TREATMENT METHODS USING GHB
Provided herein are methods of treating fibromyalgia, post-traumatic stress disorder, irritable bowel syndrome, and irritable bowel disease in a patient with a slow wave sleep deficit by administering oxybate or a pharmaceutically acceptable salt thereof.
1 . A method of treating the symptoms associated with fibromyalgia in a patient in need thereof, the method comprising:
(a) identifying a patient with fibromyalgia with a slow wave sleep (SWS) deficit as determined by sleep polysomnography; and
(b) administering a therapeutically effective amount of oxybate or a pharmaceutically acceptable salt thereof to the patient.
2 . The method of claim 1 , wherein the identified patient exhibits SWS of less than about 10%.
3 . The method of claim 1 , wherein the identified patient exhibits SWS of less than about 5%.
4 . The method of any one of claims 1 - 3 , wherein the administration provides an improvement in the patient's Fibromyalgia Impact Questionnaire (FIQ) score or Tender Points Index (TPI) score compared to prior to the treatment.
5 . The method of any one of claims 1 - 4 , wherein the administration provides an improvement in the patient's Pain Visual Analogue Scale (P-VAS) score compared to prior to the treatment.
6 . The method of any one of claims 1 - 5 , wherein the administration provides an improvement in the patient's Fatigue Visual Analogue Scale (F-VAS) score compared to prior to the treatment.
7 . The method of any one of claims 1 - 6 , wherein the administration provides an improvement in the patient's Tender Points Count (TPC) score compared to prior to the treatment.
8 . The method of any one of claims 1 - 7 , wherein the oxybate or a pharmaceutically acceptable salt thereof is a mixed salt oxybate.
9 . The method of claim 8 , wherein the mixed salt oxybate comprises sodium oxybate, potassium oxybate, magnesium oxybate and calcium oxybate, and wherein the mixed salt oxybate comprises about 5%-40% sodium oxybate (wt/wt %).
10 . The method of claim 8 , wherein the mixed salt oxybate comprises about 5%-40% of sodium oxybate (wt/wt %), about 10%-40% of potassium oxybate (wt/wt %), about 5%-30% of magnesium oxybate (wt/wt %), and about 20%-80% of calcium oxybate (wt/wt %).
11 . The method of claim 8 , wherein the mixed salt oxybate comprises about 8% mol. equiv. of sodium oxybate, about 23% mol. equiv. of potassium oxybate, about 21% mol. equiv. of magnesium oxybate and about 48% mol. equiv. calcium oxybate.
12 . The method of any one of claims 1 - 7 , wherein the oxybate or a pharmaceutically acceptable salt comprises sodium oxybate.
13 . The method of any one of claims 1 - 12 , wherein about 4.5 g-6.0 g of the oxybate or a pharmaceutically acceptable salt thereof is administered per day.
14 . The method of claim 13 , wherein about 4.5 g of the oxybate or a pharmaceutically acceptable salt thereof is administered per day.
15 . The method of claim 13 , wherein about 6.0 g of the oxybate or a pharmaceutically acceptable salt thereof is administered per day.
16 . A method of treating the symptoms associated with post-traumatic stress disorder (PTSD) in a patient in need thereof, the method comprising:
(a) identifying a patent with PTSD with a SWS deficit as determined by sleep EEG; and
(b) administering a therapeutically effective amount of oxybate or a pharmaceutically acceptable salt thereof.
17 . The method of claim 16 , wherein the identified patient exhibits SWS of less than about 10%.
18 . The method of claim 16 wherein the identified patient exhibits SWS of less than about 5%.
19 . The method of claim 18 , wherein the administration provides an improvement in the patient's sleep symptoms associated with PTSD compared to prior to the treatment.
20 . The method of claim 18 , wherein the administration provides an improvement in the patient's insomnia, nightmares, somniphobia, or other sleep-related symptoms of PTSD compared to prior to the treatment.
21 . The method of any one of claims 16 - 20 , wherein the oxybate or a pharmaceutically acceptable salt thereof is a mixed salt oxybate.
22 . The method of claim 21 , wherein the mixed salt oxybate comprises sodium oxybate, potassium oxybate, magnesium oxybate and calcium oxybate, and wherein the mixed salt oxybate comprises about 5%-40% sodium oxybate (wt/wt %).
23 . The method of claim 21 , wherein the mixed salt oxybate comprises about 5%-40% of sodium oxybate (wt/wt %), about 10%-40% of potassium oxybate (wt/wt %), about 5%-30% of magnesium oxybate (wt/wt %), and about 20%-80% of calcium oxybate (wt/wt %).
24 . The method of claim 21 , wherein the mixed salt oxybate comprises about 8% mol. equiv. of sodium oxybate, about 23% mol. equiv. of potassium oxybate, about 21% mol. equiv. of magnesium oxybate and about 48% mol. equiv. calcium oxybate.
25 . The method of any one of claims 16 - 20 , wherein the oxybate or a pharmaceutically acceptable salt thereof comprises sodium oxybate.
26 . A method of treating the symptoms associated with irritable bowel disease (IBD) or irritable bowel syndrome (IBS) in a patient in need thereof, the method comprising:
(a) identifying a patent with IBD or IBS with a SWS deficit as determined by sleep EEG; and
(b) administering a therapeutically effective amount of oxybate or a pharmaceutically acceptable salt thereof.
27 . The method of claim 26 , wherein the identified patient exhibits SWS of less than about 10%.
28 . The method of claim 26 , wherein the identified patient exhibits SWS of less than about 5%.
29 . The method of claim 28 , wherein the administration provides an improvement in the patient's sleep symptoms associated with IBS or IBD compared to prior to the treatment.
30 . The method of claim 28 , wherein the administration provides an improvement in the patient's insomnia associated with IBS or IBD compared to prior to the treatment.
31 . The method of any one of claims 26 - 30 , wherein the oxybate or a pharmaceutically acceptable salt thereof is a mixed salt oxybate.
32 . The method of claim 31 , wherein the mixed salt oxybate comprises sodium oxybate, potassium oxybate, magnesium oxybate and calcium oxybate, and wherein the mixed salt oxybate comprises about 5%-40% sodium oxybate (wt/wt %).
33 . The method of claim 31 , wherein the mixed salt oxybate comprises about 5%-40% of sodium oxybate (wt/wt %), about 10%-40% of potassium oxybate (wt/wt %), about 5%-30% of magnesium oxybate (wt/wt %), and about 20%-80% of calcium oxybate (wt/wt %).
34 . The method of claim 31 , wherein the mixed salt oxybate comprises about 8% mol. equiv. of sodium oxybate, about 23% mol. equiv. of potassium oxybate, about 21% mol. equiv. of magnesium oxybate and about 48% mol. equiv. calcium oxybate.
35 . The method of any one of claims 26 - 30 , wherein the oxybate or a pharmaceutically acceptable salt thereof comprises sodium oxybate.
36 . The method of claim 1 - 35 , wherein the method comprises:
(a) administering an initial daily dose of the oxybate or a pharmaceutically acceptable salt thereof to the patient and
(b) titrating the dose to provide a therapeutically effective amount of the oxybate or a pharmaceutically acceptable salt thereof.
37 . The method of claim 36 , wherein the initial daily dose is from about 0.5 g to about 4.5 g of the oxybate or a pharmaceutically acceptable salt thereof is administered per day.
38 . The method of claim 37 , wherein the initial daily dose is about 4.5 g of the oxybate or a pharmaceutically acceptable salt thereof is administered per day.
39 . The method of any one of claims 36 - 38 , wherein the titration step (b) comprises administering ascending doses of the oxybate or a pharmaceutically acceptable salt thereof.
40 . The method of claim 39 , wherein dose is increased by about 0.5 g to 1.5 g per week.
41 . The method of any one of claims 36 - 38 , wherein the titration step (b) comprises administering descending doses of the oxybate or a pharmaceutically acceptable salt thereof.
42 . The method of claim 41 , wherein dose is decrease by about 0.5 g to 9.0 g per week.
43 . The method of any one of claims 36 - 42 , wherein the titration step (b) comprises switching a patient from a once a day dose to a twice a day dose of the oxybate or a pharmaceutically acceptable salt thereof.
44 . The method of any one of claims 36 - 42 , wherein the titration step (b) comprises switching a patient from a twice a day dose to a three times a day dose of the oxybate or a pharmaceutically acceptable salt thereof.
45 . The method of any one of claims 36 - 42 , wherein the titration step (b) comprises switching a patient from a twice a day dose to a once a day dose of the oxybate or a pharmaceutically acceptable salt thereof.
46 . The method of any one of claims 36 - 42 , wherein the titration step (b) comprises switching a patient from a three times a day dose to a twice a day dose of the oxybate or a pharmaceutically acceptable salt thereof.
47 . The method of any one of claims 36 - 46 , wherein the titration step (b) is from about 1 week to about 14 weeks.
48 . The method of any one of claims 1 - 12 and 16 - 47 , wherein about 0.25 g-10.0 g, 2.0 g-10.0 g; about 3.0 g-9.5 g; or about 4.5 g-9.0 g of the oxybate or a pharmaceutically acceptable salt thereof is administered per day.
49 . The method of claim 48 , wherein the oxybate or a pharmaceutically acceptable salt thereof is administered twice per day.
50 . The method of claim 48 , wherein the oxybate or a pharmaceutically acceptable salt thereof is administered once per day.
51 . The method of any one of claims 1 - 12 and 16 - 50 , wherein about 4.5 g of the oxybate or a pharmaceutically acceptable salt thereof is administered per day.
52 . The method of claim 51 , wherein about 2.25 g of the oxybate or a pharmaceutically acceptable salt thereof is administered twice per day.
53 . The method of any one of claims 1 - 12 and 16 - 50 , wherein about 6.0 g of the oxybate or a pharmaceutically acceptable salt thereof is administered per day.
54 . The method of claim 53 , wherein about 3.0 g of the oxybate or a pharmaceutically acceptable salt thereof is administered twice per day.
55 . The method of any one of claims 1 - 12 and 16 - 50 , wherein about 7.5 g of the oxybate or a pharmaceutically acceptable salt thereof is administered per day.
56 . The method of claim 55 , wherein about 3.75 g of the oxybate or a pharmaceutically acceptable salt thereof is administered twice per day.
57 . The method of any one of claims 1 - 12 and 16 - 50 , wherein about 9.0 g of the oxybate or a pharmaceutically acceptable salt thereof is administered per day.
58 . The method of claim 57 , wherein about 4.5 g of the oxybate or a pharmaceutically acceptable salt thereof is administered twice per day.
59 . The method of any one of claims 1 - 58 , wherein the oxybate or a pharmaceutically acceptable salt thereof composition is a liquid.
60 . The method of claim 59 , wherein the concentration of the oxybate or a pharmaceutically acceptable salt thereof in the liquid is from 350 mg/ml-650 mg/ml, or about 450 mg/ml-550 mg/ml.
61 . The method of claim 49 , wherein the concentration of the oxybate or a pharmaceutically acceptable salt thereof in the liquid is about 0.5 g/mL.
62 . The method of any one of claims 1 - 61 , wherein the oxybate or a pharmaceutically acceptable salt thereof is administered at bedtime.
63 . The method of any one of claims 1 - 62 , wherein the oxybate or a pharmaceutically acceptable salt thereof is administered at bedtime and about 2.5 h-4 h after the bedtime administration.
64 . The method of any one of claims 1 - 63 , wherein the administration provides increased percentage of SWS compared to prior to the administration.
65 . The method of any one of claims 1 - 64 , wherein the administration provides increased percentage of REM sleep compared to prior to the administration.
66 . The method of any one of claims 1 - 65 , wherein the administration provides improved sleep quality as determined by the Pittsburgh Sleep Quality Index (PSQI).