Cost-effectiveness analysis of pregabalin versus gabapentin in the management of neuropathic pain due to diabetic polyneuropathy or post-herpetic neuralgia

ABSTRACT

Objective: To estimate the cost-effectiveness of branded pregabalin (PGB) versus generic gabapentin (GBP) in patients with neuropathic pain (NeP) due to painful diabetic polyneuropathy (DPN) or post-herpetic neuralgia (PHN) in Spain.

Methods: Using stochastic simulation, we estimated the cost-effectiveness of PGB 150–600?mg/d vs. GBP 900–3600?mg/d in a hypothetical cohort of 1000 patients. The model used data from three randomized controlled clinical trials. Pain was evaluated using a 0–10 scale. Mean baseline pain was 6.9 in both treatment groups. The model assigned untreated pain scores over 84 days. Treated scores were calculated using weekly changes in pain scores from trials. Outcomes included the numbers of days with no or mild pain (score < 4), days with ≥ 30% and ≥ 50% reductions in pain intensity, quality-adjusted life-years (QALYs), and estimated health costs.

Results: Compared with GBP, PGB yielded an estimated mean of 8 (standard error, 0.4) additional days with no or mild pain, 6 (0.4) days with ≥ 30% reduction in pain intensity, 9 (0.5) days with ≥ 50% reduction in pain intensity, and a gain of 0.1186 (0.0002) QALYs for 12 weeks. The estimated total health costs of therapies were €1049 (€35) for PGB and €951 (€38) for GBP, respectively. Incremental cost-effectiveness ratio (ICER) for PGB versus GBP were a mean of €12 (95% confidence interval, €1–24) per additional day with no or mild pain, €431 (dominant–€876) per additional patient with no or mild pain, and €20?535 (€1607–40?345) per QALY gained.

Conclusions: According with data used in this modeling in patients with NeP due to DPN and/or PHN, PGB was shown to be more cost-effective than generic gabapentin in Spain.     

Anxiety-like behaviour is attenuated by gabapentin, morphine and diazepam in a rodent model of HIV anti-retroviral-associated neuropathic pain

Neuropathic pain is commonly associated with affective disorders such as anxiety and depression. We have previously characterised a rodent model of HIV, anti-retroviral-associated neuropathy in which rats develop hypersensitivity to a punctate mechanical stimulus and display anxiety-like behaviour in the open field paradigm. To assess the potential of this behavioural paradigm for the assessment of pain related co-morbidities in rodent models of pain, here we test the sensitivity of this anxiety-like behaviour to the analgesic agents gabapentin and morphine in comparison to the known anxiolytic drug diazepam. We found that gabapentin (30 mg/kg, i.p.) and morphine (2.5 mg/kg, i.p.), which reduce mechanical hypersensitivity in these rats, significantly reduces measures of thigmotaxis in the open field. The effect of gabapentin and morphine did not differ significantly from diazepam (1 mg/kg, i.p.). This study highlights the potential use of this rodent model and behavioural paradigm in the validation of the affective component of novel analgesic pharmacological targets and elucidation of underlying pathophysiological mechanisms.     

Partial medial meniscectomy produces osteoarthritis pain-related behaviour in female C57BL/6 mice

Murine models of osteoarthritis (OA) provide a potentially powerful tool to elucidate mechanisms responsible for OA pain. However, few studies have examined pain behaviours in relevant OA models in mice. We have therefore characterized the time course and pharmacological sensitivities of pain-related behaviours in a model of OA in C57Bl/6 mice induced by partial medial meniscectomy. Progressive degenerative joint damage developed in a time-dependent manner and was first detected 4 weeks after surgery. Pain was assessed by monitoring weight bearing, mechanical hyperalgesia, cold allodynia, mechanical allodynia and vocalisation in response to knee compression for 12 weeks postsurgery. No significant weight-bearing deficits were observed during the course of the study. Significant mechanical allodynia was present in the ipsilateral hind limb from 9 weeks after surgery. Hind limb mechanical hyperalgesia and cold allodynia, and increased vocalisation in response to knee compression developed in the ipsilateral limb in 2 phases. An early phase of hypersensitivities lasted for up to 3 weeks and was reversed by treatment with a nonsteroidal anti-inflammatory drug (NSAID), diclofenac. Pain then resolved for several weeks, followed by a second phase of NSAID-insensitive pain after 7 weeks postsurgery. During this phase, all pain behaviours could be reversed by morphine. In contrast, other analgesic drugs (paracetamol, gabapentin, and tramadol) had selective effects on only 1 or 2 modalities. Pain levels fluctuated during the second phase, with transient periods of reduced pain. At these times, underlying hypersensitivities could be unmasked by administration of naloxone, indicating that reduced pain was due to endogenous opioids.     

加巴喷丁在老年人带状疱疹后三叉神经痛中的应用

目的探讨加巴喷丁应用于老年带状疱疹后三叉神经痛治疗的临床疗效。方法将2009年1月,2010年5月收治的60例老年带状疱疹后三叉神经痛患者,随机分为对照组和治疗组各30例,对照组口服卡马西平、维生素肌肉注射、神经阻滞治疗。治疗组在对照组治疗的基础上口服加巴喷丁,比较两组患者的临床疗效及不良反应。结果治疗组30例中治愈17例,显效12例,总有效率为96．7％（29／30）,显著高于对照组的86．7％（26／30）（P〈0．05）。两组患者均未发生严重不良反应。结论口服加巴喷丁治疗带状疱疹后神经痛效果确切,见效快,能明显缓解患者症状,副反应小,值得临床推广。     

加巴喷丁与普瑞巴林治疗带状疱疹后神经痛的效果比较

目的观察加巴喷丁和普瑞巴林治疗带状疱疹后神经痛(post-herpetic neuralgia,PHN)的效果以及对患者睡眠的影响。方法 60例PHN患者按随机数字表法分为加巴喷丁组和普瑞巴林组各30例,分别给予加巴喷丁900 mg/d口服和普瑞巴林150 mg/d口服,疗程均为28天。观察治疗前后疼痛和睡眠的改善情况及药物不良反应。结果两组患者治疗后各时点与治疗前相比疼痛评分随时间下降,睡眠时间增加(P<0.05);普瑞巴林组治疗后各时点的疼痛视觉模拟评分(Visualanalogue scale,VAS)低于加巴喷丁组(P<0.05),24小时睡眠时间大于加巴喷丁组(P<0.05);两组未出现严重的药物不良反应,普瑞巴林组嗜睡发生率明显低于加巴喷丁组(P<0.05),其余不良反应发生率两组间比较差异均无统计学意义(P>0.05)。结论普瑞巴林治疗PHN更安全有效,优于加巴喷丁。     

加巴喷丁治疗不宁腿综合征的系统评价

目的系统评价加巴喷丁治疗不宁腿综合征的临床疗效和安全性。方法计算机检索PubMed、EBMbase、CENTRAL及CBM等数据库,全面收集加巴喷丁治疗不宁腿综合征的随机对照试验(RCT)。按Cochrane系统评价方法对纳入研究进行资料提取和质量评价后,采用RevMan5.1软件进行Meta分析。结果共纳入7个RCT,1 163例患者,包括4个安慰剂平行对照试验和3个安慰剂交叉试验。Meta分析结果显示:①不宁腿综合征改变量(IRLSSG评分),加巴喷丁组明显优于安慰剂组[MD=–3.24,95%CI(–4.40,–2.09),P<0.000 01];②反应率(用研究者评价的CGI-I评分),加巴喷丁组(77%)较安慰剂组(50%)有更高的反应率[RR=1.81,95%CI(1.54,2.11),P<0.000 01];③睡眠质量:加巴喷丁组较安慰剂组能更好地减少睡眠紊乱[MD=–11.31,95%CI(–14.46,–8.16)]、保证睡眠质量[MD=0.27,95%CI(0.10,0.44)]和减轻日间嗜睡[MD=–3.96,95%CI(–6.42,–1.50)];④不宁腿综合征疼痛评分,加巴喷丁组较安慰剂组更好地减轻疼痛[MD=–0.97,95%CI(–1.47,–0.47)]。不良反应主要有嗜睡(3.1%～26.5%)、头晕(2.1%～19.5%),且加巴喷丁组发生率更高(嗜睡:P<0.000 01;头晕:P<0.000 1)。结论加巴喷丁能有效改善不宁腿综合征患者的病情,提升睡眠质量,减轻疼痛,耐受性良好。     

重复经颅磁刺激联合加巴喷丁治疗脊髓损伤后神经病理性疼痛的临床观察

目的探讨重复经颅磁刺激（rTMS）联合加巴喷丁治疗脊髓损伤（SCI）后神经病理性疼痛（NP）的临床疗效。 方法纳入苏州瑞盛康复医院神经康复科自2017年1月至2018年12月收治的60例SCI后NP患者,用随机数字表法分为观察组与对照组,每组30例。2组患者均口服加巴喷丁,观察组给予M1区10 Hz的rTMS治疗,对照组给予M1区相同模式、相同音量的声音假刺激,在治疗前和治疗后第1、2、4、6周分别采用视觉模拟评分法（VAS）对疼痛进行评定,治疗前、后采用汉密顿抑郁量表（HAMD）及焦虑量表（HAMA）分别对抑郁程度和焦虑程度评定,同时观察加巴喷丁最大用量和不良反应及TMS治疗不良事件。 结果治疗后第1周,2组患者的VAS评分较治疗前均无明显改善差异无统计学意义（P>0.05）,2组患者的VAS评分比较,比较差异无统计学意义（P>0.05）;治疗后第2、4、6周,观察组患者的VAS评分均低于对照组,第6周差异更为显著,差异具有统计学意义（P<0.05）。治疗6周后,观察组患者的HAMD评分和HAMA评分优于对照组,差异具有统计学意义（P<0.05）。 结论加巴喷丁联合rTMS治疗SCI后NP具有较好的临床疗效,能够有效控制疼痛,改善SCI患者的抑郁、焦虑情绪状态以及因疼痛导致的睡眠障碍,具有较好的安全性、可靠性。     

Difference in background factors between responders to gabapentin enacarbil treatment and responders to placebo: pooled analyses of two randomized,double-blind,placebo-controlled studies in Japanese patients with restless legs syndrome

ObjectiveRestless legs syndrome (RLS) is a sensorimotor disorder that is characterized by uncomfortable and unpleasant sensations mainly in the legs. Two placebo-controlled studies (Phase II/III and post-marketing) in Japanese patients with RLS failed to demonstrate the efficacy of gabapentin enacarbil (GE) 600 mg in the change from baseline in International Restless Legs Syndrome Rating Scale (IRLS) score at the end of the treatment period. The high response to placebo is thought to be a possible reason why the post-marketing study failed. The objectives of these post hoc analyses were to determine potential predictive factors associated with improvement in IRLS score with GE treatment and to identify subgroups with higher placebo responses.MethodsWe combined data from the two Japanese studies and analyzed change from baseline in IRLS score in the pooled population and subgroups defined by several patient characteristics. Moreover, we calculated the variable importance of each factor and performed predictive enrichment analysis to identify an enrichable subpopulation with greater improvement by GE treatment.ResultsThe post hoc analyses suggested that higher baseline IRLS score (≥21) and higher body mass index (≥25 kg/m²) were associated with higher placebo responses. On the other hand, positive family history of RLS, prior use of dopaminergic receptor agonists, and higher baseline ferritin level (≥50 ng/mL) were associated with higher responses to GE.ConclusionsOur results suggest that patients with typical idiopathic RLS characteristics, including positive family history and no low ferritin level, would be expected to derive the greatest benefits from GE treatment.     

Discriminative stimulus effects of tiagabine and related GABAergic drugs in rats

Rationale Tiagabine is an anticonvulsant drug which may also have sleep-enhancing properties. It acts by inhibiting reuptake at the gamma-aminobutyric acid (GABA) transporter (GAT-1). Objectives The aim of the study was to determine whether tiagabine acted as a discriminative stimulus and, if so, whether other GABAergic compounds would generalise to it. Materials and methods Rats were trained to discriminate tiagabine (30 mg/kg p.o.) from vehicle, and generalisation to drugs that modulate GABA was assessed. Results Gaboxadol (5–20 mg/kg p.o.), a selective extrasynaptic GABA_A agonist, generalised to tiagabine, although the extent of the generalisation was inconclusive. Indiplon (1 mg/kg p.o.), a benzodiazepine-like hypnotic, also partially generalised to tiagabine, although zolpidem and S-zopiclone did not. Baclofen, a GABA_B receptor agonist, and gabapentin, which increases synaptic GABA, did not generalise to tiagabine. (+)-Bicuculline (3 mg/kg i.p.), a GABA_A receptor antagonist, blocked the tiagabine cue, but the less brain-penetrant salt form, bicuculline methochloride, had no effect. Conclusions These data suggest that tiagabine generates a discriminative stimulus in rats, and provides a central GABA-mediated cue, but is distinct from the other GABAergic compounds tested.     

加巴喷丁治疗难治性慢性咳嗽的有效性及安全性

目的 探讨加巴喷丁治疗难治性慢性咳嗽的有效性及安全性.方法 56例难治性慢性咳嗽患者分为对照组26例与研究组30例,对照组患者给予临床常规治疗,研究组患者给予加巴喷丁胶囊(300 ～ 1800 mg/d).共持续治疗12周,评价治疗前后所有患者的莱彻斯特咳嗽问卷(LCQ)评分、咳嗽严重程度(VAS评分)、咳嗽次数,同时观察药物不良反应发生情况.结果 治疗后,研究组患者的LCQ评分、VAS评分、咳嗽次数分别为(16.7±3.4)、(26.7±10.5)mm、(22.5±7.9)次m,相对于治疗前与对照组,LCQ评分、VAS评分显著增高,咳嗽次数显著减少(P＜0.05).研究组的药物不良反应发生率达到40％,但与对照组比较差异无统计学意义(P＞0.05).结论 加巴喷丁治疗难治性慢性咳嗽具有较好的临床疗效,但不良反应发生率较高,建议应在兼顾疗效和副作用的基础上给予该药物治疗.