Vortioxetine for major depressive disorder

Tolerability

The tolerability of vortioxetine is comparable with other serotonergic antidepressants. In pooled analysis of pre-marketing studies, 5% to 8% of patients receiving vortioxetine (5 to 20 mg/d) discontinued treatment because of adverse effects (AEs), compared with 4% in the placebo group. Nausea was the most commonly reported AE leading to discontinuation and appeared to be dose dependent.

AEs, such as nausea, constipation, and vomiting, most commonly occurred in the first week of treatment, with a median duration of 2 weeks.⁵ In the 6- to 8-week trials, the most common AEs were nausea, constipation, and vomiting. In longer trials (24 to 64 weeks), the most common AE was nausea.

In 6- to 8-week placebo-controlled studies, vortioxetine was not associated with any clinically significant effect on vital signs or laboratory values in hematology, urinalysis, or serum chemistry (except sodium). Hyponatremia, the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH), has occurred. The risk of developing SIADH and resultant hyponatremia is greater in geriatric patients and patients taking a diuretic.

Abruptly discontinuing vortioxetine can cause transient withdrawal symptoms, including headache and muscle tension, especially at a higher dosage (15 to 20 mg/d). Gradual tapering can reduce withdrawal symptoms.

Specific clinical issues

All antidepressants have a “black-box” warning about the potential for clinical worsening and increased suicidality early in treatment. Closely monitor patients for suicidal ideation and behaviors during the first months of treatment and with dosage changes.

Vortioxetine is categorized as pregnancy category C. Newborns exposed to a selective serotonin reuptake inhibitor (SSRI) in pregnancy may have an increased risk of persistent pulmonary hypertension during the neonatal period. When taken during the third trimester of pregnancy, SSRIs and serotonin-norepinephrine reuptake inhibitors can cause serious neonatal complications, including respiratory distress, cyanosis, apnea, and seizures, which may require longer hospitalization, respiratory support, or tube feeding for the infant. Consider risks and benefits of third-trimester use of an antidepressant. It is not known if vortioxetine is present in human breast milk.

Clinical studies on vortioxetine in pediatric patients have not been conducted.

No dosage adjustment is recommended on the basis of age for geriatric patients. No dose adjustment of vortioxetine is necessary on the basis of race, sex, ethnicity, renal function, or mild to moderate hepatic impairment. See Table 3 for practice points when prescribing vortioxetine. See Table 4 for contraindications to vortioxetine.

Dosing

The recommended starting dosage is 10 mg, administered orally once daily without regard to meals. Dosage should then be increased to 20 mg/d, as clinically warranted and tolerated. Consider a dosage decrease to 5 mg/d in patients who do not tolerate higher dosages or require drug adjustment because of drug-drug interaction or poor 2D6 metabolizer status.

Bottom Line

FDA-approved for major depressive disorder in adults, vortioxetine reduced depressive symptoms in 6 positive, double-blind, placebo-controlled, and randomized studies. The multimodal activity of vortioxeine can be a useful alternative to serotonergic antidepressants for some patients who are partial responders or nonresponders. Tolerability is comparable with other serotonergic antidepressants.

Related Resources

• Alam MY, Jacobsen PL, Chen Y, et al. Safety, tolerability, and efficacy of vortioxetine (Lu AA21004) in major depressive disorder: results of an open-label, flexible-dose, 52-week extension study. Int Clin Psychopharmacol. 2014; 29(1):36-44.

• Mahableshwarkar AR, Jacobsen PL, Chen Y. A randomized, double-blind trial of 2.5 mg and 5 mg vortioxetine (Lu AA21004) versus placebo for 8 weeks in adults with major depressive disorder. Curr Med Res Opin. 2013;29(3):217-226.

Drug Brand Names

Linezolid • Zyvox Vortioxetine • Brintellix

Methylene blue • Urolene Blue Warfarin • Coumadin

Tramadol • Ultram

Disclosure

The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.