Doxepin isomers and isomeric mixtures and methods of using the same to treat sleep disorders
View Patent ↗The invention relates to use of the cis-(Z) isomer or isomeric mixtures containing specified ratios of the cis-(Z) and trans-(E) isomers of doxepin, metabolites of doxepin, pharmaceutically-acceptable salts of doxepin and prodrugs of the same; compositions containing the same, for the treatment of sleep disorders.
1. A method for the treatment of a patient suffering from sleep maintenance insomnia characterized by fragmented sleep during the 8 th hour of sleep, comprising:
identifying a patient having a sleep disorder in which, for a given 8 hour period of desired sleep, the patient experiences fragmented sleep during the final 60 minutes of said period; and
administering to said patient, prior to the start of the sleep period, a dosage of doxepin or a pharmaceutically-acceptable salt thereof that is effective to improve sleep maintenance insomnia by reducing early awakenings during the 8 th hour of the sleep period, wherein the dosage ranges from about 0.1 to about 20 milligrams, wherein the doxepin or salt thereof is a geometric isomer mixture containing about 18.2% to about 100.0% of the cis-(Z) isomer or is 100% cis-(Z) isomer.
2. The method of claim 1 , wherein said geometric isomer mixture contains more than 20% of the cis-(Z) isomer.
3. The method of claim 1 , wherein said geometric isomer mixture contains more than 50% of the cis-(Z) isomer.
4. The method of claim 1 , wherein said geometric isomer mixture contains more than 90% of the cis-(Z) isomer.
5. The method of claim 1 , wherein said geometric isomer mixture contains more than 95% of the cis-(Z) isomer.
6. The method of claim 1 , wherein said geometric isomer mixture contains about 20% to about 99.9% of the cis-(Z) isomer.
7. The method of claim 1 , wherein the dosage is about 1 to about 6 milligrams.
8. A method for the treatment of a patient suffering from sleep maintenance insomnia characterized by early awakenings during the 8 th hour of sleep, comprising:
identifying a patient having a sleep disorder in which, for a given 8 hour period of desired sleep, the patient experiences early awakenings during the final 60 minutes of said period; and
administering to said patient, prior to the start of the sleep period, a dosage of doxepin or a pharmaceutically-acceptable salt thereof that is effective to improve sleep maintenance insomnia by reducing early awakenings during the 8 th hour of the sleep period, wherein the dosage ranges from about 0.1 to about 20 milligrams, wherein the doxepin or salt thereof is a geometric isomer mixture containing about 18.2% to about 100.0% of the cis-(Z) isomer or is 100% cis-(Z) isomer.
9. The method of claim 8 , wherein said geometric isomer mixture contains more than 20% of the cis-(Z) isomer.
10. The method of claim 8 , wherein said geometric isomer mixture contains more than 50% of the cis-(Z) isomer.
11. The method of claim 8 , wherein said geometric isomer mixture contains more than 90% of the cis-(Z) isomer.
12. The method of claim 8 , wherein said geometric isomer mixture contains more than 95% of the cis-(Z) isomer.
13. The method of claim 8 , wherein said geometric isomer mixture contains about 20% to about 99.9% of the cis-(Z) isomer.
14. The method of claim 8 , wherein the dosage is about 1 to about 6 milligrams.