Methods of treating certain depressive disorders and delirium tremens
The disclosure provides a method of treating a patient having postpartum depression, premenstrual dysphoric disorder, menopausal depression, or delirium tremens comprising administering an effective amount of an injectable neurosteroid formulation to the patient. In certain embodiments the injectable neurosteroid formulation is an injectable ganaxolone formulation. Two types of injectable neurosteroid formulations may be used in the disclosed methods. The first such formulation is an injectable formulation containing ganaxolone and sulfobutyl ether β-cyclodextrin in a 1:1 inclusion complex. The second such formulation is an injectable neurosteroid formulation comprising a neurosteroid, preferably ganaxolone, but which may be a neurosteroid selected from allopregnanolone, ganaxolone, alphaxalone, alphadolone, hydroxydione, minaxolone, pregnanolone, tetrahydrocorticosterone, and combinations of the foregoing; a surface stabilizer selected from hydroxyl ethyl starch, dextran, and povidone; and a surfactant.
1. A method of treating postpartum depression, premenstrual dysphoric disorder, menopausal depression, or delirium tremens comprising administering an effective amount of an injectable ganaxolone formulation a patient in need thereof; wherein the ganaxolone formulation is an ganaxolone formulation; wherein the injectable ganaxolone formulation comprising nanoparticles having a D50 of from about 10 to about 2000 nm;
wherein the nanoparticles comprise
ganaxolone;
a surface stabilizer, wherein the surface stabilizer is hydroxyl ethyl starch, and the weight to weight ratio of ganaxolone to surface stabilizer is about 5:1 to about 0.5:1; and
an ionic surfactant.
2. The method of claim 1 wherein the ganaxalone formulation is an intravenous formulation.
3. The method of claim 2 , wherein formulation comprises 0.1 mg/mL to 15 mg/mL ganaxolone.
4. A method of treating postpartum depression, premenstrual dysphoric disorder, menopausal depression, or delirium tremens comprising administering an effective amount of an injectable neurosteroid formulation to a patient in need thereof; wherein the formulation comprising nanoparticles having a D50 of from about 10 to about 2000 nm; wherein the nanoparticles comprise
a neurosteroid selected from allopregnanolone, ganaxolone, alphaxalone, alphadolone, hydroxydione, minaxolone, pregnanolone, tetrahydrocorticosterone, and combinations of the foregoing;
a surface stabilizer, wherein the surface stabilizer is hydroxyl ethyl starch; and
an ionic surfactant.
5. The method of claim 4 , wherein the neurosteroid is ganaxolone.
6. The method of claim 4 , wherein the neurosteroid is allopregnanolone.
7. The method of claim 4 , wherein the surface stabilizer is hydroxyethyl starch, and the weight to weight ratio of neurosteroid to surface stabilizer is about 5:1 to about 0.5:1.
8. The method of claim 4 , wherein the (wt:wt) ratio of the neurosteroid to the surface stabilizer is about 4:1 to about 3:1.
9. The method of claim 4 , wherein
the nanoparticles have a D50 of 10 nm to 300 nm; and
the formulation additionally comprises 0.5% to 1.5% weight percent sodium chloride.
10. The method of claim 2 , wherein the patient is administered 0.1 mg/kg to 200 mg/kg ganaxolone as a single bolus dose.
11. The method of claim 10 , wherein the single bolus dose provides a sufficient amount of ganaxolone to provide a plasma C max of ganaxolone of at least 60 ng/mL in the patient.
12. The method of claim 2 , wherein the patient is administered the formulation as an intravenous infusion for 1 hour to 10 consecutive days at a rate of 1 to 10 mg ganaxolone/hr/kg, with or without an initial bolus dose.
13. The method of claim 2 , wherein the intravenous ganaxolone formulation is administered to the patient at the rate of 2 mg/hr to 4 mg/hr.
14. The method of claim 2 , wherein the intravenous ganaxolone formulation is administered to the patient at a rate sufficient to provide a steady state plasma concentration of 50 ng/ml to 100 ng/ml.
15. The method of claim 13 , wherein the intravenous ganaxolone formulation is administered for 36 hrs to 72 hrs.
16. The method of claim 1 , wherein the patient is a patient having premenstrual dysphoric disorder and the patient is administered a daily oral dose of ganaxolone of 100 mg to 2000 mg administered from day 18-24 of the patient's menstrual cycles until day 2-4 of the patient's menstrual cycle.
17. The method of claim 1 , wherein the patient is a patient having menopausal depression and the patient is administered a daily oral dose of ganaxolone of 100 mg to 2000 mg ganaxolone.
18. The method of claim 17 , wherein the patient is administered the ganaxolone in combination with an SSRI or SNRI antidepressant.
19. The method of claim 1 , wherein the patient is a patient having delirium tremens and the patient is administered a ganaxolone intravenous infusion at a rate of 50 mg/hr to 500 mg/hr for 1 to 5 days.
20. The method of claim 19 , wherein the patient is administered the ganaxolone in combination with an intravenous benzodiazepine infusion.