Вортиоксетин (Бринтелликс, Brintellix, Trintellix, Vortioxetine)

нажмите, чтобы увидеть

3.4.2. Sleep disruption

In clinical trials with vortioxetine the incidence of sleep-related TEAEs (insomnia, initial insomnia, middle insomnia, hyposomnia, sleep disorder, dyssomnia, poor quality sleep, terminal insomnia) was low and not dose related, with an incidence of 2.0 to 5.1% compared to 4.4% with placebo (Baldwin et al., 2013). This differs from SSRIs and SNRIs, which have an incidence of sleep-related TEAEs significantly higher than placebo (Brecht et al., 2007 and Stein and Lopez, 2011). Serotonin is a key regulator of the sleep/wake cycle, with the serotonergic system being active during awake time and inactive during sleep (Adrien, 2002 and Datta and Maclean, 2007). Since preclinical studies indicate that vortioxetine increases brain 5-HT levels to a greater extent than SERT inhibitors, vortioxetine's placebo-like level of sleep-related TEAEs is intriguing and remains to be investigated.

Vortioxetine is active at 5-HT1A, 5-HT1B, 5-HT3 and 5-HT7 receptors, all of which are involved in sleep stage regulation (Adrien, 2002, Monti and Jantos, 2008 and Hedlund, 2009). Thus, 5-HT1A receptor stimulation promotes wakefulness and 5-HT1A and 5-HT1B receptor stimulation and 5-HT7 receptor antagonism reduce rapid eye movement (REM) sleep (Adrien, 2002, Bonaventure et al., 2007 and Bonaventure et al., 2012). In line with this, a recent polysomnographic study of vortioxetine in healthy subjects showed REM-suppressing properties (Wilson et al., 2013). In rats, stimulation of 5-HT3 receptors in the dorsal raphe nucleus has been reported to reduce REM sleep (Monti and Jantos, 2008). It remains to be studied whether a 5-HT3 receptor antagonist could have the opposite effect on REM sleep. Interestingly, vortioxetine at a given SERT occupancy seemed to affect REM sleep to a lesser degree than paroxetine in healthy subjects, which may support the hypothesis that 5-HT3 receptor antagonism contributes to its overall effect on sleep stages (Wilson et al., 2013). A study in rats indicated that a 5-HT7 receptor antagonist can counteract SSRI-induced micro-arousals (i.e., non-REM or REM sleep interrupted by a 10-s epoch of wakefulness), which is thought to mimic clinically observed SSRI-induced sleep fragmentation (Bonaventure et al., 2007). Hence, it may be hypothesized that vortioxetine's 5-HT7 receptor antagonism could have a beneficial effect against sleep fragmentation. In conclusion, 5-HT and several 5-HT receptors have a prominent and complex role in sleep/wake regulation. Understanding the impact of vortioxetine's 5-HT3 and 5-HT7 receptor antagonistic properties on its benign effect on sleep is particularly interesting for future studies.
( http://www.sciencedirect.com/science/ar ... 5814001272 )