EP-4740949-A2 - TREATMENT OF PANIC DISORDER USING BOTULINUM TOXIN

Abstract

Methods are disclosed for treating social anxiety disorder, obsessive compulsive disorder, and/or panic disorder in a subject. The methods include administering a therapeutically effective amount of a neurotoxin to a corrugator supercilli and/or a procerus muscle of the subject to cause paralysis of the corrugator supercilli and/or a procerus muscle in the subject. The neurotoxin can be Botulinum toxin A, such as at a dose of about 20 to about 50 units of Botulinum toxin A.

Inventors

• FINZI ERIC
• ROSENTHAL NORMAN E.

Assignees

• Healis Therapeutics, Inc.

Dates

Publication Date

20260513

Application Date

20141111

Claims (15)

1. A Botulinum toxin for use in a method of treating a social anxiety disorder, an obsessive compulsive disorder or a panic disorder in a subject comprising administering a therapeutically effective amount of the neurotoxin to a corrugator supercilii and/or a procerus muscle of the subject, to cause paralysis of the corrugator supercilii and/or a procerus muscle, thereby treating the social anxiety disorder, the obsessive compulsive disorder or the panic disorder in the subject.
2. The Botulinum toxin for the use of claim 1, wherein the Botulinum toxin is Botulinum toxin A.
3. The Botulinum toxin for the use of claim 1 or 2, wherein the therapeutically effective amount of the neurotoxin is administered to both the corrugator supercilii and the procerus muscle.
4. The Botulinum toxin for the use of any one of claims 1-3, wherein the subject does not have any other psychiatric disorder.
5. The Botulinum toxin for the use of any one of claims 1-4, wherein the subject does not have a muscular disorder or paralysis.
6. The Botulinum toxin for the use of any one of claims 1-5, wherein the therapeutically effective amount of the Botulinum toxin is about 20 to about 50 Unit equivalents of Botulinum toxin type A, and wherein the neurotoxin is administered to the corrugator supercilii and the procerus muscle in the subject, particularly further comprising the use of an additional dose of about 20 to about 50 Unit equivalents of Botulinum toxin type A administered to the corrugator supercilii and the procerus muscle.
7. The Botulinum toxin for the use of any one of claims 2-6, wherein the Botulinum toxin is Botulinum toxin A formulated so that it does not cross a blood-brain barrier in the subject.
8. Botulinum toxin A for use in a method of treating social anxiety disorder, obsessive compulsive disorder or panic disorder in a subject that does not have an underlying muscular physical condition that is treatable with Botulinum toxin A, comprising administering a therapeutically effective amount of Botulinum toxin A to a corrugator supercilii muscle and a procerus muscle of the subject to cause paralysis of the corrugator supercilii muscle and procerus muscle, wherein the Botulinum A toxin is formulated so that it does not cross the blood brain barrier.
9. The Botulinum toxin A for the use of claim 8, wherein the therapeutically effective amount is about 20 to about 40 Unit equivalents, or wherein the therapeutically effective amount is about 29 to about 40 Unit equivalents, particularly wherein the therapeutically effective amount comprises a second dose of about 30 to about 60 Unit equivalents of Botulinum toxin type A which is administered to the corrugator supercilii muscle and the procerus muscle after about two to six months.
10. The Botulinum toxin A for the use of claim 8 or claim 9, wherein the underlying muscular physical condition is torticollis.
11. The Botulinum toxin A for the use of any one of claims 8-10, further comprising administering to the subject a therapeutically effective amount of an additional modality of treatment for the social anxiety disorder, obsessive compulsive disorder or panic disorder, particularly wherein the additional modality of treatment comprises administration of an antidepressant, psychotherapy, a beta blocker, or behavioral therapy.
12. The Botulinum toxin A for the use of any one of claim 8-11, wherein the subject has the social anxiety disorder, particularly wherein the additional modality of treatment comprises a selective serotonin reuptake inhibitor (SSRI), an alpha adrenergic antagonist, an anti-convulsant, a mood stabilizer, an anti-psychotic, a beta blocker, a benzodiazepine, a glucocorticoid, monoamine-oxidase inhibitor (MAOIs), a heterocyclic anti-depressant, or a tricyclic anti-depressant.
13. The Botulinum toxin A for the use of any one of claims 8-11, wherein the subject has the obsessive compulsive disorder, particularly wherein the additional modality of treatment comprises a selective serotonin reuptake inhibitor (SSRI), a tricyclic antidepressant, a benzodiazepine or an atypical antipsychotic.
14. The Botulinum toxin A for the use of any one of claims 8-11, wherein the subject has the panic disorder, particularly wherein the additional modality of treatment comprises a selective serotonin reuptake inhibitor (SSRI), a monoamine oxidase inhibitor (MAOI), a tricyclic antidepressant or a norepinephrine reuptake inhibitor or a benzodiazepine.
15. The Botulinum toxin A for the use of any one of claims 8-14, wherein the method further comprises performing a psychological assessment on the subject.

Description

PRIORITY CLAIM This claims the benefit of U.S. Provisional Application No. 61/903,292, filed November 12, 2013, which is incorporated by reference herein. FIELD This disclosure relates to the field of psychiatric disorders and in particular, to methods for treating social anxiety disorder, obsessive compulsive disorder and panic disorder that utilize a neurotoxin such as botulinum toxin A. BACKGROUND Anxiety disorders are a group of psychological conditions whose key features include excessive anxiety, fear, worry, avoidance, and compulsive rituals, and produce or result in inordinate morbidity, overutilization of healthcare services, and functional impairment. These disorders are among the most prevalent psychiatric conditions in the United States; women are more likely than men to experience anxiety disorders. Anxiety disorders listed in the Diagnostic and Statistical Manual of Mental Disorders (4th Ed., The American Psychiatric Association, Washington, D.C., U.S.A., 1994, pp. 393 to 444), include panic disorder with and without agoraphobia, agoraphobia without history of panic disorder, specific phobia, social phobia, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), acute stress disorder, generalized anxiety disorder (GAD), anxiety disorder due to a general medical condition, substance-induced anxiety disorder, and specific phobias. Panic disorder is an anxiety disorder whose essential feature is the presence of recurrent panic attacks that are discrete periods of intense fear or discomfort. The attacks usually last minutes (or, rarely, hours), are unexpected and do not, as in simple phobia, tend to occur immediately before or on exposure to a situation that almost always causes anxiety. Panic attacks typically begin with the sudden onset of intense apprehension or fear, and are accompanied by physical symptoms such as shortness of breath, dizziness, faintness, choking, palpitations, trembling, sweating, shaking, nausea, numbness, hot flushes or chills, chest pain or the like. Panic disorder may be associated with agoraphobia, in severe cases of which the person concerned is virtually housebound. In obsessive-compulsive disorder, the primary symptom is recurrent obsessions (i.e., recurrent and intrusive thoughts, images or urges that cause marked anxiety) and/or compulsions (i.e., repetitive behaviors or mental acts that are performed to reduce the anxiety generated by one's obsessions) of sufficient severity to cause distress, be time consuming or to interfere significantly with a person's normal routine or lifestyle. Anxiety is an associated feature of this disorder: an affected person may, for example, show a phobic avoidance of situations that involve the cause of the obsession. Typical obsessions concern contamination, doubting (including self-doubt) and disturbing sexual or religious thoughts. Typical compulsions include washing, checking, ordering, and counting. Social anxiety disorder is characterized by the persistent fear of social or performance situations in which embarrassment may occur, such as parties, meetings, eating in front of others, writing in front of others, public speaking, conversations, meeting new people, and other related situations. Exposure to social or performance situations provokes an immediate anxiety response, as well as sweating, trembling, racing or pounding heartbeat, mental confusion, and a desire to flee. Social avoidance and isolation can also become extreme, especially in the more generalized condition. There is a need for new treatment agents to alleviate the symptoms of social anxiety disorder, obsessive compulsive disorder or a panic disorder, in order to allow subjects with these conditions to live more productive and enjoyable lives. SUMMARY Methods are disclosed for treating an anxiety disorder in a subject, such as social anxiety disorder, an obsessive compulsive disorder and/or a panic disorder. The methods include administering a therapeutically effective amount of a neurotoxin to a corrugator supercilli and/or a procerus muscle of the subject to cause paralysis of the corrugator supercilli and/or a procerus muscle, thereby treating the social anxiety disorder, the obsessive compulsive disorder or the panic disorder in the subject. In some embodiments, the methods include selecting a subject with an anxiety disorder, such as a social anxiety disorder, an obsessive compulsive disorder and/or a panic disorder, and administering a therapeutically effective amount of Botulinum toxin A to a corrugator supercilli muscle and a procerus muscle of the subject, in order to cause paralysis of the corrugator supercilli muscle and procerus muscle and treat the social anxiety disorder, the obsessive compulsive disorder or the panic disorder in the subject. In some non-limiting examples, the subject does not have an underlying muscular physical condition such as torticollis or blepharospasm that is treatable with Botulinum A toxin. In other e