Pregabalin For Neuropathic Pain Research Articles

Pregabalin for Neuropathic Pain in Post-radiotherapy Head and Neck Cancer Patients: A Retrospective Study and Review of the Literature.

Head and neck cancer (HNC) patients may experience neuropathic pain (NP) due to radiotherapy (RT), which may become chronic. Pregabalin, an anticonvulsant, alters the transmission of painful stimuli at the synaptic level, modifying their perception. Pregabalin is used in NP treatment, but limited data exist on RT-treated HNC patients. This retrospective study aimed to present a case series of HNC patients with chronic NP after RT managed with pregabalin. HNC patients' records from the Department of Oral Medicine and Pathology and Hospital Dentistry, School of Dentistry, National and Kapodistrian University of Athens (NKUA), were searched. Outcome measures were obtained using the Douleur Neuropathique 4 (DN4) scale for NP and the numeric rating scale (NRS) for pain. The use of additional analgesic medication was also recorded. Five HNC (four oral and one nasopharyngeal cancer) patients (mean age 58.5 years) who had received RT (mean total dose 64.7 gray (Gy)) and developed chronic (i.e., present for at least three months after RT) NP, characterized by a positive DN4 score ≥4, were identified. The initial assessment was five months to six years after RT (mean DN4=4.6±0.89 and mean NRS=6±3.08). "Burning," "pins and needles," and "numbness" were the NP descriptors mostly used. Pregabalin was titrated up to 150-300 mg per day; paracetamol and/or tramadol were also administered (daily doses 3000 mg and 100-150 mg, respectively). A substantial pain relief (≥50%) according to the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) (mean DN4=1.6±1.67 and NRS=1.6±1.67) was reported after two to three months of treatment, when tapering was initiated. Two patients (2/5) had complete remission of symptoms (DN4=0, NRS=0). No serious adverse effects were reported; one patient reported excess salivation. Pregabalin may be a promising option for managing RT-related chronic NP in HNC patients. Further studies, including randomized controlled trials on RT-treated HNC patients, should be conducted.

Non-opioid psychiatric medications for chronic pain: systematic review and meta-analysis.

The escalating number of deaths related to opioid usage has intensified the pursuit of non-opioid alternatives for managing chronic pain. It's often observed that psychiatric comorbidities coexist in patients suffering from chronic pain. There are a variety of psychotropic medications that have demonstrated effectiveness in treating both psychiatric symptoms and pain. This systematic review and meta-analysis aim to assess the effectiveness of various psychiatric drugs in managing specific types of chronic pain, including fibromyalgia, neuropathic pain, and chronic low back pain. A comprehensive search of five major databases was conducted through February 2023 to identify randomized controlled trials (RCTs) that met our inclusion criteria, focusing on outpatients Over 18 years of age with chronic pain. The study assessed the effectiveness of duloxetine, mirogabalin, pregabalin, gabapentin, and tricyclic antidepressants (TCAs), including serotonin-norepinephrine reuptake inhibitors (SNRIs), across various chronic pain conditions such as fibromyalgia, neuropathic pain, and chronic low back pain. The primary outcome measures included pain reduction, improvement in function, and quality of life. Of the 29 RCTs in the systematic review, 20 studies qualified for the meta-analysis. The analysis was stratified by pain type and treatment duration (short-term ≤14 weeks vs. long-term >14 weeks), using Hedge's g standardized mean differences and a random-effects model, along with sensitivity and subgroup analyses. The overall short-term intervention effect across all studies was significant (SMD -1.45, 95% CI -2.15 to -0.75, p < 0.001), with considerable heterogeneity (I2 = 99%). For fibromyalgia, both duloxetine and mirogabalin demonstrated substantial efficacy with SMDs of -2.42 (95% CI -3.67 to -1.18, p < 0.0001) and -2.10 (95% CI -3.28 to -0.92, p = 0.0005), respectively. Conversely, treatments for neuropathic pain and chronic low back pain, including those with amitriptyline and desipramine, did not show significant benefits. The effectiveness of gabapentin could not be conclusively determined due to limited representation in the data. Additionally, no consistent long-term benefits were observed for any of the medications. While the results of this study underscore the importance of exploring non-opioid alternatives for chronic pain management, particularly in light of the opioid crisis, it is crucial to interpret the findings carefully. Our analysis suggests that certain psychiatric medications, such Duloxetine and mirogabalin demonstrated significant short-term efficacy in fibromyalgia patients. However, their effectiveness in treating neuropathic pain and chronic low back pain was not statistically significant. Additionally, the effectiveness of gabapentin and other medications, such as pregabalin for neuropathic pain, could not be conclusively determined due to limited data and high study heterogeneity. No consistent long-term benefits were observed for any of the drugs studied, raising questions about their sustained efficacy in chronic pain management. These findings highlight the need for further research to understand better the role of psychiatric medications in managing specific chronic pain conditions without prematurely concluding that they are ineffective or unsuitable for these purposes.

Efficacy of Combination Therapy with Pregabalin in Neuropathic Pain: A Preclinical Study in the Rat L5 Spinal Nerve Ligation Model.

Neuropathic pain is sometimes difficult to manage because of limited efficacy of analgesic monotherapy even at high doses. Combination therapy may help address this issue, but there is little evidence for its effectiveness. Therefore, we evaluated the efficacy of combination therapy with pregabalin, an anchor drug for treating neuropathic pain, using the rat L5 spinal nerve ligation model. Experiments were performed on four-week-old L5 spinal nerve ligated male Sprague-Dawley rats. Mechanical allodynia was assessed using the von Frey test, where the 50% withdrawal threshold was evaluated for five drugs: pregabalin, duloxetine, venlafaxine, tramadol, and celecoxib. The single-drug experiment included 112 rats, where each drug was tested independently. Median effective doses (ED50s) were determined. Combinations of pregabalin with each of the other four drugs were tested (n=84). The 50% withdrawal threshold in the von Frey test was evaluated. The ED50 of each combination was determined experimentally. Isobolographic analyses were conducted to assess the synergistic potential of the drug combinations, excluding pregabalin-celecoxib, since the ED50 of celecoxib could not be determined. In the single-drug experiment, all drugs except celecoxib resulted in a dose-dependent increase in the 50% withdrawal threshold 2 h after administration, with a maximum possible effect ranging from 4.4% to 79.6%. Similarly, all pregabalin combinations demonstrated a dose-dependent increase in the 50% withdrawal threshold, with pregabalin-tramadol showing the greatest increment. Isobolographic analysis of this combination revealed synergistic effects. Specifically, the combination index was γ=0.4 (<1). Combinations of pregabalin with duloxetine and venlafaxine demonstrated additive (γ=0.9) and antagonistic effects (γ=2.0), respectively. This study demonstrated that combination of pregabalin with tramadol has synergistic antiallodynic effects, while that with duloxetine has additive effects. Moreover, pregabalin combined with venlafaxine was potentially antagonistic. Pregabalin combined with tramadol may serve as a promising drug combination for the effective management of neuropathic pain.

Pharmacotherapeutics of aprepitant and pregabalin in neuropathic pain and refractory pruritus in a patient diagnosed with a cutaneous T-cell lymphoma

Background/Aims Palliative care nurse specialists are required to have a high level of knowledge and expertise in the management of complex symptoms. As a result of patient complexity, clinicians are often faced with advising on multiple drug regimes. This often requires clinical nurse specialists to have knowledge of pharmacotherapeutics to ensure safe and rational prescribing. In the form of a case study, the author has critically discussed the use of aprepitant and pregabalin in the management of neuropathic pain and refractory pruritus in a patient diagnosed with a cutaneous T cell lymphoma. These drugs are not routinely prescribed together and therefore the author has explored potential pharmacokinetic interactions. Case presentation The case presented a 49-year-old lady with an advanced metastatic cutaneous T-cell lymphoma with failed remission despite extensive oncological treatment. She was referrd to the to hospital specialist palliative care team for treatment of refractory pruritus and neuropathic pain. Conclusion Aprepitant is considered an effective anti-pruritic agent that is normally well tolerated; however, careful consideration must be taken because of extensive drug interactions. Caution is also required in patients with hepatic impairment. Pregabalin is often used in specialist palliative care for the management of neuropathic pain because of its efficacy and ease of titration. Caution must be taken in prescribing in patients with renal impairment. As pregabalin is not bound to plasma proteins nor metabolised by the liver, the risk of pharmacokinetic interaction with aprepitant is minimal. As both drugs cross the blood brain-barrier, clinicians must monitor for adverse central nervous system activity. This case study highlights the importance of pharmacotherapeutics in ensuring safe and rational prescribing, with the need to continue to integrate this knowledge into future practice as nurse prescribers.

Duloxetine and pregabalin in neuropathic pain of lung cancer patients.

IntroductionNeuropathic pain occurs in 1% of the population and is difficult to manage. This chronic pain causes psychological distress and impacts patient's quality of life, especially in cancer patients. The aim of this study was to show and compare the efficacy of pregabalin and duloxetine, which are reported in the group of first‐line treatment at European Federation of Neurological Societies (EFNS) guidelines on the pharmacological treatment of neuropathic pain (2010 revision) in lung cancer patients by using visual analogue scale (VAS) and Leeds Assessment of Neuropathic Symptoms and Sign (LANSS).Patients and MethodsA prospective, randomized, open label, 3 month of study was conducted. A total of 44 patients that were diagnosed with neuropathic pain (14 women and 30 men) were included in the study. Patient's LANSS and VAS values were recorded before treatment. Then, 22 patients undergo pregabalin and 22 patients undergo duloxetine therapy. But due to side effects (dizziness, constipation), two patients had stopped to use pregabalin. Their LANSS and VAS values were recorded after 1 and 3 months of therapy.ResultsWhen we compare LANSS and VAS scores before treatment, after 1 and 3 months of treatment with pregabalin and duloxetine, a significant decrease was observed in both groups at the 1 and 3 months (p < .01). Duloxetine is superior to pregabalin in reducing the LANSS scores when we compare two groups.ConclusionsBoth duloxetine and pregabalin are effective in the treatment of neuropathic pain of lung cancer patients. And as far as we know, this is the first study comparing the efficacy of duloxetine and pregabalin in the neuropathic pain of lung cancer patients.

Efficacy of Pregabalin in Neuropathic Pain after Spinal Cord Injury.

Efficacy of Pregabalin in Neuropathic Pain after Spinal Cord Injury.

Efficacy and Safety of Pregabalin in Neuropathic Pain Followed Spinal Cord Injury: A Review and Meta-Analysis of Randomized Controlled Trials.

Pregabalin has been approved for the treatment of the neuropathic pain following spinal cord injury (SCI). We performed a systemic review and meta-analysis of randomized, controlled, multicenter trials to evaluate the efficacy and safety of pregabalin for SCI-induced neuropathic pain. Research searching was performed in PubMed and EMBASE databases and the Cochrane library in May 2018. Clinical controlled trials using pregabalin for the pain treatment following SCI in adults (18 y old and above) were included. Pain and safety-related adverse events were considered as outcomes. Meta-analysis was conducted using Revman 5.0 software. Five publications (pregabalin, patients=261, placebo, patients=216) were included in our study. After at least 4-week's treatment with pregabalin (flexible dose, 150 to 600 mg/d), pregabalin-treated patients showed reduced pain -1.54, 95% confidence interval (CI) (-2.33, -0.75), P=0.0001; improved >30% 1.83, 95% CI (1.37, 2.46), P<0.0001 and >50% pain relief 2.40, 95% CI (1.53, 3.77), P=0.0001; increased adverse events 1.36, 95% CI (1.18, 1.577), P<0.0001; and reduced Hospital Anxiety and Depression Scale - anxiety -1.50, 95% CI (-2.99, -0.00), P=0.05 and - depression -0.34, 95% CI (-0.55, -0.12), P=0.002 scores compared with placebo-treated patients. Stratified meta-analysis showed there was no difference in primary adverse events (drowsiness, dizziness, peripheral edema, and dry mouth) between pregabalin and placebo groups (P≥0.05). Our results showed pregabalin was efficacious and might be safe treatment for chronic pain followed SCI.

Pregabalin for neuropathic pain in adults.

Pregabalin for neuropathic pain in adults.

Access And Reimbursement For Emerging Neuropathic Pain Agents In The EU5: Avoiding The Sting Of Low-Cost Competition And Tightening Budgets

This research examines access and reimbursement challenges for emerging neuropathic pain (NP) agents in the EU5 (France, Germany, Italy, Spain, UK) given rising disease prevalence, long-available and low-priced analgesics, and growing generic presence in key drug classes. Across the EU5, 259 GPs and pain specialists were surveyed regarding their prescribing for NP, while 15 payers who influence reimbursement were interviewed. Interviewed payers demand staunch demonstration of clear clinical benefits from emerging NP therapies, specifying robust efficacy and/or safety improvements over existing standards of care (SOC). Similarly, the largest percentage of surveyed physicians across countries (25-46%) identify efficacy benefit versus SOC as their main driver for prescribing new drugs, followed by safety/tolerability advantages. Notably, payers interviewed consider the profile of emerging antiepileptic mirogabalin not sufficiently differentiated from that of pregabalin (Lyrica), warning that if superior efficacy is not proven, premium pricing and advantageous positioning cannot be justified. This is especially pertinent as our research also reveals that despite ongoing patent protection of pregabalin in NP, availability of generic pregabalin for non-NP indications represents a pricing and uptake barrier for new NP brands given off-label generic use in several EU5 markets. Yet, surveyed physicians’ estimated uptake of mirogabalin is 29-42%, with expected use relatively early in the treatment algorithm. This likely reflects the imprecise nature of prescribing owing to the complex pathology of NP. In addition, physicians cite NP-subtype-specific labeling as an uptake lever, reflecting interviewed payer consensus, which pinpoints NP-subtype-specific labelling as financially advantageous given the smaller patient population versus drugs with a broad pain label. Optimal access and reimbursement are achievable for emerging NP agents that showcase superiority over SOC. Targeting NP/NP subtypes specifically would curry favor among payers due to reduced budgetary impact, and could encourage uptake over more-broadly labelled alternatives which may not target key mechanisms underlying neuropathy.

Pregabalin for Neuropathic Pain: Why Benefits Could Be Expected for Multiple Pain Conditions.

Limited research exists to support the extrapolation of the analgesic efficacy of pregabalin from one neuropathic pain condition to another. This retrospective analysis evaluated similarities in the efficacy of pregabalin for treating neuropathic pain associated with post-herpetic neuralgia (PHN), diabetic peripheral neuropathy (DPN), and spinal cord injury (SCI) in a Japanese population, as a basis for considering the extrapolation of these data to other neuropathic pain conditions. Data were analysed across pregabalin doses within each pain condition, from three comparable 13- to 16-week, randomized, double-blind, placebo-controlled trials (RCTs) and the corresponding 52-week, open-label extension trials of pregabalin in Japanese patients with PHN, DPN or SCI. Efficacy outcomes in the RCTs included endpoint and weekly mean pain and sleep interference scores; endpoint proportions of responders in pain; Patient Global Impression of Change scores; and 36-Item Short Form Health Survey (SF-36) scores or Hospital Anxiety and Depression Scale (HADS) assessments. Study discontinuation rates were compared between treatment groups. The extension trials assessed pain intensity, using the Short-Form McGill Pain Questionnaire. In the RCTs for all pain conditions, significant improvements in comparison with placebo in mean pain and sleep interference scores were evident after 1 week with pregabalin and were sustained throughout the treatment periods (p < 0.05). At the study endpoint, in comparison with placebo, a significantly greater percentage of pregabalin-treated patients experienced a ≥30 % reduction in pain across the RCTs (p < 0.05), and pregabalin significantly improved six of 16 SF-36 subscale scores in the PHN and DPN trials (p < 0.05). In the SCI trial, pregabalin-treated patients had numerically better outcomes of HADS scores. In the extension trials, improvements in pain intensity were maintained over a 52-week period. Similarities in the pregabalin efficacy profiles, including time to onset and magnitude of response, were confirmed regardless of the neuropathic pain condition. These data support the potential for extrapolating analgesic efficacy to other neuropathic pain conditions. CLINICALTRIALS. NCT00394901, NCT00553475, NCT00407745, NCT00424372, NCT00553280, NCT01202227.

The antiallodynic action of pregabalin in neuropathic pain is independent from the opioid system.

BackgroundClinical management of neuropathic pain, which is pain arising as a consequence of a lesion or a disease affecting the somatosensory system, partly relies on the use of anticonvulsant drugs such as gabapentinoids. Therapeutic action of gabapentinoids such as gabapentin and pregabalin, which act by the inhibition of calcium currents through interaction with the α2δ-1 subunit of voltage-dependent calcium channels, is well documented. However, some aspects of the downstream mechanisms are still to be uncovered. Using behavioral, genetic, and pharmacological approaches, we tested whether opioid receptors are necessary for the antiallodynic action of acute and/or long-term pregabalin treatment in the specific context of neuropathic pain.ResultsUsing the cuff model of neuropathic pain in mice, we show that acute pregabalin administration at high dose has a transitory antiallodynic action, while prolonged oral pregabalin treatment leads to sustained antiallodynic action, consistent with clinical observations. We show that pregabalin remains fully effective in μ-opioid receptor, in δ-opioid receptor and in κ-opioid receptor deficient mice, either female or male, and its antiallodynic action is not affected by acute naloxone. Our work also shows that long-term pregabalin treatment suppresses tumor necrosis factor-α overproduction induced by sciatic nerve constriction in the lumbar dorsal root ganglia.ConclusionsWe demonstrate that neither acute nor long-term antiallodynic effect of pregabalin in a context of neuropathic pain is mediated by the endogenous opioid system, which differs from opioid treatment of pain and antidepressant treatment of neuropathic pain. Our data are also supportive of an impact of gabapentinoid treatment on the neuroimmune aspect of neuropathic pain.

Preventive Analgesia with Pregabalin in Neuropathic Pain from “Failed Back Surgery Syndrome”: Assessment of Sleep Quality and Disability.

Pregabalin group (PGB) is an antiepileptic used to treat neuropathic pain. We evaluated analgesic efficacy and safety for postoperative/chronic pain, disability, and sleep quality in patients who underwent spine surgery administered with PGB, or not, during the presurgical and postsurgical periods. Retrospective cohort study of 60 patients (two groups with 30 patients) with full information on 50 (29 with PGB and 21 without PGB). Ten patients were dismissed as information was lacking. The PGB group (P) (29 patients) received 75 mg/12 hours before surgery, 150 mg 10 hours after surgery, and 150 mg/12 hours 3 days after surgery. The control group (C; 21 patients) took no PGB. Neuropathic pain was assessed before surgery, and 2 and 6 months later using visual analog scales (VAS), DN4, disability (Oswestry), and sleep quality. No serious adverse events occurred with PGB. The median VAS pain score at rest was lower in the PGB group at 2 months postsurgery (1 vs 2, P = 0.032), as was the median DN4 score (0 vs 3, P = 0.032) and the median Oswestry disability index (ODI: 12 vs 18, P = 0.001). At 6 months postsurgery, pain scores were also lower in the PGB group for VAS (0 vs 4, P = 0.001), DN4 score (0 vs 4, P = 0.001) and the ODI (10 vs 24, P = 0.001). Improvement in the functionality and sleep quality of the PGB group was noteworthy (P = 0.018). PGB has analgesic/antihyperalgesic effects on postoperative neuropathic pain after surgery for lumbar disc hernia. Our findings show that this benefit increases with time.

A systematic review of pharmacoeconomic studies for pregabalin.

With anticonvulsant, anxiolytic, and analgesic properties, pregabalin has been evaluated for neuropathic pain and fibromyalgia (FM). These chronic conditions diminish patients' quality of life and increase healthcare utilization and costs. To assess the current understanding of economic outcomes associated with pregabalin in neuropathic pain and FM. Using keywords related to economic outcomes and pregabalin, we systematically searched MEDLINE- and EMBASE-indexed literature and nonindexed "grey" literature on neuropathic pain and FM published from March 2001 to October 2012. Included studies reported economic findings associated with pregabalin. In the past 11 years, 55 publications assessed the direct costs, resource use, or cost-effectiveness of pregabalin for neuropathic pain and FM. Studies generally lacked comparability due to heterogeneous patient populations, assumptions, time periods, and geographies. In the US, following treatment initiation, pregabalin resulted in similar or higher levels of healthcare use for FM compared with duloxetine. In contrast, medical costs for neuropathic pain did not significantly differ after initiation of pregabalin vs. duloxetine or other standard therapies in the US, but in Spain and Sweden, retrospective database studies suggested that pregabalin was cost-saving vs. gabapentin. Few economic analyses estimated indirect costs. Neuropathic pain and FM are associated with high healthcare resource use and costs. Economic studies of pregabalin in neuropathic pain and FM indicate some results favorable to other forms of care, but heterogeneity among study designs and populations hinder comparisons. Future economic analyses should aim to address data gaps regarding effects of pregabalin on productivity and resource use.

Effects of pregabalin on the activity of glutamate transporter type 3

Pregabalin, (S)-3-aminomethyl-5-methyl hexanoic acid, is a ligand for the α2δ subunit (a component of voltage-gated calcium channels) and has analgesic and anticonvulsant properties. Glutamate uptake by glutamate transporters may be a mechanism for these properties. We investigated the effects of pregabalin on the activity of the neuronal glutamate transporter type 3 (EAAT3). EAAT3 was expressed in Xenopus laevis oocytes. Two-electrode voltage clamping was used to record membrane currents before, during, and after applying l-glutamate (30 μM) in the presence or absence of pregabalin. Currents were also measured in oocytes pretreated with a protein kinase C (PKC) activator (phorbol-12-myristate-13-acetate, PMA), PKC inhibitors (chelerythrine or staurosporine), or a phosphatidylinositol-3-kinase (PI3K) inhibitor wortmannin. The exposure of the oocytes injected with EAAT3 mRNA to serial concentrations of pregabalin (0.06-60 μM) significantly increased their responses to 30 μM l-glutamate. A kinetic study showed that pregabalin significantly increased V(max) without changing K(m). Treatment of oocytes with PMA, pregabalin, or pregabalin plus PMA significantly increased transporter currents vs controls, but treatment with PMA plus pregabalin did not increase the responses further vs PMA or pregabalin alone. In addition, pretreatment of oocytes with two PKC inhibitors (chelerythrine or staurosporine), or inhibitor wortmannin, significantly reduced basal and pregabalin-enhanced EAAT3 activity. Pregabalin increased EAAT3 activity and PKC and PI3K were involved. This may explain the analgesic effect of pregabalin in neuropathic pain.

Pregabalin in Neuropathic Pain Related to DPN, Cancer and Back Pain: Analysis of a 6-Week Observational Study

Background: Neuropathic pain is associated with many conditions. Pregabalin has demonstrated efficacy in randomized, controlled trials (RCTs) in peripheral and central neuropathic pain. Observational studies complement findings from RCTs by enabling an agent to be studied in real-world patients and circumstances. Methods: Patients with neuropathic pain were treated with pregabalin 150-600 mg/day in this 6 week observational study. Analyses of subsets of patients with painful diabetic peripheral neuropathy (DPN; n=4633), back pain with a neuropathic component (n=3800), and cancer-related neuropathic pain (n=345) were undertaken. Results: The mean pregabalin doses ranged from 219 to 250 mg/day across the disease groups. Mean baseline pain scores (6.4 to 7.0 across the three disease states) indicated patients had moderate to severe pain. Pregabalin was associated with a rapid and significant reduction in pain from week 1 to endpoint in all groups. Over 80% in each of the groups had a � 30% pain reduction in their pain at 6 weeks, and over two-thirds had a � 50% reduction. Pain-related sleep interference decreased rapidly and significantly. Most patients (87%) were either very satisfied or satisfied with the action of pregabalin. General well-being improved significantly over the 6 weeks. Pregabalin was generally well tolerated; the most common adverse event overall was dizziness (1.4%). Few patients (� 6.1%/group) discontinued due to adverse events. Conclusions: In neuropathic pain patients in day-to-day practice, pregabalin was associated with notable reductions in pain and sleep interference. The benefits of pregabalin were reflected in the high level of patient satisfaction and improvement in general well-being.

Pregabalin: a treatment option for dystonia?

To date, no studies are available on the effect of pregabalin in dystonia. A patient with subarachnoidal and cerebral hemorrhage was treated with pregabalin for neuropathic pain. Upon withdrawal of the medication she experienced spontaneous and painful supination in the right foot and internal hip rotation when standing up. When pregabalin was reinstituted, these dystonic symptoms subsided, but reappeared when the medication was again discontinued. One possible explanation for these symptoms could be neuronal hyperactivity within still-functioning pathways in connection with the motor cortex. Preponderance of activity in potentially compensatory structures could be suppressed by pregabalin: therefore, its potential benefit in subacute secondary dystonia in cases with orbital brain involvement is suggested.

Efficacy and safety of combination therapy with 5% lidocaine medicated plaster and pregabalin in post-herpetic neuralgia and diabetic polyneuropathy

ABSTRACTObjective: Neuropathic pain is often difficult to treat due to a complex pathophysiology. This study evaluated the efficacy, tolerability and safety of combination therapy with 5% lidocaine medicated plaster and pregabalin for neuropathic pain in patients with post-herpetic neuralgia (PHN) or painful diabetic polyneuropathy (DPN).Methods: Patients completing 4-week monotherapy with 5% lidocaine medicated plaster or pregabalin were enrolled in an 8-week combination phase. Patients with adequate response to monotherapy (recalled average pain intensity of 4 or less on 11-point numeric rating scale in the previous 3 days [NRS-3 score]) continued their previous therapy, whereas those with insufficient response received combination therapy. Efficacy endpoints included change in NRS-3 from combination phase baseline, Patient and Clinical Global Impression of Change (PGIC/CGIC), and patient's satisfaction with treatment. Safety evaluation included adverse events (AEs), drug-related AEs (DRAEs), and withdrawal due to AEs.Clinical trial registration: EudraCT No. 2006-003132-29.Results: Of 229 patients in the per-protocol set (PPS: 68 PHN and 161 DPN), 71 received 5% lidocaine medicated plaster monotherapy, 57 had pregabalin added to 5% lidocaine medicated plaster, 57 pregabalin monotherapy and 44 received 5% lidocaine medicated plaster in addition to continued pregabalin treatment. There were no meaningful differences in demographic data between the treatment groups. Patients continuing on monotherapy demonstrated additional decreases in NRS-3 scores. Patients receiving combination therapy achieved clinically relevant reduction in NRS-3 values in addition to improvement achieved during the 4 weeks of monotherapy. Improvement was similar between the two combination therapy groups. Considerable improvements in patients’ treatment satisfaction were reported. Incidences of AEs were in line with previous reports for the two treatments and combination therapy was generally well tolerated.Conclusions: In patients with PHN and painful DPN failing to respond to monotherapy, combination therapy with 5% lidocaine medicated plaster and pregabalin provides additional clinically relevant pain relief and is safe and well-tolerated.

Efficacy of pregabalin in neuropathic pain in paediatric oncological patients

Objective To evaluate the safety and efficacy of pregabalin in the management of chemotherapy-induced neuropathic pain in patients with childhood solid tumors and leukaemia. Materials and methods In an open-label study, 30 children (11 boys and 19 girls; mean age 13.5 years) who were treated for solid tumors and leukaemia, and developed a painful peripheral neuropathy, were medicated with pregabalin in the daily dose of 150–300 mg for 8 weeks. Results Twenty-eight patients completed the 8-week follow-up. A significant and long-lasting pain relief was noted in 86% of these patients. Median VAS score decreased by 59% at the 8th week from baseline. Adverse effects were infrequent and transient. Conclusion The treatment with pregabalin resulted in a significant improvement in pain symptoms. The use of pregabalin in children is off-label so far. However, this drug seems to be a safe and effective remedy, which could significantly broaden the therapeutic spectrum in paediatric oncological patients suffering from neuropathic pain.

Efficacy of pregabalin and gabapentin for neuropathic pain in spinal-cord injury: an evidence-based evaluation of the literature

Spinal-cord injury (SCI) is a leading cause of neuropathic pain (NP). Current pharmaceutical treatments for NP in SCI patients are not effective. Two promising options are gabapentin (GP) and pregabalin (PB). Their predominant mechanism of action is believed to be the inhibition of calcium currents, leading in turn to reduced neurotransmitter release and attenuation of postsynaptic excitability. This could explain much of their efficacy in the treatment of both seizure disorders and pain syndromes. However, evidence for their efficacy in attenuating NP of SCI is still controversial. To efficiently integrate valid information and provide a basis for rational decision making, through determining PB and GP efficacy in treating NP in SCI. Literature was systematically reviewed. Medline, Embase, CINAHL and Cochrane Database were searched using search terms 'gabapentin', 'pregabalin', 'neurontin', 'lyrica', 'neuropathic pain' and 'spinal-cord injury'. Studies were assessed independently by two authors. Five studies were eligible for inclusion. Two of them studied PB and three GP. Both GP and PB appear to be efficacious for NP in SCI. A clear comparison between the two drugs could not be performed. The literature data suggest that PB is more efficacious than GP in many important variables for NP in SCI, although PB use is followed by more side effects than GP. PB reduced Visual Analogue Score (VAS) in both studies (P < 0.001 and P = 0.016). On the other hand, for GP a maximum dosage of 3,600 mg/day reduced VAS score (P = 0.000), whereas a maximum dosage of 1,200 mg/day failed to do so. There is a lack of studies comparing GP and PB in treating NP in SCI. This systematic review indicates the possible efficacy of PB and GP in NP of SCI. Recommendations for future research to inform clinical practice should include cost-effectiveness studies and dose-response analysis in order to determine the schema employed and the duration of treatment.

Gabapentin and pregabalin for chronic neuropathic and early postsurgical pain: current evidence and future directions

Gabapentin and pregabalin bind to the alpha-2-delta calcium channel subunit and represent a novel analgesic drug class. The evidence base supporting their use for chronic neuropathic and early postsurgical pain is reviewed. Multiple, large, high-quality trials have demonstrated the safety and efficacy of gabapentin and pregabalin in neuropathic pain. Treatment-related improvement of pain and sleep positively impact upon quality of life. Sedation, dizziness and ataxia are important and relatively common adverse effects, however. Accumulating evidence indicates that gabapentin, and possibly pregabalin, also exert important effects following surgery. Multiple high-quality trials have demonstrated analgesic and opioid-sparing efficacy with gabapentin following various surgical procedures. Gabapentin and pregabalin reduce movement-evoked pain and this can lead to enhanced functional postoperative recovery. Postoperative opioid sparing is of questionable relevance since few trials have shown reduced opioid-related adverse effects. Sedation, dizziness and ataxia have been reported in only a few trials. Future larger-scale perioperative trials focused on safety assessment are needed, however. Gabapentin and pregabalin are efficacious treatments for neuropathic and postsurgical pain. Future research addressing several specific questions would serve to better delineate their optimal roles in treating these and other pain conditions.