Challapalli, V., Tremont-Lukats, I.W., McNicol, E.D., Lau, J., & Carr, D.B. (2005). Systemic administration of local anesthetic agents to relieve neuropathic pain. Cochrane Database of Systematic Reviews, 19(4). 

STUDY PURPOSE: To assess lidocaine given in different doses in comparison with a placebo, diphenhydramine as a placebo, and active controls (morphine sulfate, ketamine, or amantadine). Mexiletine was compared to an inactive placebo and an active placebo (amitriptyline and gabapentin). Tocainide was used in one trial against carbamazepine. Pain was rated on an 11-point numeric rating scale (NRS). 

DATABASES USED: MEDLINE 1996–2004; EMBASE 1980–2002; CancerLit through December 2002; Cochrane Central Register of Controlled Trials through the second quarter of 2004; System for Information on Grey literature in Europe (SIGLE) and LILACS 1996–2001; hand searches of conference proceedings, textbooks, original articles, and reviews

• FINAL NUMBER STUDIES INCLUDED = 30 
• KEY SAMPLE CHARACTERISTICS: Thirty randomized, double-blind, controlled clinical trials, 16 with IV lidocaine, 12 with mexiletine, one trial with lidocaine plus mexiletine sequentially, and one trial with tocainide. Twenty-one trials were crossover studies, and nine were parallel. Measurement of pain intensity or pain relief was in minutes. All studies used a 0–100 m Visual Analog Scale (VAS) or a 0–10 numeric scale. The mean age was 51.7 years. The median number of participants per trial was 28. Multiple diagnoses were represented.

Intravenous lidocaine and its oral analog mexiletine were more effective than a placebo in decreasing neuropathic pain, were safe, and were as effective as other analgesics. The treatment effect was similar for both drugs. The analgesic effect was clinically important.

More than one half of the 29 trials were of low or fair methodological quality. One third did not adequately describe the method for random allocation, and 80% did not estimate the number of participants needed to have statistical power. However, some of these deficiencies could be because of incomplete reporting. Five trials did not describe exclusion criteria.

There is a need to study specific diseases and patient satisfaction to assess if statistically significant pain relief is clinically meaningful.