Low-dose doxepin for treatment of sleep disorders in elderly patients

Abstract

Methods of treating sleep disorders, particularly certain aspects of insomnia, in elderly patients (65 years and older) by administering initial daily dosages of doxepin of 1-3 mg. These ultra-low initial dosages are more effective in elderly versus non-elderly patients in decreasing wake time during sleep, latency to persistent sleep and wake time after sleep, and are particularly efficacious in treating those conditions in the last hour of an 8-hour sleep cycle. Also, the dosages described herein are safe for elderly individuals.

1 . A method for treating insomnia in an elderly patient, comprising: 
 administering to a patient over the age of 65 an initial daily dosage of 1 mg doxepin, a pharmaceutically acceptable salt or a prodrug thereof;    evaluating whether a desired improvement in sleep is achieved by the patient at the initial dosage; and    if the desired improvement in sleep is not achieved, increasing the dosage of doxepin, the salt or the prodrug thereof incrementally until the desired dosage is achieved or until a maximum desired dosage is reached.    
     
     
         2 . The method of  claim 1 , wherein the maximum desired dosage is selected from the group consisting of 1.5, 2, 2.5, and 3 milligrams.  
     
     
         3 . A method for treating insomnia in an elderly individual at risk for amnesia or memory impairment resulting from sleep medication, comprising: 
 identifying an individual over the age of 65 that is at risk of or suffering from amnesia or memory impairment resulting from a sleep medication;    administering to the individual an initial daily dosage of 1 milligram doxepin, a pharmaceutically acceptable salt or a prodrug thereof;    evaluating whether a desired improvement in sleep or in avoidance of amnesia or memory impairment is achieved by the individual at the initial dosage; and    if the desired improvement in sleep or in avoidance of amnesia or memory impairment is not achieved, increasing the dosage of doxepin, the salt, or the prodrug incrementally until the desired dosage is achieved or until a maximum desired dosage is reached.    
     
     
         4 . The method of  claim 4 , wherein the maximum desired dosage is selected from the group consisting of 1.5, 2, 2.5, and 3 milligrams.  
     
     
         5 . A method of decreasing wake time during sleep (WTDS) in a patient over the age of 65, comprising: 
 administering to the patient an initial daily dosage of 1 mg doxepin, a pharmaceutically acceptable salt or a prodrug thereof;    evaluating whether a desired improvement in WTDS is achieved by the individual at the initial dosage; and    if the desired improvement is not achieved, increasing the dosage of doxepin, the salt, or the prodrug incrementally until the desired dosage is achieved or until a maximum desired dosage is reached.    
     
     
         6 . The method of  claim 5 , wherein the maximum desired dosage is selected from the group consisting of 1.5, 2, 2.5, and 3 milligrams.  
     
     
         7 . A method of decreasing latency to persistent sleep (LPS) in a patient over the age of 65, comprising administering to the patient an initial daily dosage of 3 mg doxepin, a pharmaceutically acceptable salt or a prodrug thereof.  
     
     
         8 . A method for treating insomnia, comprising: 
 identifying a patient over the age of 65 who is susceptible to one or more of the following side effects caused by sleep medication: nervous system side effects; psychiatric side effects; respiratory side effects; skin side effects; musculoskeletal side effects; and connective tissue side effects; and    administering doxepin to the patient in a dosage of 1 mg to 6 mg.    
     
     
         9 . The method of  claim 8 , wherein the identifying step comprises: 
 identifying a patient who is susceptible to central nervous system side effects caused by sleep medication.    
     
     
         10 . The method of  claim 9 , wherein the central nervous system side effect is at least one of somnolence, headache, dizziness, lethargy, and balance disorder.  
     
     
         11 . The method of  claim 9 , wherein the identifying step comprises: 
 identifying a patient who is susceptible to psychiatric side effects caused by sleep medication.    
     
     
         12 . The method of  claim 11 , wherein the psychiatric side effect is at least one of anxiety, confusion, and abnormal dreams.  
     
     
         13 . A method for treating insomnia in an elderly patient, comprising: 
 administering to a patient over the age of 65 an initial daily dosage of 0.5 mg doxepin, a pharmaceutically acceptable salt or a prodrug thereof;    evaluating whether a desired improvement in sleep is achieved by the patient at the initial dosage; and    if the desired improvement in sleep is not achieved, increasing the dosage of doxepin, the salt or the prodrug thereof incrementally until the desired dosage is achieved or until a maximum desired dosage is reached.    
     
     
         14 . A method for treating insomnia in an elderly individual at risk for amnesia or memory impairment resulting from sleep medication, comprising: 
 identifying an individual over the age of 65 that is at risk of or suffering from amnesia or memory impairment resulting from a sleep medication;    administering to the individual an initial daily dosage of 0.5 milligram doxepin, a pharmaceutically acceptable salt or a prodrug thereof;    evaluating whether a desired improvement in sleep or in avoidance of amnesia or memory impairment is achieved by the individual at the initial dosage; and    if the desired improvement in sleep or in avoidance of amnesia or memory impairment is not achieved, increasing the dosage of doxepin, the salt, or the prodrug incrementally until the desired dosage is achieved or until a maximum desired dosage is reached.    
     
     
         15 . A method of decreasing wake time during sleep (WTDS) in a patient over the age of 65, comprising: 
 administering to the patient an initial daily dosage of 0.5 mg doxepin, a pharmaceutically acceptable salt or a prodrug thereof;    evaluating whether a desired improvement in WTDS is achieved by the individual at the initial dosage; and    if the desired improvement is not achieved, increasing the dosage of doxepin, the salt, or the prodrug incrementally until the desired dosage is achieved or until a maximum desired dosage is reached.    
     
     
         16 . The method of any of  claim 15 , wherein the maximum desired dosage is selected from the group consisting of 1.5, 2, 2.5, and 3 milligrams.  
     
     
         17 . A method of decreasing latency to persistent sleep (LPS) in a patient over the age of 65, comprising administering to the patient an initial daily dosage of 0.5 mg doxepin, a pharmaceutically acceptable salt or a prodrug thereof.  
     
     
         18 . A method for treating insomnia, comprising: 
 identifying a patient over the age of 65 who is susceptible to one or more of the following side effects caused by sleep medication: nervous system side effects; psychiatric side effects; respiratory side effects; skin side effects; musculoskeletal side effects; and connective tissue side effects; and    administering doxepin to the patient in a dosage of 0.5 mg to 10 mg.    
     
     
         19 . A method of decreasing WASO in a patient over the age of 65, comprising: 
 administering to the patient an initial daily dosage of 1 mg doxepin, a pharmaceutically acceptable salt or a prodrug thereof;    evaluating whether a desired improvement in WASO is achieved by the individual at the initial dosage; and    if the desired improvement is not achieved, increasing the dosage of doxepin, the salt, or the prodrug incrementally until the desired dosage is achieved or until a maximum desired dosage is reached.    
     
     
         20 . A method of decreasing WASO in a patient over the age of 65, comprising: 
 identifying a patient over the age of 65 in need of a decrease in WASO; and    administering to the patient between 0.5 mg and 6 mg doxepin, a pharmaceutically acceptable salt or a prodrug thereof.    
     
     
         21 . A method of decreasing WTDS in a patient over the age of 65, comprising: 
 identifying a patient over the age of 65 in need of a decrease in WTDS; and    administering to the patient between 0.5 mg and 6 mg doxepin, a pharmaceutically acceptable salt or a prodrug thereof.    
     
     
         22 . A method of reducing awakenings by reducing WTAS in a patient over the age of 65, comprising: 
 administering to the patient an initial daily dosage of 1 mg doxepin, a pharmaceutically acceptable salt or a prodrug thereof;    evaluating whether a desired improvement in awakenings is achieved by the individual at the initial dosage; and    if the desired improvement is not achieved, increasing the dosage of doxepin, the salt, or the prodrug incrementally until the desired dosage is achieved or until a maximum desired dosage is reached.    
     
     
         23 . A method of reducing awakenings in a patient over the age of 65, comprising: 
 identifying a patient over the age of 65 in need of a reduced awakenings associated with WTAS; and    administering to the patient between 0.5 mg and 6 mg doxepin, a pharmaceutically acceptable salt or a prodrug thereof.    
     
     
         24 . A method of increasing total sleep time (TST) in a patient over the age of 65, comprising: 
 administering to the patient an initial daily dosage of 1 mg doxepin, a pharmaceutically acceptable salt or a prodrug thereof;    evaluating whether a desired improvement in TST is achieved by the individual at the initial dosage; and    if the desired improvement is not achieved, increasing the dosage of doxepin, the salt, or the prodrug incrementally until the desired dosage is achieved or until a maximum desired dosage is reached.    
     
     
         25 . A method of increasing total sleep time in a patient over the age of 65, comprising: 
 identifying a patient over the age of 65 in need of a increased total sleep time; and    administering to the patient between 1 mg and 6 mg doxepin, a pharmaceutically acceptable salt or a prodrug thereof.    
     
     
         26 . A method for decreasing fragmented sleep in a patient over the age of 65, comprising: 
 identifying a patient over the age of 65 suffering from fragmented sleep; and    administering to the patient doxepin, a pharmaceutically acceptable salt or prodrug thereof in a dosage between about 0.5 mg and 6 mg.    
     
     
         27 . A method of lessening the severity of a sleep illness in a patient over the age of 65, comprising: 
 administering to the patient an initial daily dosage of 1 mg doxepin, a pharmaceutically acceptable salt or a prodrug thereof;    evaluating whether a desired improvement in sleep illness severity is achieved by the individual at the initial dosage; and    if the desired improvement is not achieved, increasing the dosage of doxepin, the salt, or the prodrug incrementally until the desired dosage is achieved or until a maximum desired dosage is reached.    
     
     
         28 . A method of providing improved therapeutic effect in a patient over the age of 65, comprising: 
 administering to the patient an initial daily dosage of 1 mg doxepin, a pharmaceutically acceptable salt or a prodrug thereof;    evaluating whether a desired improvement in sleep therapeutic effect is achieved by the individual at the initial dosage; and    if the desired improvement is not achieved, increasing the dosage of doxepin, the salt, or the prodrug incrementally until the desired dosage is achieved or until a maximum desired dosage is reached.