The FDA ( U.S. Food and Drug Administration ) has approved a supplemental new drug application ( sNDA ) for Trintellix ( Vortioxetine ), a medication used for adults with major depressive disorder ( MDD ), also known as depression.
The Trintellix U.S. prescribing information now includes head-to-head clinical study data that demonstrated superiority to a commonly-used selective serotonin reuptake inhibitor ( SSRI ), Escitalopram ( Lexapro ) in improving treatment-emergent sexual dysfunction ( TESD ).
In the study, patients with well-treated depression who were experiencing TESD while taking an SSRI ( Paroxetine, Sertraline or Citalopram ) were switched to Vortioxetine or Escitalopram.
This is the first time an antidepressant has included data of this type in its labeling.
Sexual dysfunction is one of the most common and bothersome side effects in patients with depression when an SSRI is prescribed.
Treatment-emergent sexual dysfunction can affect any aspect of the sexual response cycle including desire, arousal and orgasm.
In an eight-week head-to-head, randomized, double-blind study, well-treated adult MDD patients with treatment-emergent sexual dysfunction ( n=447 ) were switched to Vortioxetine ( n=225 ) or Escitalopram ( n=222 ), from Citalopram, Paroxetine, or Sertraline, due to SSRI-induced sexual dysfunction.
For both Vortioxetine and Escitalopram, patients were started on 10 mg, increased to 20 mg at week one, followed by flexible dosing ( 10 mg or 20 mg ).
Vortioxetine demonstrated statistically significant improvement versus Escitalopram from baseline to week eight as measured by mean Change in Sexual Functioning Questionnaire Short Form ( CSFQ-14 ) Total Score ( 8.8 vs. 6.6, p=0.013 ).
Both drugs maintained prior improvement in depression based on overall score on standardized depression rating scale.
The mechanism of the antidepressant effect of Vortioxetine is not fully understood. It is an inhibitor of serotonin ( 5-HT ) reuptake and that is thought to be a mechanism of its action. It is also an agonist at 5-HT1A receptors, a partial agonist at 5-HT1B receptors and an antagonist at 5-HT3, 5-HT1D and 5-HT7 receptors.
The contribution of each of these activities to antidepressant effect has not been established.
It is considered to be the first and only compound with this combination of pharmacodynamic activity.
The clinical relevance of this is unknown.
The most commonly observed adverse events in MDD patients treated with Vortioxetine in 6-8 week placebo-controlled studies ( incidence greater than or equal to 5% and at least twice the rate of placebo ) were nausea, constipation and vomiting.
Overall, 5 to 8% of the patients who received Vortioxetine 5 to 20 mg/day in short-term trials discontinued treatment due to an adverse reaction, the most common being nausea, compared with 4% of placebo-treated patients in these studies.
Voluntary reports of sexual dysfunction with Vortioxetine in 6-8 week controlled trials were less than 5%.
Because voluntary reports of sexual dysfunction are known to be underreported, a separate, self-rated questionnaire was provided to patients prospectively in clinical studies with Vortioxetine.
When assessed proactively in patients without sexual dysfunction at baseline, reports of treatment emergent sexual dysfunction across doses 5 mg, 10 mg, 20 mg were 16%, 20%, 29% in males ( n=212 ) respectively and females 22%, 23% and 34% ( n=226 ) respectively, compared to 14% ( n=162 ) and 20% ( n=135 ), respectively, in placebo.
In clinical studies, Vortioxetine had no significant effect on body weight as measured by the mean change from baseline in 6-8 week placebo-controlled studies.
In the 6-month, double-blind, placebo-controlled phase of a long-term study in patients who had responded to Vortioxetine during the initial 12-week, open-label phase, there was no significant effect on body weight between Vortioxetine and placebo-treated patients.
Some reports of weight gain have been received since product approval.
Vortioxetine has not been associated with any clinically significant effects on vital signs, including systolic and diastolic blood pressure and heart rate, as measured in placebo-controlled studies.
Also known as clinical depression, major depressive disorder is the leading cause of disability worldwide and a major contributor to the overall global burden of disease.
Major depressive disorder may trigger emotional, cognitive and physical symptoms, which includes depressed mood, loss of interest or pleasure, significant weight loss or gain or change in appetite, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue or loss of energy, feelings of worthlessness or excessive guilt, diminished ability to think or concentrate, or indecisiveness, and recurrent suicidal ideation. ( Xagena )
Source: Lundbeck, 2018