[go: up one dir, main page]

WO2005046673A1 - Methode de traitement du trouble dysphorique premenstruel faisant appel a l'escitalopram - Google Patents

Methode de traitement du trouble dysphorique premenstruel faisant appel a l'escitalopram Download PDF

Info

Publication number
WO2005046673A1
WO2005046673A1 PCT/US2003/035541 US0335541W WO2005046673A1 WO 2005046673 A1 WO2005046673 A1 WO 2005046673A1 US 0335541 W US0335541 W US 0335541W WO 2005046673 A1 WO2005046673 A1 WO 2005046673A1
Authority
WO
WIPO (PCT)
Prior art keywords
escitalopram
pharmaceutically acceptable
acceptable salt
administered
calculated
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2003/035541
Other languages
English (en)
Inventor
Connie Sanchez
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
H Lundbeck AS
LESSLER JAY P
Original Assignee
H Lundbeck AS
LESSLER JAY P
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by H Lundbeck AS, LESSLER JAY P filed Critical H Lundbeck AS
Priority to CA002483920A priority Critical patent/CA2483920A1/fr
Priority to PCT/US2003/035541 priority patent/WO2005046673A1/fr
Priority to AU2003287569A priority patent/AU2003287569A1/en
Publication of WO2005046673A1 publication Critical patent/WO2005046673A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • A61K31/36—Compounds containing methylenedioxyphenyl groups, e.g. sesamin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones

Definitions

  • the present invention relates to a method of treating the symptoms of premenstrual dysphoric disorder (PMDD) in a patient in need thereof by administering an effective amount of escitalopram or a pharmaceutically acceptable salt thereof.
  • PMDD premenstrual dysphoric disorder
  • Escitalopram is an example of a class of drugs known as selective serotonin reuptake inhibitors (hereafter referred to as SSRIs). SSP s are selective for the 5-HT-uptake of serotonin, and have been used for the treatment of depression. See, for example, U.S. Patent No. Re. 34,712, which is hereby incorporated by reference.
  • Escitalopram is the S-enantiomer of citalopram and has the following
  • PMDD premenstrual dysphoric disorder
  • DSM IV-TR Diagnostic & Statistical Manual of Mental Diseases IV-TR
  • the present invention relates to a method of treating a patient (or woman) suffering from premenstrual dysphoric disorder (PMDD) by administering an effective amount of escitalopram or a pharmaceutically acceptable salt thereof.
  • the daily dose of escitalopram or a pharmaceutically acceptable salt thereof administered preferably ranges from about 5 to about 20 mg (calculated on a weight basis of escitalopram base).
  • the daily does may be, for example, from about 5 to about 10 mg, from about 10 to about 20 mg, from about 5 mg, about 10 mg, or about 20 mg (calculated on a weight basis of escitalopram base).
  • the escitalopram or salt thereof is administered as a solid.
  • the escitalopram or pharmaceutically acceptable salt thereof may be administered continuously throughout the menstrual cycle of the patient intermittently or semi- intermittently during the patient's menstrual cycle.
  • the escitalopram or salt thereof is preferably administered orally (e.g., as a solid dosage form such as a tablet or capsule) although other routes of administration may be used. According to a preferred embodiment, it is administered during the morning.
  • escitalopram refers to (S)-(+)-l-[3- dimethylamino)propyl]-l-(4-fluorophenyl)-l,3-dihydro-5-isobenzofurancarbonitrile.
  • the escitalopram is at least 95, 96, 97, 98, 99, or 99.5% pure. More preferably, it contains less than 1 or 2% w/w of the corresponding R-enantiomer.
  • the term "about” means within 10% of a given value, preferably within 5%, and more preferably within 1% of a given value.
  • PMDD menstrual dysphoric disorder
  • the disturbance markedly interferes with work or school or with usual social activities and relationships with others (e.g., avoidance of social activities, decreased productivity and efficiency at work or school).
  • the disturbance is not merely an exacerbation of the symptoms of another disorder, such as Major Depressive Disorder, Panic Disorder, Dysthymic Disorder, or a Personality Disorder (although it may be superimposed on any of these disorders).
  • Treating refers to: (1) preventing or delaying the appearance of clinical symptoms of PMDD in a woman that may be afflicted with or predisposed to PMDD but does not yet experience or display clinical or subclinical symptoms of PMDD, or (2) inhibiting PMDD, i.e., arresting or reducing the development of PMDD or at least one clinical or subclinical symptom thereof, or
  • the term "pharmaceutically acceptable” refers to additives or compositions that are physiologically tolerable and do not typically produce an allergic or similar untoward reaction, such as gastric upset, dizziness and the like, when administered to a mammal.
  • the term "effective amount” refers to an amount of escitalopram or a pharmaceutically acceptable salt thereof which, when admimstered to a female patient for PMDD, is sufficient to treat the same (e.g., an amount sufficient to alleviate the symptoms (e.g., psychological symptoms) of PMDD).
  • Pharmaceutically acceptable salts of escitalopram include, but are not limited to, salts formed with organic and inorganic acids.
  • organic salts are maleic, fumaric, benzoic, ascorbic, pamoic, succinic, oxalic, salicylic, methanesulfonic, ethanedisulfonic, acetic, propionic, tartaric, citric, gluconic, lactic, malic, mandelic, cinnamic, citraconic, aspartic, stearic, palmitic, itaconic, glycolic, p-amino-benzoic, glutamic, benzene sulfonic and theophylline acetic acid, as well as the 8-halotheophyllines, for example 8-bromotheophylline.
  • inorganic salts examples include hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric and nitric acids.
  • Preferred pharmaceutically acceptable salts of escitalopram include, but are not limited to, escitalopram oxalate and escitalopram hydrobromide. [16] The o xalate o f e scitalopram m ay b e p repared as d escribed i n
  • U.S. Patent No. Re. 34,712 and the base and other pharmaceutically acceptable salts may be obtained therefrom by standard procedures.
  • Methods for the preparation of solid pharmaceutical preparations are well known in the art. Tablets may thus be prepared by mixing the active ingredients with ordinary adjuvants and/or diluents and subsequently compressing the mixture in a convenient tabletting machine.
  • adjuvants or diluents comprise: corn starch, lactose, talcum, magnesium stearate, gelatin, lactose, gums, and the like. Any other adjuvant or additive such as colorings, flavorings, preservatives, etc. may also be used provided that they are compatible with the active ingredients.
  • escitalopram or a pharmaceutically acceptable salt thereof may be administered in any suitable way e.g. orally or parenterally, and it may be presented in any suitable form for such administration, e.g. in the form of tablets, capsules, powders, syrups, or solutions or dispersions for injection.
  • the compound of the invention is administered in the form of a solid pharmaceutical entity, suitably as a tablet or a capsule or in the form of a suspension, solution, or dispersion for injection.
  • the pharmaceutical composition prepared according to the invention may comprise escitalopram in a daily dosage form containing 5-20 mg escitalopram, preferably 10-20 mg escitalopram, including 10 mg, 15 mg, and 20 mg, and most preferred 20 mg escitalopram.
  • "Menstrual cycle” refers to the reproductive cycle of female humans. The cycle is characterized by a monthly discharge of blood, mucus, and tissues from the uterus (called menstruation) and involves changes to the lining of the uterus (the endometrium) during the rest of the month including a few days of fertility after an ovum (egg) is released by an ovary.
  • Intermittently in regards to dosage refers to administration of escitalopram or a pharmaceutically acceptable salt thereof for a number of sequential days that do not equal the total number of days in the patient's menstrual cycle.
  • a preferred intermittent dosage regiment is administration of the escitalopram or salt thereof during the luteal phase.
  • a preferred regimen is the administration of escitalopram or salt thereof beginning at the expected day of ovulation as calculated individually from normal cycle length minus 14 days, and administering the last dose on the first day of full bleeding of the subsequent cycle.
  • Examples of such a regimen are as follows: (1) 5 mg escitalopram or a salt thereof is admimstered daily for the first 2 days, and 10 mg is administered thereafter until the first day of full bleeding; (2) 5 mg escitalopram or a salt thereof may be administered daily for the first
  • 1 day, 10 mg for 1 day (the second day), and 20 mg may be administered thereafter until the first day of full bleeding; (3) 5 mg escitalopram or a salt thereof may be administered daily for the first 1 day, and 10 mg may be administered thereafter until the first day of full bleeding; (4) 5 mg escitalopram or a salt thereof may be administered daily for the first
  • a flexible daily dose between 5 mg and 20 mg can be self-administered by the patient thereafter until the first day of full bleeding; and (5) depending on the severity of the symptoms, a flexible daily dose between 5 mg and 20 mg can be self-administered by the patient until the first day of full bleeding.
  • “Intermittent dosage” in regards to dosage refers to administration of escitalopram or pharmaceutically acceptable salt thereof at a high dosage for a number of sequential days that corresponding to the patient's luteal phase, then administering a lower baseline dosage the days of the follicular phase of the patient's cycle.
  • escitalopram or salt thereof is administered daily during the follicular phase of the menstrual cycle, and 10 mg of escitalopram or salt thereof is administered beginning at the expected day of ovulation as calculated individually from normal cycle length minus 14 days, until the last dose on the first day of full bleeding of the subsequent cycle;
  • 10 mg of escitalopram or salt thereof is administered daily during the follicular phase of the menstrual cycle, and 20 mg beginning at the expected day of ovulation until the last dose on the first day of full bleeding of the subsequent cycle;
  • a low dosage from about 5 mg to about 10 mg of escitalopram or salt thereof is administered daily during the follicular phase of the menstrual cycle, then a higher dosage from about 10 mg to about 20 mg is administered beginning on the expected day of ovulation until the last dose on the first day of full
  • the daily dosage for escitalopram administration in any of the aforementioned examples of "semi- intermittent dosage" can be adjusted to correlate with the patient's cycle.
  • Example 1 [27] A double-blind, randomized, placebo-controlled trial evaluating the efficacy and safety of 3 months of intermittent treatment with 10 mg and 20 mg escitalopram per day in patients with PMDD is performed. [28] Intennittent treatment with 10 mg and 20 mg escitalopram oxalate daily is compared with placebo in a single-site, randomized, double-blind,
  • Patient contacts are to be undertaken a) in the luteal phase prior to the screening period for pre-screening, b) in the follicular phase of the cycle following the screening cycles for randomization, c) in the luteal phase of each treatment cycle and d) 28 days after the last trial visit for safety follow-up.
  • Escitalopram oxalate 10 mg and 20 mg daily (calculated by weight of escitalopram base) and placebo will be administered intermittently during the luteal phase of 3 menstrual cycles. Patients will start taking the escitalopram oxalate at the expected day of ovulation as calculated individually from normal cycle length minus 14 days. The last dose of study drug will be taken at the first day of full bleeding of the subsequent cycle.
  • escitalopram oxalate Patients should take the escitalopram oxalate in the morning.
  • the escitalopram dose will be uptitrated at each treatment cycle as follows: (a) in the 10 mg group: 5 mg escitalopram oxalate daily for 2 days, then 10 mg escitalopram oxalate daily; (b) in the 20 mg group: 5 mg escitalopram oxalate for 1 day, 10 mg escitalopram oxalate for 1 day, then 20 mg escitalopram oxalate daily [33] Escitalopram oxalate 5 mg, 10 mg and 20 mg tablets differ in size and shape.
  • escitalopram oxalate and placebo tablets will be encapsulated.
  • the treatment will consist of capsules, identical in appearance, taste and smell, which will contain escitalopram oxalate tablets with the strength 5 mg, 10 mg, 20 mg or placebo tablets.
  • a dose increase as a consequence of lack of efficacy is not planned, nor will the dose be down-regulated due to the appearance of adverse events. If the patient does not tolerate the dose administered, she will be withdrawn from the trial.
  • VAS Visual Analog Scales, ranging from 0-100 mm
  • SDS Sheehan Disability Scale, a 3 item scale of impairment of functioning
  • PGE Principal Global Evaluation, how ill the patient is feeling
  • CGI-S Clinical Global Impression-Severity Scale
  • CGI-I Clinical Global Impression - Improvement Scale
  • PMTS-O Premenstrual Tension Syndrome Scale - Observer Rating
  • Example 2 [37] The procedure described in example 1 is repeated except the escitalopram oxalate is administered continuously throughout the menstrual cycle. The daily dose is 5, 10, 15, or 20 mg of escitalopram oxalate (calculated based on the weight of escitalopram base).
  • Example 3 The procedure described in example 1 is repeated except the escitalopram oxalate is administered "semi-intermittently", i.e., at a constant low dose during the follicular phase and a higher dose during the luteal phase.
  • the regimen is: (1) 5 mg escitalopram or a salt thereof is administered daily for the first 2 days, and 10 mg is administered thereafter until the first day of full bleeding; (2) 5 mg escitalopram or a salt thereof may be administered daily for the first 1 day, 10 mg for 1 day (the second day), and 20 mg may be administered thereafter until the first day of full bleeding; (3) 5 mg escitalopram or a salt thereof may be administered daily for the first
  • a flexible daily dose between 5 mg and 20 mg can be self-administered by the patient thereafter until the first day of full bleeding; or (5) depending on the severity of the symptoms, a flexible daily dose between
  • 5 mg and 20 mg can be self-administered by the patient until the first day of full bleeding.

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention se rapporte à une méthode permettant de traiter les symptômes du trouble dysphorique prémenstruel (PMDD) chez un patient concerné, qui consiste à administrer audit patient une dose efficace d'escitalopram ou un sel pharmaceutiquement acceptable de ce dernier.
PCT/US2003/035541 2003-11-07 2003-11-07 Methode de traitement du trouble dysphorique premenstruel faisant appel a l'escitalopram Ceased WO2005046673A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
CA002483920A CA2483920A1 (fr) 2003-11-07 2003-11-07 Methode de traitement du trouble dysphorique premenstruel avec du escitalopram
PCT/US2003/035541 WO2005046673A1 (fr) 2003-11-07 2003-11-07 Methode de traitement du trouble dysphorique premenstruel faisant appel a l'escitalopram
AU2003287569A AU2003287569A1 (en) 2003-11-07 2003-11-07 A method of treating premenstrual dysphoric disorder with escitalopram

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US2003/035541 WO2005046673A1 (fr) 2003-11-07 2003-11-07 Methode de traitement du trouble dysphorique premenstruel faisant appel a l'escitalopram

Publications (1)

Publication Number Publication Date
WO2005046673A1 true WO2005046673A1 (fr) 2005-05-26

Family

ID=34572293

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2003/035541 Ceased WO2005046673A1 (fr) 2003-11-07 2003-11-07 Methode de traitement du trouble dysphorique premenstruel faisant appel a l'escitalopram

Country Status (3)

Country Link
AU (1) AU2003287569A1 (fr)
CA (1) CA2483920A1 (fr)
WO (1) WO2005046673A1 (fr)

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
PEARLSTEIN: "Selective Serotonin Reuptake Inhibitors for Premenstrual Dysphoric Disorder: The emerging Gold Standard?", DRUGS, vol. 62, no. 13, 2002, pages 1869 - 1885, XP002978411 *

Also Published As

Publication number Publication date
CA2483920A1 (fr) 2005-05-07
AU2003287569A1 (en) 2004-06-06
AU2003287569A8 (en) 2005-06-06

Similar Documents

Publication Publication Date Title
Rush et al. Comparative effects of nefazodone and fluoxetine on sleep in outpatients with major depressive disorder
Bui et al. Blood pressure and heart rate effects following a single dose of bitter orange
AT10974U1 (de) Verwendung von enantiomer-reinem escitalopram
AU2018337933A1 (en) Synthetic transdermal cannabidiol for the treatment of focal epilepsy in adults
US4590213A (en) Anti-anxiety method
US7763284B2 (en) Method for treating or preventing symptoms associated with menopause
JP2016138142A (ja) 大うつ病を有する患者において減量療法を提供する方法
EP4408418A1 (fr) Combinaison comprenant de l'atogépant pour le traitement de la migraine
KR20010015918A (ko) 안면홍조를 감소시키기 위한 플루옥세틴 히드로클로라이드
JP2022524505A (ja) 閉経周辺期及び閉経期の治療のための方法
Liu et al. Menopausal depression: comparison of hormone replacement therapy and hormone replacement therapy plus fluoxetine
Cappiello et al. Yohimbine augmentation of fluvoxamine in refractory depression: a single-blind study
Dewar et al. A clinical trial of penta-erythritol tetranitrate, a khellin derivative (recordil), and iproniazid in angina of effort
US20070123584A1 (en) Method of treating premenstrual dysphoric disorder with escitalopram
WO2005046673A1 (fr) Methode de traitement du trouble dysphorique premenstruel faisant appel a l'escitalopram
JPH029820A (ja) オステオポローシスの処置
JP2020511546A (ja) 能耳茸抽出物を有効成分として含有する婦人科疾患の予防または治療用薬学的組成物
JP7631474B2 (ja) 神経障害の予防又は改善剤
US20160243179A1 (en) Use of fenugreek extract to enhance psychological, somatic, and sexual conditions in aging males
JP2004507506A (ja) 情動不安の処置のための、花粉抽出物を含む組成物の使用
DE69827017T2 (de) Kombinationen von endometrium schonenden gestagenen und endometrium atrophisierenden gestagenen mit estrogenen, bei der oralen empfängnisverhütung
AU2019257990B2 (en) Compositions for treating female sexual dysfunction
US20080262071A1 (en) Pindolol for the Treating Premenstrual Syndrome and Premenstrual Dysphoric Disorder
Marazziti Venlafaxine treatment of obsessive-compulsive disorder
US20200038469A1 (en) Composition for treating erectile dysfunction by orchis anatolica extract

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 2483920

Country of ref document: CA

AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): BW GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP