TREATMENT OF GENERALIZED ANXIETY DISORDER WITH PAROXETINE

TRAITEMENT DE TROUBLE ANXIEUX GENERALISE AVEC DE LA PAROXETINE

English Abstract

A method of treatment of generalised anxiety disorder, which method comprises
administering an effective, non-toxic amount of paroxetine or a
pharmaceutically acceptable salt or solvate thereof, to a human or non-human
animal in need thereof.

French Abstract

L'invention concerne une méthode de traitement d'un trouble anxieux généralisé, la méthode consistant à administrer une quantité effective non toxique de paroxétine ou son sel ou solvate acceptable du point de vue pharmaceutique à un animal humain ou non humain en présentant le besoin.

Claims

Claims
1. A method of treatment of generalised anxiety disorder, which method
comprises
administering an effective, non-toxic amount of paroxetine or a
pharmaceutically
acceptable salt or solvate there of, to a human or non-human animal in need
thereof.
2. Use of paroxetine or a pharmaceutically acceptable salt or solvate thereof
in the
manufacture of a medicament for use in treatment of generalised anxiety
disorder.
3. A pharmaceutical composition for use in treatment of generalised anxiety
disorder which comprises an effective amount of paroxetine or a
pharmaceutically
acceptable salt or solvate thereof and a pharmaceutically acceptable carrier.
4. A method according to claim 1, use according to claim 2, or a
pharmaceutical
composition according to claim 3, wherein the pharmaceutically acceptable salt
of
paroxetine is the hydrochloride.
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Description

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TREATMENT OF GENERALIZED ANXIETY DISORDER WITH
PAROXETINE
The present invention relates to a method for treatment of generalised anxiety
disorder,
and especially to the use of paroxetine in such treatment.
Pharmaceutical products with antidepressant and anti-Parkinson properties are
described
in US-A-3912743 and US-A-4007196. An especially important compound among those
disclosed is paroxetine, the (-) traps isomer of 4-(4'-fluorophenyl)-3-(3',4'-
methylene-
dioxyphenoxymethyl)-piperidine (see Example 2 of US-A-4007196). The
hydrochloride salt of paroxetine is approved for human use in therapy to treat
inter alia
depression, obsessive compulsive disorder (OCD) and panic.
In commercial use, paroxetine hydrochloride is supplied as a crystalline
hemihydrate
(see EP-A-0223403 of Beecham Group). Various crystalline anhydrate forms are
also
known (see W096/24595 of SmithKline Beecham plc).
It has now been surprisingly discovered that paroxetine has potential
therapeutic utility
as a medicament for treatment of generalised anxiety disorder.
Accordingly, the present invention provides a method treatment of generalised
anxiety
disorder, which method comprises administering an effective, non-toxic amount
of
paroxetine or a pharmaceutically acceptable salt or solvate there of, to a
human or non-
human animal in need thereof.
The present invention also provides the use of paroxetine or a
pharmaceutically
acceptable salt or solvate thereof in the manufacture of a medicament for use
in
treatment of generalised anxiety disorder.
A preferred pharmaceutically acceptable salt of paroxetine is crystalline
hydrochloride.
Suitable procedures for preparing paroxetine hydrochloride include those
mentioned in
US Patents 4009196, 4721723, 4902801, 4861893 and 5039803 and PCT/GB93/00721.
Especially preferred is the hemi-hydrate, prepared as EP-A-0223403.
A medicament, for use in treatment of generalised anxiety disorder may be
prepared by
admixture of paroxetine or a pharmaceutically acceptable salt or solvate
thereof with an
appropriate carrier, which may contain a diluent, binder, filler,
disintegrant, flavouring
agent, colouring agent, lubricant or preservative in conventional manner.
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Preferably, the medicament is in unit dosage form and in a form adapted for
use in the
medical or veterinarial fields. For example, such preparations may be in a
pack form
accompanied by written or printed instructions for use as a treatment of
generalised
anxiety disorder.
The suitable dosage range for paroxetine or a pharmaceutically acceptable salt
or solvate
depends on the severity of the generalised anxiety disorder and on the
condition of the
patient. It will also depend, inter alia, upon the relation of potency to
absorbability and
the frequency and route of administration.
Paroxetine or a pharmaceutically acceptable salt or solvate thereof may be
formulated
for administration by any route, and examples are oral, sub-lingual, rectal,
topical,
parenteral, intravenous or intramuscular administration. Preparations may, if
desired, be
designed to give slow release of the paroxetine or a pharmaceutically
acceptable salt or
solvate thereof.
The medicaments may, for example, be in the form of tablets, capsules,
sachets, vials,
powders, granules, lozenges, reconstitutable powders, or liquid preparations,
for
example solutions or suspensions, or suppositories.
The medicaments. for example those suitable for oral administration, may
contain
conventional excipients such as binding agents, for example syrup, acacia,
gelatin,
sorbitol, tragacanth, or polyvinylpyrrolidone; fillers, for example lactose,
sugar,
maize-starch, calcium phosphate, sorbitol or glycerine; tabletting lubricants,
for example
magnesium stearate; disintegrants, for example starch, polyvinylpyrrolidone,
sodium
starch glycollate or microcrystalline cellulose; or pharmaceutically
acceptable setting
agents such as sodium lauryl sulphate.
Solid medicaments may be obtained by conventional methods of blending,
filling,
tabletting or the like. Repeated blending operations may be used to distribute
paroxetine
or a salt or solvate thereof throughout those medicaments employing large
quantities of
fillers. When the medicament is in the form of a tablet, powder, or lozenge,
any carrier
suitable for formulating solid pharmaceutical compositions may be used,
examples
being magnesium stearate, starch, glucose, lactose, sucrose, rice flour and
chalk.
Tablets may be coated according to methods well known in normal pharmaceutical
practice, in particular with an enteric coating. The medicament may also be in
the form
of an ingestible capsule, for example of gelatin containing paroxetine or a
salt thereof if
desired with a carrier or other excipients.
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Medicaments for oral administration as liquids may be in the form of, for
example,
emulsions, syrups, or elixirs, or may be presented as a dry product for
reconstitution
with water or other suitable vehicle before use. Such liquid medicaments may
contain
conventional additives such as suspending agents, for example sorbitol, syrup,
methyl
S cellulose, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminium
stearate
gel, hydrogenated edible fats; emulsifying agents, for example lecithin,
sorbitan
monooleate, or acacia; aqueous or non-aqueous vehicles, which include edible
oils, for
example almond oil, fractionated coconut oil, oily esters, for example esters
of
glycerine, or propylene glycol, or ethyl alcohol, glycerine, water or normal
saline;
preservatives, for example methyl or propyl p-hydroxybenzoate or sorbic acid;
and if
desired conventional flavouring or colouring agents.
Paroxetine or a pharmaceutically acceptable salt or solvate thereof may also
be
administered by a non-oral route. In accordance with routine pharmaceutical
procedure,
the medicaments may be formulated, for example for rectal administration as a
suppository. They may also be formulated for presentation in an injectable
form in an
aqueous or non-aqueous solution, suspension or emulsion in a pharmaceutically
acceptable liquid, e.g. sterile pyrogen-free water or a parenterally
acceptable oil or a
mixture of liquids. The liquid may contain bacteriostatic agents, anti-
oxidants or other
preservatives, buffers or solutes to render the solution isotonic with the
blood,
thickening agents, suspending agents or other pharmaceutically acceptable
additives.
Such forms will be presented in unit dose form such as ampoules or disposable
injection
devices or in mufti-dose forms such as a bottle from which the appropriate
dose may be
withdrawn or a solid form or concentrate which can be used to prepare an
injectable
formulation.
As mentioned hereinbefore, the effective dose of the paroxetine or
pharmaceutically
acceptable salt or solvate depends on the severity of generalised anxiety
disorder to be
treated, the condition of the patient and on the frequency and route of
administration. A
unit dose will generally contain from 2 to 1000 mg and preferably will contain
from 30
to 500 mg, in particular 20, 50, 100, 150, 200, 250, 300, 350, 400, 450, or
500 mg. The
composition may be administered once or more times a day, for example 2, 3 or
4 times
daily, and the total daily dose for a 70 kg adult will normally be in the
range 100 to 3000
mg. Preferably the unit dose will contain from 2 to 20 mg of paroxetine
(calculated as
free base) and be administered in multiples, if desired, to give the preceding
daily dose.
The present invention further provides a pharmaceutical composition for use in
treatment of generalised anxiety disorder which comprises an effective amount
of
paroxetine or a phaFmaceutically acceptable salt or solvate thereof and a
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pharmaceutically acceptable carrier. Such compositions may be prepared in the
manner
as hereinbefore described.
The following Example discloses a suitable pharmaceutical composition for use
in the
present invention.
Example
The following are mixed together in a conventional manner and compressed into
tablets
of ca. 300 mg weight containing ca. 20 mg of paroxetine (calculated as the
free base)
Paroxetine hydrochloride hemihydrate 228.8 g Dibasic
calcium phosphate dehydrate 2441.2 g
Hydroxypropylmethyl cellulose 2910 150.0 a
Sodium starch glycollate 150.0 g
Magnesium Stearate 30.0 a
Total tablet weight 3000.0 Q
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