Lacosamide in Painful Diabetic Peripheral Neuropathy

Rauck, Richard; Shaibani, Aziz; Biton, Victor; Simpson, Jeff; Koch, Brigitte

doi:10.1097/01.ajp.0000210957.39621.b2

Cited by 115 publications

(18 citation statements)

References 32 publications

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“…Lacosamide has a long-term safety profile and sustained efficacy in PDN. Apart from treating pain, use of lacosamide leads to improvements in the “physical functioning” and “vitality” subdomains of the SF-36 [37, 38].…”

Section: Resultsmentioning

confidence: 99%

Quality of Life in Painful Peripheral Neuropathies: A Systematic Review

Girach

Julian

Varrassi

et al. 2019

Pain Research and Management

104

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Objective. Neuropathic pain is a common presenting complaint of patients with peripheral neuropathy (PN) and is considered one of the most disabling neuropathic symptoms, with detrimental effects on patients’ quality of life (QoL). The aim of this review was to overview the current literature that focuses on QoL in painful PN of various aetiologies. We sought to clarify the direct effect of pain and its treatment on patients’ QoL. Methodology. A systematic computer-based literature search was conducted using the PubMed database to search for papers on QoL in painful PN. Information was extracted regarding prevalence, demographics, and response to treatment where relevant. Results. We identified 66 articles eligible for inclusion. The vast majority of studies (n=47) focused on patients with diabetic PN. Other aetiologies of painful PN where QoL has been studied to date include gluten, immune-mediated, HIV, chemotherapy-induced, and chronic idiopathic axonal polyneuropathy. Pharmacological treatment is the mainstay in managing pain and has a direct positive and independent effect on the overall QoL. Other nonpharmacological approaches can also be of benefit, either alone or as adjuvant treatments, and are discussed. Conclusion. The findings demonstrate that QoL is impaired in painful PN and should not be neglected in clinical practice. Patients’ pain management and subsequent impact on QoL should routinely be assessed and monitored.

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Section: Resultsmentioning

confidence: 99%

Quality of Life in Painful Peripheral Neuropathies: A Systematic Review

Girach

Julian

Varrassi

et al. 2019

Pain Research and Management

104

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“…Vimpat is used clinically for adjunctive control of epileptic seizures [5] and has also been approved for treatment of painful diabetic neuropathy [52]. Vimpat modulates slow inactivation of Na + channels [22; 56] with an IC 50 of 80 µM [71].…”

Section: Introductionmentioning

confidence: 99%

(S)-lacosamide inhibition of CRMP2 phosphorylation reduces postoperative and neuropathic pain behaviors through distinct classes of sensory neurons identified by constellation pharmacology

Moutal

Chew

Yang

et al. 2016

Pain

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Chronic pain affects the life of millions of people. Current treatments have deleterious side effects. We have advanced a strategy for targeting protein interactions which regulate the N-type voltage-gated calcium (CaV2.2) channel as an alternative to direct channel block. Peptides uncoupling CaV2.2 interactions with the axonal collapsin response mediator protein 2 (CRMP2) were antinociceptive without effects on memory, depression, and reward/addiction. A search for small molecules that could recapitulate uncoupling of the CaV2.2–CRMP2 interaction identified (S)-lacosamide [(S)-LCM], the inactive enantiomer of the Food and Drug Administration–approved antiepileptic drug (R)-lacosamide [(R)-LCM, Vimpat]. We show that (S)-LCM, but not (R)-LCM, inhibits CRMP2 phosphorylation by cyclin dependent kinase 5, a step necessary for driving CaV2.2 activity, in sensory neurons. (S)-lacosamide inhibited depolarization-induced Ca2+ influx with a low micromolar IC50. Voltage-clamp electrophysiology experiments demonstrated a commensurate reduction in Ca2+ currents in sensory neurons after an acute application of (S)-LCM. Using constellation pharmacology, a recently described high content phenotypic screening platform for functional fingerprinting of neurons that uses subtype-selective pharmacological agents to elucidate cell-specific combinations (constellations) of key signaling proteins that define specific cell types, we investigated if (S)-LCM preferentially acts on certain types of neurons. (S)-lacosamide decreased the dorsal root ganglion neurons responding to mustard oil, and increased the number of cells responding to menthol. Finally, (S)-LCM reversed thermal hypersensitivity and mechanical allodynia in a model of postoperative pain, and 2 models of neuropathic pain. Thus, using (S)-LCM to inhibit CRMP2 phosphorylation is a novel and efficient strategy to treat pain, which works by targeting specific sensory neuron populations.

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“…En estudios en humanos, la mayoría de los trabajos publicados se han hecho en neuropatía diabética dolorosa. El primero de ellos, en un ensayo doble ciego en 119 pacientes, los autores encuentran mejoría significativa comparada con el placebo (27). Estudios posteriores doble ciego han encontrado resultados discordantes: mientras que unos sí han alcanzado diferencias estadísticamente significativas (28,29), otros no, al menos en el objetivo primario del estudio (30 (PBO, n = 291; lacosamida 200-600 mg/día, n = 1.023; duración máxima del tratamiento de 10 semanas o 20 semanas) (31,32).…”

Section: Lacosamida Y Dolor Neuropáticounclassified

“…Se observó un pequeño aumento del intervalo PR con lacosamida, también dosis-dependiente (32). La seguridad y eficacia a largo plazo (hasta 2,5 años) en extensión abierta del tratamiento con lacosamida (hasta 400 mg/día) fue evaluada en pacientes (n = 69) con DND que habían completado el estudio de Fase II SP614 (27). La variación en las puntuaciones de la escala de dolor Likert [media ± desviación estándar (DE)] desde la basal y por todo el periodo de tratamiento fueron -2,31 ± 2,02 (p = 0,001), -3,79 ± 2,4 (p < 0,001), y -3,15 ± 2,27 (p < 0,001) para lacosamida 200 mg/día, 300 mg/ día y 400 mg/día, respectivamente.…”

Section: Lacosamida Y Dolor Neuropáticounclassified

Lacosamida en el tratamiento del dolor neuropático

Montero¹,

Curado²

2016

Rev. Soc. Esp. Dolor.

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Rev Soc Esp Dolor 2016; 23(6): 316-325Recibido: 30-11-15. Aceptado: 20-02-16. Dolor 2016;23(6):316-325. Alcántara Montero A y González Curado A. Lacosamida en el tratamiento del dolor neuropático. Rev Soc Esp ABSTRACTMost of the clinical practice guidelines consulted agree that tricyclics, dual (venlafaxine/duloxetine) antidepressants, gabapentin/pregabalin antiepileptics, lidocaine 5 % patches and capsaicin 8 % patches are the first-line drugs in the treatment of peripheral neuropathic pain, being tramadol and some strong opioids (morphine, oxycodone and tapentadol) second-line drugs treatment. Moreover, the prevalence of neuropathic pain refractory to treatment is about 1,5 % of the population, so that an estimated 50 % of patients not responding to prescribed treatment. There are other antiepileptics who not have neuropathic pain indication by regulatory agencies, such as lamotrigine, topiramate or oxcarbazepine, but are used in routine clinical practice off-label.Although not approved the use of lacosamide in the treatment of neuropathic pain, some authors believe that could be a good option for patients who do not respond to standard treatments.The following article summarizes the main pharmacological characteristics of lacosamide as well as the literature available in neuropathic pain.Key words: Lacosamide, neuropathic pain. RESUMENLa mayor parte de las guías de práctica clínica consultadas coinciden en señalar que los antidepresivos tricíclicos, duales (venlafaxina/duloxetina), los antiepilépticos gabapentina/pregabalina, apósitos de lidocaína 5 % y parches de capsaicina 8 % constituyen los fármacos de primera línea en el tratamiento del dolor neuropático periférico, siendo el tramadol y algunos opioides potentes (morfina, oxicodona y tapentadol) fármacos de segunda línea de tratamiento. Por otra parte, la prevalencia de dolor neuropático refractario al tratamiento se acerca al 1,5 % de la población, de forma que se calcula que un 50 % de los pacientes no responde al tratamiento prescrito. Existen otros antiepilépticos que no tienen indicación en dolor neuropático por las agencias reguladoras, como la lamotrigina, topiramato u oxcarbazepina, pero se utilizan en la práctica clínica habitual fuera de indicación.Aunque no está aprobado el uso de lacosamida en el tratamiento del dolor neuropático, algunos autores consideran que podría ser una buena opción para aquellos pacientes que no responden a los tratamientos habituales.En el siguiente artículo se resumen las principales características farmacológicas de lacosamida, así como la bibliografía disponible en dolor neuropático.Palabras clave: Lacosamida, dolor neuropático. INTRODUCCIÓNSe define el dolor neuropático (DN) como el dolor que aparece como consecuencia directa de una lesión o enfermedad del sistema somatosensorial (1). El DN crónico no tiene función biológica alguna, e impone con frecuencia alteraciones físicas, emocionales, sociales y económicas, las cuales dificultan profundamente la vida de los pacientes que lo sufren. Es un problema clínico imp...

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Lacosamide in Painful Diabetic Peripheral Neuropathy

Abstract: Lacosamide seems to attenuate pain in diabetic neuropathy in doses up to 400 mg/d and improves quality of life issues.

Cited by 115 publications

References 32 publications

Quality of Life in Painful Peripheral Neuropathies: A Systematic Review

Quality of Life in Painful Peripheral Neuropathies: A Systematic Review

(S)-lacosamide inhibition of CRMP2 phosphorylation reduces postoperative and neuropathic pain behaviors through distinct classes of sensory neurons identified by constellation pharmacology

Lacosamida en el tratamiento del dolor neuropático

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