Effect of Pregabalin on Radiotherapy-Related Neuropathic Pain in Patients With Head and Neck Cancer: A Randomized Controlled Trial

Abstract

Purpose Neuropathic pain is an unavoidable treatment-related adverse event among patients with head and neck cancer who are undergoing radiotherapy. We aimed to test the efficacy and safety of pregabalin versus placebo in the treatment of radiotherapy-related neuropathic pain. Patients and Methods This randomized, double-blind, placebo-controlled trial was conducted in four centers in China. Eligible patients with a mean pain intensity score of 4 or more on an 11-point numeric rating scale were randomly assigned to receive either active treatment with a flexible dose of pregabalin or placebo for 16 weeks. The primary efficacy outcome was pain reduction measured on the numeric rating scale. Result There were 128 patients who received treatment as randomly assigned. Pain intensity reduction was 2.44 in the pregabalin arm and 1.58 in the placebo arm at week 16, yielding an adjusted mean difference of 0.87 (95% CI, 0.30 to 1.44; P = .003). In the pregabalin arm, 38 patients (59.4%) achieved at least 30% pain relief versus 21 (32.8%) in the placebo arm ( P = .006). Nineteen patients (29.7%) in the pregabalin group and five (7.8%) in the placebo group achieved 50% or greater pain relief ( P = .003). Total scores on the Profile of Mood States-Short Form, pain severity and functional interference of Brief Pain Inventory-Short Form, as well as the physiology and psychology domain of the WHO Quality of Life-BREF all were reduced significantly at week 16 in patients who received pregabalin compared with those who received placebo. There was no significant difference ( P = .29) in the incidence of experiencing at least one adverse event in the pregabalin arm (n = 35; 54.7%) versus the placebo arm (n = 29; 45.3%). Conclusion Patients treated with pregabalin with radiotherapy-related neuropathic pain had greater pain alleviation, better mood states, and higher quality of life compared with patients in the placebo group, with a good tolerability.

Pharmacotherapeutic Options for Managing Neuropathic Pain: A Systematic Review and Meta-Analysis

“…Four RCTs testing the effect of pregabalin [ 10 , 12 , 14 , 15 ] and two RCTs testing the effect of mirogabalin [ 11 , 13 ] were included in the meta-analysis. The combined NNT using a random-effects model was 8.40 (4.85; 31.15) (test for heterogeneity: χ 2 = 24.2; d f = 5; P =0.0002; I 2 = 79.32%) ( Figure 2(b) .…”

Opioid therapy vs. multimodal analgesia in head and neck Cancer (OPTIMAL-HN): study protocol for a randomized clinical trial

“…An opioid crisis also looms over North America with thousands of lives being claimed to opioid misuse, addiction, and overdose [13]. Importantly, neuropathic pain does not respond effectively to opioid therapy and often requires escalating doses, thereby exacerbating opioid side effects [17][18][19][20].…”

“…Few studies have explored the role Gabapentinoids play in treating radiation-induced neuropathic pain. A randomized double-blinded placebo-controlled clinical trial by Jiang et al established that in HNC patients who suffered from chronic radiotherapy-related neuropathic pain after treatment, Pregabalin improved pain scores and quality of life compared with placebo [20]. Gabapentinoids have also been found to interact synergistically with opioids through the inhibition of nociception and simultaneous decrease in hyperexcitation [5].…”

Pain management in patients undergoing radiation therapy for head and neck cancer – a descriptive study

“…In accordance with the WHO pain ladder, strong opioids are the mainstay of analgesic therapy in treating moderate to severe cancer-related pain, including HNC pain [14][15][16]. Previous studies have described that adequate pain relief for patients with HNC who suffer from RT-related oral mucositis is difficult to achieve [13,[17][18][19][20][21]. For this group of patients, local guidelines at Pain and Rehabilitation Centre (PRC), University Hospital, Linköping, Sweden, are based on the WHO ladder, i.e., acetaminophen, non-steroid anti-inflammatory drugs (NSAID), and opioid analgesics [15].…”

“…As a complement all patients with HNC undergo weekly oral care checks by the hospital dentist and use daily mouthwash with lidocaine hydrochloride and mycostatin. When the pain mechanism is considered to be neuropathic, adjuvant analgesia can be provided with gabapentinoids such as pregabalin [21]. Attention is given to side effects of opioid therapy such as dry mouth, constipation, nausea, and decreased alertness [19,22].…”