Combination of sedative and a neurotransmitter modulator, and methods for improving sleep quality and treating depression

• US 20050176680A1
• Filed: 12/08/2004
• Published: 08/11/2005
• Est. Priority Date: 12/11/2003
• Status: Abandoned Application

• Current Assignee: Sepracor Incorporated (Sumitomo Chemical Company Limited)
• Original Assignee: Sepracor Incorporated (Sumitomo Chemical Company Limited)
• Inventors: Lalji, Karim, Caron, Judy, Barberich, Timothy J., Wessel, Thomas
• Application Number:
  US11/007,795
• Publication Number:
  US 20050176680A1
• Time in Patent Office: Days
• US Class Current: 514/58
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/4985 Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/724 Cyclodextrins
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

One aspect of the present invention relates to pharmaceutical compositions containing two or more active agents that when taken together can be used to treat, e.g., insomnia and/or depression. The first component of the pharmaceutical composition is a GABA receptor modulating compound. The second component of the pharmaceutical composition is a serotonin reuptake inhibitor, a norepinephrine reuptake inhibitor, a 5-HT_2A modulator, or dopamine reuptake inhibitor. In certain embodiments, the pharmaceutical composition comprises eszopiclone. In a preferred embodiment, the pharmaceutical composition comprises eszopiclone and fluoxetine. The present invention also relates to a method of treating a sleep abnormality, treating insomnia, treating depression, augmenting antidepressant therapy, eliciting a dose-sparing effect, reducing depression relapse, improving the efficacy of antidepressant therapy or improving the tolerability of antidepressant therapy, comprising co-administering to a patient in need thereof a GABA-receptor-modulating compound; and a SRI, NRI, 5-HT_2A modulator or DRI.

Claims

1. A pharmaceutical composition comprising eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a serotonin reuptake inhibitor.

2. A pharmaceutical composition comprising eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a serotonin reuptake inhibitor, wherein said serotonin reuptake inhibitor is citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, paroxetine, sertraline, clominpramine, femoxetine, indapline, alaprolclate, cericlamine, or ifoxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

3. The pharmaceutical composition of claim 2, wherein said serotonin reuptake inhibitor is fluoxetine, fluvoxamine, milnacipran, or paroxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

4. The pharmaceutical composition of claim 3, wherein said serotonin reuptake inhibitor is fluoxetine, paroxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of either of them.

5. The pharmaceutical composition of claim 4, wherein said serotonin reuptake inhibitor is fluoxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.

6. The pharmaceutical composition of claim 5, wherein said fluoxetine is fluoxetine hydrochloride, or a pharmaceutically acceptable solvate, clathrate, polymorph, or co-crystal thereof.

7. A pharmaceutical composition consisting essentially of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a serotonin reuptake inhibitor; and

at least one pharmaceutically acceptable carrier.

8. A pharmaceutical composition consisting essentially of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a serotonin reuptake inhibitor, wherein said serotonin reuptake inhibitor is citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, paroxetine, sertraline, clominpramine, femoxetine, indapline, alaprolclate, cericlamine, or ifoxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them; and

at least one pharmaceutically acceptable carrier.

9. The pharmaceutical composition of claim 8, wherein said serotonin reuptake inhibitor is fluoxetine, fluvoxamine, milnacipran, or paroxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

10. The pharmaceutical composition of claim 9, wherein said serotonin reuptake inhibitor is fluoxetine, paroxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of either of them.

11. The pharmaceutical composition of claim 10, wherein said serotonin reuptake inhibitor is fluoxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.

12. The pharmaceutical composition of claim 11, wherein said fluoxetine is fluoxetine hydrochloride, or a pharmaceutically acceptable solvate, clathrate, polymorph, or co-crystal thereof.

13. A method of treating a patient suffering from a sleep abnormality, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of a serotonin reuptake inhibitor.

25. The method of any one of claims 13 to 24, wherein said sleep abnormality is difficulty falling asleep, difficulty staying asleep, or waking up too early.

14. A method of treating a patient suffering from a sleep abnormality, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of a serotonin reuptake inhibitor, wherein said serotonin reuptake inibitor is citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, paroxetine, sertraline, clominpramine, femoxetine, indapline, alaprolclate, cericlamine, or ifoxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

15. The method of claim 14, wherein said serotonin reuptake inhibitor is fluoxetine, fluvoxamine, milnacipran, or paroxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

16. The method of claim 15, wherein said serotonin reuptake inhibitor is fluoxetine, paroxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of either of them.

17. The method of claim 16, wherein said serotonin reuptake inhibitor is fluoxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.

18. The method of claim 17, wherein said fluoxetine is fluoxetine hydrochloride, or a pharmaceutically acceptable solvate, clathrate, polymorph, or co-crystal thereof.

19. A method of treating a patient suffering from a sleep abnormality, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a therapeutically effective amount of a serotonin reuptake inhibitor; and

at least one pharmaceutically acceptable carrier.

20. A method of treating a patient suffering from a sleep abnormality, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a therapeutically effective amount of a serotonin reuptake inhibitor, wherein said serotonin reuptake inibitor is citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, paroxetine, sertraline, clominpramine, femoxetine, indapline, alaprolclate, cericlamine, or ifoxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them; and

at least one pharmaceutically acceptable carrier.

21. The method of claim 20, wherein said serotonin reuptake inhibitor is fluoxetine, fluvoxamine, milnacipran, or paroxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

22. The method of claim 21, wherein said serotonin reuptake inhibitor is fluoxetine, paroxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of either of them.

23. The method of claim 22, wherein said serotonin reuptake inhibitor is fluoxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.

24. The method of claim 23, wherein said fluoxetine is fluoxetine hydrochloride, or a pharmaceutically acceptable solvate, clathrate, polymorph, or co-crystal thereof.

26. A method of treating a patient suffering from insomnia, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of a serotonin reuptake inhibitor.

38. The method of any of claims 26 to 37, wherein said insomnia is transient insomnia.

39. The method of any of claims 26 to 37, wherein said insomnia is short-term insomnia.

40. The method of any of claims 26 to 37, wherein said insomnia is chronic insomnia.

27. A method of treating a patient suffering from insomnia, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of a serotonin reuptake inhibitor, wherein said serotonin reuptake inibitor is citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, paroxetine, sertraline, clominpramine, femoxetine, indapline, alaprolclate, cericlamine, or ifoxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

28. The method of claim 27, wherein said serotonin reuptake inhibitor is fluoxetine, fluvoxamine, milnacipran, or paroxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

29. The method of claim 28, wherein said serotonin reuptake inhibitor is fluoxetine, paroxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of either of them.

30. The method of claim 29, wherein said serotonin reuptake inhibitor is fluoxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.

31. The method of claim 30, wherein said fluoxetine is fluoxetine hydrochloride, or a pharmaceutically acceptable solvate, clathrate, polymorph, or co-crystal thereof.

32. A method of treating a patient suffering from insomnia, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a therapeutically effective amount of a serotonin reuptake inhibitor; and

at least one pharmaceutically acceptable carrier.

33. A method of treating a patient suffering from insomnia, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a therapeutically effective amount of a serotonin reuptake inhibitor, wherein said serotonin reuptake inibitor is citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, paroxetine, sertraline, clominpramine, femoxetine, indapline, alaprolclate, cericlamine, or ifoxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them; and

at least one pharmaceutically acceptable carrier.

34. The method of claim 33, wherein said serotonin reuptake inhibitor is fluoxetine, fluvoxamine, milnacipran, or paroxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

35. The method of claim 34, wherein said serotonin reuptake inhibitor is fluoxetine, paroxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of either of them.

36. The method of claim 35, wherein said serotonin reuptake inhibitor is fluoxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.

37. The method of claim 36, wherein said fluoxetine is fluoxetine hydrochloride, or a pharmaceutically acceptable solvate, clathrate, polymorph, or co-crystal thereof.

41. A method of treating a patient suffering from depression, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of a serotonin reuptake inhibitor.

53. The method of any of claims 41 to 52, wherein said depression is a major depressive disorder.

42. A method of treating a patient suffering from depression, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of a serotonin reuptake inhibitor, wherein said serotonin reuptake inibitor is citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, paroxetine, sertraline, clominpramine, femoxetine, indapline, alaprolclate, cericlamine, or ifoxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

43. The method of claim 42, wherein said serotonin reuptake inhibitor is fluoxetine, fluvoxamine, milnacipran, or paroxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

44. The method of claim 43, wherein said serotonin reuptake inhibitor is fluoxetine, paroxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of either of them.

45. The method of claim 44, wherein said serotonin reuptake inhibitor is fluoxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.

46. The method of claim 45, wherein said fluoxetine is fluoxetine hydrochloride, or a pharmaceutically acceptable solvate, clathrate, polymorph, or co-crystal thereof.

47. A method of treating a patient suffering from depression, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a therapeutically effective amount of a serotonin reuptake inhibitor; and

at least one pharmaceutically acceptable carrier.

48. A method of treating a patient suffering from depression, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, a therapeutically effective amount of a serotonin reuptake inhibitor, wherein said serotonin reuptake inibitor is citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, paroxetine, sertraline, clominpramine, femoxetine, indapline, alaprolclate, cericlamine, or ifoxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them;

and at least one pharmaceutically acceptable carrier.

49. The method of claim 48, wherein said serotonin reuptake inhibitor is fluoxetine, fluvoxamine, milnacipran, or paroxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

50. The method of claim 49, wherein said serotonin reuptake inhibitor is fluoxetine, paroxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of either of them.

51. The method of claim 50, wherein said serotonin reuptake inhibitor is fluoxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.

52. The method of claim 51, wherein said fluoxetine is fluoxetine hydrochloride, or a pharmaceutically acceptable solvate, clathrate, polymorph, or co-crystal thereof.

54. A pharmaceutical composition comprising eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a norepinephrine reuptake inhibitor.

55. A pharmaceutical composition comprising eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a norepinephrine reuptake inhibitor, wherein said norepinephrine reuptake inhibitor is desipramine, maprotiline, lofepramine, reboxetine, oxaprotiline, fezolamine, tomoxetine, or (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

56. The pharmaceutical composition of claim 55, wherein said norepinephrine reuptake inhibitor is desipramine, reboxetine, oxaprotiline, or (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

57. The pharmaceutical composition of claim 56, wherein said norepinephrine reuptake inhibitor is (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.

58. A pharmaceutical composition consisting essentially of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a norepinephrine reuptake inhibitor; and

at least one pharmaceutically acceptable carrier.

59. A pharmaceutical composition consisting essentially of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a norepinephrine reuptake inhibitor, wherein said norepinephrine reuptake inhibitor is desipramine, maprotiline, lofepramine, reboxetine, oxaprotiline, fezolamine, tomoxetine, or (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them; and

at least one pharmaceutically acceptable carrier.

60. The pharmaceutical composition of claim 59, wherein said norepinephrine reuptake inhibitor is desipramine, reboxetine, oxaprotiline, or (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

61. The pharmaceutical composition of claim 60, wherein said norepinephrine reuptake inhibitor is (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.

62. A method of treating a patient suffering from a sleep abnormality, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of norepinephrine reuptake inhibitor.

70. The method of any one of claims 62 to 69, wherein said sleep abnormality is difficulty falling asleep, difficulty staying asleep, or waking up too early.

63. A method of treating a patient suffering from a sleep abnormality, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of norepinephrine reuptake inhibitor, wherein said norepinephrine reuptake inhibitor is desipramine, maprotiline, lofepramine, reboxetine, oxaprotiline, fezolamine, tomoxetine, or (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

64. The method of claim 63, wherein said norepinephrine reuptake inhibitor is desipramine, reboxetine, oxaprotiline, or (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

65. The method of claim 64, wherein said norepinephrine reuptake inhibitor is (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.

66. A method of treating a patient suffering from a sleep abnormality, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a therapeutically effective amount of norepinephrine reuptake inhibitor;

and at least one pharmaceutically acceptable carrier.

67. A method of treating a patient suffering from a sleep abnormality, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a therapeutically effective amount of norepinephrine reuptake inhibitor, wherein said norepinephrine reuptake inhibitor is desipramine, maprotiline, lofepramine, reboxetine, oxaprotiline, fezolamine, tomoxetine, or (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them; and

at least one pharmaceutically acceptable carrier.

68. The method of claim 67, wherein said norepinephrine reuptake inhibitor is desipramine, reboxetine, oxaprotiline, or (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

69. The method of claim 68, wherein said norepinephrine reuptake inhibitor is (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.

71. A method of treating a patient suffering from insomnia, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of norepinephrine reuptake inhibitor.

79. The method of any of claims 71 to 78, wherein said insomnia is transient insomnia.

80. The method of any of claims 71 to 78, wherein said insomnia is short-term insomnia.

81. The method of any of claims 71 to 78, wherein said insomnia is chronic insomnia.

72. A method of treating a patient suffering from insomnia, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of norepinephrine reuptake inhibitor, wherein said norepinephrine reuptake inhibitor is desipramine, maprotiline, lofepramine, reboxetine, oxaprotiline, fezolamine, tomoxetine, or (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

73. The method of claim 72, wherein said norepinephrine reuptake inhibitor is desipramine, reboxetine, oxaprotiline, or (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

74. The method of claim 73, wherein said norepinephrine reuptake inhibitor is (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

75. A method of treating a patient suffering from insomnia, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a therapeutically effective amount of norepinephrine reuptake inhibitor;

and at least one pharmaceutically acceptable carrier.

76. A method of treating a patient suffering from insomnia, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a therapeutically effective amount of norepinephrine reuptake inhibitor, wherein said norepinephrine reuptake inhibitor is desipramine, maprotiline, lofepramine, reboxetine, oxaprotiline, fezolamine, tomoxetine, or (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt;

solvate, clathrate, polymorph, or co-crystal of any one of them; and

at least one pharmaceutically acceptable carrier.

77. The method of claim 76, wherein said norepinephrine reuptake inhibitor is desipramine, reboxetine, oxaprotiline, or (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

78. The method of claim 77, wherein said norepinephrine reuptake inhibitor is (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

82. A method of treating a patient suffering from depression, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of norepinephrine reuptake inhibitor.

90. The method of any of claims 82 to 89, wherein said depression is a major depressive disorder.

83. A method of treating a patient suffering from depression, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of norepinephrine reuptake inhibitor, wherein said norepinephrine reuptake inhibitor is desipramine, maprotiline, lofepramine, reboxetine, oxaprotiline, fezolamine, tomoxetine, or (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

84. The method of claim 83, wherein said norepinephrine reuptake inhibitor is desipramine, reboxetine, oxaprotiline, or (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

85. The method of claim 84, wherein said norepinephrine reuptake inhibitor is (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

86. A method of treating a patient suffering from depression, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a therapeutically effective amount of norepinephrine reuptake inhibitor;

and at least one pharmaceutically acceptable carrier.

87. A method of treating a patient suffering from depression, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a therapeutically effective amount of norepinephrine reuptake inhibitor, wherein said norepinephrine reuptake inhibitor is desipramine, maprotiline, lofepramine, reboxetine, oxaprotiline, fezolamine, tomoxetine, or (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them; and

at least one pharmaceutically acceptable carrier.

88. The method of claim 87, wherein said norepinephrine reuptake inhibitor is desipramine, reboxetine, oxaprotiline, or (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

89. The method of claim 88, wherein said norepinephrine reuptake inhibitor is (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

91. A pharmaceutical composition comprising eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a dopamine reuptake inhibitor.

92. A pharmaceutical composition comprising eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a dopamine reuptake inhibitor, said dopamine reuptake inhibitor is amineptine, bupropion, GBR-12935, venlafaxine, desmethylvenlafaxine, or 2β

-propanoyl-3β

-(4-tolyl)-tropane, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

93. The pharmaceutical composition of claim 92, wherein said dopamine reuptake inhibitor is bupropion, or GBR-12935, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of either of them.

94. The pharmaceutical composition of claim 93, wherein said dopamine reuptake inhibitor is bupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.

95. The pharmaceutical composition of claim 92, wherein said dopamine reuptake inhibitor is venlafaxine, desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of either of them.

96. The pharmaceutical composition of claim 95, wherein said desmethylvenlafaxine is racemic desmethylvenlafaxine, (+)-desmethylvenlafaxine, or (−

)-desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

97. A pharmaceutical composition consisting essentially of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a dopamine reuptake inhibitor; and

at least one pharmaceutically acceptable carrier.

98. A pharmaceutical composition consisting essentially of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a dopamine reuptake inhibitor, said dopamine reuptake inhibitor is amineptine, bupropion, GBR-12935, venlafaxine, desmethylvenlafaxine, or 2β

-propanoyl-3β

-(4-tolyl)-tropane, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them; and

at least one pharmaceutically acceptable carrier.

99. The pharmaceutical composition of claim 98, wherein said dopamine reuptake inhibitor is bupropion, or GBR-12935, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of either of them.

100. The pharmaceutical composition of claim 99, wherein said dopamine reuptake inhibitor is bupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.

101. The pharmaceutical composition of claim 98, wherein said dopamine reuptake inhibitor is venlafaxine, desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of either of them.

102. The pharmaceutical composition of claim 101, wherein said desmethylvenlafaxine is racemic desmethylvenlafaxine, (+)-desmethylvenlafaxine, or (−

)-desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

103. A method of treating a patient suffering from a sleep abnormality, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of a dopamine reuptake inhibitor.

115. The method of any one of claims 103 to 114, wherein said sleep abnormality is difficulty falling asleep, difficulty staying asleep, or waking up too early.

104. A method of treating a patient suffering from a sleep abnormality, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of a dopamine reuptake inhibitor, wherein said dopamine reuptake inhibitor is amineptine, bupropion, GBR-12935, venlafaxine, desmethylvenlafaxine, or 2β

-propanoyl-3β

-(4-tolyl)-tropane, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

105. The method of claim 104, wherein said dopamine reuptake inhibitor is bupropion, or GBR-12935, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of either of them.

106. The method of claim 105, wherein said dopamine reuptake inhibitor is bupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.

107. The method of claim 104, wherein said dopamine reuptake inhibitor is venlafaxine, desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of either of them.

108. The method of claim 107, wherein said desmethylvenlafaxine is racemic desmethylvenlafaxine, (+)-desmethylvenlafaxine, or (−

)-desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

109. A method of treating a patient suffering from a sleep abnormality, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a therapeutically effective amount of a dopamine reuptake inhibitor; and

at least one pharmaceutically acceptable carrier.

110. A method of treating a patient suffering from a sleep abnormality, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a therapeutically effective amount of a dopamine reuptake inhibitor, wherein said dopamine reuptake inhibitor is amineptine, bupropion, GBR-12935, venlafaxine, desmethylvenlafaxine, or 2β

-propanoyl-3β

-(4-tolyl)-tropane, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them; and

at least one pharmaceutically acceptable carrier.

111. The method of claim 110, wherein said dopamine reuptake inhibitor is bupropion, or GBR-12935, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of either of them.

112. The method of claim 111, wherein said dopamine reuptake inhibitor is bupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.

113. The method of claim 110, wherein said dopamine reuptake inhibitor is venlafaxine, desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of either of them.

114. The method of claim 113, wherein said desmethylvenlafaxine is racemic desmethylvenlafaxine, (+)-desmethylvenlafaxine, or (−

)-desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

116. A method of treating a patient suffering from insomnia, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of a dopamine reuptake inhibitor.

128. The method of any of claims 116 to 127, wherein said insomnia is transient insomnia.

129. The method of any of claims 116 to 127, wherein said insomnia is short-term insomnia.

130. The method of any of claims 116 to 127, wherein said insomnia is chronic insomnia.

117. A method of treating a patient suffering from insomnia, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of a dopamine reuptake inhibitor, wherein said dopamine reuptake inhibitor is amineptine, bupropion, GBR-12935, venlafaxine, desmethylvenlafaxine, or 2β

-propanoyl-3β

-(4-tolyl)-tropane, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

118. The method of claim 117, wherein said dopamine reuptake inhibitor is bupropion, or GBR-12935, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of either of them.

119. The method of claim 118, wherein said dopamine reuptake inhibitor is bupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.

120. The method of claim 117, wherein said dopamine reuptake inhibitor is venlafaxine, desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of either of them.

121. The method of claim 120, wherein said desmethylvenlafaxine is racemic desmethylvenlafaxine, (+)-desmethylvenlafaxine, or (−

)-desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

122. A method of treating a patient suffering from insomnia, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a therapeutically effective amount of a dopamine reuptake inhibitor; and

at least one pharmaceutically acceptable carrier.

123. A method of treating a patient suffering from insomnia, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a therapeutically effective amount of a dopamine reuptake inhibitor, wherein said dopamine reuptake inhibitor is amineptine, bupropion, GBR-12935, venlafaxine, desmethylvenlafaxine, or 2β

-propanoyl-3β

-(4-tolyl)-tropane, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them; and

at least one pharmaceutically acceptable carrier.

124. The method of claim 123, wherein said dopamine reuptake inhibitor is bupropion, or GBR-12935, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of either of them.

125. The method of claim 124, wherein said dopamine reuptake inhibitor is bupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.

126. The method of claim 123, wherein said dopamine reuptake inhibitor is venlafaxine, desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of either of them.

127. The method of claim 126, wherein said desmethylvenlafaxine is racemic desmethylvenlafaxine, (+)-desmethylvenlafaxine, or (−

)-desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

131. A method of treating a patient suffering from depression, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of a dopamine reuptake inhibitor.

143. The method of any of claims 131 to 142, wherein said depression is a major depressive disorder.

132. A method of treating a patient suffering from depression, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of a dopamine reuptake inhibitor, wherein said dopamine reuptake inhibitor is amineptine, bupropion, GBR-12935, venlafaxine, desmethylvenlafaxine, or 2β

-propanoyl-3β

-(4-tolyl)-tropane, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

133. The method of claim 132, wherein said dopamine reuptake inhibitor is bupropion, or GBR-12935, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of either of them.

134. The method of claim 133, wherein said dopamine reuptake inhibitor is bupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.

135. The method of claim 132, wherein said dopamine reuptake inhibitor is venlafaxine, desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of either of them.

136. The method of claim 135, wherein said desmethylvenlafaxine is racemic desmethylvenlafaxine, (+)-desmethylvenlafaxine, or (−

)-desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

137. A method of treating a patient suffering from depression, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a therapeutically effective amount of a dopamine reuptake inhibitor; and

at least one pharmaceutically acceptable carrier.

138. A method of treating a patient suffering from depression, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a therapeutically effective amount of a dopamine reuptake inhibitor, wherein said dopamine reuptake inhibitor is amineptine, bupropion, GBR-12935, venlafaxine, desmethylvenlafaxine, or 2β

-propanoyl-3β

-(4-tolyl)-tropane, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them; and

at least one pharmaceutically acceptable carrier.

139. The method of claim 138, wherein said dopamine reuptake inhibitor is bupropion, or GBR-12935, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of either of them.

140. The method of claim 139, wherein said dopamine reuptake inhibitor is bupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.

141. The method of claim 138, wherein said dopamine reuptake inhibitor is venlafaxine, desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of either of them.

142. The method of claim 141, wherein said desmethylvenlafaxine is racemic desmethylvenlafaxine, (+)-desmethylvenlafaxine, or (−

)-desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

144. A pharmaceutical composition comprising eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a 5-HT_2A modulator.

145. The pharmaceutical composition of claim 144, wherein the 5-HT2A modulator is a 5-HT_2A antagonist.

146. The pharmaceutical composition of claim 144, wherein the 5-HT2A modulator is a 5-HT_2A inverse agonist.

147. A pharmaceutical composition comprising eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a 5-HT_2A modulator, wherein said 5 HT_2A modulator is MDL 100907, SR 46349B, YM 992, fananserin, oxazolidine compounds A, phenylindole compounds A, piperidinyl compounds B, spiroazacyclic compounds C, or azacyclic compounds D, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

148. The pharmaceutical composition of claim 147, wherein said 5-HT_2A modulator is MDL 100907, SR 46349B, YM 992, fananserin, oxazolidine compounds A, or phenylindole compounds A, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co crystal of any one of them.

149. The pharmaceutical composition of claim 148, wherein said 5-HT_2A modulator is MDL 100907, SR 46349B, YM 992, or fananserin, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

150. The pharmaceutical composition of claim 147, wherein said 5-HT_2A modulator, wherein said 5-HT_2A modulator is piperidinyl compounds B, spiroazacyclic compounds C, or azacyclic compounds D, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

151. A pharmaceutical composition consisting essentially of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a 5-HT_2A modulator; and

at least one pharmaceutically acceptable carrier.

152. The pharmaceutical composition of claim 151, wherein the 5-HT_2A modulator is a 5-HT_2A antagonist.

153. The pharmaceutical composition of claim 151, wherein the 5-HT_2A modulator is a 5-HT_2A inverse agonist.

154. A pharmaceutical composition consisting essentially of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a 5-HT_2A modulator, wherein said 5 HT_2A modulator is MDL 100907, SR 46349B, YM 992, fananserin, oxazolidine compounds A, phenylindole compounds A, piperidinyl compounds B, spiroazacyclic compounds C, or azacyclic compounds D, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them; and

at least one pharmaceutically acceptable carrier.

155. The pharmaceutical composition of claim 154, wherein said 5-HT_2A modulator is MDL 100907, SR 46349B, YM 992, fananserin, oxazolidine compounds A, or phenylindole compounds A, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

156. The pharmaceutical composition of claim 155, wherein said 5-HT_2A modulator is MDL 100907, SR 46349B, YM 992, or fananserin, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

157. The pharmaceutical composition of claim 154, wherein said 5-HT_2A modulator, wherein said 5 HT_2A modulator is piperidinyl compounds B, spiroazacyclic compounds C, or azacyclic compounds D, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

158. A method of treating a patient suffering from a sleep abnormality, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of a 5-HT_2A modulator.

159. The method of claim 158, wherein the 5-HT_2A modulator is a 5-HT_2A antagonist.

160. The method of claim 158, wherein the 5-HT_2A modulator is a 5-HT_2A inverse agonist.

172. The method of any one of claims 158 to 171, wherein said sleep abnormality is difficulty falling asleep, difficulty staying asleep, or waking up too early.

161. A method of treating a patient suffering from a sleep abnormality, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of a 5-HT_2A modulator, wherein said 5-HT_2A modulator is MDL 100907, SR 46349B, YM 992, fananserin, oxazolidine compounds A, phenylindole compounds A, piperidinyl compounds B, spiroazacyclic compounds C, azacyclic compounds D, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

162. The method of claim 161, wherein the 5-HT_2A modulator is MDL 100907, SR 46349B, YM992, fananserin, oxazolidine compounds A, or phenylindole compounds A, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

163. The method of claim 162, wherein the 5-HT_2A modulator is MDL 100907, SR 46349B, YM 992, or fananserin, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

164. The method of claim 161, wherein the 5-HT_2A modulator is piperidinyl compounds B, spiroazacyclic compounds C, azacyclic compounds D, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

165. A method of treating a patient suffering from a sleep abnormality, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a therapeutically effective amount of a 5-HT_2A modulator; and

at least one pharmaceutically acceptable carrier.

166. The method of claim 165, wherein the 5-HT_2A modulator is a 5-HT_2A antagonist.

167. The method of claim 165, wherein the 5-HT_2A modulator is a 5-HT_2A inverse agonist.

168. A method of treating a patient suffering from a sleep abnormality, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a therapeutically effective amount of a 5-HT_2A modulator, wherein said 5-HT_2A modulator is MDL 100907, SR 46349B, YM 992, fananserin, oxazolidine compounds A, phenylindole compounds A, piperidinyl compounds B, spiroazacyclic compounds C, azacyclic compounds D, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them; and

at least one pharmaceutically acceptable carrier.

169. The method of claim 168, wherein the 5-HT_2A modulator is MDL 100907, SR 46349B, YM 992, fananserin, oxazolidine compounds A, or phenylindole compounds A, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

170. The method of claim 169, wherein the 5-HT_2A modulator is MDL 100907, SR 46349B, YM 992, or fananserin, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

171. The method of claim 168, wherein the 5-HT_2A modulator is piperidinyl compounds B, spiroazacyclic compounds C, azacyclic compounds D, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

173. A method of treating a patient suffering from insomnia, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of a 5-HT_2A modulator.

174. The method of claim 173, wherein the 5-HT_2A modulator is a 5-HT_2A antagonist.

175. The method of claim 173, wherein the 5-HT_2A modulator is a 5-HT_2A inverse agonist.

187. The method of any of claims 173 to 186, wherein said insomnia is transient insomnia.

188. The method of any of claims 173 to 186, wherein said insomnia is short-term insomnia.

189. The method of any of claims 173 to 186, wherein said insomnia is chronic insomnia.

176. A method of treating a patient suffering from insomnia, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of a 5-HT_2A modulator, wherein said 5-HT_2A modulator is MDL 100907, SR 46349B, YM 992, fananserin, oxazolidine compounds A, phenylindole compounds A, piperidinyl compounds B, spiroazacyclic compounds C, azacyclic compounds D, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

177. The method of claim 176, wherein the 5-HT_2A modulator is MDL 100907, SR 46349B, YM 992, fananserin, oxazolidine compounds A, or phenylindole compounds A, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

178. The method of claim 177, wherein the 5-HT_2A modulator is MDL 100907, SR 46349B, YM 992, or fananserin, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

179. The method of claim 176, wherein the 5-HT_2A modulator is piperidinyl compounds B, spiroazacyclic compounds C, azacyclic compounds D, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

180. A method of treating a patient suffering from insomnia, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a therapeutically effective amount of a 5-HT_2A modulator; and

at least one pharmaceutically acceptable carrier.

181. The method of claim 180, wherein the 5-HT_2A modulator is a 5-HT_2A antagonist.

182. The method of claim 180, wherein the 5-HT_2A modulator is a 5-HT_2A inverse agonist.

183. A method of treating a patient suffering from insomnia, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a therapeutically effective amount of a 5-HT_2A modulator, wherein said 5-HT_2A modulator is MDL 100907, SR 46349B, YM 992, fananserin, oxazolidine compounds A, phenylindole compounds A, piperidinyl compounds B, spiroazacyclic compounds C, azacyclic compounds D, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them; and

at least one pharmaceutically acceptable carrier.

184. The method of claim 183, wherein the 5-HT_2A modulator is MDL 100907, SR 46349B, YM 992, fananserin, oxazolidine compounds A, or phenylindole compounds A, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

185. The method of claim 184, wherein the 5-HT_2A modulator is MDL 100907, SR 46349B, YM 992, or fananserin, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

186. The method of claim 183, wherein the 5-HT_2A modulator is piperidinyl compounds B, spiroazacyclic compounds C, azacyclic compounds D, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

190. A method of treating a patient suffering from depression, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of a 5-HT_2A modulator.

191. The method of claim 190, wherein the 5-HT_2A modulator is a 5-HT_2A antagonist.

192. The method of claim 190, wherein the 5-HT_2A modulator is a ⁵-HT_2A inverse agonist.

204. The method of any of claims 190 to 203, wherein said depression is a major depressive disorder.

193. A method of treating a patient suffering from depression, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof, and a therapeutically effective amount of a 5-HT_2A modulator, wherein said 5-HT_2A modulator is MDL 100907, SR 46349B, YM 992, fananserin, oxazolidine compounds A, phenylindole compounds A, piperidinyl compounds B, spiroazacyclic compounds C, azacyclic compounds D, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

194. The method of claim 193, wherein the 5-HT_2A modulator is MDL 100907, SR 46349B, YM 992, fananserin, oxazolidine compounds A, or phenylindole compounds A, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

195. The method of claim 194, wherein the 5-HT_2A modulator is MDL 100907, SR 46349B, YM 992, or fananserin, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

196. The method of claim 193, wherein the 5-HT_2A modulator is piperidinyl compounds B, spiroazacyclic compounds C, azacyclic compounds D, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

197. A method of treating a patient suffering from depression, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a therapeutically effective amount of a 5-HT_2A modulator; and

at least one pharmaceutically acceptable carrier.

198. The method of claim 197, wherein the 5-HT_2A modulator is a 5-HT_2A antagonist.

199. The method of claim 197, wherein the 5-HT_2A modulator is a 5-HT_2A inverse agonist.

200. A method of treating a patient suffering from depression, comprising the step of co-administering to a patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof;

a therapeutically effective amount of a 5-HT_2A modulator, wherein said 5-HT_2A modulator is MDL 100907, SR 46349B, YM 992, fananserin, oxazolidine compounds A, phenylindole compounds A, piperidinyl compounds B, spiroazacyclic compounds C, azacyclic compounds D, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them; and

at least one pharmaceutically acceptable carrier.

201. The method of claim 200, wherein the 5-HT_2A modulator is MDL 100907, SR 46349B, YM 992, fananserin, oxazolidine compounds A, or phenylindole compounds A, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

202. The method of claim 201, wherein the 5-HT_2A modulator is MDL 100907, SR 46349B, YM 992, or fananserin, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

203. The method of claim 200, wherein the 5-HT_2A modulator is piperidinyl compounds B, spiroazacyclic compounds C, azacyclic compounds D, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

205. A method for increasing the efficacy of antidepressant therapy in a patient comprising administering to the patient in need thereof, undergoing antidepressant therapy, a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.

209. The method of claim 205, 206, 207 or 208, wherein the eszopiclone is administered chronically or long-term.

211. The method of any of claims 205 to 210, wherein the antidepressant is citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, paroxetine, sertraline, clominpramine, femoxetine, indapline, alaprolclate, cericlamine, ifoxetine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

212. The method of any of claims 205 to 210, wherein the antidepressant is desipramine, maprotiline, lofepramine, reboxetine, oxaprotiline, fezolamine, tomoxetine, (S,S)-hydroxybupropion, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

213. The method of any of claims 205 to 210, wherein the antidepressant is bupropion, venlafaxine, or desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

214. The method of claim 213, wherien the desmethylvenlafaxine is racemic desmethylvenlafaxine, (+)-desmethylvenlafaxine, or (−

)-desmethylvenlafaxine, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal of any one of them.

215. The method of any of claims 205 to 210, wherein the antidepressant is a dopamine reuptake inhibitor or an atypical antidepressant.

206. A method for augmentation of antidepressant therapy in a patient comprising administering to the patient in need thereof, undergoing antidepressant therapy, a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.

207. A method for eliciting a dose sparing effect in a patient undergoing treatment with an antidepressant, comprising administering to the patient in need thereof, undergoing antidepressant therapy, a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.

208. A method for reducing depression relapse in a patient who received antidepressant treatment, comprising administering to the patient in need thereof a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.

210. A method for improving the tolerability of antidepressant therapy in a patient suffering from depression, comprising administering to the patient in need thereof, undergoing antidepressant therapy, a therapeutically effective amount of eszopiclone, or a pharmaceutically acceptable salt, solvate, clathrate, polymorph, or co-crystal thereof.