(19) & (11) EP 1 896 025 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 31/46 (2006.01) A61K 9/12 (2006.01) 28.12.2011 Bulletin 2011/52 A61P 25/22 (2006.01) A61P 25/24 (2006.01) (21) Application number: 06760136.9 (86) International application number: PCT/US2006/019335 (22) Date of filing: 18.05.2006 (87) International publication number: WO 2006/127418 (30.11.2006 Gazette 2006/48) (54) SCOPOLAMINE FOR THE TREATMENT OF DEPRESSION AND ANXIETY SCOPOLAMIN FÜR DIE BEHANDLUNG VON DEPRESSION UND ÄNGSTLICHKEIT UTILISATION DE LA SCOPOLAMINE POUR TRAITER LA DEPRESSION ET L’ANXIETE (84) Designated Contracting States: (72) Inventors: AT BE BG CH CY CZ DE DK EE ES FI FR GB GR • FUREY, Maura, L. HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI Silver Spring, MD 20910 (US) SK TR • DREVETS, Wayne, C. Gaithersburg, MD 20878 (US) (30) Priority: 25.05.2005 US 137114 (74) Representative: Cole, William Gwyn et al (43) Date of publication of application: avidity IP 12.03.2008 Bulletin 2008/11 Merlin House Falconry Court (60) Divisional application: Baker’s Lane 10182809.3 Epping, Essex CM16 5DQ (GB) (73) Proprietor: GOVERNMENT OF THE UNITED (56) References cited: STATES OF AMERICA, as WO-A-98/31346 CA-A- 1 022 930 representedby THE SECRETARY, DEPARTMENT DE-A1- 3 926 751 OF HEALTH AND HUMAN SERVICES • PAYK TH. R.: "Treatment of Depression" Rockville, MD 20852-3804 (US) JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY, vol. 7, no. Suppl.1, 1994, pages S3- S5, XP009072089 USA Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 1 896 025 B1 Printed by Jouve, 75001 PARIS (FR) EP 1 896 025 B1 Description BACKGROUND OF THE INVENTION 5 FIELD OF THE INVENTION [0001] This invention relates generally to the field of treatment of depression and anxiety in subjects diagnosed with depression and anxiety. Specifically, the invention relates to the treatment of depression and anxiety with scopolamine, or analogs thereof. 10 BACKGROUND ART [0002] Despite the availability of a wide range of antidepressant drugs, clinical trials indicate that 30% to 40% of patients with major depression fail to respond to first- line antidepressant treatment, despite adequate dosage, duration, 15 and compliance. Moreover, in those patients who do experience symptomatic relief following conventional anti- depres- sant treatment, clinical improvement is not evident for 3-4 weeks. [0003] Some effective antidepressant medications such as tricylic antidepressant drugs have potent antimuscarinic effects [7-9]; however, there has been no study to evaluate systematically the efficacy of an anticholinergic as an antidepressantagent. Successful clinical treatment of depression has depended on the use of tricyclic agents, monoamine 20 oxidase inhibitors and selective serotonin reuptake inhibitors (SSRI). Moreover, over the past two decades of antide- pressant drug development, the muscarinic antagonist effects of early antidepressant drugs (i.e., the tricyclic antide- pressant agents) were viewed almost exclusively as producing unwanted side effects without contributing at all to therapeutic effects [14-16]. As a result, efforts to develop new antidepressant treatments included an emphasis on developing compounds that specifically did not have antagonist effects at muscarinic cholinergic receptors [17]. 25 [0004] DE 3926751 discloses storage stable alcoholic solutions of alkaloids, e.g. atropine, scopolamine,hyo- L- scyamine, their quaternary ammonium compounds and atropine-like compounds, containing a porous adsorbent crys- talline powder in bead form. [0005] WO 98/31346 discloses the preparation of particles for human inhalation. [0006] CA 1022930 discloses anticholinergically active compounds having bronchospasmolytic activity. 30 [0007] Payk Th. R., "Treatment of Depression" Journal of Geriatric Psychiatry and Neurology, vol 7., no. Suppl. 1, 1994, pages S3-S5 discloses that plant extracts have been used for thousands of years for the treatment of depression. SUMMARY OF THE INVENTION 35 [0008] This invention relates to the uses set forth in the claims. [0009] Broadly described herein, are methods of treating major depressive disorder in a subject diagnosed with major depressive disorder, comprising administering to the subject a composition comprising a therapeutically effective amount of scopolamine, or an analog thereof, in a pharmaceutically acceptable carrier, whereby the administration of the com- position treats major depressive disorder in the subject. 40 [0010] Described herein are methods of treating treatment- resistant major depressive disorder in a subject diagnosed with treatment-resistant major depressive disorder, comprising administering to the subject a composition comprising a therapeutically effective amount of scopolamine, or an analog thereof, in a pharmaceutically acceptable carriers whereby the administration of the composition treats treatment-resistant major depressive disorder in the subject. [0011] Described herein are methods of treating depressed phase of bipolar disorder in a subject diagnosed with 45 depressed phase of bipolar disorder, comprising administering to the subject a composition comprising a therapeutically effective amount of scopolamine, or an analog thereof, in a pharmaceutically acceptable carrier, whereby the adminis- tration of the composition treats depressed phase of bipolar disorder in the subject. [0012] Described herein are methods of treating panic disorder in a subject diagnosed with panic disorder, comprising administering to the subject a composition comprising a therapeutically effective amount of scopolamine, or an analog 50 thereof, in a pharmaceutically acceptable carrier, whereby the administration of the composition treats panic disorder in the subject. [0013] Described herein are methods of treating social phobia (social anxiety disorder) in a subject diagnosed with social phobia (social anxiety disorder), comprising administering to the subject a composition comprising a therapeutically effective amount of scopolamine, or an analog thereof, in a pharmaceutically-acceptable carrier, whereby the adminis- 55 tration of the composition treats social phobia (social anxiety disorder) in the subject. [0014] Described herein are methods of treating post-traumatic stress disorder in a subject diagnosed with post- traumatic stress disorder, comprising administering to the subject a composition comprising a therapeutically effective amount of scopolamine, or an analog thereof, in a pharmaceutically acceptable carrier, whereby the administration of 2 EP 1 896 025 B1 the composition treats post-traumatic stress disorder in the subjects [0015] Described herein are methods of treating generalized anxiety disorder in a subject diagnosed with generalized anxiety disorder, comprising administering to the subject a composition comprising a therapeutically effective amount of scopolamine, or an analog thereof, in a pharmaceutically acceptable carrier, whereby the administration of the com- 5 position treats generalized anxiety disorder in the subject. [0016] Described herein is an inhaler comprising a composition comprising scopolamine, or an analog thereof, in a pharmaceutically acceptable carrier. [0017] Also described herein is a kit comprising an inhaler comprising a composition comprising scopolamine, or an analog thereof, in a pharmaceutically acceptable carrier, and instructions regarding using the inhaler. 10 [0018] Additional advantages of the invention will be set forth in part in the description that follows, and in part will be obvious from the description, or may be learned by practice of the invention. The advantages of the invention will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed. 15 [0019] Thus, provided herein are compositions and improved uses for quickly and efficiently treating the disorders mentioned in the claims without producing unwanted side effects usually associated with such agents. BRIEF DESCRIPTION OF THE DRAWINGS 20 [0020] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several embodiments of the invention and together with the description, serve to explain the principles of the invention. Figure 1 shows a study that included a series of seven sessions, each involving a 15-minute intravenous infusion of either a placebo saline solution, or 4 Pg/kg of scopolamine. Session one was designed to be single-blind during 25 which all subjects received a placebo infusion to allow for a baseline evaluation. The next six sessions were separated into two blocks of three sessions each; one block included a series of three placebo infusions (P Block) and the other a series of three scopolamine infusions (S Block). Individuals were randomized into either the P/S (placebo/ scopolamine) series or the S/P (scopolamine/placebo) series, using a double-blind design. In total, all subjects