METHOD OF TREATING THERMOREGULATORY DYSFUNCTION WITH PAROXETINE

Abstract

The present invention relates to a method for treating a patient suffering from a thermoregulatory dysfunction, especially hot flashes and flushes associated with hormonal changes due to naturally occurring menopause (whether male or female) or due to chemically or surgically induced menopause. The method is also applicable to treating the hot flashes, hot flushes, or night sweats associated with disease states that disrupt normal hormonal regulation of body temperature.

Claims

1. A method for treating a patient suffering from a thermoregulatory dysfunction comprising administering to said patient a compound selected from paroxetine, a pharmaceutically acceptable salt thereof, a hydrate or solvate of either, in any polymorphic form, and mixtures thereof; said compound being in an amount, based on the paroxctine moiety, which is at least about 0.1 mg/day up to less than a therapeutically effective antidepressant dosage of paroxetine.

2. The method of claim 1 wherein said compound is administered in an amount of at least 0.5 mg/day.

3. The method of claim 1 wherein said compound is administered in an amount of at least 1 mg/day.

4. The method of claim 1 wherein said compound is administered in an amount of at least 2 mg/day.

5. The method of claim 1 wherein said compound is administered in an amount of at least 4 mg/day.

6. The method of claim 1 wherein said compound is administered in an amount of not more than about 9.5 mg/day.

7. The method of claim 1 wherein said compound is administered in an amount of not more than about 9 mg/day.

8. The method of claim 1 wherein said compound is administered in an amount of not more than about 8.5 mg/day.

9. The method of claim 1 wherein said compound is administered in an amount of not more than about 8 mg/day.

10. The method of claim 1 wherein said compound is administered in an amount selected from 2 mg/day, 2.5 mg/day, 3 mg/day, 3.5 mg/day, 4 mg/day, 4.5 mg/day, 5 mg/day, 5.5 mg/day, 6 mg/day, 6.5 mg/day, 7 mg/day, 7.5 mg/day, 8 mg/day, and 8.5 mg/day.

11. The method of claim 1 wherein said thermoregulatory dysfunction is the result of a condition selected from female menopausal related hormonal changes, male menopausal related hormonal changes, chemically induced hormonal changes, surgically induced hormonal changes, hormonal disruption disease states, and any combination thereof.

12. The method of claim 1 wherein said therrnoregulatory dysfunction is a condition selected from the group consisting of hot flashes, hot flushes, night sweats and combinations thereof.

Description

BRIEF DESCRIPTION OF THE DRAWING

[0016] Not Applicable

DETAILED DESCRIPTION OF THE INVENTION

[0017] The present invention is a method of treating a thermoregulatory dysfunction treatment using paroxetine as free base or a pharmaceutically acceptable salt thereof, in an anhydratc, a hydrate, or solvate form, in any non-crystalline or any crystalline polymorphic form of any of the foregoing in a dosage of from about 0.1 mg/day up to less than an antidepressant therapeutically effective amount of paroxetine. The invention is also a dosage form of paroxetine in a dose which is less than that effective for its use as an antidepressant.

[0018] For the present invention, paroxetine may be in the form of the free base or any pharmaceutically acceptable salt thereof. Pharmaceutically acceptable salts include, but are not limited to, hydohalides (such as hydrochloride, hydrobromide, hydroiodide), sufates (such as sulfate, bisulfate), phosphates (such as mono, di, or tri basic phosphate), oxalate, mesylate, tosylate, pamoate, citrate, carbonate, bicarbonate, maleate, malate, fumarate, as well as many others set forth in the patent references indicated in paragraph 0010 above. Preferably, the paroxetine is present as the free base, the hydrochloride salt, or the mesylate salt or mixtures thereof. Most preferably the paroxetine is present as the hydrochloride salt or the mesylate salt. Paroxetine for use in the present invention may be in the anhydrate, hemihydrate, monohydrate, or higher hydrate forms. Paroxetine for use in the present invention may also be either amorphous or crystalline, the choice being made by the formulator depending upon the formulation and dissolution characteristics desired. Crystalline forms have better stability, but amorphous forms have faster dissolution profiles.

[0019] The dosage is about 0.1 mg/day up to less than an antidepressant effective amount of paroxetine (based on the free base, anhydrate); preferably up to about 9.5 mg/day. Preferably the paroxetine can be administered to achieve the invention in amounts of at least 0.5 mg/day, more preferably at least 1 mg/day, still more preferably at least 2 mg/day, even more preferably at least 4 mg/day, up to preferably not more than about 9 mg/day, more preferably not more than about 8.5 mg/day, still more preferably not more than 8 mg/day. Other non-limiting dosages that are specifically suitable for the present invention include 2 mg/day, 2.5 mg/day, 3 mg/day, 3.5 mg/day, 4 mg/day, 4.5 mg/day, 5 mg/day, 5.5 mg/day, 6 mg/day, 6.5 mg/day, 7 mg/day, 7.5 mg/day, 8 mg/day, and 8.5 mg/day.

[0020] The present invention is applicable to the treatment of thermoregulatory dysfunction and in particular to such conditions (without limitation) as hot flushes, hot flashes, night sweats, etc. whether or not related to menopause (female or male), perimenopause, hormone ablative therapy (including, but not limited to, anti-estrogenic therapy and antiandrogenic therapy), treatments with other chemical agent or therapeutic agents that are antiestrogenic or antiandrogenic or interfere with thermoregulatory function, surgical procedures (such as, without limitation castration, hysterectomy, ooectomy, etc), and disease states interfering with normal thermoregulatory functioning. Most preferably, the present invention is directed to the treatment of perimenopausal and postmenopausal hot flashes, hot flushes and night sweats in women, whether due to aging, therapeutically induced menopause, or surgically induced menopause. The invention is also preferably directed to hot flashes or hot flushes or night sweats in men whether such symptoms are due to aging, chemical castration, hormonal ablative therapy, or surgical castration.

EXAMPLES

[0021] The following non-limiting Examples are presented only to exemplify various embodiments of the invention and do not limit it in any fashion.

Example 1

[0022] Females having hot flashes associated with menopause are administered paroxetine (based on free base non-solvate, anhydrite) as follows:

TABLE-US-00001 Form of Form of Paroxetine Dosage Paroxetine Dosage Hydrochloride 1.0 Mesylate 1.0 Hydrochloride 2.0 Mesylate 2.0 Hydrochloride 3.0 Mesylate 3.0 Hydrochloride 4.0 Mesylate 4.0 Hydrochloride 5.0 Mesylate 5.0 Hydrochloride 6.0 Mesylate 6.0 Hydrochloride 7.0 Mesylate 7.0 Hydrochloride 8.0 Mesylate 8.0 Hydrochloride 9.0 Mesylate 9.0 Hydrochloride 9.5 Mesylate 9.5

[0023] After a few days to weeks, the symptoms ameliorate.

Example 2

[0024] Females having hot flashes associated with menopause are administered paroxetine (based on free base non-solvate, anhydrate) as follows:

TABLE-US-00002 Form of Form of Form of Paroxetinc Paroxetine Paroxetine HCl Dosage HCl Dosage HCl Dosage Anhydrous 1.0 Hemihydrate 1.0 Monohydrate 1.0 Anhydrous 2.0 Hemihydrate 2.0 Monohydrate 2.0 Anhydrous 3.0 Hemihydrate 3.0 Monohydrate 3.0 Anhydrous 4.0 Hemihydrate 4.0 Monohydrate 4.0 Anhydrous 5.0 Hemihydrate 5.0 Monohydrate 5.0 Anhydrous 6.0 Hemihydrate 6.0 Monohydrate 6.0 Anhydrous 7.0 Hemihydrate 7.0 Monohydrate 7.0 Anhydrous 8.0 Hemihydrate 8.0 Monohydrate 8.0 Anhydrous 9.0 Hemihydrate 9.0 Monohydrate 9.0 Anhydrous 9.5 Hemihydrate 9.5 Monohydrate 9.5

[0025] After a few days to weeks, the symptoms ameliorate.