Doxepin trans isomers and isomeric mixtures and methods of using the same to treat sleep disorders
View Patent ↗The invention relates to use of the trans-(E) isomer or isomeric mixtures containing specified ratios of the trans-(E) and cis-(Z) 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 treating insomnia characterized by difficulties with sleep maintenance, the method comprising:
administering a dosage of doxepin or a pharmaceutically acceptable salt thereof to 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, wherein the dosage of doxepin is between about 1 and about 6 mg, wherein the doxepin or salt thereof is a geometric isomer mixture containing about 88.3% to about 100.0% of the trans-(E) isomer or is 100% trans-(E) isomer, and wherein the dosage is administered prior to the start of the sleep period.
2. The method of claim 1 , wherein said geometric isomer mixture contains more than 90% of the trans-(E) isomer.
3. The method of claim 1 , wherein said geometric isomer mixture contains more than 95% of the trans-(E) isomer.
4. The method of claim 1 , wherein said geometric isomer mixture contains more than 98% of the trans-(E) isomer.
5. The method of claim 1 , wherein said geometric isomer mixture contains more than 99% of the trans-(E) isomer.
6. The method of claim 1 , wherein said geometric isomer mixture contains at least 99.5% or 99.9% of the trans-(E) isomer.
7. The method of claim 1 , wherein the dosage is effective to improve the insomnia while minimizing next day residual sedation.
8. The method of claim 1 , wherein the dosage is about 1 milligram.
9. The method of claim 1 , wherein the dosage is about 3 milligrams.
10. The method of claim 1 , wherein the dosage is about 6 milligrams.
11. A method for treating insomnia characterized by difficulties with sleep maintenance, the method comprising:
administering a dosage of doxepin or a pharmaceutically acceptable salt thereof to 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, wherein the dosage of doxepin is between about 1 and about 6 mg, wherein the doxepin or salt thereof is a geometric isomer mixture containing about 88.3% to about 100.0% of the trans-(E) isomer or is 100% trans-(E) isomer, and wherein the dosage is administered prior to the start of the sleep period.
12. The method of claim 11 , wherein said geometric isomer mixture contains more than 90% of the trans-(E) isomer.
13. The method of claim 11 , wherein said geometric isomer mixture contains more than 95% of the trans-(E) isomer.
14. The method of claim 11 , wherein said geometric isomer mixture contains more than 98% of the trans-(E) isomer.
15. The method of claim 11 , wherein said geometric isomer mixture contains more than 99% of the trans-(E) isomer.
16. The method of claim 11 , wherein said geometric isomer mixture contains at least 99.5% or 99.9% of the trans-(E) isomer.
17. The method of claim 11 , wherein the dosage is effective to improve the insomnia while minimizing next day residual sedation.
18. The method of claim 11 , wherein the dosage is about 1 milligram.
19. The method of claim 11 , wherein the dosage is about 3 milligrams.
20. The method of claim 11 , wherein the dosage is about 6 milligrams.