Botulinum Toxin and the Treatment of Primary Disorders of Mood and Affect
The invention provides methods for treating primary disorders of mood and affect, including depressive disorders, anxiety and sleep disorders and CNS disorders comprising the administration of a neurotoxin.
1 . A method of treating major depression in a subject in need thereof, comprising the steps of:
identifying a subject with major depression; and
administering to a soft tissue outside the neurocranium of the subject a composition comprising botulinum toxin and a pharmaceutically acceptable carrier, wherein said botulinum toxin is in an amount not sufficient to cause muscular impairment but sufficient to induce a suppressive effect in the central nervous system (CNS), wherein the CNS suppressive effect is associated with a decrease in at least cholinergic neuron transmission or choline acetyltransferase activity, or a combination thereof;
thereby reducing at least one symptom of the major depression.
2 . (canceled)
3 . The method of claim 1 , wherein the botulinum toxin is botulinum toxin type A from the Hall strain of Clostridium botulinum.
4 . (canceled)
5 . The method of claim 1 , wherein administration is by intramuscular injection.
6 . The method of claim 1 , wherein administration is by non-intramuscular injection.
7 . The method of claim 1 , wherein the botulinum toxin is administered to at least one of the neck, the scalp, the face, the periocular region, and the forehead of the subject.
8 . The method of claim 1 , wherein the composition is administered other than into a brow muscle of the subject.
9 - 10 . (canceled)
11 . The method of claim 1 , wherein the composition does not contain human blood products.
12 . The method of claim 1 , wherein the composition further comprises a polycationic protein.
13 - 15 . (canceled)
16 . The method of claim 1 , wherein the identifying step further comprises determining a level of acetylcholine or glutamate neurotransmission in the brain or CNS of the subject.
17 . (canceled)
18 . A method of treating a central nervous system disorder in a subject in need thereof, said method comprising the steps of:
identifying a subject with a central nervous system disorder; and
administering to a soft tissue outside of the neurocranium of the subject a composition comprising botulinum toxin and a pharmaceutically acceptable carrier, wherein said botulinum toxin is in an amount not sufficient to cause muscular impairment but sufficient to decease levels of acetylcholine,
wherein said central nervous system disorder is at least one selected from the group consisting of seizures, generalized seizures, mental retardation, delirium, hyperactivity syndrome, attention deficit disorder (ADD), cerebral vascular disease, stroke, neurodegenerative disease, dementia, Huntington's disease, Alzheimer's disease, Parkinson's disease, psychosis, and schizophrenia,
thereby reducing or improving at least one symptom of the subject's central nervous system disorder.
19 - 28 . (canceled)
29 . The method of claim 18 , wherein the botulinum toxin is of immunotype A from the Hall strain of Clostridium botulinum.
30 - 31 . (canceled)
32 . The method of claim 18 , wherein the botulinum toxin-containing composition further comprises a polycation protein.
33 . The method of claim 18 , wherein the botulinum toxin-containing composition does not contain human blood products.
34 . The method of claim 18 , wherein the botulinum toxin-containing composition is administered by intramuscular injection.
35 . The method of claim 18 , wherein botulinum toxin-containing composition is administered by non-intramuscular injection.
36 . A method of lowering glutamate neurotransmission in the brain of a subject, said method comprising administering to a soft tissue region outside the neurocarnium of the subject a composition comprising a pharmaceutically acceptable carrier and botulinum toxin, wherein said botulinum toxin is in an amount not sufficient to cause muscular impairment.
37 - 39 . (canceled)
40 . The method of claim 1 , wherein the botulinum toxin is administered to the subject in a soft tissue area that enhances uptake by the portal hypophyseal drainage system.
41 - 51 . (canceled)
52 . The method of claim 1 , wherein the symptom is at least one selected from the group consisting of depressed mood, diminished interest in activities, diminished pleasure in activities, significant weight loss, significant weight gain, insomnia, hypersomnia, psychomotor agitation, psychomotor retardation, fatigue, energy loss, feelings of guilt, feelings of worthlessness, impaired concentration, indecisiveness, recurring thoughts of death, and recurring thoughts of suicide.
53 . The method of claim 1 , wherein the botulinum toxin is immunotype A and is administered at a dose of 1.25-3,000 units.
54 . The method of claim 1 , wherein the administration comprises intraosseous administration to at least one area selected from the periocular region, the forehead, the scalp, and the face.