SK15672000A3 - Treatment of generalized anxiety disorder with paroxetine - Google Patents

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.

Description

Use of paroxetine for the treatment of generalized anxiety conditions

Technical field

The present invention relates to the use of paroxetine or a pharmaceutically acceptable salt or solvate thereof for the treatment of generalized anxiety conditions.

BACKGROUND OF THE INVENTION

Pharmaceutical products having anti-depressant and anti-Parkinson's properties are described in US-A-3912743 and US-A-4007196. An especially important compound among those disclosed is paroxetine, the (-) trans isomer of 4- ^{(4-fluorophenyl)} -3- (3 ^', 4'-methylenedioxyphenoxymethyl) -piperidine (see Example 2 US-A-4007196). Paroxetine hydrochloride is approved for use in human medicine for the treatment of, inter alia, conditions, depression, obsessive-compulsive disorder (OCD), and panic conditions.

For commercial use, the hydrochloride is supplied as a crystalline hemihydrate (see EP-0223403 from Beecham Group). Various crystalline forms of the anhydrate are also known (see WO96 / 24595 from SmithKline Beecham plc).

It has now surprisingly been found that paroxetine has potential therapeutic efficacy as a medicament for the treatment of generalized anxiety disorders.

SUMMARY OF THE INVENTION

The present invention provides the use of paroxetine or a pharmaceutically acceptable salt or solvate thereof for the manufacture of a medicament for the treatment of generalized anxiety disorders in a human or animal indicative of such treatment.

A preferred pharmaceutically acceptable salt of paroxetine is crystalline hydrochloride. Suitable processes for the manufacture of paroxetine hydrochloride include those disclosed in US patents 4009196, 4721723, 4902801, 4861893 and 5039803 and PCT / GB93 / 00721. Most preferred is a hemihydrate produced according to EP-A-0223403.

A medicament for use in the treatment of generalized anxiety disorders may be made by conventional mixing of paroxetine or a pharmaceutically acceptable salt or solvate with an appropriate carrier, which may contain a diluent, binder, filler, disintegrant, dye, tubing or preservative.

Preferably, the medicament is in unit dosage form and in a form adapted for use in human or veterinary medicine. E.g. such preparations may be in the form of a pack with enclosed written instructions for use as a medicament for the treatment of generalized anxiety disorders.

The appropriate dosage range for paroxetine or a pharmaceutically acceptable salt or solvate thereof will depend on the severity of the anxiety disorder and the condition of the patient. It will also depend, inter alia, on the rate of absorption, 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, sublingual, rectal, topical, parenteral, intravenous or intramuscular. If desired, the compositions may be formulated so that the release of paroxetine or a pharmaceutically acceptable salt or solvate thereof is slow.

The dosage form can be e.g. tablets, capsules, sacks, ampoules, powders, granules, lozenges, powders for dissolution or liquid preparations, e.g. solutions or suspensions or suppositories.

Drugs, e.g. those suitable for oral administration may contain conventional excipients such as binding agents, e.g. syrup, acacia, gelatin, sorbitol, tragacanth or polyvinylpyrrolidone; fillers such as e.g. lactose, sugar, corn starch, calcium phosphate, sorbitol or glycerin; tableting lubricants, e.g. magnesium stearate; disintegrants, e.g. starch, polyvinylpyrrolidone, sodium starch glycolate or microcrystalline cellulose; or pharmaceutically acceptable stabilizers, such as e.g. sodium lauryl sulphate.

Solid pharmaceutical compositions can be obtained by conventional methods of mixing, filling, tabletting, and the like. Repeated blending procedures can be used to distribute paroxetine or a salt or solvate thereof in drugs that contain a large number of fillers. When the drug is in the form of a tablet, powder or lozenges, any carrier suitable for the formulation of solid pharmaceutical preparations may be used, by way of example.

- are magnesium stearate, starch, glucose, lactose, sucrose, rice flour and calcium carbonate.

The tablets may be coated by methods well known in conventional pharmaceutical practice, in particular by enteric coating. The medicament may also be in the form of oral capsules, e.g. gelatin containing paroxetine or a salt thereof, optionally with a carrier or other excipients.

Medicaments for oral administration in the form of fluids may be e.g. emulsions, syrups or brine, or they may be in the form of a dry substance to be dissolved in water or other suitable carrier before use. Such liquid medicaments may contain conventional additives such as suspending agents, e.g. sorbitol, syrup, methylcellulose, gelatin, hydroxyethylcellulose, carboxymethylcellulose, magnesium stearate, hydrogenated edible fats; emulsifying agents, e.g. Iecithin, sorbitan monooleate or acacia; aqueous or non-aqueous vehicles which include edible oils, e.g. almond oil, fractionated coconut oil, oily esters, e.g. glycerin esters or propylene glycol or ethyl alcohol, glycerin, water or normal saline; preservatives, e.g. methyl or propyl p-hydroxybenzoate or sorbic acid, and optionally conventional flavoring or coloring agents.

Paroxetine, or a pharmaceutically acceptable salt or solvate thereof, may also be administered by a route other than oral. According to routine pharmaceutical procedures, drugs may be formulated, e.g. for rectal administration in the form of suppositories. They can also be made into an injectable form in the form of an aqueous or non-aqueous solution, a suspension in a pharmaceutically acceptable liquid, i. in sterile pyrogen-free water or in a parenterally acceptable oil or liquid mixture. The fluid may contain bacteriostatically active agents, antioxidants or other preservatives, buffers or solutes, maintaining a solution isotonic in the blood, thickeners, suspending agents, or other pharmaceutically acceptable additives. Such forms may be in unit dosage form, such as e.g. ampoules or injections or as multidose forms, such as vials from which a suitable dose can be selected, or as a solid form or concentrate which can be used to prepare an injectable preparation.

As mentioned above, the effective dose of paroxetine or a pharmaceutically acceptable salt or solvate thereof depends on the severity of the generalized anxiety

The disorders to be treated, the condition of the patient and the frequency and route of administration. A single 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 daily, e.g. 2, 3 or 4 times a day and the total daily dose for an adult weighing 70 kg may range from 100 to 3000 mg. Preferably, a single dose will contain from 2 to 20 mg of paroxetine (calculated as the free base) and will be administered, if desired, in multiple doses to achieve said daily dose.

The present invention further provides a pharmaceutical composition for use in the treatment of generalized anxiety disorders comprising an effective amount of paroxetine or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutically acceptable carrier. Such formulations can be made to cause as previously mentioned.

The following example illustrates a pharmaceutical composition for use in the present invention.

DETAILED DESCRIPTION OF THE INVENTION

Example

The following ingredients are mixed in a conventional manner and compressed into tablets weighing approximately 300 mg containing approximately 20 mg paroxetine (calculated as free base).

Paroxetine hemihydrate 228.8 g calcium phosphate dihydrate 2441.2 g Hydroxypropylmethylcellulose 150.0 g

Starch glycolate sodium 150.0 g

Magnesium stearate 30.0 g

Total tablet weight 3000.0 g

Claims (3)

PATENT CLAIMS Use of paroxetine or a pharmaceutically acceptable salt or solvate thereof for the manufacture of a medicament for the treatment of generalized anxiety disorders. The use of claim 1, wherein the pharmaceutically acceptable salt is paroxetine hydrochloride. A pharmaceutical composition for use in the treatment of generalized anxiety disorders comprising an effective amount of paroxetine or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutically acceptable carrier.