Combination Therapy for Treating or Preventing Depression or Other Mood Diseases

Abstract

The present invention provides compositions and methods for treating diseases or disorders using a therapeutically effective amount of a rapid-acting antidepressant (RAAD) and a therapeutically effective amount of a mTOR inhibitor and/or immunosuppressant. In certain embodiments, the RAAD and the mTOR inhibitor and/or immunosuppressant are part of a single pharmaceutical composition.

What is claimed is: 
     
         1 . A kit comprising:
 a rapid-acting antidepressant (RAAD),   a mammalian target of rapamycin (mTOR) inhibitor, and   instructions for administering the RAAD and the mTOR inhibitor to a human subject in need thereof to treat or ameliorate a mood disorder in the human subject.   
     
     
         2 . The kit of  claim 1 , wherein the instructions comprise instructions for administering an amount of the RAAD and an amount of the mTOR inhibitor to the human subject. 
     
     
         3 . The kit of  claim 2 , wherein the amount of the RAAD to be administered to the human subject is from 0.15 mg/kg to 10 mg/kg. 
     
     
         4 . The kit of  claim 2 , wherein the amount of the mTOR inhibitor to be administered to the human subject is from 0.5 mg to 40 mg. 
     
     
         5 . The kit of  claim 1 , wherein the instructions comprise instructions for frequency of administering the RAAD and frequency of administering the mTOR inhibitor to the human subject. 
     
     
         6 . The kit of  claim 5 , wherein the frequency of the RAAD administration to the human subject is from at least daily to at most once per month. 
     
     
         7 . The kit of  claim 5 , wherein the frequency of the mTOR inhibitor administration to the human subject is from at least daily to at most once per month. 
     
     
         8 . The kit of  claim 1 , wherein the kit further comprises an applicator. 
     
     
         9 . The kit of  claim 1 , wherein the instructions comprise instructions for administering the RAAD and the mTOR inhibitor simultaneously to the human subject. 
     
     
         10 . The kit of  claim 1 , wherein the instructions comprise instructions for administering the RAAD and the mTOR inhibitor separately to the human subject. 
     
     
         11 . The kit of  claim 10 , wherein
 (a) the RAAD is ketamine or any salt, solvate, enantiomer, tautomer, or geometric isomer thereof, and the mTOR inhibitor is rapamycin or any salt thereof, and   (b) the instructions comprise instructions for administering from 0.15 mg/kg to 10 mg/kg of the RAAD intravenously to the human subject and instructions for administering from 0.5 mg to 40 mg of the mTOR inhibitor orally to the human subject.   
     
     
         12 . The kit of  claim 1 , wherein the instructions comprise instructions for administering the mTOR inhibitor to the human subject at least once before administering the RAAD to the human subject. 
     
     
         13 . The kit of  claim 1 , wherein the instructions comprise instructions for administering the RAAD and the mTOR inhibitor separately to the human subject by a route independently selected from the group consisting of nasal, inhalational, topical, oral, buccal, rectal, pleural, peritoneal, vaginal, intramuscular, subcutaneous, transdermal, epidural, intratracheal, otic, intraocular, intrathecal, and intravenous. 
     
     
         14 . A kit comprising:
 a rapid-acting antidepressant (RAAD), and   a mammalian target of rapamycin (mTOR) inhibitor,   wherein the RAAD and the mTOR inhibitor are present in the kit at an amount such that administration of the RAAD and the mTOR inhibitor to a human subject in need thereof treats a mood disorder in the human subject.   
     
     
         15 . The kit of  claim 14 , wherein the RAAD comprises ketamine, hydroxynorketamine, rapastinel, lanicemine, D-cycloserine, scopolamine, psilocybin, lysergic acid, ayahuasca (or any preparations, fractions, or partially or fully purified fractions thereof), DMT, Brexanolone, 3α-Hydroxy-3β-methyl-21-(4-cyano-1H-pyrazol-1′-yl)-19-nor-5β-pregnan-20-one, (L)-4-Chlorokynurenine, NV-5138, D-methadone, MGS-0039, midatofel, selfotel, apimostinel, basimglurant, decoglurant, ganaxolone, racemic dextromethorphan, dextromethorphan, phencyclidine, dizocilpine, CERC-301, CGP 37849, 1-aminocylopropanecarboxylic acid, traxoprodil, Ro 25-6981, eliprodil, or any salt, solvate, enantiomer, tautomer, and geometric isomer thereof, or any mixture thereof. 
     
     
         16 . The kit of  claim 14 , wherein the RAAD comprises a N-methyl-D-aspartate (NMDA) receptor modulator. 
     
     
         17 . The kit of  claim 16 , wherein the NMDA receptor modulator comprises ketamine, or any salt, solvate, enantiomer, tautomer, and geometric isomer thereof, or any mixture thereof. 
     
     
         18 . The kit of  claim 16 , wherein the NMDA receptor modulator is racemic ketamine, or any salt or solvate thereof, or any mixture thereof. 
     
     
         19 . The kit of  claim 16 , wherein the NMDA receptor modulator is (R)-ketamine, or any salt or solvate thereof, or any mixture thereof. 
     
     
         20 . The kit of  claim 16 , wherein the NMDA receptor modulator is (S)-ketamine, or any salt or solvate thereof, or any mixture thereof. 
     
     
         21 . The kit of  claim 14 , wherein the mTOR inhibitor comprises BEZ235, rapamycin (sirolimus), everolimus, AZD8055, temsirolimus, KU-0063794, PI-103, torkinib, tacrolimus, ridaforolimus, INK-128, Voxtalisib, Torin-1, Omipalisib, OSI-027, PF-04691502, apitolisib, GSK1059615, WYE-354, gedatolisib, AZD-2014, Torin-2, WYE-125132, BGT226, Palomid-529, PP121, WYE-687, CH5132799, Way-600, ETP-46464, GDC-0349, XL388, zotarolimus, or any salt, solvate, enantiomer, tautomer, and geometric isomer thereof, or any mixture thereof. 
     
     
         22 . The kit of  claim 14 , wherein the mTOR inhibitor comprises rapamycin or any salt, solvate, enantiomer, tautomer, or geometric isomer thereof, or any mixture thereof. 
     
     
         23 . The kit of  claim 14 , wherein the mTOR inhibitor comprises temsirolimus, or any salt, solvate, enantiomer, tautomer, or geometric isomer thereof, or any mixtures thereof. 
     
     
         24 . The kit of  claim 14 , wherein the amount of the RAAD is from 1 mg to 200 mg. 
     
     
         25 . The kit of  claim 14 , wherein the amount of the mTOR inhibitor is from 0.5 mg to 40 mg. 
     
     
         26 . The kit of  claim 14 , wherein the mood disorder is selected from the group consisting of major depressive disorder, persistent depressive disorder (dysthymia), disruptive mood dysregulation disorder, premenstrual dysphoric disorder, substance/medication-induced depressive disorder, anxiety disorder, and posttraumatic stress disorder. 
     
     
         27 . The kit of  claim 14 , wherein the kit further comprises instructions for administering an amount of the RAAD and an amount of the mTOR inhibitor to the human subject. 
     
     
         28 . The kit of  claim 27 , wherein
 (a) the RAAD is ketamine or any salt, solvate, enantiomer, tautomer, or geometric isomer thereof, and the mTOR inhibitor is rapamycin or any salt thereof, and   (b) the instructions comprise instructions for administering from 0.15 mg/kg to 10 mg/kg of the RAAD intravenously to the human subject and for administering from 0.5 mg to 40 mg of the mTOR inhibitor orally to the human subject.   
     
     
         29 . The kit of  claim 14 , wherein the kit further comprises instructions for frequency of administering the RAAD and frequency of administering the mTOR inhibitor to the human subject. 
     
     
         30 . The kit of  claim 14 , wherein the kit further comprises an applicator.