unchanged from baseline values after the sham treatments. Patients' daily oral nonopioid analgesic requirements decreased by 49 and 14% after active and sham PENS treatments, respectively. The post-treatment physical and mental components of the SF-36, the BDI, and the POMS all showed a significantly greater improvement with active versus sham treatments. Active PENS treatment improved the neuropathic pain symptoms in all patients. CONCLUSIONS: PENS is a useful nonpharmacological therapeutic modality for treating diabetic neuropathic pain. In addition to decreasing extremity pain, PENS therapy improved physical activity, sense of well-being, and quality of sleep while reducing the need for oral nonopioid analgesic medication.     

Gabapentin in traumatic nerve injury pain: a randomized, double-blind, placebo-controlled, cross-over, multi-center study

A double-blind, randomized, placebo-controlled cross-over multi-center study was conducted to evaluate the efficacy and safety of gabapentin in the treatment of neuropathic pain caused by traumatic or postsurgical peripheral nerve injury, using doses up to 2400 mg/day. The study comprised a run-in period of two weeks, two treatment periods of five weeks separated by a three weeks’ washout period. The primary efficacy variable was the change in the mean pain intensity score from baseline to the last week of treatment. Other variables included pain relief, health related quality of life (SF-36), interference of sleep by pain, Clinician and Patient Global Impression of Change, and adverse effects. Nine centers randomized a total of 120 patients, 22 of whom withdrew. There was no statistically significant difference between the treatments for the primary outcome efficacy variable. However, gabapentin provided significantly better pain relief (p = 0.015) compared with placebo. More patients had at least a 30% pain reduction with gabapentin compared with placebo (p = 0.040) and pain interfered significantly less with sleep during gabapentin treatment compared with placebo (p = 0.0016). Both the Patient (p = 0.023) and Clinician (p = 0.037) Global Impression of Change indicated a better response with gabapentin compared with placebo. Gabapentin was well tolerated. The most common adverse effects were dizziness and tiredness.     

Double-blind, randomized crossover study of the percutaneous efficacy and tolerability of a topical indomethacin spray versus placebo in the treatment of tendinitis

Percutaneous efficacy and tolerability of a new topical indomethacin spray compared with a corresponding placebo product were evaluated in a double-blind, randomized crossover study in 30 patients with tendinitis, i.e. 28 patients with peri-arthritis of the shoulder and two with epicondylitis. Each patient was treated with 4% indomethacin spray or the corresponding placebo product three to five times daily for a period of 14 days and then received the other treatment for the same period of time. The indomethacin spray demonstrated a clear efficacy compared with the placebo based on both objective criteria (elevation, abduction and internal rotation) and subjective criteria (spontaneous pain, pain on movement, pressure-induced pain, functional disturbances and sleep disturbances). Tolerability was excellent: only two patients had minor local cutaneous irritation with the indomethacin spray, which did not require interruption of treatment. Treatment with indomethacin spray appeared to be effective in 80% and well-tolerated in 93% of the patients studied.     

Clinical efficacy of fidarestat, a novel aldose reductase inhibitor, for diabetic peripheral neuropathy: a 52-week multicenter placebo-controlled double-blind parallel group study

OBJECTIVE: The purpose of this study was to evaluate the efficacy of fidarestat, a novel aldose reductase (AR) inhibitor, in a double-blind placebo controlled study in patients with type 1 and type 2 diabetes and associated peripheral neuropathy. RESEARCH DESIGN AND METHODS: A total of 279 patients with diabetic neuropathy were treated with placebo or fidarestat at a daily dose of 1 mg for 52 weeks. The efficacy evaluation was based on change in electrophysiological measurements of median and tibial motor nerve conduction velocity, F-wave minimum latency, F-wave conduction velocity (FCV), and median sensory nerve conduction velocity (forearm and distal), as well as an assessment of subjective symptoms. RESULTS: Over the course of the study, five of the eight electrophysiological measures assessed showed significant improvement from baseline in the fidarestat-treated group, whereas no measure showed significant deterioration. In contrast, in the placebo group, no electrophysiological measure was improved, and one measure significantly deteriorated (i.e., median nerve FCV). At the study conclusion, the fidarestat-treated group was significantly improved compared with the placebo group in two electrophysiological measures (i.e., median nerve FCV and minimal latency). Subjective symptoms (including numbness, spontaneous pain, sensation of rigidity, paresthesia in the sole upon walking, heaviness in the foot, and hypesthesia) benefited from fidarestat treatment, and all were significantly improved in the treated versus placebo group at the study conclusion. At the dose used, fidarestat was well tolerated, with an adverse event profile that did not significantly differ from that seen in the placebo group. CONCLUSIONS: The effects of fidarestat-treatment on nerve conduction and the subjective symptoms of diabetic neuropathy provide evidence that this treatment alters the progression of diabetic neuropathy.     

一例糖尿病外周神经病变患者的循证治疗

目的针对一例糖尿病外周神经病变患者,检索当前最佳证据,为患者选择药物治疗方案提供依据,减轻患者症状,提高生活质量。方法根据循证临床实践的方法,提出问题,检索证据,对所获证据进行评价,并结合患者意愿制定治疗方案。结果共纳入15个随机对照试验,14个系统评价／Meta分析和1个临床指南。证据结果表明：①稳定而良好的血糖控制是治疗糖尿病神经病变的基础;②不推荐醛糖还原酶抑制剂、神经生长因子用于治疗糖尿病神经病变;③α-硫辛酸能改善糖尿病神经病变患者症状;④三环类抗抑郁药,抗惊厥药,5-羟色胺和去甲肾上腺素摄取抑制剂可减轻糖尿病神经病变患者疼痛;⑤B族维生素与复方辣椒碱乳膏可用于治疗糖尿病神经病变。结合患者情况,应用证据治疗3月后,患者血糖水平保持正常,症状缓解。结论采用循证治疗的方法,为糖尿病外周神经病变患者制定合理的治疗方案,可有效提高治疗效果。     

Efficacy of pregabalin in neuropathic pain evaluated in a 12-week, randomised, double-blind, multicentre, placebo-controlled trial of flexible- and fixed-dose regimens

Pregabalin binds with high affinity to the alpha2-delta subunit protein of voltage-gated calcium channels and, thereby, reduces release of excitatory neurotransmitters. This 12-week randomised, double-blind, multicentre, placebo-controlled, parallel-group study evaluated the efficacy and safety of pregabalin in patients with chronic postherpetic neuralgia (PHN) or painful diabetic peripheral neuropathy (DPN). Patients were randomised to placebo (n=65) or to one of two pregabalin regimens: a flexible schedule of 150, 300, 450, and 600 mg/day with weekly dose escalation based on patients' individual responses and tolerability (n=141) or a fixed schedule of 300 mg/day for 1 week followed by 600 mg/day for 11 weeks (n=132). Both flexible- and fixed-dose pregabalin significantly reduced endpoint mean pain score (primary outcome) versus placebo (P=0.002, P<0.001) and were significantly superior to placebo in improving pain-related sleep interference (P<0.001). The most common adverse events (AEs) for pregabalin-treated patients were dizziness, peripheral oedema, weight gain (not affecting diabetes control), and somnolence. These results are consistent with previous studies' demonstrating pregabalin's efficacy, tolerability, and safety for treatment of chronic neuropathic pain associated with DPN or PHN. Pregabalin dosing aimed at optimal balance of efficacy and tolerability provides significant pain relief and may reduce risks for AEs and therapy discontinuation.     

Safety and effectiveness of topiramate for the management of painful diabetic peripheral neuropathy in an open-label extension study

OBJECTIVE: The aim of this study was to further assess the long-term safety and effectiveness of open-label topiramate therapy in subjects with moderately to severely painful diabetic peripheral neuropathy (DPN). METHODS: Adults aged 18 to 75 years received open-label topiramate (25-600 mg/d for 26 weeks) in an extension of a previously published randomized, double-blind trial comparing topiramate with placebo. Safety analyses included adverse event (AE) reports and clinical laboratory tests. Metabolic end points included body weight and glycosylated hemoglobin (HbA(1c)). Effectiveness analyses included a 100-mm pain visual analog (PVA) scale, worst and current pain severity, and sleep disruption. RESULTS: Two hundred five subjects participated in this open-label extension study (118 formerly treated with topiramate and 87 who formerly received placebo). The groups did not differ in baseline demographics or disease characteristics. One hundred twenty-four (60.5%) subjects (68.6% of former topiramate recipients and 49.4% of former placebo recipients) completed the extension study; the most common reason for discontinuation was an AE (27.3% of subjects). AEs among subjects who received > or =1 dose of topiramate (n = 298) included upper respiratory tract infection (16.1%), anorexia (15.1%), diarrhea (12.8%), nausea (12.8%), paresthesia (10.7%), and headache (10.1%). Baseline pain scores were lower in those formerly treated with topiramate (n = 117) than in the former placebo group (n = 86) (PVA: 43.3 vs 52.5, P = 0.014; worst pain: 1.9 vs 2.5, P < 0.001; current pain: 1.6 vs 1.9, P = 0.026; sleep disruption: 3.6 vs 4.6, P = 0.021). At the final visit, PVA, current pain, and sleep disruption scores were not significantly different between the former topiramate and former placebo groups, but worst pain differed significantly (1.4 vs 1.8; P = 0.025). Mean weight loss from the start of topiramate therapy was 5.2 and 5.3 kg in the former topiramate and former placebo groups, respectively (P < 0.001 vs baseline). Mean HbA(1c) values before and after topiramate treatment were 7.7% and 7.4%, respectively, in the former topiramate group (P = 0.004 vs baseline), and 7.6% and 7.1%, respectively, in the former placebo group (P < 0.001 vs baseline). CONCLUSION: Although 39.5% of subjects discontinued, most often due to AEs, the results of this 26-week, open-label extension study with topiramate (up to 600 mg/d) in subjects with moderately to severely painful DPN suggest that pain relief was effective and durable.     

Efficacy and safety of tanezumab versus naproxen in the treatment of chronic low back pain

Tanezumab is a humanized monoclonal antibody that specifically inhibits nerve growth factor as a treatment for chronic pain. This phase IIB study investigated the efficacy and safety of tanezumab for chronic low back pain vs placebo and naproxen. Patients (N = 1347) received intravenous tanezumab (5, 10, or 20 mg every 8 weeks), naproxen (500 mg twice daily), or placebo. The primary efficacy end point was mean change in daily average low back pain intensity (LBPI) from baseline to week 16. Secondary end points included mean change from baseline to week 16 in the Roland Morris Disability Questionnaire and Patient’s Global Assessment (PGA) of low back pain. Tanezumab 10 and 20 mg had similar efficacy profiles and significantly improved LBPI, Roland Morris Disability Questionnaire, and PGA scores vs both placebo and naproxen (P ? .05). Tanezumab 5 mg provided improvement of PGA scores vs placebo (P ? .05), and naproxen resulted in significant improvement of LBPI vs placebo (P ? .05). Adverse event incidence was comparable across tanezumab doses but higher than with placebo or naproxen. Arthralgia, pain in extremity, headache, and paresthesia were the most commonly reported adverse events by tanezumab-treated patients. The most frequently reported adverse events resulting in discontinuation of tanezumab treatment were arthralgia and paresthesia; the highest frequency was observed with tanezumab 20 mg (both 1.4%). Serious adverse event incidence was similar across treatments. In conclusion, tanezumab provided significantly greater improvement in pain, function, and global scores vs placebo and naproxen in patients with chronic low back pain.