Association of low-dose naltrexone and transcranial direct current stimulation in fibromyalgia: a randomized, double-blinded, parallel clinical trial

INTRODUCTION: Fibromyalgia is a complex, generalized, and diffuse chronic musculoskeletal pain. Pharmacological approaches are widely used to relieve pain and increase quality of life. Low-Dose Naltrexone (LDN) was shown to increase the nociceptive threshold in patients with fibromyalgia. Transcranial Direct Current Stimulation (tDCS) is effective for pain management. OBJECTIVE: The purpose of this study was to evaluate the analgesic and neuromodulatory effects of a combination of LDN and tDCS in patients with fibromyalgia. METHODS: This was a randomized, double-blinded, parallel, placebo/sham-controlled trial (NCT04502251; RBR-7HK8N) in which 86 women with fibromyalgia were included, and written informed consent was obtained from them. The patients were allocated into four groups: LDN + tDCS (n = 21), LDN + tDCS Sham (n = 22), placebo + tDCS (n = 22), and placebo+tDCS Sham (n = 21). The LDN or placebo (p.o.) intervention lasted 26 days; in the last five sessions, tDCS was applied (sham or active, 20 min, 2 mA). The following categories were assessed: sociodemographic, Visual Analog Pain Scale (VAS), Pain Catastrophizing Scale (PCS), State-Trait Anxiety Inventory (STAI), Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Inventory (BDI-II), Profile of Chronic Pain Scale (PCP:S), Pain Pressure Threshold (PPT), and Conditioned Pain Modulation (CPM). Blood samples were collected to analyze BDNF serum levels. RESULTS: At baseline, no significant difference was found regarding all measurements. VAS pain was significantly reduced in the LDN + tDCS (p = 0.010), LDN + tDCS Sham (p = 0.001), and placebo+tDCS Sham (p = 0.009) groups. In the PCP:S, the LDN+tDCS group showed reduced pain frequency and intensity (p = 0.001), effect of pain on activities (p = 0.014) and emotions (p = 0.008). Depressive symptoms reduced after all active interventions (p > 0.001). CONCLUSION: Combined LDN+tDCS has possible benefits in reducing pain frequency and intensity; however, a placebo effect was observed in pain using VAS, and further studies should be performed to analyze the possible association.