Intranasal administration of ketamine to treat depression

Abstract

Methods and compositions for the treatment of treatment-resistant depression are described. More specifically, the invention demonstrates that intranasal administration of ketamine is effective to ameliorate the symptoms of depression in a patient who has not responded to an adequate trial of one antidepressant in the current episode and has recurrent or chronic depressive symptoms (>2 years).

1 . A method of treating a human patient afflicted with treatment-resistant-depression, comprising intranasally administering a metered dose of a composition comprising ketamine and at least one pharmaceutically acceptable excipient to said patient wherein the amount of ketamine in the metered dose is sufficient to reduce or eliminate the symptoms of said treatment-resistant depression. 
     
     
         2 . The method of  claim 1 , wherein said ketamine is administered at a dose of between about 0.1 mg/kg per day to about 3.0 mg/kg/day. 
     
     
         3 . The method of  claim 1 , wherein the symptoms of said treatment-resistant depression are alleviated within 2 hours of intranasal administration of said ketamine. 
     
     
         4 . The method of  claim 1 , wherein said method comprises intranasal administration of a single dose of said ketamine. 
     
     
         5 . The method of  claim 1 , wherein said method comprises intranasal administration of multiple doses of said ketamine. 
     
     
         6 . The method of  claim 1 , wherein a single intranasal administration of said ketamine is sufficient to alleviate the effects of said depression for 7 days. 
     
     
         7 . The method of  claim 1 , further comprising administering a pharmaceutically effective dose of a second agent, wherein said second agent is an antidepressant agent. 
     
     
         8 . The method of  claim 7  wherein said antidepressant agent is selected from the group consisting of at least one member of lithium, a pharmaceutical antidepressant, an herbal antidepressant, an anticonvulsant, a mood stabilizer, an antipsychotic agent, and a benzodiazepine. 
     
     
         9 . A kit comprising a carrier for delivering a medicament intranasally containing in close confinement therein one or more components, wherein: a) a first component contains ketamine; and b) a second component contains a psychotropic medication useful in the treatment of depression. 
     
     
         10 . The kit of  claim 9  wherein said second component is selected from the group consisting of lithium, pharmaceutical antidepressant, an herbal antidepressant, an anticonvulsant, a mood stabilizer, an antipsychotic agent, and a benzodiazepine. 
     
     
         11 . A device for patient self-administration of ketamine comprising a nasal spray inhaler containing an aerosol spray formulation of ketamine and a pharmaceutically acceptable dispersant, wherein the device is metered to disperse an amount of the aerosol formulation by forming a spray that contains a dose of ketamine effective to alleviate depression but which dose of ketamine is determined by a physician or medical care provider to be below a level that causes dysphoria. 
     
     
         12 . A method of treating a human patient afflicted with treatment-resistant depression, comprising intravenously administering multiple doses of a composition comprising ketamine to said patient at a dosage sufficient to reduce or eliminate the symptoms of said treatment-resistant depression. 
     
     
         13 . The method of  claim 12 , wherein said ketamine is in a pharmaceutically acceptable carrier and is administered at a dose of between about 0.1 mg/kg per day to about 3.0 mg/kg/day. 
     
     
         14 . The method of  claim 12 , wherein the symptoms of said treatment-resistant depression are alleviated within two hours of administration of said ketamine. 
     
     
         15 . The method of  claim 12 , wherein the composition is administered at least six times in fourteen days. 
     
     
         16 .- 21 . (canceled) 
     
     
         22 . The method of  claim 12 , wherein the composition is administered at least nine times in 21 days. 
     
     
         23 . The method of  claim 12 , further comprising administering a pharmaceutically effective dose of a second agent, wherein said second agent is an antidepressant agent. 
     
     
         24 . The method of  claim 23 , wherein said antidepressant agent is selected from the group consisting of at least one member of lithium, a pharmaceutical antidepressant, an herbal antidepressant, an anticonvulsant, a mood stabilizer, an antipsychotic agent, and a benzodiazepine. 
     
     
         25 . A method of treating a human patient afflicted with treatment-resistant depression, comprising transdermally administering a composition comprising ketamine to said patient at a dosage sufficient to reduce or eliminate the symptoms of said treatment-resistant depression. 
     
     
         26 . The method of  claim 25 , wherein said ketamine is in a pharmaceutically acceptable carrier and is administered at a dose of between about 0.1 mg/kg per day to about 3.0 mg/kg/day. 
     
     
         27 . The method of  claim 25 , wherein the symptoms of said treatment-resistant depression are alleviated within two hours of transdermal administration of said ketamine. 
     
     
         28 . The method of  claim 25 , wherein said method comprises transdermal administration of multiple doses of said ketamine. 
     
     
         29 . The method of  claim 25 , further comprising administering a pharmaceutically effective dose of a second agent, wherein said second agent is an antidepressant agent. 
     
     
         30 . The method of  claim 25 , wherein said antidepressant agent is selected from the group consisting of at least one member of lithium, a pharmaceutical antidepressant, an herbal antidepressant, an anticonvulsant, a mood stabilizer, an antipsychotic agent, and a benzodiazepine. 
     
     
         31 . A device for patient self-administration of ketamine comprising a transdermal patch containing a formulation of ketamine and a pharmaceutically acceptable carrier, wherein the device is metered to disperse an amount of the formulation that contains a dose of ketamine effective to alleviate depression but which dose of ketamine is determined by a physician or medical care provider to be below a level that causes dysphoria. 
     
     
         32 . The method of  claim 1  wherein the pharmaceutically acceptable excipient comprises a mucosal penetration enhancing agent. 
     
     
         33 . The method of  claim 1  wherein the pharmaceutically acceptable excipient comprises a dispersing agent. 
     
     
         34 . The method of  claim 1  wherein the intranasal administration comprises an aerosol spray. 
     
     
         35 . The method of  claim 33  wherein the pharmaceutically acceptable excipient comprises a surfactant. 
     
     
         36 . The method of  claim 1  wherein the pharmaceutically acceptable excipient comprises a propellant. 
     
     
         37 . The method of  claim 1  wherein said ketamine is administered at a dose of between about 0.01 mg/kg per day to about 1.0 mg/kg/day. 
     
     
         38 . The method of  claim 34  wherein the aerosol spray comprises a dry powder. 
     
     
         39 . The method of  claim 34  wherein the aerosol spray comprises a liquid aerosol formulation. 
     
     
         40 . The method of  claim 1  wherein the treatment resistant depression comprises dysthymia.