Evaluation of the Efficacy and Tolerance of Low Doses of Ethosuximide in the Treatment of Peripheral Neuropathic Pain

Multicenter, randomized, double-blind, placebo-controlled therapeutic trial evaluating the efficacy and safety of low doses of ethosuximide in neuropathic pain patients.

• Ethosuximide (Drug): Taking the treatment (1 daily intake during the evening meal) according to increasing dosage: Step 1: 2.5 ml (125 mg) / day for 7 days Step 2: 5 ml (250 mg) / day for 7 days Step 3: 7.5 ml (375 mg) / day for 7 days Step 4 (final): 10 ml (500 mg) / day for the remainder of the study (12 weeks).
• Placebo (Drug): Taking the treatment (1 daily intake during the evening meal) according to increasing dosage: Step 1: 2.5 ml (125 mg) / day for 7 days Step 2: 5 ml (250 mg) / day for 7 days Step 3: 7.5 ml (375 mg) / day for 7 days Step 4 (final): 10 ml (500 mg) / day for the remainder of the study (12 weeks).

Primary outcomes

• Neuropathic pain intensity [Day 0]: Variation in pain intensity (NRS, Numerical Rating Scale 0-10) averaged over the 7 days prior to the start of treatment (D0) and over the last 7 days of treatment (12 weeks).
• Neuropathic pain intensity [Day 84]: Variation in pain intensity (NRS, Numerical Rating Scale 0-10) averaged over the 7 days prior to the start of treatment (D0) and over the last 7 days of treatment (12 weeks).

Secondary outcomes

• Patient's Global Impression of Change (PGIC scale) [Day 0, Day 28, Day 56, Day 84]: Assessment of the patient's feelings about the effectiveness of the treatment.
• Health related quality of life [Day 0, Day 28, Day 56, Day 84]: Assessment of the patient's quality of life with EQ-5D-3L questionnaire
• Quantitative sensory testing (QST) [Day 0, Day 28, Day 56, Day 84]: Assessment of mechanical sensitivity using the von Frey test (static allodynia) and the brush test (dynamic allodynia).
• adverse event [Throughout the study]: Assessment of the tolerability of the treatment by patients and clinicians

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Male or female (under effective contraception: pill, implant, IUD, sterilization) aged 18 years or older, suffering from peripheral neuropathic pain (DN4 ≥ 4) for more than 3 months, of intensity ≥ 4 on a numerical scale from 0 to 10, and whose analgesic treatment has been stable for more than a month,
* Patients affiliated to the French Social Security system,
* Patients whose free and informed consent has been obtained.

Exclusion Criteria:

* Pregnancy (βHCG+ blood) or breastfeeding,
* Neuropathic pain due to spinal cord or brain injury, phantom limb pain or algohallucinosis,
* Fibromyalgia or algodystrophy,
* Chronic pain syndrome that the patient cannot distinguish and/or is more intense than peripheral neuropathic pain,
* Significant abnormalities in liver (transaminases > 3N, cholestasis) and renal (MDRD < 60 mL/min) tests,
* Ongoing comorbidities: cancer, neurodegenerative pathology
* Severe depressive disorder in progress (as determined by the clinician), history of suicide attempts or hospitalization for depression,
* Diabetic patients (contraindicated due to the high sugar concentration of ethosuximide, 3g / 5 ml),
* Patients who have previously received ethosuximide (epilepsy or clinical trial),
* Surgery planned throughout the entire trial,
* Medical and surgical history incompatible with the study,
* Dependence on alcohol and/or drugs (for compliance purposes),
* Known allergy to succinimides (ethosuximide, methsuximide, phensuximide),
* Psychotic disorders,
* Epileptic patients,
* Patients benefiting from a legal protection measure (curatorship, guardianship, deprived of liberty or subject to judicial safeguard).