METHODS OF TREATING EPILEPSY OR STATUS EPILEPTICUS
Described herein are methods of treating epilepsy or status epilepticus, e.g., convulsive status epilepticus, e.g., early status epilepticus, established status epilepticus, refractory status epilepticus, super-refractory status epilepticus, e.g., super-refractory generalized status epilepticus; non-convulsive status epilepticus, e.g., generalized status epilepticus, complex partial status epilepticus; generalized periodic epileptiform discharges; periodic lateralized epileptiform discharges; a seizure, e.g., acute repetitive seizures, cluster seizures, the method comprising administering to the subject a neuroactive steroid.
1 . A method of treating a subject having a seizure-related disorder of refractory status epilepticus (RSE) or super-refractory status epilepticus (SRSE), the method comprising:
administering to said subject, an effective amount of allopregnanolone,
wherein, concurrent with said administering, said subject is under general anesthesia, thereby treating said subject.
2 . A method of treating a subject having a seizure-related disorder of refractory status epilepticus (RSE) or super-refractory status epilepticus (SRSE), the method comprising:
administering a first load dose of allopregnanolone;
administering a second dose of allopregnanolone, which is lower than said first dose; and
administering a third downward taper dose of allopregnanolone, said allopregnanolone doses being sufficient to treat said subject.
3 . The method of claim 2 , wherein said subject is not under general anesthesia for one or both of: at least a portion of the second dose and at least a portion of the third dose.
4 . The method of claim 2 , wherein said subject is under general anesthesia during the administration of the first dose and during administration of a portion of the second dose.
5 - 8 . (canceled)
9 . The method of claim 2 , wherein the amount of allopregnanolone delivered/unit time in the second dose, as measured in μg/kg/hour, is at least 2, 3, 4, 5, or 6 times lower than that of the first dose.
10 . The method of claim 2 , wherein one, two or all of said doses are injected administrations.
11 - 12 . (canceled)
13 . The method of claim 2 , further comprising administering an amount of an effective to place said subject under general anesthesia.
14 . The method of claim 2 , wherein said anesthetic is selected from benzodiazepine, propofol, pentobarbital, and ketamine.
15 - 24 . (canceled)
25 . The method of claim 2 , wherein said second dose is initiated while the subject is under general anesthesia.
26 . (canceled)
27 . The method of claim 2 , wherein the administration of the first dose of allopregnanolone is initiated within a preselected period of time, wherein said period begins with: the administration of said anesthetic; or the induction of general anesthesia.
28 - 54 . (canceled)
55 . The method of claim 2 , said first dose is administered over a period of time that is 30 to 120 minutes, 45 to 100 minutes, or 50 to 70 minutes, in duration.
56 - 59 . (canceled)
60 . The method of claim 2 , wherein the administration said second dose is initiated within a preselected time period, wherein said time period begins with: the administration of said anesthetic; the induction of general anesthesia; the beginning of the first dose; the end of the first dose; or the achievement of a predetermined level of allopregnanolone in the plasma.
61 . The method of claim 60 , wherein said time period begins with the end of the first dose.
62 - 64 . (canceled)
65 . The method of claim 2 , wherein the second dose begins 50 to 70, 55 to 65, or 60 minutes after the beginning or end of the administration of the first dose.
66 - 67 . (canceled)
68 . The method of claim 2 , wherein the first dose and the initiation of the second dose are performed with the same delivery device.
69 . The method of claim 2 , wherein said second dose is administered for a period of time that is between 48 and 192 hours, 60 and 144 hours, 60 and 120 hours, 80 and 110 hours, or 90 and 100 hours.
70 - 91 . (canceled)
92 . The method of claim 2 , wherein administering said downward taper dose comprises administering a continuously decreasing amount of allopregnanolone.
93 . (canceled)
94 . The method of claim 2 , wherein said downward taper dose comprises administering a plurality of step doses, wherein each subsequent step dose is lower than the step dose that precedes it.
95 - 111 . (canceled)
112 . The method of claim 2 , wherein the administration of the second dose and the initiation of third/taper dose are performed with the same delivery device.
113 - 116 . (canceled)
117 . The method of claim 2 , wherein the allopregnanolone is provided in a composition comprising a cyclodextrin selected from sulfo butyl ether β-cyclodextrin and CAPTISOL.
118 . The method of claim 2 , wherein the allopregnanolone is provided at a concentration of 0.1 to 10 mg/mL allopregnanolone.
119 - 123 . (canceled)
124 . The method of claim 117 , wherein the cyclodextrin is present in the composition at 1-30% by weight of cyclodextrin per volume of composition.
125 - 128 . (canceled)
129 . The method of claim 117 , wherein the cyclodextrin is present in the composition at 12% by weight of cyclodextrin per volume of composition and the allopregnanolone is provided at a concentration of 5 mg/mL allopregnanolone.
130 - 164 . (canceled)