Pharmacological and non-pharmacological strategies for preventing postherpetic neuralgia: a systematic review and network meta-analysis

Abstract

Background: Postherpetic neuralgia (PHN) is a refractory complication of herpes zoster (HZ). To prevent PHN, various strategies have been aggressively adopted. However, the efficacy of these strategies remains controversial. Therefore, we aimed to estimate the relative efficacy of various strategies used in clinical practice for preventing PHN using a network meta-analysis (NMA).

Methods: We performed a systematic and comprehensive search to identify all randomized controlled trials. The primary outcome was the incidence of PHN at 3 months after acute HZ. We performed both frequentist and Bayesian NMA and used the surface under the cumulative ranking curve (SUCRA) values to rank the interventions evaluated.

Results: In total, 39 studies were included in the systematic review and NMA. According to the SUCRA value, the incidence of PHN was lower in the order of continuous epidural block with local anesthetics and steroids (EPI-LSE), antiviral agents with subcutaneous injection of local anesthetics and steroids (AV + sLS), antiviral agents with intracutaenous injection of local anesthetics and steroids (AV + iLS) at 3 months after acute HZ. EPI-LSE, AV + sLS and AV + iLS were also effective in preventing PHN at 1 month after acute HZ. And paravertebral block combined with antiviral and antiepileptic agents was effective in preventing PHN at 1, 3, and 6 months.

Conclusions: The continuous epidural block with local anesthetics and steroid, antiviral agents with intracutaneous or subcutaneous injection of local anesthetics and a steroid, and paravertebral block combined with antiviral and antiepileptic agents are effective in preventing PHN.

Keywords: Anesthesia; Anticonvulsants; Autonomic Nerve Block; Bayes Theorem; Epidural; Injections; Local; Nerve Block; Network Meta-Analysis; Neuralgia; Postherpetic; Stellate Ganglion; Steroids; Systematic Review; Therapeutics..

Fig. 1

Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) flowchart of included and excluded trials. RCT: randomized controlled trial.

Fig. 2

Network plot of included studies. The nodes show each strategy and the edges show the available direct comparisons among the strategies. The nodes and edges are weighed based on the number of included patients and inverse of standard error of effect. (A) The incidence of postherpetic neuralgia at 3 months after acute herpes zoster, (B) the incidence of postherpetic neuralgia at 1 month after acute herpes zoster, (C) the incidence of postherpetic neuralgia at 6 months after acute herpes zoster, (D) pain score measured at 3 months after acute herpes zoster, (E) pain score measured at 1 month after acute herpes zoster, and (F) pain score measured at 6 months after acute herpes zoster. CTR: control, RTx: radiotherapy, VZVIG: varicella zoster vaccine immunoglobulin, ACTH: adrenocorticotrophic hormone.

Fig. 3

Inconsistency plot between the direct and indirect effect estimates for the same comparison. Inconsistency factor (IF) as the absolute difference with 95% confidence interval (CI) between the direct and indirect estimates for each paired comparison is presented. IF values close to 0 indicate that the two sources are in agreement. (A) The incidence of postherpetic neuralgia at 3 months after acute herpes zoster, (B) the incidence of postherpetic neuralgia at 1 month after acute herpes zoster, (C) the incidence of postherpetic neuralgia at 6 months after acute herpes zoster, (D) pain score measured at 3 months after acute herpes zoster, and (E) pain score measured at 1 month after acute herpes zoster.

Fig. 4

Predictive interval plots (PrIs) compared with control. A diamond shape represents the mean summary effects. The black line represents the 95% confidence interval (CI), and the red line represents the PrI. PrIs provide an interval that is expected to encompass the estimate of a future study. (A) The incidence of postherpetic neuralgia at 3 months after acute herpes zoster, (B) the incidence of postherpetic neuralgia at 1 month after acute herpes zoster, and (C) the incidence of postherpetic neuralgia at 6 months after acute herpes zoster. CTR: control, RTx: radiotherapy, VZVIG: varicella zoster vaccine immunoglobulin, ACTH: adrenocorticotrophic hormone.

Fig. 5

The expected mean ranking and surface of under cumulative ranking curve (SUCRA) values for each strategy. The X-axis corresponds to the expected mean ranking based on the SUCRA value, and the Y-axis corresponds to the SUCRA value. (A) The incidence of postherpetic neuralgia at 3 months after acute herpes zoster, (B) the incidence of postherpetic neuralgia at 1 month after acute herpes zoster, (C) the incidence of postherpetic neuralgia at 6 months after acute herpes zoster, (D) pain score measured at 3 months after acute herpes zoster, and (E) pain score measured at 1 month after acute herpes zoster.

Fig. 6

Comparison-adjusted funnel plot. (A) The incidence of postherpetic neuralgia at 3 months after acute herpes zoster, (B) the incidence of postherpetic neuralgia at 1 month after acute herpes zoster, (C) the incidence of postherpetic neuralgia at 6 months after acute herpes zoster, (D) pain score measured at 3 months after acute herpes zoster, and (E) pain score measured at 1 month after acute herpes zoster.

Fig. 7

The surface of under cumulative ranking curve (SUCRA) values from the Bayesian model compared with SUCRA values from the frequentist model. The X-axis corresponds to the SUCRA values from the frequentist model and the Y-axis corresponds to the SUCRA values from the Bayesian model. (A) The incidence of postherpetic neuralgia at 3 months after acute herpes zoster, (B) the incidence of postherpetic neuralgia at 1 month after acute herpes zoster, (C) the incidence of postherpetic neuralgia at 6 months after acute herpes zoster, (D) pain score measured at 3 months after acute herpes zoster, (E) pain score measured at 1 month after acute herpes zoster.