Novel methods

Abstract

The disclosure provides the use of particular substituted heterocycle fused gamma-carboline compounds as pharmaceuticals for the treatment of residual symptoms of psychosis or schizophrenia. The disclosure also provides novel long acting injectable formulations of particular substituted heterocycle fused gamma-carboline compounds and use of such long acting injectable formulations for the treatment of residual symptoms of psychosis or schizophrenia.

1 - 30 . (canceled) 
     
     
         31 . A method for the treatment of major depressive disorder comprising administering to a patient in need thereof an effective amount of a Compound of Formula I: 
       
         
           
           
               
               
           
         
         wherein:
 X is —N(CH 3 )— and Y is —C(O)—; 
 in free or pharmaceutically acceptable salt form. 
 
       
     
     
         32 . The method according to  claim 31 , wherein the compound of Formula I is in pharmaceutically acceptable salt form. 
     
     
         33 . The method according to  claim 31 , wherein the compound of Formula I is in toluene sulfonic acid addition salt form. 
     
     
         34 . The method according to  claim 31 , wherein the effective amount of the Compound of Formula I is 20 mg to 60 mg per day, measured as the weight of the corresponding free base form of the Compound. 
     
     
         35 . The method according to  claim 33 , wherein the effective amount of the Compound of Formula I is 20 mg to 60 mg per day, measured as the weight of the corresponding free base form of the Compound. 
     
     
         36 . The method according to  claim 31 , wherein the effective amount of the Compound of Formula I is 40 mg to 60 mg per day, measured as the weight of the corresponding free base form of the Compound. 
     
     
         37 . The method according to  claim 33 , wherein the effective amount of the Compound of Formula I is 40 mg to 60 mg per day, measured as the weight of the corresponding free base form of the Compound. 
     
     
         38 . The method according to  claim 31 , wherein the effective amount of the Compound of Formula I is about 40 mg per day, measured as the weight of the corresponding free base form of the Compound. 
     
     
         39 . The method according to  claim 33 , wherein the effective amount of the Compound of Formula I is about 40 mg per day, measured as the weight of the corresponding free base form of the Compound. 
     
     
         40 . The method according to  claim 31 , wherein the compound is in toluenesulfonic acid addition salt form and the effective amount of the Compound of Formula I is 60 mg of the salt form administered once per day (equivalent to about 41.7 mg of the free base). 
     
     
         41 . The method according to  claim 31 , wherein the Compound of Formula I is formulated in a tablet or capsule for oral administration. 
     
     
         42 . The method according to  claim 40 , wherein the Compound of Formula I is formulated in a tablet or capsule for oral administration. 
     
     
         43 . The method according to  claim 42 , wherein the tablet or capsule comprises one more pharmaceutically acceptable excipients selected from the group consisting of pregelatinized maize starch, polyvinyl pyrrolidone, hydroxypropyl cellulose, lactose, microcrystalline cellulose, calcium phosphate, magnesium stearate, talc, silica, potato starch, sodium starch glycolate, and sodium lauryl sulfate. 
     
     
         44 . The method according to  claim 31 , wherein the Compound of Formula I is used in combination or for co-administration with another active therapeutic agent. 
     
     
         45 . The method according to  claim 44 , wherein the other active therapeutic agent is selected from the group consisting of a 5-HT 2A  receptor agonist, a 5-HT 2A  receptor antagonist, an ion channel modulator, a serotonin-2 receptor antagonist/reuptake inhibitor (SARI), and an atypical antipsychotic. 
     
     
         46 . The method according to  claim 44 , wherein the other active therapeutic agent is selected from the group consisting of ketanserin, eplivanserin, volinanserin, pruvanserin, ritanserin, nefazodone, serzone, trazodone, amitriptyline, amoxapine, bupropion, citalopram, clomipramine, desipramine, doxepin, duloxetine, escitalopram, fluoxetine, fluvoxamine, imipramine, isocarboxazid, maprotiline, mirtazapine, nefazodone, nortriptyline, paroxetine, phenelzine sulfate, protriptyline, sertraline, tranylcypromine, trazodone, trimipramine, venlafaxine, clozapine, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone, paliperidone, asenapine, lurasidone, iloperidone, cariprazine, amisulpride, zotepine, and sertindole. 
     
     
         47 . The method according to  claim 31 , wherein the Compound of Formula I is used as a sole therapeutic agent. 
     
     
         48 . The method according to  claim 40 , wherein the Compound of Formula I is used in combination or for co-administration with another active therapeutic agent, wherein the other active therapeutic agent is selected from the group consisting of a 5-HT 2A  receptor agonist, a 5-HT 2A  receptor antagonist, an ion channel modulator, a serotonin-2 receptor antagonist/reuptake inhibitor (SARI), and an atypical antipsychotic. 
     
     
         49 . The method according to  claim 40 , wherein the Compound of Formula I is used in combination or for co-administration with another active therapeutic agent, wherein the other active therapeutic agent is selected from the group consisting of ketanserin, eplivanserin, volinanserin, pruvanserin, ritanserin, nefazodone, serzone, trazodone, amitriptyline, amoxapine, bupropion, citalopram, clomipramine, desipramine, doxepin, duloxetine, escitalopram, fluoxetine, fluvoxamine, imipramine, isocarboxazid, maprotiline, mirtazapine, nefazodone, nortriptyline, paroxetine, phenelzine sulfate, protriptyline, sertraline, tranylcypromine, trazodone, trimipramine, venlafaxine, clozapine, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone, paliperidone, asenapine, lurasidone, iloperidone, cariprazine, amisulpride, zotepine, and sertindole. 
     
     
         50 . The method according to  claim 40 , wherein the Compound of Formula I is used as a sole therapeutic agent.