Vortioxetine as a new frontier in the treatment of chronic neuropathic pain: a review and update.

Chronic neuropathic pain (CNP) is a disabling medical condition that impairs the health-related quality-of-life of affected patients. A high prevalence of anxiety, depression, sleep disturbance and cognitive impairment has frequently been reported in association with CNP, making the management of this disease complex and often multidisciplinary. Dual-acting agents such as selective serotonin and noradrenalin reuptake inhibitors (SNRIs) are considered particularly useful in the modulation of pain and in treatment of the mood disorders frequently associated with CNP. Recent evidence suggests that the top-down inhibitory control of pain involves the engagement and enhancement of descending endogenous opioidergic, cannabinoid and serotonergic systems, with the effect of serotonin being particularly related to the receptor subtypes that are preferentially activated; indeed serotonin induces analgesia via activation of 5-HT7 receptors and hyperalgesia via activation of 5-HT3 receptors. Vortioxetine (VO) is a novel multimodal serotonergic antidepressant with a unique mechanism of action. It has been demonstrated recently in experimental and clinical studies to have efficacy on pain hypersensitivity and on mood disorders. This drug inhibits the serotonin transporter with a high affinity, antagonises the 5-HT3, 5-HT1D and 5HT7 serotonin receptors, and activates the 5-HT1A and 5-HT1B receptors. In clinical studies, VO has proved effective at a dose of 10-20 mg/daily in short- and long-term treatment of patients with chronic orofacial pain, demonstrating a higher rate of clinical response and remission, a better acceptability, safety rate and tolerability, and a lower latency of action compared with other antidepressants. In the light of these recent findings, VO may be considered as a new pharmacological treatment also in relation to various types of CNP, particularly in elderly patients with concomitant mood disorders and cognitive impairment. The purpose of this review is to provide an up-to-date overview of the pharmacology and clinical applications of VO and to highlight its potential therapeutic properties and advantages in the management of CNP.