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.

1 . A method of treating a psychiatric disorder in a patient, comprising:
 (a) administering vortioxetine; then   (b) stopping the administration of vortioxetine; and   (c) administering a first dose of an MAOI as soon as it is safe after step (b);   
       wherein the psychiatric disorder is selected from the group consisting of depression, major depressive disorder, pre-menstrual dysphoric disorder, acute depressive episodes with bipolar I, treatment-emergent sexual dysfunction, treatment resistant depression, general anxiety disorder, obsessive compulsive disorder, panic disorder, post-traumatic stress disorder, social anxiety disorder, bulimia nervosa, cognitive dysfunction in pre-menstrual dysphoric disorder, attention deficit hyperactivity disorder, attention deficit hyperactivity disorder in adult patients, and combinations thereof, and 
       wherein the patient has at least one of the following characteristics:
 (i) BMI of at least about 35 kg/m 2 ; 
 (ii) waist size greater than about 42 inches; 
 (iii) % body fat greater than about 40%; 
 (iv) % android body fat greater than about 40%; 
 (v) % gynoid body fat greater than about 40%; 
 (vi) total body fat greater than about 40 kg or 
 (vii) intermediate CYP2D6 metabolizer. 
 
     
     
         2 . The method of  claim 1 , wherein said psychiatric disorder is major depressive disorder. 
     
     
         3 . The method of  claim 1 , wherein the patient has a BMI of at least about 40 kg/m 2 . 
     
     
         4 . The method of  claim 1 , wherein the patient has a BMI of at least 50 kg/m 2 . 
     
     
         5 . The method of  claim 1 , wherein the patient has waist size greater than about 48 inches. 
     
     
         6 . The method of  claim 1 , wherein the patient has a percent body fat of at least about 50%. 
     
     
         7 . The method of  claim 1 , wherein the patient has a percent android body fat of at least about 50%. 
     
     
         8 . The method of  claim 1 , wherein the patient has a percent gynoid body fat of at least about 50%. 
     
     
         9 . The method of  claim 1 , wherein the patient has a total body fat of at least about 50 kg. 
     
     
         10 . The method of  claim 1 , wherein the patient is an intermediate CYP2D6 metabolizer and is not obese. 
     
     
         11 . The method of  claim 1 , wherein the patient is an intermediate CYP2D6 metabolizer. 
     
     
         12 . The method of  claim 1 , wherein when the patient has an estimated t 1/2  of vortioxetine which is more than about 110 hours, step (c) is at least 5 weeks. 
     
     
         13 . The method of  claim 1 , wherein the first dose of MAOI is administered at a time which is at least 5 weeks after step (b). 
     
     
         14 . The method of  claim 1 , wherein the first dose of MAOI is administered at a time which is more than 24 days after step (b). 
     
     
         15 . The method of  claim 1 , wherein the first dose of MAOI is administered at a time which is more than 24 days after step (b) and when the patient's plasma concentration of vortioxetine is less than 0.14% of the patient's steady state blood plasma level of vortioxetine. 
     
     
         16 . The method of  claim 1 , wherein the first dose of MAOI is administered at a time which is more than 24 days after step (b) and when the patient's plasma concentration is less than 0.0054 ng/mL.