Naltrexone Plus Transcranial Current Stimulation May Reduce Pain in Fibromyalgia

Transcranial Electrical Stimulation
Transcranial Electrical Stimulation
Researchers evaluated the analgesic effects of naltrexone plus transcranial direct current stimulation in patients with fibromyalgia.

Combination therapy of low-dose naltrexone and transcranial direct current stimulation (tDCS) may reduce pain in patients with fibromyalgia, according to study results published in Brazilian Journal of Anaesthesiology.

Researchers conducted a randomized, parallel, double-blind, placebo/sham-controlled trial ( Identifier: NCT04502251) to study the analgesic and neuromodulatory effects of naltrexone plus tDCS in fibromyalgia.

Participants were randomly assigned to receive low-dose naltrexone (4.5 mg) plus tDCS, naltrexone plus tDCS sham, placebo plus tDCS sham, or placebo plus tDCS. However, in the final 5 sessions, active or sham tDCS was administered for 20 minutes.

The researchers assessed the following variables: Visual Analog Pain Scale (VAS; primary outcome), State-Trait Anxiety Inventory, Beck Depression Inventory, Conditioned Pain Modulation, Pain Catastrophizing Scale, Fibromyalgia Impact Questionnaire, Profile of Chronic Pain Scale (PCP:S), Pain Pressure Threshold, and sociodemographic factors. Brain-derived neurotrophic factor levels were assessed using blood samples.

A total of 86 women aged between 18 and 65 years with fibromyalgia were included in the study; 21 received naltrexone plus tDCS, 22 received naltrexone plus tDCS sham, 21 received placebo plus tDCS sham, and 22 received placebo plus tDCS.

Measurements among all groups were similar at baseline (P >.05). After placebo/sham or active treatment, VAS pain was significantly lower among individuals in the naltrexone plus tDCS (P =.010), placebo plus tDCS sham (P =.009), and naltrexone plus tDCS sham (P =.001) groups between day 1 and day 26.

Based on the PCP:S, the naltrexone plus  tDCS group had significantly reduced interference with activities (P =.014); effect of pain on emotions (P =.008); and pain frequency and intensity (P =.001). All active interventions were associated with reduced depressive symptoms (P >.001).

This study was limited by the different approaches used, as well as by the primary use of subjective variables.

The study researchers concluded that “combined [low-dose naltrexone plus]  tDCS has possible benefits in reducing pain frequency and intensity; however, a placebo effect was observed in pain on VAS,” which necessitates further studies.


de Paulaa TMH, Castroab MS, Medeiros LF, et al. Association of low-dose naltrexone and transcranial direct current stimulation in fibromyalgia: a randomized, double-blinded, parallel clinical trial. Braz J Anesthesiol. Published online August 18, 2022. doi:10.1016/j.bjane.2022.08.003