7.2. Benefits versus adverse effects

pyramidal cells) [80, 94]. Positive results on cognitive function (memory and executive func-

Vortioxetine is a 5-HT3, 5-HT7, and 5-HT1D receptor antagonist, a 5-HT1B receptor partial agonist, a 5-HT1A receptor agonist, and an inhibitor of the serotonin transporter. It enhances 5- HT (more than a SSRI), NE, DA, acetylcholine, and HA levels in rat brain regions associated with MDD (like the PFC and the ventral hippocampus). Furthermore, it increases glutamatergic

Its discovery program origins in the hypothesis were derived from researches of combined serotonin transporter inhibition and 5-HT1A receptor modulation; subsequently, the profile was modified toward a combination of serotonin transporter inhibition, 5-HT1A receptor

The drug is available as immediate-release tablets for oral administration which contain the

10 mg yellow, almond-shaped biconvex film-coated tablet 15 mg orange, almond-shaped biconvex film-coated tablet 20 mg red, almond-shaped biconvex film-coated tablet

consider 5 mg/day for patients who do not tolerate higher doses

CYP2D6 (primarily), CYP3A4/CYP3A5, CYP2C9, CYP2C19, CYP2C8, CYP2A6, CYP2B6

Diminish vortioxetine dose by half when a strong CYP2D6 inhibitor is associated

CYP inducers Augment vortioxetine dose when a strong CYP inducer is coadministered for more than

14 days (up to no more than three times the original dose)

5–10 mg/day therapy can be discontinued abruptly

neurotransmission, probably through inhibiting GABA interneurons [80, 92, 94].

tioning) were also highlighted in clinical trials [92].

142 Pharmacokinetics and Adverse Effects of Drugs - Mechanisms and Risks Factors

agonistic activity, and 5-HT3 receptor antagonism [95].

beta-polymorph of vortioxetine hydrobromide (Table 8).

Administration Orally, once daily, without regard to meals

Absorption Tmax 7–11 hours

Percentage of protein binding 98%

pathways

CYP2D6 inhibitors

Table 8. Pharmacological aspects of vortioxetine [91, 96, 97].

Metabolism CYP

(>5%)

Drug interactions

Common adverse reactions

Volume of distribution Approximately 2600 L Half-life Approximately 66 hours Absolute bioavailability 75% (unaffected by food)

Dosage forms 5 mg pink, almond-shaped biconvex film-coated tablet

Dosage Initial dosage is 10 mg, augment to 20 mg/day, as tolerated

Elimination 59% in the urine and 26% in the feces, as metabolites

Nausea, constipation, and vomiting

7.1. Pharmacological properties

Sanchez et al. reviewed preclinical studies and clinical trials and concluded that vortioxetine is different from SSRI and SNRI antidepressants on the strength of its multimodal mechanism of action, both inhibition of the potent serotonin transporter and direct modulation of 5-HT receptors [95].

Studies evaluating the drug have shown the following benefits:


Vortioxetine was well tolerated both in short-term and in long-term studies. Mild to moderate nausea was the most commonly registered side effect, and its frequency was dose related [95, 102]. Due to the lack of well-controlled studies, its administration in pregnancy and lactation is not recommended (Table 9) [91].

With more than 50 antidepressant drugs available worldwide (most of them approved for more than 10 years), vortioxetine is the newest agent and needs to determine its place in MDD therapy [97].


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Table 9. The most frequent adverse effects of vortioxetine [91, 96, 97, 103].
