The effect of lacosamide in peripheral neuropathic pain: A randomized, double-blind, placebo-controlled, phenotype-stratified trial. 2024

Malin Erika Carmland, and Melissa Dall Kreutzfeldt, and Jakob Vormstrup Holbech, and Peter Kolind Brask-Thomsen, and Thomas Krøigård, and Peter Nørregaard Hansen, and Hatice Tankisi, and Troels Staehelin Jensen, and Flemming Winther Bach, and Søren Hein Sindrup, and Nanna Brix Finnerup
Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark.

Neuropathic pain is common and difficult to treat. The sodium channel blocker lacosamide is efficacious in animal models of pain, but its effect on neuropathic pain in humans is inconclusive. In a multicentre, randomized, double-blinded placebo-controlled phenotype stratified trial, we examined if lacosamide produced better pain relief in patients with the irritable nociceptor phenotype compared to those without. The primary outcome was the change in daily average pain from baseline to last week of 12 weeks of treatment. Secondary and tertiary outcomes included pain relief, patient global impression of change and presence of 30% and 50% pain reduction. The study was prematurely closed with 93 patients included and 63 randomized to lacosamide or placebo in a 2:1 ratio, of which 49 fulfilled the per protocol criteria and was used for the primary objective. We did not find a better effect of lacosamide in patients with the irritable nociceptor phenotype, the 95% CI for the primary objective was 0.41 (-1.2 to 2.0). For all patients randomized, lacosamide had no effect on the primary outcome, but significantly more patients were responders to lacosamide than during placebo, with an NNT of 4.0 (95% CI 2.3-16.1) and 5.0 (95% CI 2.8-24.5) for 30% and 50% pain reduction respectively. We did not identify any predictors for response. Lacosamide was generally well tolerated. We could not confirm that lacosamide was more efficacious in patients with the irritable nociceptor type, but the study was prematurely closed, so we cannot exclude a small difference. Treatment of neuropathic pain is often a trial and error process. Little is known about which patient benefit from which kind of medication. The sodium channel blocker lacosamide shows variable effect on neuropathic pain. Pain sensory phenotype, as defined by quantitative sensory testing, did not predict response to treatment with lacosamide.

UI MeSH Term Description Entries
D009437 Neuralgia Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. Nerve Pain,Neurodynia,Paroxysmal Nerve Pain,Neuralgia, Atypical,Neuralgia, Iliohypogastric Nerve,Neuralgia, Ilioinguinal,Neuralgia, Perineal,Neuralgia, Stump,Neuralgia, Supraorbital,Neuralgia, Vidian,Neuropathic Pain,Atypical Neuralgia,Atypical Neuralgias,Iliohypogastric Nerve Neuralgia,Iliohypogastric Nerve Neuralgias,Ilioinguinal Neuralgia,Ilioinguinal Neuralgias,Nerve Neuralgia, Iliohypogastric,Nerve Neuralgias, Iliohypogastric,Nerve Pain, Paroxysmal,Nerve Pains,Nerve Pains, Paroxysmal,Neuralgias,Neuralgias, Atypical,Neuralgias, Iliohypogastric Nerve,Neuralgias, Ilioinguinal,Neuralgias, Perineal,Neuralgias, Stump,Neuralgias, Supraorbital,Neuralgias, Vidian,Neurodynias,Neuropathic Pains,Pain, Nerve,Pain, Neuropathic,Pain, Paroxysmal Nerve,Pains, Nerve,Pains, Neuropathic,Pains, Paroxysmal Nerve,Paroxysmal Nerve Pains,Perineal Neuralgia,Perineal Neuralgias,Stump Neuralgia,Stump Neuralgias,Supraorbital Neuralgia,Supraorbital Neuralgias,Vidian Neuralgia,Vidian Neuralgias
D010147 Pain Measurement Scales, questionnaires, tests, and other methods used to assess pain severity and duration in patients or experimental animals to aid in diagnosis, therapy, and physiological studies. Analgesia Tests,Analogue Pain Scale,Formalin Test,McGill Pain Questionnaire,Nociception Tests,Pain Assessment,Pain Intensity,Pain Severity,Tourniquet Pain Test,Visual Analogue Pain Scale,Analog Pain Scale,Assessment, Pain,McGill Pain Scale,Visual Analog Pain Scale,Analgesia Test,Analog Pain Scales,Analogue Pain Scales,Formalin Tests,Intensity, Pain,Measurement, Pain,Nociception Test,Pain Assessments,Pain Intensities,Pain Measurements,Pain Questionnaire, McGill,Pain Scale, Analog,Pain Scale, Analogue,Pain Scale, McGill,Pain Severities,Pain Test, Tourniquet,Questionnaire, McGill Pain,Scale, Analog Pain,Scale, Analogue Pain,Scale, McGill Pain,Severity, Pain,Test, Analgesia,Test, Formalin,Test, Nociception,Test, Tourniquet Pain,Tests, Nociception,Tourniquet Pain Tests
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D004311 Double-Blind Method A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment. Double-Masked Study,Double-Blind Study,Double-Masked Method,Double Blind Method,Double Blind Study,Double Masked Method,Double Masked Study,Double-Blind Methods,Double-Blind Studies,Double-Masked Methods,Double-Masked Studies,Method, Double-Blind,Method, Double-Masked,Methods, Double-Blind,Methods, Double-Masked,Studies, Double-Blind,Studies, Double-Masked,Study, Double-Blind,Study, Double-Masked
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000078334 Lacosamide An acetamide derivative that acts as a blocker of VOLTAGE-GATED SODIUM CHANNELS. It is used as an anticonvulsant, for adjunctive or monotherapy, in the treatment of PARTIAL SEIZURES. N-benzyl-2-acetamido-3-methoxypropionamide,N-benzyl-AcMeOPrNH2,Vimpat,N benzyl 2 acetamido 3 methoxypropionamide,N benzyl AcMeOPrNH2
D016896 Treatment Outcome Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series. Rehabilitation Outcome,Treatment Effectiveness,Clinical Effectiveness,Clinical Efficacy,Patient-Relevant Outcome,Treatment Efficacy,Effectiveness, Clinical,Effectiveness, Treatment,Efficacy, Clinical,Efficacy, Treatment,Outcome, Patient-Relevant,Outcome, Rehabilitation,Outcome, Treatment,Outcomes, Patient-Relevant,Patient Relevant Outcome,Patient-Relevant Outcomes
D026941 Sodium Channel Blockers A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity. Channel Blockers, Sodium,Sodium Channel Blocker,Sodium Channel Inhibitor,Sodium Channel Inhibitors,Blocker, Sodium Channel,Channel Blocker, Sodium,Channel Inhibitor, Sodium,Channel Inhibitors, Sodium,Inhibitor, Sodium Channel,Inhibitors, Sodium Channel

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