A CRITICAL-REVIEW OF CONTROLLED CLINICAL-TRIALS FOR PERIPHERAL NEUROPATHIC PAIN AND COMPLEX REGIONAL PAIN SYNDROMES

The purpose of this review was to identify and analyze the controlled clinical trial data for peripheral neuropathic pain (PNP) and complex regional pain syndromes (CRPS). A total of 72 articles were found, whi ch included 92 controlled drug trials using 48 different treatments. T he methods of these studies were critically reviewed and the results s ummarized and compared. The PNP trial literature gave consistent suppo rt (two or more trials) for the analgesic effectiveness of tricyclic a ntidepressants, intravenous and topical lidocaine, intravenous ketamin e, carbamazepine and topical aspirin. There was limited support (one t rial) for the analgesic effectiveness of oral, topical and epidural cl onidine and for subcutaneous ketamine. The trial data were contradicto ry for mexiletine, phenytoin, topical capsaicin, oral non-steroidal an ti-inflammatory medication, and intravenous morphine. Analysis of the trial methods indicated that mexiletine and intravenous morphine were probably effective analgesics for PNP, while non-steroidals were proba bly ineffective, Codeine, magnesium chloride, propranolol, lorazepam, and intravenous phentolamine all failed to provide analgesia in single trials. There were no long-term data supporting the analgesic effecti veness of any drug and the etiology of the neuropathy did not predict treatment outcome. Review of the controlled trial literature for CRPS identified several potential problems with current clinical practices. The trial data only gave consistent support for analgesia with cortic osteroids, which had long-term effectiveness. There was limited suppor t for the analgesic effectiveness of topical dimethylsulfoxyde (DMSO), epidural clonidine and intravenous regional blocks (IVRBs) with brety lium and ketanserin. The trial data were contradictory for intranasal calcitonin and intravenous phentolamine and analysis of the trial meth ods indicated that both treatments were probably ineffective for most patients. There were consistent trial data indicating that guanethidin e and reserpine IVRBs were ineffective, and limited trial data indicat ing that droperidol and atropine IVRBs were ineffective. No placebo co ntrolled data were available to evaluated sympathetic ganglion blocks (SGBs) with local anesthetics, surgical sympathectomy, or physical the rapy. Only the capsaicin trials presented data which allowed for meta- analysis, This meta-analysis demonstrated a significant capsaicin effe ct with a pooled odds ratio of 2.35 (95% confidence intervals 1.48, 3. 22). The methods scores were higher (P < 0.01) for the PNP trials (66. 2 +/- 1.5, n = 66) than the CRPS trials (57.6 +/- 2.9, n = 26). The CR PS trials tended to use less subjects and were less likely to use plac ebo controls, double-blinding, or perform statistical tests for differ ences in outcome measures between groups. There was almost no overlap in the controlled trial literature between treatments for PNP and CRPS , and treatments used in both conditions (intravenous phentolamine and epidural clonidine) had similar results. (C) 1997 International Assoc iation for the Study of Pain. Published by Elsevier Science B.V.