The Effect of Early Use of Supplemental Therapy on Preventing Postherpetic Neuralgia: A Systematic Review and Meta-analysis.

Background Postherpetic neuralgia (PHN) is the most common and refractory complication of herpes zoster (HZ). Aggressive treatment of acute pain in HZ has the potential to prevent the development of PHN, but the preventive efficacy of supplemental therapy commonly used in clinical practice is controversial. Objectives Our aim is to examine the efficacy of supplemental therapy in preventing PHN. Study design A meta-analysis. Setting All of the selected studies are randomized controlled trials (RCTs). Methods A systematic and comprehensive database search was performed in CENTRAL (1976 to March 2016), MEDLINE (1977 to January 2016), and EMBASE (May 1980 to December 2016). According to the selection criteria, data of the included studies were extracted by 2 independent reviewers. RevMan 5.3 (The Nordic Cochrane Centre for The Cochrane Collaboration, Copenhagen, Denmark) was used to perform this meta-analysis. Results Nine trials, with a total of 1,757 participants (888 in the treatment group and 867 in the control group), were included in the final analysis. Of the 9 trials, 3 compared systemic adjunct therapies with the control, and 6 trials compared interventional procedures with the control. The early use of supplemental therapy was associated with a significantly less incidence of PHN in 3 months after acute rash presence (RR 0.53, 95%CI 0.34 to 0.81, P = 0.004). The systemic adjunct treatments subgroup was not found with any benefit (RR 0.76, 95%CI 0.46 to 1.26, P = 0.29). A significant decrease in visual analog scale (VAS) score was reported in all of the 9 trials when compared with baseline, but the decrease slopes of the pain scores between the treatment group and the control group were similar in 5 trials. The most common adverse events in systemic adjunct treatments group were dizziness, nausea, dyspepsia, and dry mouth. The interventional procedures group was associated with procedure-related complications such as mild hypotension, voice change, dysphagia, drowsiness, and headache. Limitations There were only a few RCTs and most of them lacked adequate allocation concealment and blinding. Further, the English-only approach might have omitted trials published in non-English journals. Finally, some of the secondary outcomes of data were insufficient for meta-analysis, and future studies are warranted. Conclusion This meta-analysis demonstrates that the early use of supplemental therapy can significantly reduce the incidence of PHN. The subgroup analysis shows that supplemental interventional procedures have a beneficial effect on preventing PHN, while supplemental systemic adjunct treatments do not. The early use of interventional procedures for acute pain may be a preferred choice for patients without contraindication, but evidence is moderate. More data from high-quality RCTs will be needed to confirm these results.Key words: Postherpetic neuralgia, systemic treatment, local anesthesia, analgesia, meta-analysis.