Toxicity assessment of concurrent gabapentin/pregabalin administration with high-dose melphalan in autologous hematopoietic cell transplant recipients.

A theoretical pharmacokinetic interaction mediated through L-amino acid transporter 1 and 2 exists between gabapentin (GP) and pregabalin (PG) with melphalan. Peripheral neuropathy is a common toxicity of various multiple myeloma regimens commonly utilized prior to autologous hematopoietic cell transplant (auto-HCT) with high-dose melphalan (HD-Mel). Therefore, it is likely concurrent administration of either GP or PG will occur in patients receiving HD-Mel conditioning for auto-HCT, which could potentially increase cellular uptake and worsen the mucosal injury. A retrospective chart review of adult patients from January 2012 to July 2016 who received HD-Mel (140-200 mg/m2) at West Virginia University Medicine was performed to assess toxicity and outcomes in these patients. A total of 80 patients were included in the study, with 30 patients receiving GP or PG and 50 control patients. There were no significant differences in grade 2 or higher mucositis, admissions for nausea/vomiting/diarrhea, intravenous opioid requirements, oral topical therapies, antidiarrheal medication use, rescue anti-emetics, days of nausea or vomiting, pain scores, neutrophil or platelet engraftment, treatment-related mortality, progression-free survival, or overall survival. Our data suggest that it is safe to continue GP/PG therapy throughout HD-Mel therapy, with no negative transplant outcomes. Prospective studies or evaluations of larger databases are necessary to better characterize the clinical effect of concomitant therapy.

Capsaicin 8% dermal patch in clinical practice: an expert opinion.

INTRODUCTION: Neuropathic pain (NP) is caused by a lesion or disease of the somatosensory system, which can severely impact patients' quality of life. The current-approved treatments for NP comprise of both centrally acting agents and topical drugs, including capsaicin 8% dermal patches, which is approved for the treatment of peripheral NP. AREAS COVERED: The authors summarize literature data regarding capsaicin use in patients who suffer from NP and discuss the clinical applications of this topical approach. EXPERT OPINION: Overall, the capsaicin 8% dermal patch is as effective in reducing pain intensity as other centrally active agents (i.e. pregabalin). Some studies have also reported fewer systemic side effects, a faster onset of action and superior treatment satisfaction compared with systemic agents. In our opinion, capsaicin 8% dermal patches also present additional advantages, such as a good systemic tolerability, the scarcity of adverse events, the possibility to combine it with other agents, and a good cost-effective profile. It is important to note that, as the mechanism of action of capsaicin 8% is the 'defunctionalization' of small afferent fibers through interaction with TRPV1 receptors, the peripheral expression of this receptor on nociceptor fibers, is crucial to predict patient's response to treatment.

Chemotherapy-induced peripheral neuropathy (CIPN) and its treatment: an NIH Collaboratory study of claims data.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling complication of many chemotherapies. We investigated the feasibility of using health plan claims and administrative data to identify CIPN occurrence by comparing patients who received neurotoxic and non-neurotoxic chemotherapies. METHODS: The sample included over 53,000,000 patients from two regional and one national insurer in the USA (> 400,000 exposed to chemotherapy). Peripheral neuropathy was identified using a broad definition (definition 1) and a specific definition (i.e., drug-induced polyneuropathy code) (definition 2). RESULTS: CIPN incidence as measured by definition 1 within 6 months of chemotherapy initiation was 18.1% and 6.2% for patients who received neurotoxic and non-neurotoxic chemotherapy, respectively (relative risk neurotoxic vs. non-neurotoxic (RR), 2.93 (95% CI, 2.87-2.98)). For definition 2, these incidences were 3.6% and 0.1% (RR, 25.2 (95% CI, 22.8-27.8)). The incidences of new analgesic prescriptions for neurotoxic and non-neurotoxic groups were as follows: gabapentin, 7.1%/1.7%; pregabalin, 0.69%/0.31%; and duloxetine, 0.78%/0.76%. The incidence of CIPN as defined by definitions 1 and 2 was low compared with that of published research studies, but the relative risk of CIPN among patients who received neurotoxic chemotherapies compared with those who received non-neurotoxic chemotherapies was high using definition 2. CONCLUSIONS: These data suggest that as used currently by clinicians, administrative codes likely underestimate CIPN incidence. Thus, studies using administrative data to estimate CIPN incidence are not currently feasible. However, the drug-induced polyneuropathy code is a specific indicator of CIPN in administrative data and may be useful for investigating predictors or potentially preventive therapies of CIPN.

Consequences on economic outcomes of generic versus brand-name drugs used in routine clinical practice: the case of treating peripheral neuropathic pain or generalized anxiety disorder with pregabalin.

BACKGROUND: Discrepancies are seen between arguments in favor of and against prescribing generic versus brand-name drugs. OBJECTIVE: To provide real-world evidence on treatment persistence, economic and clinical outcomes of pregabalin, generic versus brand-name (Lyrica®, Pfizer), routinely used to treat neuropathic pain (NP) or generalized anxiety disorder (GAD). METHODS: Electronic medical records from subjects' first starting treatment with pregabalin between January-2015 and June-2016 were analyzed. Persistence, resources utilization, and costs were assessed, along with remitter and responder rates. RESULTS: A total of 4860 records were analyzed. Discontinuation was lower with brand-name than with generic in NP (adjusted hazard ratio [HR]: 0.70 [95% CI: 0.58-0.85], p < 0.001) and GAD patients (HR: 0.63 [0.45-0.84], p < 0.001). Adjusted mean total costs were lower with brand-name: €1500 [1428-1573] vs. €2003 [1864-2143] in NP and €1528 [1322-1734] vs. €2150 [1845-2454] in GAD (both p < 0.001). More patients were remitters/ responders with brand-name in NP (55.0% vs. 46.7% and 59.2% vs. 48.4%, respectively; p < 0.001) and GAD (58.6% vs. 48.7% and 64.6% vs. 47.2%, respectively; p < 0.001). CONCLUSIONS: As a consequence of higher persistence in routine practice, patients who first started therapy with pregabalin brand-name versus generic showed better pain or anxiety outcomes at a lower cost to payers in Spain.

Gabapentin and Pregabalin Use and Association with Adverse Outcomes among Hemodialysis Patients.

Background Gabapentin and pregabalin are used to manage neuropathic pain, pruritus, and restless legs syndrome in patients on hemodialysis. These patients may be especially predisposed to complications related to these agents, which are renally cleared, but data regarding the risk thereof are lacking.Methods From the US Renal Data System, we identified 140,899 Medicare-covered adults receiving hemodialysis with Part D coverage in 2011. Using Cox regression models in which we adjusted for demographics, comorbidities, duration of exposure, number of medications, and use of potentially confounding concomitant medications, we investigated the association between gabapentin and pregabalin, modeled as separate time-varying exposures, and time to first emergency room visit or hospitalization for altered mental status, fall, and fracture. We evaluated risk according to daily dose categories: gabapentin (>0-100, >100-200, >200-300, and >300 mg) and pregabalin (>0-100 and >100 mg).Results In 2011, 19% and 4% of patients received gabapentin and pregabalin, respectively. Sixty-eight percent of gabapentin or pregabalin users had a diagnosis of neuropathic pain, pruritus, or restless legs syndrome. Gabapentin was associated with 50%, 55%, and 38% higher hazards of altered mental status, fall, and fracture, respectively, in the highest dose category, but even lower dosing was associated with a higher hazard of altered mental status (31%-41%) and fall (26%-30%). Pregabalin was associated with up to 51% and 68% higher hazards of altered mental status and fall, respectively.Conclusions Gabapentin and pregabalin should be used judiciously in patients on hemodialysis, and research to identify the most optimal dosing is warranted.

Cost-effectiveness modeling for neuropathic pain treatments: investigating the relative importance of parameters using an open-source model.

AIMS: The study objective was to develop an open-source replicate of a cost-effectiveness model developed by National Institute for Health and Care (NICE), in order to explore uncertainties in health economic modeling of novel pharmacological neuropathic pain treatments. MATERIALS AND METHODS: The NICE model, consisting of a decision tree with branches for discrete levels of pain relief and adverse event (AE) severities, was replicated using R, and used to compare a hypothetical neuropathic pain drug to pregabalin. Model parameters were sourced from NICE's clinical guidelines and associated with probability distributions to account for underlying uncertainty. A simulation-based scenario analysis was conducted to assess how uncertainty in efficacy and AEs affected the net monetary benefit (NMB) for the hypothetical treatment at a cost-effectiveness threshold of £20,000 per QALY. RESULTS: Relative to pregabalin, an increase in efficacy was associated with greater NMB than an improvement in tolerability. A greater NMB was observed when efficacy was marginally higher than that of pregabalin, while maintaining the same level of AEs than when efficacy was equivalent to pregabalin, but with a more substantial reduction in AEs. In the latter scenario, the NMB was only positive at a low cost-effectiveness threshold. LIMITATIONS: The replicate model shares the limitations described in the NICE guidelines. There is a lack of support in scientific literature for the assumption that increased efficacy is associated with a greater reduction in tolerability. The replicate model also included a single comparator, unlike the NICE model. CONCLUSIONS: Pain relief is a stronger driver of NMB than tolerability, at a cost-effectiveness threshold of £20,000 per QALY. Health technology assessment decisions which are influenced by NICE's model may reward efficacy gains, even if they are associated with more severe AEs. This contrasts with recommendations from clinical guidelines for neuropathic pain, which place more equal weighting on improvements in efficacy and tolerability as value drivers.

Cost of treating peripheral neuropathic pain with pregabalin or gabapentin at therapeutic doses in routine practice.

AIM: To analyze the cost of peripheral neuropathic pain (PNP) treatment with pregabalin or gabapentin at therapeutic doses in routine clinical practice. METHODS: Analysis of a retrospective, observational study of electronic medical records of patients treated for PNP with therapeutic doses of pregabalin or gabapentin, with 2 years' follow-up, considering PNP type, comorbidities, concomitant analgesia and resource use. RESULTS: The weighted total average cost/patient was lower for pregabalin than gabapentin (€2464 [2197-2730] vs €3142 [2670-3614]; p = 0.014) due to significantly lower both healthcare and non-healthcare costs. This is explained by a significantly lower use of concomitant analgesia, fewer primary care visits and fewer days of sick leave. CONCLUSION: At therapeutic doses, pregabalin was found to have lower healthcare and non-healthcare costs than gabapentin in routine practice.

Healthcare Costs and Medication Adherence Among Patients with Fibromyalgia: Combination Medication vs. Duloxetine, Milnacipran, Venlafaxine, and Pregabalin Initiators.

OBJECTIVE: To examine medication adherence and healthcare costs for combination prescription initiators (duloxetine/milnacipran/venlafaxine with pregabalin) vs. monotherapy initiators (duloxetine, milnacipran, venlafaxine, and pregabalin) among patients with fibromyalgia syndrome (FMS). METHODS: Our retrospective cohort study used claims data for the South Carolina Blue Cross Blue Shield State Health Plan (SHP). Patients with FMS ≥ 18 years of age, with prescription initiation from July 1, 2007, through June 30, 2010, and SHP enrollment for 12 months pre- and post-index periods were included (combination: n = 100; pregabalin: n = 665; duloxetine: n = 713; milnacipran: n = 131; venlafaxine: n = 272). Medication adherence measures included high adherence (medication possession ratio ≥ 80%) and total supply days. Healthcare costs comprised direct medical expenditures. Propensity score methods of inverse probability of treatment weights were used to control for selection bias due to differing pre-index characteristics. RESULTS: Odds ratios for high adherence were significantly increased (P < 0.05) among the combination cohort vs. the venlafaxine (2.15), duloxetine (1.39), and pregabalin (2.20) cohorts. Rate ratios for total supply days were significantly higher (P < 0.05) for combination vs. venlafaxine (1.23), duloxetine (1.08), and pregabalin (1.32) cohorts. Expenditures for total health care were significantly higher (P < 0.05) for combination vs. duloxetine ($26,291 vs. $17,190), milnacipran ($33,638 vs. $22,886), and venlafaxine ($26,586 vs. $16,857) cohorts. CONCLUSIONS: Medication adherence was considerably better for combination prescription initiators; however, expenditures for total health care were higher. Still, our findings suggest important clinical benefits with the use of combination prescription therapy, and prospective studies of medication adherence are warranted to examine causal relationships with outcomes not captured by healthcare claims databases.

PainVision® Apparatus for Assessment of Efficacy of Pulsed Radiofrequency Combined with Pharmacological Therapy in the Treatment of Postherpetic Neuralgia and Correlations with Measurements.

Objective. PainVision device was a developed application for the evaluation of pain intensity. The objective was to assess the efficacy and safety of pulsed radiofrequency (PRF) combined with pharmacological therapy in the treatment of postherpetic neuralgia (PHN). We also discussed the correlation of the measurements. Method. Forty patients with PHN were randomized for treatment with PRF combined with pharmacological therapy (PRF group, n = 20) or pharmacological therapy (control group, n = 20) at postoperative 48 hours. The efficacy measure was pain degree (PD) that was assessed by PainVision and visual analog scale (VAS), short form Mcgill pain questionnaire (SF-Mcgill), and numeric rate scale sleep interference score (NRSSIS). Correlations between PD, VAS, SF-Mcgill, and NRSSIS were determined. Results. The PD for persistent pain (PP) and breakthrough pain (BTP) at postoperative 48 hours assessed by PainVision were significantly lower in PRF group than in control group (PD-PP, P < 0.01; PD-BTP, P < 0.01). PD and VAS were highly correlated for both persistent pain (r = 0.453, ρ = 0.008) and breakthrough pain (r = 0.64, ρ = 0.001). Conclusion. PRF was well tolerated and superior to isolated pharmacological therapy in the treatment of PHN. PainVision device showed great value in the evaluation of pain intensity and PD had an excellent correlation with VAS and SF-Mcgill.

Bioequivalence assessment of two pregabalin capsules in healthy Mediterranean Arab volunteers.

BACKGROUND: Treatment of neuropathic pain has always been challenging, not only from the pharmaco-therapeutic/toxicological point of view, but also due to the unpredictable pharmacokinetic (PK) variations among different generic formulations of the same drug, which require further dose optimization. OBJECTIVES: This progressive work aims to evaluate the bioequivalence (BE) of a generic product of 150 mg pregabalin capsule (antineuropathic drug) vs. the reference brand drug Lyrica^®. METHOD: An LC-MS/MS bioanalytical method was developed and validated according to the International Conference on Harmonization (ICH) guidelines in order to be used for the analysis of pregabalin in plasma. BE of capsules was tested by comparison against the reference brand capsules in accordance with the requirements of the declarations of Helsinki, the current Good Clinical Practice (GCP) Guidelines and the ICH. The resulting data were compared against corresponding pregabalin data published on other human races. RESULTS: The relationship between concentration and peak area ratio was found to be linear within the range 0.096 - 6.068 µg/mL for pregabalin. The correlation coefficient (r) was equal to 0.9983. Statistical comparison of the main PK parameters showed no significant difference between test and reference. The mean Cmax values for test and reference were 4.290 and 4.164 µg/mL, and the mean AUC0-last values were 24.275 h×µg/mL and 23.674 h×µg/mL, respectively. The 90% CIs of geometric mean ratios (test/reference) for pregabalin were 100.34 - 104.78%, 100.34 - 104.70%, and 95.65 - 110.96% for AUC0-last, AUC0-∞, and Cmax, respectively, thus fall within the international specified BE limit (80 - 125%). Both products were well tolerated by all the volunteers and there were no significant differences on physical examination or in vital signs and laboratory tests between groups. All volunteers completed the study and were discharged in good health. CONCLUSION: The tested generic capsules appear to be bioequivalent to the reference brand and are expected to have a similar efficacy and safety profile.

Pregabalin prescriptions in the United Kingdom: a drug utilisation study of The Health Improvement Network (THIN) primary care database.

AIM: In Europe, pregabalin is approved for treatment of neuropathic pain, general anxiety disorder (GAD) and as adjunctive therapy for epilepsy. The purpose of this study was to assess utilisation of pregabalin in the UK, including patients with a recorded history of substance abuse, from a large general practice database. METHODS: This observational drug utilisation study (DUS) analysed pregabalin prescription data from the UK Health Improvement Network primary care database between September 2004 and July 2009. Patient demographics, diagnoses (by READ codes) and pregabalin dosing data were collected. Diagnosis codes were used as proxy for approved indication for pregabalin. RESULT: A cohort of 18,951 patients was prescribed pregabalin; dosing information was available for 13,480 (71.1%). Median age of patients was 58 years, and majority were female (60.1%). Median (interquartile range) prescribed average daily dose (ADD) of pregabalin for all patients was 150.0 (162.5) mg/day; this was highest in patients with epilepsy (191.9 mg/day), followed by neuropathic pain (158.0 mg/day) and GAD (150.0 mg/day). Only 1.0% (136/13,480) of patients were prescribed an ADD of pregabalin over the maximum approved dose of 600 mg/day. Of these, 18.4% (25/136) of patients had a history of substance abuse compared with 14.0% (1884/13,480) in the full population. CONCLUSION: Data from this DUS indicated that the majority of pregabalin prescribing in the UK was consistent with product labelling. The proportion of patients with prescribed ADD > 600 mg/day was small and with a similar proportion with a history of substance abuse as in the full population.

Cost-Effectiveness of Capsaicin 8% Patch Compared with Pregabalin for the Treatment of Patients with Peripheral Neuropathic Pain in Scotland.

We evaluated the cost-effectiveness of capsaicin 8% patch (QUTENZA™) versus pregabalin in patients with PNP from the perspective of the National Health Service (NHS) and Personal and Social Services in Scotland, UK. A decision-tree cost-effectiveness model was developed for non-diabetic patients with peripheral neuropathic pain (PNP) who were pregabalin-naïve and had not achieved adequate pain relief or tolerated conventional first- or second-line treatments. Patients entering the model received either a single application of capsaicin 8% patch or titrated daily dosing with pregabalin; after 8 weeks patients were classified as responders, non-responders, or were assumed to discontinue treatment due to intolerable adverse events. Responders continued to receive baseline treatment at intervals observed in clinical practice. Non-responders and those who discontinued treatment were assumed to receive last-line therapy (duloxetine). The base-case time horizon was 2 years. Model inputs for effectiveness, discontinuations and health-state utilities were taken from a head-to-head non-inferiority study (ELEVATE, NCT01713426). Other inputs were obtained from published sources or clinical expert opinion. Costs were expressed in GBP 2013/14. Results were presented as incremental cost-effectiveness ratios (ICER), i.e. cost per quality-adjusted life-year (QALY) gained. Model assumptions were tested with scenario analyses. Parameter uncertainty was tested using one-way and probabilistic sensitivity analyses. Compared with dose-optimized pregabalin, capsaicin 8% patch was the dominant treatment strategy (total cost difference, -£11; total QALY gain, 0.049). Capsaicin 8% patch was also the dominant treatment strategy versus pregabalin in 6 out of 7 scenario analyses. The model was most sensitive to variation in time to capsaicin 8% patch retreatment (maximum ICER, £7,951/QALY at lower-bound 95% confidence interval). At a willingness-to-pay threshold of £20,000/QALY, the probability of capsaicin 8% patch being cost-effective versus pregabalin was 97%. Capsaicin 8% patch is a cost-effective treatment option compared with dose-optimized pregabalin in patients with PNP who have failed one or more previous systemic treatments.

Mechanical Conflict System: A Novel Operant Method for the Assessment of Nociceptive Behavior.

A new operant test for preclinical pain research, termed the Mechanical Conflict System (MCS), is presented. Rats were given a choice either to remain in a brightly lit compartment or to escape to a dark compartment by crossing an array of height-adjustable nociceptive probes. Latency to escape the light compartment was evaluated with varying probe heights (0, .5, 1, 2, 3, and 4 mm above compartment floor) in rats with neuropathic pain induced by constriction nerve injury (CCI) and in naive control rats. Escape responses in CCI rats were assessed following intraperitoneal administration of pregabalin (10 and 30 mg/kg), morphine (2.5 and 5 mg/kg), and the tachykinin NK1 receptor antagonist, RP 67580 (1 and 10 mg/kg). Results indicate that escape latency increased as a function of probe height in both naive and CCI rats. Pregabalin (10 and 30 mg/kg) and morphine (5 mg/kg), but not RP 67580, decreased latency to escape in CCI rats suggesting an antinociceptive effect. In contrast, morphine (10 mg/kg) but not pregabalin (30 mg/kg) increased escape latency in naive rats suggesting a possible anxiolytic action of morphine in response to light-induced fear. No order effects following multiple test sessions were observed. We conclude that the MCS is a valid method to assess behavioral signs of affective pain in rodents.

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

OBJECTIVE: 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. DESIGN: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: PGB has analgesic/antihyperalgesic effects on postoperative neuropathic pain after surgery for lumbar disc hernia. Our findings show that this benefit increases with time.

Conversion from thrice- to twice-daily pregabalin dosing for pain: Economic and clinical outcomes in a veteran population.

PURPOSE: Results of a study analyzing economic and clinical outcomes one year after conversion from thrice- to twice-daily pregabalin dosing for pain are presented. METHODS: A retrospective chart review was conducted at two Veterans Affairs facilities. The analyzed population included all patients receiving pregabalin for pain whose dosing was converted from thrice- to twice-daily pregabalin dosing during a one-year period. The primary endpoint was the economic impact of the conversion. Secondary endpoints included reversion to thrice-daily pregabalin dosing, pregabalin discontinuation, addition of medications for pain, and unscheduled neuropathy-related visits. RESULTS: Among the 57 patients included in the data analysis, 41 continued to take pregabalin twice daily, 10 had pregabalin discontinued, and 6 had dosing reverted to thrice daily. The mean age of patients and the distribution of add-on pain medications did not differ significantly between patients whose pregabalin dosing frequency remained at twice daily and patients whose frequency reverted to thrice daily. The costs associated with pregabalin therapy differed significantly between the preconversion and postconversion periods. A savings of $115,867 was realized from this conversion for both facilities combined over the course of one year. CONCLUSION: In patients receiving pregabalin for pain, conversion from thrice- to twice-daily pregabalin dosing-while maintaining the same daily dose-resulted in substantial cost savings while having little effect on clinical outcomes.

Efectividad y seguridad de gabapentina y pregabalina como monoterapia de primera línea en adultos con dolor neuropático / Effectiveness and safety of gabapentin and pregabalin as first-line monotherapy in adults with neuropathic pain

Antecedentes: Descripción de la condición de salud de interés: La Asociación Internacional del Estudio del Dolor en el año 2011 definió el dolor neuropático como una afección neurológica crónica causado por una lesión o enfermedad del sistema nervioso. Se debe a una lesión o mal funcionamiento del sistema nervioso, a un daño del nervio en sí (u otra parte del sistema sensorial) y no a una activación anormal de las vías nociceptoras. El mecanismo generador del dolor neuropático se halla en cualquier sitio a lo largo del recorrido de las vías nociceptivas (las vías que conducen la información de tipo doloroso), sin estimular inicialmente a los nociceptores (los receptores de dolor), a diferencia de lo que sucede con el dolor nociceptivo o fisiológico. Descripción de las tecnologías: Gabapentina y pregabalina son medicamentos anticonvulsivantes empleados en el tratamiento del dolor neuropático; a ctúan disminuyendo la liberación de neurotransmisores excitadores, lo que reduce la entrada de calcio en las terminaciones nerviosas. Las dos tecnologías tienen registro sanitario INVIMA para la indicación de interés. Evaluación de efectividad y seguridad: Pregunta de evaluación: En adultos con dolor neuropático, ¿cuál es la efectividad y seguridad de gabapentina y pregabalina comparadas con amitriptilina, oxcarbazepina, duloxetina, tramadol (sólo o en combinaciones) o lidocaína en parches, como monoterapia de primera línea para el alivio del dolor? La pregunta de evaluación fue refinada y validada con base en: autorización de mercadeo de \r\nlas tecnologías para la indicación de interés (registro sanitario INVIMA), listado de medicamentos vitales no disponibles, cobertura de las tecnologías en el Plan Obligatorio de Salud (POS) (Acuerdo 029 de 2011), revisión de grupos terapéuticos (clasificación ATC: Anatomical, Therapeutic, Chemical classification system), recomendaciones de guías de práctica clínica actualizadas, disponibilidad de evidencia sobre efectividad y seguridad (reportes de evaluación de tecnologías y revisiones sistemáticas de la literatura), uso de las tecnologías (listas nacionales de recobro, estadísticas de prescripción, etc), \r\nestudios de carga de enfermedad y consulta con un experto temático (especialista clínico). No se dentificaron otros comparadores relevantes para la evaluación. Población: Adultos con dolor neuropático tipo: Neuropatía diabética periférica; Neuralgia posherpética; Dolor neuropático asociado con lesión de la médula espinal. \r\nLa población se refinó después de revisar la evidencia disponible, considerando además, que los efectos de las tecnologías bajo evaluación podrían diferir entre pacientes con distintos tipos de dolor neuropático. Metodología: Búsqueda de literatura, Búsqueda en bases de datos electrónicas. Conclusiones: En pacientes con neuropatía diabética periférica, gabapentina es una opción con ventajas en efectividad, sin ventajas en seguridad y tolerabilidad. En la misma población, pregabalina sin discriminar por dosis no tiene ventajas en efectividad; en dosis ≥ 300 mg es una opción con ventajas en efectividad, no es segura y no presenta ventajas en tolerabilidad; para dosis ≤ 150 mg la evidencia sobre su efectividad no es concluyente, no presenta ventajas en cuanto a seguridad y tolerabilidad. En pacientes con neuralgia posherpética, la evidencia sobre la efectividad de gabapentina no es concluyente, para el mismo tipo de dolor, pregabalina es una opción desfavorable en términos de efectividad y de seguridad a altas dosis. En pacientes con dolor neuropático asociado con lesión de la médula espinal no se identificó evidencia sobre la efectividad de gabapentina o pregabalina. En la misma población, gabapentina no tiene ventajas en tolerabilidad, por su parte, pregabalina no es segura y no presenta ventajas en tolerabilidad. La calidad de la evidencia para las comparaciones de interés y desenlaces descritos es alta.