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EP2129383A1 - Traitement de troubles de l'anxiété par la minocycline - Google Patents

Traitement de troubles de l'anxiété par la minocycline

Info

Publication number
EP2129383A1
EP2129383A1 EP08709396A EP08709396A EP2129383A1 EP 2129383 A1 EP2129383 A1 EP 2129383A1 EP 08709396 A EP08709396 A EP 08709396A EP 08709396 A EP08709396 A EP 08709396A EP 2129383 A1 EP2129383 A1 EP 2129383A1
Authority
EP
European Patent Office
Prior art keywords
disorder
medicament
minocycline
use according
treatment
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.)
Withdrawn
Application number
EP08709396A
Other languages
German (de)
English (en)
Inventor
Michael Frederick Snape
Julie Hutchinson
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.)
Neuropharm Ltd
Original Assignee
Neuropharm Ltd
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 Neuropharm Ltd filed Critical Neuropharm Ltd
Publication of EP2129383A1 publication Critical patent/EP2129383A1/fr
Withdrawn legal-status Critical Current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
    • A61K31/65—Tetracyclines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics

Definitions

  • the present invention relates to the treatment of anxiety disorders.
  • Anxiety disorders such as obsessive compulsive disorder (OCD) are widespread throughout the world's population. For instance, recent studies have suggested prevalence rates of OCD of 0.8% in adults and 0.25% in children of the age of 5-15 years. However, earlier studies have in fact suggested rates as high as 1-3% in adults and 1-2% in children and adolescents (Heyman et al., BMJ, vol. 333, 2006, pp. 424-429).
  • OCD is a prototypical anxiety state exhibiting two key features. Firstly, the sufferer has repeated thoughts (obsessions) of a severely anxious nature, which may relate to contamination by germs, losing control of oneself or harming others for example. Secondly, the sufferer engages in repeated, ineffectual behaviours or thoughts (compulsions) in order to try and reverse his obsessional anxieties. Examples of these behaviours include repeated hand washing in order to try and remove germs, and counting breathes in order to try and avoid harm coming to others. These repeated anxieties and rituals cause enormous distress to the affected individual and severe disruption to their lives and those of their families and close acquaintances. As a result, suicide rates are much higher amongst OCD sufferers than in the general population, as are occurrences of other Anxiety disorders such as depression, social phobia and substance abuse.
  • glutamate levels and autoimmune- mediated neuronal damage are related, as evidenced by the following findings: the induction of experimental autoimmune encephalitis is improved by the use of glutamate antagonists; glia are intimately involved in the regulation of synaptic function; inflammatory processes within the brain involve neuroglia, which induce release of glutamate; and glutamate activates neuroglia which may, in turn, cause further release of glutamate.
  • a treatment for this type of disorder should ideally be one which prevents the effects of glutamate on brain cells and, at the same time, prevents autoimmune damage to brain cells.
  • This dual mode of action should find a basis in the activation of uptake of glutamate by glial cells within the brain. Accordingly, an idealised therapeutic acting via glial glutamate transporters would both inhibit autoimmune related neuroglial activation and decrease overactivity of the central nervous system (CNS) in the production of glutamate.
  • CNS central nervous system
  • SSRIs Selective Serotonin Re-uptake Inhibitors
  • SSRIs include commercially-available anti-depressants and anxiolytic medications such as clomipramine (AnafranilTM), fluvoxamine (LuvoxTM), fluoxetine (ProzacTM) and sertraline (ZoloftTM).
  • the anti-depressants citalopram (CelexaTM), escitalopram (LexaproTM) and paroxetine (PaxilTM) are also commonly prescribed to treat the symptoms of OCD, in particular in paediatric and adolescent patients.
  • Tetracyclines have been used for some time in humans as antibiotics against many bacterial infections.
  • minocycline is a semi-synthetic tetracycline which has been in use for over 30 years. It has a relatively small molecular weight (495kDa) and is highly lipophilic. It tends to penetrate the cerebrospinal fluid (CSF) of humans better than doxycycline and other tetracyclines, is readily absorbed after oral ingestion and has a low propensity to produce antibiotic resistance. Because of this, therefore, it is commonly used in the treatment of chronic conditions such as acne and rosacea, although is also thought to have neuroprotective effects (Yong et a/., The Lancet: Neurology, vol. 3, 2004, pp. 744-751).
  • Minocycline has recently been shown to be effective against glutamate- mediated effects in a variety of in vitro and in vivo systems, for instance in neurons and retinal cells exposed to high levels of glutamate or other compounds acting on glutamate receptors. It has also been shown that the beneficial effects of minocycline are accompanied by the compound having the ability to enhance glial glutamate transport as well as an inhibition of microglial proliferation (Darman et a/., Journal of Neuroscience, vol. 24(34), 2004, pp. 7566-7575; He et al. Brain Research, vol. 909, 2001 , pp. 187-193). Minocycline is also active in in vivo models of autoimmune mediated nerve damage.
  • WO-A-2007/014154 discloses the use of tretracycline derivatives in the treatment of a wide variety of disorders. Although concerned primarily with the treatment of bacterial infection, it is suggested that the compounds could be used to treat neurological disorders, including anxiety and obsessive-compulsive disorder.
  • the present invention is based upon the surprising discovery that minocycline is efficacious in the treatment of anxiety disorders and, in particular, OCD. This finding is surprising, given that the only well-established use of minocyclines is as an antibiotic in the treatment of bacterial infections such as acne and rosacea or in neuroprotection, i.e. to treat Parkinson's disease and spinal-cord injury. In particular, the present invention is suitable for the treatment of children and paediatrics.
  • a minocycline compound or a prodrug thereof; or a pharmaceutically acceptable salt thereof is used in the manufacture of a medicament for the treatment of an anxiety disorder in children and adolescents.
  • minocycline is used in the manufacture of a medicament for the treatment of an anxiety disorder, wherein the medicament is for sequential or simultaneous administration with at least one antidepressant or anxiolytic medication or pro-drug thereof.
  • a composition comprises minocycline and fluoxetine.
  • kits for treating an anxiety disorder comprises a medicament as defined above and instructions that the medicament is to be used for the treatment of the disorder.
  • Minocycline is also known as 4,7-bis(dimethylamino)-4,4a,5,5a,6,8,9- heptahydro-10,11 ,12a-trihydroxy-1 ,3,12-trioxo-2-naphthacenecarboxamide and has the CAS number 10118-90-8.
  • Minocycline is represented by formula I:
  • Minocycline is currently marketed as an antibiotic under several trade names including Minomycin ,TM , Minocin TM , Arestin .TM , Akamin ,TM , Aknemin ,TM SolodynTM and DynacinTM.
  • the compounds for use in the present invention may be chiral. They may be in the form of one or more stereoisomers, i.e. enantiomers or diastereomers, or a racemate.
  • the compounds of the invention may be prepared in racemic form, or prepared in individual enantiomeric form by specific synthesis or resolution as will be appreciated in the art.
  • the compounds may, for example, be resolved into their enantiomers by standard techniques, such as the formation of diastereomeric pairs by salt formation with an optically active acid followed by fractional crystallisation and regeneration of the free base.
  • the enantiomers of the compounds may be separated by high performance liquid chromatography (HPLC) using a chiral column.
  • HPLC high performance liquid chromatography
  • the minocycline compound used according to the claimed invention is used in the form of one or more of its stereoisomers.
  • the minocycline compounds may be used in its free base form or as a pharmaceutically acceptable salt thereof.
  • pharmaceutically acceptable salts include, for example, addition salts of inorganic or organic acids.
  • inorganic acid addition salts include, for example, salts of hydrobromic acid, hydrochloric acid, nitric acid, phosphoric acid and sulphuric acid.
  • Organic acid addition salts include, for example, salts of acetic acid, benzenesulphonic acid, benzoic acid, camphorsulphonic acid, citric acid, 2-(4-chlorophenoxy)-2- methylpropionic acid, 1 ,2-ethanedisulphonic acid, ethanesulphonic acid, ethylenediaminetetraacetic acid (EDTA), fumaric acid, glucoheptonic acid, gluconic acid, glutamic acid, N-glycolylarsanilic acid, 4-hexylresorcinol, hippuric acid, 2-(4- hydroxybenzoyl)benzoic acid, 1-hydroxy-2-naphthoic acid, 3-hydroxy-2-naphthoic acid, 2-hydroxyethanesulphonic acid, lactobionic acid, n-dodecyl sulphuric acid, maleic acid, malic acid, mandelic acid, methanesulphonic acid, methyl sulphuric
  • salts may be used in therapy in accordance with the present invention.
  • Such salts may be prepared by reacting the minocycline compound with a suitable acid in a conventional manner.
  • the minocycline compound per se for use in the invention may also be prepared by any suitable method known in the art, for example as described in Charest et al., Science, vol. 308, 2005, pp. 395-398, which is incorporated herein by reference. Any mixtures of final products or intermediates obtained can be separated on the basis of the physico-chemical differences of the constituents in a known manner, into the pure final products or intermediates, for example by chromatography, distillation, fractional crystallisation, or by the formation of a salt if appropriate or possible under the circumstances.
  • the minocycline compound may be used either on its own, i.e. as a monotherapy, or in combination with other tetracycline derivatives or one or more of the currently-used pharmacological treatments for anxiety disorders, as an adjunctive therapy.
  • the one or more currently-used drugs is typically selected from anti-depressants and anxiolytic medications, preferably selected from clomipramine (AnafranilTM), fluvoxamine (LuvoxTM), fluoxetine (ProzacTM) and sertraline (ZoloftTM).
  • a medicament for use in the present invention may comprise one or more prodrugs of the desired minocycline compound and/or of the adjunctive drugs mentioned above.
  • prodrug refers to compounds that are drug precursors which, following administration, release the drug in vivo via some chemical or physiological process.
  • anxiety disorder refers to mental disorders attributable to diseases of the nervous system. Examples of such disorders are OCD; other anxiety states related to OCD such as body dysmorphic disorder (i.e. concerns about appearance); other psychiatric states related to OCD such as substance abuse; and other general anxiety states such as generalised anxiety disorder (GAD) and eating disorders.
  • OCD generalised anxiety disorder
  • Other paediatric onset psychiatric disorders which co-occur with OCD, such as Tourette's disorder, attention deficit hyperactivity disorder and impulse control disorder are further examples.
  • a child or paediatric patient is understood to be approximately within the age range 8 to 11 years, while an adolescent patient is understood to be approximately within the age range 12 to 17 years.
  • the present invention is effective in the treatment of the above-mentioned anxiety disorders in all patient types and, in particular, paediatric and adolescent patients.
  • This is a preferred embodiment of the present invention, as OCD and its associated disorders are particularly prevalent amongst these patient types.
  • OCD OCD
  • the size of the adult population in the USA alone, which could potentially benefit from the present invention may be as large as 2.2 million.
  • the active compound may be administered orally, rectally, parenterally or by inhalation (pulmonary delivery). Oral administration is preferred, particularly for administration to paediatric and adolescent patients.
  • the medicaments used in the present invention may take the form of any of the known pharmaceutical compositions for such methods of administration.
  • the compositions may be formulated in a manner known to those skilled in the art so as to give a controlled release, for example rapid, extended or sustained release, of the active(s) included in the medicament for use in the present invention.
  • the drug actives comprised therein may be incorporated as separate dosage forms or may be formulated into a single dosage form. Whether formulated as separate or combined dosage forms, it may be beneficial to facilitate simultaneous, sequential or extended release of the different actives into the patient's system.
  • a single dosage form would be formulated for controlled release of the actives by any formulation technique conventionally known in the art, while separate dosage forms may be administered according to a sequential, i.e. staggered, dosage regimen.
  • the medicament even if the medicament only comprises a minocycline compound as its active, it may nevertheless be desired to formulate the medicament for controlled release into the patient, again according to conventional formulation techniques known in the art.
  • the medicaments used in the invention may contain about 0.1 to about 99% by weight of active compound and typically contain proportions of active formulated in accordance with standardised active levels for different patient types and/or different strengths of medicament depending upon the desired dosage regimen, for example.
  • the medicaments are generally prepared in unit dosage form.
  • a unit dose comprises the one or more active ingredients in an amount of about 0.1 to about 500 mg, more preferably about 20 to about 350mg, and even more preferably about 50 to about 200mg.
  • Excipients used in the preparation of these medicaments may be standard excipients known in the art for this purpose.
  • Appropriate dosage levels may be determined by any suitable method known to one skilled in the art. It will be understood, however, that the specific dose level for any particular patient will depend upon a variety of factors including the activity of the specific compound employed, the age, body weight, general health, sex, diet, time of administration, route of administration, rate of excretion, drug combination and the severity of the disease undergoing treatment. For example, for paediatric patients, a typical dosage is about 4mg/kg, which is subsequently reduced to about 2mg/kg and is administered every 12 hours. For an adult patient, a typical dosage is about 200mg/kg, which is subsequently reduced to about 100mg/kg and is administered about every 12 hours.
  • Medicaments for oral administration include known pharmaceutical forms for such administration, for example tablets, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, or syrups or elixirs.
  • Medicaments intended for oral use may be prepared according to any method known to the art for the manufacture of pharmaceutical compositions, and such medicaments may contain one or more agents in order to provide pharmaceutically elegant and palatable preparations.
  • suitable agents include sweetening agents, flavouring agents, colouring agents or preserving agents. Tablets contain the active ingredient(s) in admixture with non-toxic pharmaceutically acceptable excipients, which are suitable for the manufacture of tablets.
  • excipients may be, for example, inert diluents, such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, for example corn starch or alginic acid; binding agents, for example starch gelatin, acacia, microcrystalline cellulose or polyvinyl pyrrolidone; and lubricating agents, for example magnesium stearate, stearic acid or talc.
  • the tablets may be uncoated or they may be coated by known techniques to delay disintegration and absorption of the drug(s) in the patient and thereby provide a sustained action over a longer period.
  • a time delay material such as glyceryl monostearate or glyceryl distearate may be employed for this purpose.
  • Formulations for oral use may also be presented as hard capsules, preferably gelatin capsules, wherein the active ingredient is mixed with an inert solid diluent, for example calcium carbonate, calcium phosphate or kaolin.
  • an inert solid diluent for example calcium carbonate, calcium phosphate or kaolin.
  • soft, preferably gelatin, capsules, in which the active ingredient is mixed with water or an oil medium such as peanut oil, liquid paraffin or olive oil, may be provided.
  • the medicaments used in the present invention may also be in the form of aqueous suspensions containing the active materials in admixture with excipients suitable for the manufacture of aqueous suspensions.
  • Suitable excipients include suspending agents, for example sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinyl pyrrolidone, gum tragacanth and gum acacia; dispersing or wetting agents such as a naturally occurring phosphatide, for example lecithin, or condensation products of an alkylene oxide with fatty acids, for example polyoxyethylene stearate, or condensation products of ethylene oxide with long-chain aliphatic alcohols, for example heptadecaethyleneoxycetanol, or condensation products of ethylene oxide with partial esters derived from fatty acids, for example polyoxyethylene sorbitan monooleate.
  • suspending agents for example sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, poly
  • the aqueous suspensions may also contain one or more additional agents such as preservatives, for example ethyl or n-propyl p-hydroxybenzoate; colouring agents; flavouring agents; and sweetening agents, such as sucrose or saccharin.
  • preservatives for example ethyl or n-propyl p-hydroxybenzoate
  • colouring agents for example ethyl or n-propyl p-hydroxybenzoate
  • flavouring agents such as sucrose or saccharin.
  • sweetening agents such as sucrose or saccharin.
  • Oily suspensions may be formulated by suspending the active ingredient in a vegetable oil, for example arachis oil, olive oil, sesame oil or coconut oil, polyoxyethylene hydrogenated castor oil, fatty acids such as oleic acid, or in a mineral oil such as liquid paraffin or in other surfactants or detergents.
  • the oily suspensions may contain a thickening agent, for example beeswax, hard paraffin or cetyl alcohol.
  • Sweetening agents, such as those set forth above, and flavouring agents may be added to provide a palatable oral preparation. These compositions may be preserved by the addition of an antioxidant such as ascorbic acid.
  • Dispersible powders and granules suitable for preparation of an aqueous suspension by the addition of water typically provide the active ingredient in admixture with a dispersing or wetting agent, suspending agent and one or more preservatives.
  • suitable sweetening, flavouring and colouring agents may also be present.
  • the medicaments used in the present invention may also be in the form of oil-in-water emulsions.
  • the oily phase may be a vegetable oil, for example olive oil or arachis oil, or a mineral oil, for example liquid paraffin, or mixtures of these.
  • Suitable emulsifying agents may be naturally occurring gums, for example gum acacia or gum tragacanth, naturally occurring phosphatides, for example soya bean, lecithin, and esters or partial esters derived from fatty acids and hexitol anhydrides, for example sorbitan monooleate and condensation products of the said partial esters with ethylene oxide, for example polyoxyethylene sorbitan monooleate.
  • the emulsions may contain additional agents such as sweetening and flavouring agents.
  • Syrups and elixirs may be formulated with sweetening agents, for example glycerol, propylene glycol, sorbitol or sucrose.
  • Such formulations may also contain a demulcent, a preservative and flavouring and colouring agents.
  • the medicaments may be in the form of a sterile injectable aqueous or oleaginous suspension. This suspension may be formulated according to the known art using those suitable dispersing or wetting agents and suspending agents, which have been mentioned above.
  • the sterile injectable preparation may also be in a sterile injectable solution or suspension in a non-toxic parenterally acceptable diluent or solvent, for example as a solution in 1 ,3-butanediol.
  • a non-toxic parenterally acceptable diluent or solvent for example as a solution in 1 ,3-butanediol.
  • acceptable vehicles and solvents that may be employed are water, Ringer's solution and isotonic sodium chloride solution.
  • sterile, fixed oils are conventionally employed as a solvent or suspending medium.
  • any conventionally known bland fixed oil may be employed including synthetic mono- or diglycerides.
  • fatty acids such as oleic acid, find use in the preparation of injectable medicaments.
  • the medicaments for use in the invention may also be administered in the form of suppositories for rectal administration of the drug.
  • These medicaments can be prepared by mixing the drug with a suitable non-irritating excipient, which is solid at ordinary temperatures but liquid at the rectal temperature and will therefore melt in the rectum to release the drug.
  • suitable non-irritating excipient include cocoa butter and polyethylene glycols.
  • the medicament used according to the present invention is provided in the form of a kit comprising the medicament and instructions that the medicament is to be used for the treatment of one or more anxiety disorders and, preferably, OCD. If the medicament comprises the minocycline compound and one or more additional drug actives in separate dosage forms, the instructions provide details of the dosage regimen to be employed.
  • Minocycline reduces the severity of symptoms of anxiety disorders in all patient types, and particularly of OCD in children and adolescents.
  • a standard instrument used for the assessment of such symptom severity is the Yale Brown Obsessive Compulsive Scale (YBOCS).
  • YBOCS Yale Brown Obsessive Compulsive Scale
  • Results of testing using minocycline show that it reduces the severity of scores on the YBOCS scale when used as a monotherapy.
  • minocycline produces an augmentation of the response to existing approved medicines used in the treatment of OCD, particularly in paediatric patients. More specifically, a reduction in the YBOCS score in patients currently receiving such conventional medicines has been observed.
  • Example 1 describe the positive effects of using minocycline upon OCD in adolescent patients.
  • the effect of minocycline was investigated during an open- label, exploratory study in adolescents with OCD, some of whom were not receiving concomitant medication, and some of whom were receiving FDA approved medicines for the treatment of obsessive compulsive disorder. In these latter patients, the response to treatment with existing medication was partial, as is frequently the case.
  • Example 1 describe the positive effects of using minocycline upon OCD in adolescent patients.
  • the effect of minocycline was investigated during an open- label, exploratory study in adolescents with OCD, some of whom were not receiving concomitant medication, and some of whom were receiving FDA approved medicines for the treatment of obsessive compulsive disorder. In these latter patients, the response to treatment with existing medication was partial, as is frequently the case.
  • Example 1 describe the positive effects of using minocycline upon OCD in adolescent patients.
  • This Example reflects the response of the first patient studied.
  • the methods by which this patient was assessed were as follows.
  • the primary measure of change in OCD symptoms was the children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), which is a validated, semi-structured instrument adapted from YBOCS and is designed to measure the clinical symptoms of OCD in children and adolescents.
  • the secondary measures used to capture a variety of aspects of OCD were: • The National Institute of Mental Health Global Obsessive Compulsive Scale (NIMH-GOCS), which is an overall score of OC behaviours, in the opinion of the investigator.
  • NIMH-GOCS National Institute of Mental Health Global Obsessive Compulsive Scale
  • NIMH CGI-I National Institute of Mental Health Clinical Global Impression of Severity of Illness and Improvement
  • CGAS Children's Global Assessment Scale
  • MASC which is a well-known measure of feelings about anxiety, completed by the patient. • The Children's Depression Rating Scale - Revised (CDRS-R) and the Columbia Social Skills Rating System (SSRS), which are used to capture signs and symptoms of depression and suicidal ideation, allowing the investigator to intervene, if required.
  • CDRS-R Children's Depression Rating Scale - Revised
  • SSRS Columbia Social Skills Rating System
  • the duration of the investigation of the patient was 14 weeks in total, comprised of a 2 weeks' screening period followed by 12 weeks of treatment with minocycline.
  • the initial dose for this and all subsequent patients was 50mg twice daily, which approximates to 2mg.kg. ⁇ 1 day '1 , according to the average weight for the age range included in the study.
  • the dose of minocycline was increased to approximately to 4 mg.kg. "1 day "1 , depending on the results achieved on the CY-BOCS, as compared to the baseline score. If a CY-BOCS score of more than 10 was recorded the dose of minocycline was increased, while if a score had reached 10 or less (i.e. remission) the dose was maintained at 50 mg twice daily for the remainder of the study.
  • minocycline is widely distributed in the body tissues and fluids, penetration into the CSF approximates to 26% of plasma level.
  • the effective concentration range as measured from in vitro studies is 0.1-1 ⁇ g/mL.
  • the mean peak concentration achieved after 200 mg minocycline is 2.25 ⁇ g/mL, with the concentration in the CSF reaching 0.56 ⁇ g/mL. This represents 50% of the response level from in vitro tests and is well-tolerated in trials for CNS disorders.
  • the titration of minocycline up to the maximum daily dose currently licensed was intended to maximize the potential of the drug to decrease the clinical symptoms of OCD, in terms of reduction in CY-BOCS score.
  • the reduction in CY- BOCS to 10 or less was considered to offer a clinically significant benefit to the patients treated.
  • the first patient tested was a 16 year old female, diagnosed with OCD and ADHD-combined type. She was enrolled and treated with minocycline for 12 weeks. The patient received a dose of 50mg BID of minocycline for the first two weeks of the study. At the end of week 2, the patient's dose of minocycline was increased to 200mg/day and was maintained at this dose for the remainder of the trial.
  • the patient's NIMH Global Obsessive-Compulsive Scale score decreased from a score of "8" at baseline to a score of "4" indicative of sub-clinical obsessive-compulsive behavior.
  • Example 2 Following progression of the investigation according to the methodology above, four patients were recruited who were receiving medications currently approved by FDA for the treatment of obsessive compulsive disorder in children and adolescents. The response of these patients was incomplete despite use of current approved medications, and so minocycline was added to their treatment regimen as an adjunctive therapy.

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Abstract

L'invention concerne l'utilisation d'un composé de minocycline ou d'un promédicament de ce dernier, ou d'un sel pharmaceutiquement acceptable de celui-ci, dans la fabrication d'un médicament destiné au traitement d'un trouble de l'anxiété chez des enfants ou des adolescents.
EP08709396A 2007-02-28 2008-02-14 Traitement de troubles de l'anxiété par la minocycline Withdrawn EP2129383A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB0703909.2A GB0703909D0 (en) 2007-02-28 2007-02-28 Treatment of anxiety disorders
PCT/GB2008/000504 WO2008104734A1 (fr) 2007-02-28 2008-02-14 Traitement de troubles de l'anxiété par la minocycline

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EP2129383A1 true EP2129383A1 (fr) 2009-12-09

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EP (1) EP2129383A1 (fr)
AU (1) AU2008220668A1 (fr)
GB (1) GB0703909D0 (fr)
WO (1) WO2008104734A1 (fr)

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AU2008220668A1 (en) 2008-09-04
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