• Efficacy: Pain Intensity - Visual Analogue Scale (VAS) [ Time Frame: Day 1 (First study visit post-disallowed drug cessation period) and 7 days after maximal-tolerated dose attained (Final Study Visit) ] [ Designated as safety issue: No ]
• Efficacy: Pain Intensity - Numerical Rating Scale (NRS) [ Time Frame: Every week during dose titration period (Days 3 and 6) and 30 days after final study visit. ] [ Designated as safety issue: No ]
• Efficacy: Pain Quality - Neuropathic Pain Symptom Inventory (NPSI) and Short Form McGill Pain Questionnaire (SF-MPQ) [ Time Frame: Day 1 (First study visit post-disallowed drug cessation period) and 7 days after maximal-tolerated dose attained (Final Study Visit) ] [ Designated as safety issue: No ]
• Efficacy: Quality of Life - Short Form 12v2 (SF-12v2) [ Time Frame: Day 1 (First study visit post-disallowed drug cessation period) and 7 days after maximal-tolerated dose attained (Final Study Visit) ] [ Designated as safety issue: No ]

Pain remains the most debilitating symptom for adult patients suffering from complex regional pain syndrome (CRPS). Most CRPS patients gain little to no relief from current painkillers. The purpose of this study is to evaluate the efficacy and safety of ethosuximide in search of much-needed adjunctive therapy to relieve the pain and suffering associated with CRPS.

This is a single centre, parallel-group, double-blind, randomized, placebo-controlled pilot clinical trial for adults suffering from complex regional pain syndrome (CRPS).

Twelve (12) subjects diagnosed with CRPS will be enrolled and randomized to receive orally, either ethosuximide or placebo. If the maximum trial medication dosage (1500mg) is reached, the subject will be in the study for a maximum of 10 weeks from screening (Clinic Visit 1) to the end of the drug cessation period. The minimum period a subject could complete the study would be 4 weeks presuming they were not previously on any disallowed drugs and only found the 500mg dose tolerable.

• Drug: Placebo
• Drug: Ethosuximide

Inclusion Criteria:

• Male or female, age ≥18 years old;
• Diagnosis of Complex Regional Pain Syndrome (CRPS) using International Association for the Study of Pain criteria >6 months;
• Normal liver function (AST level <3x normal level);
• Normal kidney function (serum creatinine <133µmol/L);
• Full blood count, haematocrit >38%;
• Willing and able to give informed consent and of completing study questionnaires;
• Stable (no change in past two months) but suboptimal pain pharmacotherapy (i.e. additional pain control felt by patient and physician to be necessary);
• Able to attend research centre according to the visit schedule;
• Women of child-bearing potential must be using a reliable form of contraception i.e. oral contraceptives, a barrier method (condom or diaphragm), intra-uterine device or abstinence.

Exclusion Criteria:

• Optimal response to opioids, antidepressants, anticonvulsants or anti- inflammatory medications;
• Any history or indication of kidney or liver disease;
• Any history of alcohol abuse;
• Presence of diabetes;
• Subjects taking other anti-epileptic drugs, including gabapentin, pregabalin, topiramate, phenytoin, carbamazepine, and oxcarbazepine;
• Pregnancy (a serum bHCG pregnancy test will be performed as part of the initial blood panel);
• Known or suspected allergy to succinimides, ethosuximide, methsuximide (Celontin®), phensuximide;
• Any history of mental illness or disorder, which in the investigators opinion, interferes with the subjects ability to accurately report treatment response;
• Participation in other clinical trial in the 30 days prior to enrolment.