Page 56 - GTM-2-2

Global Translational Medicine New insights into chronic pain management

receptors; they have few side effects and high tolerability inhibition compared with other antidepressants; that
profile, compared to tricyclics [37] . is why vortioxetine has low potential pharmacokinetic
[44]
Vortioxetine is an antidepressant with multimode interactions compared with other agent (Figure 4).
mechanism of action [38-41] . Vortioxetine enhances the The efficacy and tolerability of vortioxetine were also
release of six active mediators: serotonin, noradrenaline, demonstrated in elderly patients with recurrent major
acetylcholine, dopamine, histamine, and glutamate. As depressive disorder . Talmon et al. demonstrated the
[46]
SSRI, vortioxetine can inhibit serotonin (5HT) transporter. antioxidant and anti-inflammatory activity of vortioxetine
The distinctive feature of vortioxetine is its action as ligands in human monocytes and macrophages. Their findings
on five types of serotonin receptors: agonist of 5HT1A indicate that vortioxetine alongside its antidepressive
receptors, partial agonist of 5HT1B, and antagonists effect may have immunomodulatory properties . Thus,
[47]
of 5HT3, 5HT1D, and 5HT7 receptors (Figure 2). The vortioxetine has more advantages compared with other
inhibition of 5HT3 receptor plays an important role in the antidepressants. It is an effective antidepressant and one of
enhancement of antinociceptive effect by serotonin and the most tolerable drugs. It does not inhibit cytochrome
noradrenaline increase and also the decrease of gamma- and can be safely used in elderly patients. In addition to the
aminobutyric acid release . antidepressive effect, it may influence the pathogenesis of
[42]
systemic inflammation.
Vortioxetine was chosen for the current study as it is more
effective than other antidepressants and has a safety profile. 2. Materials and methods
Twenty-one antidepressants were compared for efficacy and
acceptability in the acute treatment of adults with major The clinical study protocol was approved by Interuniversity
depressive disorder in systematic review and network Medical and Pharmaceutical Ethic Committee l and was
meta-analysis by Cipriani et al. (Figure 3). In head-to- performed in accordance with ethical standards, developed
[43]
head studies, agomelatine, amitriptyline, escitalopram, in line with the ethical standards of the Declaration of
mirtazapine, paroxetine, venlafaxine, and vortioxetine were
more effective than other antidepressants, whereas fluoxetine,
fluvoxamine, reboxetine, and trazodone were the least
efficacious drugs. For acceptability, agomelatine, citalopram,
escitalopram, fluoxetine, sertraline, and vortioxetine were
more tolerable than other antidepressants .
[43]
Vortioxetine and its metabolites did not show
any potential for clinically meaningful cytochrome

Figure 3. Comparison of 21 antidepressants for the acute treatment
of adults with unipolar major depressive disorder. Two-dimensional
graph about efficacy and acceptability of antidepressants in head-to-
head studies was taken from Cipriani et al. . In head to head studies,
[43]
vortioxetine was more effective than other antidepressants (range of ORs
1.96). Vortioxetine was more tolerable than other antidepressants (range
of ORs 0.77). Data are reported as odds ratios (ORs) in comparison with
reboxetine, which is the reference drug. Error bars are 95% credible
intervals (CrIs). Individual drugs are represented by different colored
Figure 2. Multimode mechanism of action of vortioxetine. Vortioxetine nodes. Desvenlafaxine, levomilnacipran, and vilazodone were not
inhibits the serotonin (5HT) transporter and acts as ligands at five types included in the head-to-head analysis because these three antidepressants
of serotonin receptors: Agonist of 5HT1A receptors, partial agonist had only placebo-controlled trials.
of 5HT1B, and antagonists of 5HT3, 5HT1D, and 5HT7 receptors. ORs: Odds ratios; 1: Agomelatine; 2: Amitriptyline; 3: Bupropion;
Vortioxetine also blocks downregulation. Through the multimode 4: Citalopram; 5: Clomipramine; 7: Duloxetine; 8: Escitalopram; 9:
mechanism of action, vortioxetine enhances the release of six active Fluoxetine; 10: Fluvoxamine; 12: Milnacipran; 13: Mirtazapine; 14:
mediators: Serotonin, noradrenaline, acetylcholine, dopamine, histamine, Nefazodone; 15: Paroxetine; 16: Reboxetine; 17: Sertraline; 18: Trazodone;
and glutamate. 19: Venlafaxine; 21: Vortioxetine.

Volume 2 Issue 2 (2023) 3 https://doi.org/10.36922/gtm.312