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Almost 100 years after the first report of the thalamic syndrome, the scientific basis for the treatment of central post-stroke pain (CPSP) is remarkably small. Therefore, the authors aimed to provide evidence-based recommendations for the treatment of CPSP.The authors performed a systematic review of the literature on the pharmacologic treatment of CPSP. All studies and case series were included and evaluated according to their level of evidence. Only CPSP was considered, not other types of central pain.Amitriptyline and lamotrigine are the only oral drugs proven to be effective in the treatment of CPSP in a placebo-controlled study. IV drugs such as lidocaine, propofol, and ketamine have shown efficacy for short-term control of CPSP, but their application and potential side effects make them unsuitable for long-term treatment. The novel antiepileptic drug gabapentin has been reported to control CPSP in a few patients.Amitriptyline, lamotrigine, and gabapentin provide a more favorable efficacy and safety profile than the classic antiepileptic drugs carbamazepine and phenytoin, for which no placebo-controlled evidence of efficacy was found. Clinical trials are urgently needed to optimize pharmacologic treatment of CPSP.