ULTRA LOW DOSE DOXEPIN AND METHODS OF USING THE SAME TO TREAT SLEEP DISORDERS

1 . A method for treating insomnia comprising administering to a patient doxepin, a pharmaceutically acceptable salt thereof, or a prodrug thereof in a daily dosage ranging from about 0.0001 to about 0.49 milligrams.

2 . The method of claim 1 , wherein the pharmaceutically acceptable salt of doxepin is the hydrochloride salt thereof.

3 . The method of claim 1 , wherein the prodrug of doxepin is a prodrug ester.

4 . The method of claim 1 , wherein the daily dosage is about 0.0001 to about 0.1 milligrams.

5 . The method of claim 1 , wherein the daily dosage ranges from about 0.001 to about 0.1 milligrams.

6 . The method of claim 1 , wherein the daily dosage is about 0.01 to about 0.099 milligrams.

7 . The method of claim 1 , wherein the insomnia is a chronic insomnia or a non-chronic insomnia.

8 . The method of claim 7 , wherein the non-chronic insomnia is a transient or a short term insomnia.

9 . The method of claim 1 , wherein the insomnia is selected from the group consisting of onset insomnia and maintenance insomnia.

10 . The method of any of claims 1 - 9 , wherein the patient is not suffering from depression.

11 . The method of any of claims 1 - 9 , wherein the patient is suffering from depression.

12 . The method of claim 1 , further comprising administering at least one of ramelteon, eszopiclone, zolpidem tartrate, or zaleplon.

13 . The method of claim 1 , further comprising administering at least one additional sleep medication.

14 . The method of claim 13 , wherein the at least one additional sleep medication is selected from a 5-HT2 antagonist, ketanserin, a H3 agonist, an orexin antagonist, a noradrenergic antagonist, a galanin agonist, a CRH antagonist, Gaboxadol, other GABA-A direct antagonists, a GABA reuptake inhibitor, tiagabine, a growth hormone, a growth hormone agonist, estrogen, an estrogen agonist, or a melatonin agonist.

15 . A composition comprising doxepin, a pharmaceutically acceptable salt thereof, or a prodrug of doxepin in a dosage of about 0.0001 milligrams to about 0.49 milligrams.

16 . The composition of claim 15 , further comprising a pharmaceutically acceptable carrier.

17 . The composition of claim 15 , wherein the pharmaceutically acceptable salt of doxepin is the hydrochloride salt thereof.

18 . The composition of claim 15 , wherein the prodrug is an ester.

19 . The composition of claim 15 , comprising a dosage of about 0.001 to about 0.1 milligrams of doxepin, a pharmaceutically acceptable salt of doxepin or a prodrug doxepin.

20 . The composition of claim 15 , comprising a dosage of about 0.01 to about 0.099 milligrams of doxepin, a pharmaceutically acceptable salt of doxepin or a prodrug of doxepin.

21 . The composition of claim 15 , wherein the composition is in a form suitable for oral or nasal administration.

22 . The composition of any of claim 15 , 16 , 17 , 18 , 19 , 20 , or 21 , further comprising at least one of ramelteon, eszopiclone, zolpidem tartrate, or zaleplon.

23 . The composition of any of claim 15 , 16 , 17 , 18 , 19 , 20 , or 21 , further comprising at least one additional sleep medication.

24 . The composition of claim 25 , wherein the at least one additional sleep medication is selected from a 5-HT2 antagonist, ketanserin, a H3 agonist, an orexin antagonist, a noradrenergic antagonist, a galanin agonist, a CRH antagonist, Gaboxadol, other GABA-A direct antagonists, a GABA reuptake inhibitor, tiagabine, a growth hormone, a growth hormone agonist, estrogen, an estrogen agonist, or a melatonin agonist.

25 . A method of shortening the time required to achieve a maximum plasma concentration of doxepin in a patient receiving doxepin therapy comprising administering to the patient about 0.0001 milligrams to about 0.49 milligrams of doxepin in a pharmaceutical composition without food.

26 . A method of shortening the time required to achieve sleep onset comprising administering to the patient about 0.0001 milligrams to about 0.49 milligrams of doxepin in a pharmaceutical composition without food.

27 . A method of treating a sleep disorder comprising providing a patient with about 0.0001 milligrams to about 0.49 milligrams of doxepin and providing the patient with instructions to take the doxepin without food.

28 . A method of increasing the oral bioavailability of doxepin, comprising administering with food to a patient a pharmaceutical oral dosage form of doxepin in an amount of about 0.0001 milligrams to about 0.49 milligrams.

29 . A method of increasing the oral bioavailability of doxepin to a patient receiving doxepin therapy, comprising administering to the patient with food a pharmaceutical oral dosage form of doxepin comprising about 0.0001 milligrams to about 0.49 milligrams of doxepin, wherein the administration results in an AUC 0-∞ , that is greater than that achieved by the administration of the same amount of doxepin without food.

30 . A method of treating depression or anxiety, comprising administering about 0.0001 milligrams to about 0.49 milligrams of doxepin with food.

31 . A method of treating depression or anxiety, comprising providing a patient with doxepin in an amount of about 0.0001 milligrams to about 0.49 milligrams and providing the patient with instructions to take the doxepin with food.

32 . A method of treating depression or anxiety comprising providing a patient with doxepin in an amount of about 0.0001 milligrams to about 0.49 milligrams and providing the patient with information regarding a doxepin food effect.

33 . A method of decreasing the oral bioavailability of doxepin, comprising administering to a patient a pharmaceutical oral dosage form of doxepin comprising doxepin in an amount of about 0.0001 milligrams to about 0.49 milligrams without food.

34 . A method of decreasing the oral bioavailability of doxepin to a patient receiving doxepin therapy, comprising administering to the patient without food a pharmaceutical oral dosage form of doxepin comprising doxepin in an amount of about 0.0001 milligrams to about 0.49 milligrams, wherein the administration results in an AUC 0-∞ that is less than that achieved by the administration of the same amount of doxepin with food.

35 . A method of alleviating a doxepin food effect comprising administering about 0.0001 milligrams to about 0.49 milligrams of doxepin to a patient in need thereof, wherein the patient is in a non-fasted state.

36 . A method of alleviating a doxepin food effect comprising administering about 0.0001 milligrams to about 0.49 milligrams of doxepin to a patient in need thereof, wherein the patient is in a fasted state.

37 . A method of minimizing side effects associated with a doxepin therapy, comprising administering about 0.0001 milligrams to about 0.49 milligrams of doxepin to a patient with food.

38 . A method for improving the consistency of pharmacokinetics associated with doxepin therapy, in which a patient receives a multiple doxepin dosages over multiple days, comprising administering about 0.0001 milligrams to about 0.49 milligrams of doxepin to the patient in a fixed temporal relationship to food intake by the patient.

39 . A product comprising doxepin in an amount of about 0.0001 milligrams to about 0.49 milligrams and written instructions associated therewith to take the doxepin without food.

40 . A product comprising doxepin in an amount of about 0.0001 milligrams to about 0.49 milligrams and written instructions associated therewith to take the doxepin with food.

41 . A product comprising doxepin in an amount of about 0.0001 milligrams to about 0.49 milligrams and written information associated therewith regarding a doxepin food effect.