Methods of treating depression with vortioxetine

Abstract

The present disclosure relates to methods of transitioning patients or obese patients being treated with vortioxetine to treatment with a monoamine oxidase inhibitor (MAOI). The methods provided include delaying administration of the MAOI for certain time periods after stopping administration of vortioxetine. The patients or obese patients possess various capabilities of metabolizing vortioxetine. The current disclosure also includes methods of switching patients to a MAOI intended to treat psychiatric disorders while being treated with vortioxetine. The methods disclosed further comprise determining vortioxetine plasma clearance and washout time for patients with different body fat status and / or different CYP2D6 metabolizer status.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation-in-part application of U.S. patent application Ser. No. 15 / 838,944, filed Dec. 12, 2017, which is a continuation-in-part application of U.S. patent application Ser. No. 15 / 474,675, filed on Mar. 30, 2017, the disclosure of each of which is hereby incorporated by reference in its entirety for all purposes.BACKGROUND[0002]Serotonergic antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are drugs that are used for treating various depression and anxiety related disorders. Vortioxetine, also called Brintellix or Trintellix, is a serotonergic antidepressant that is used for treating major depressive disorders, and has been characterized as an SSRI which also acts as a 5HT agonist, antagonist, and transport inhibitor. Vortioxetine can function as a serotonin modulator and stimulator, which can antagonize postsynaptic serotonin rec...

AI Technical Summary

Benefits of technology

[0007]Applicants have discovered that although vortioxetine is presently considered safe, even for patients with poor and intermediate CYP2D6 enzyme function (i.e., “poor and intermediate CYP2D6 metabolizers”), patients with specific physiological characteristics as described herein experience a substantially greater exposure to vortioxetine than previously known, and therefore after ceasing administration of vortioxetine, require substantially longer “washout” periods prior to starting administration of an MAOI in order to reduce the risk of serotonin syndrome to acceptable levels. More specifically, the present applicants have found that while all drugs exhibit some level of variability in exposure among different patients, previously unknown linkages between body fat and elimination half-life result in substantially higher than anticipated vortioxetine exposure in some patient populations as described herein. In addition, even patients with e.g., BMI values in the “normal” range (about 18.5-24.9) can exhibit substantially reduced vortioxetine elimination (e.g., as represented by elevated elimination half-life (t1 / 2) values compared to the mean terminal half-life of “approximately 66 hours” reported in section 12.3 of the TRINTELLIX label, revised March 2017) when the patient is an intermediate or poor CYP2D6 metabolizer. Thus, as disclosed herein, the present inventors have found that specific patient populations require substantially different and longer “washout” periods prior to starting administration of an MAOI intended to treat psychological disorders after treatment with vortioxetine.

Problems solved by technology

However, when using vortioxetine, switching a patient to an MAOI may elevate the serotonin levels too much and may greatly increase the patient's risks of developing serotonin syndrome, or serotonin toxicity, for which there is no antidote, and which can be life threatening or fatal if not monitored carefully.

In some cases, the risks of transitioning from treatment with vortioxetine to an MAOI may be perceived as so severe that a physician may not even attempt treatment with vortioxetine in case a transition to treatment with an MAOI may be required.

However, this recommendation presumes that every patient requires the same washout period and may overlook that certain patient populations may require different washout periods when transitioning from vortioxetine to an MAOI.

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