Treatment of suicidal ideation or behavior using inhibitors of nicotinic acetylcholine receptors

• US 9,180,191 B2
• Filed: 10/15/2010
• Issued: 11/10/2015
• Est. Priority Date: 10/16/2009
• Status: Active Grant

• Current Assignee: University of South Florida (State University System of Florida)
• Original Assignee: University of South Florida (State University System of Florida)
• Inventors: Sheehan, David Vincent, Shytle, Roland Douglas
• Primary Examiner(s): Crow, Robert T
• Assistant Examiner(s): Nguyen, John P
• Application Number:
  US13/502,239
• Publication Number:
  US 20120269906A1
• Time in Patent Office: 1,852 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/407 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• CPC Class Codes: A61K 33/14 Alkali metal chlorides; Alkaline earth metal chlorides
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 Antidepressants

Abstract

The invention concerns methods of treating suicidal ideation or behavior in a subject in need thereof, comprising decreasing endogenous nicotinic acetylcholine receptor (nAChR) activity in the subject; therapeutic packages for treating suicidal ideation or behavior; and methods for determining the efficacy of a treatment for suicidal ideation or behavior. In some embodiments, the treatment methods comprise administering to the subject an effective amount of an inhibitor of a nAChR, such as a lithium compound, mecamylamine, clozapine, or asenapine.

Claims

1. A method of treating suicidality in a subject in need thereof, comprising administering to the subject an effective amount of mecamylamine or TC-5214.

2. The method of claim 1, wherein the subject has suicidal thoughts and is at risk of committing suicide.

3. The method of claim 1, wherein the subject has tried to commit suicide or has a history of suicide attempts.

4. The method of claim 1, wherein the subject is further suffering from ambulatory bipolar disorder, schizophrenia, or both.

5. The method of claim 1, wherein the subject is identified as suffering from suicidality using a suicidality tracking scale capable of direct mapping to the Columbia Classification Algorithm for Suicide Assessment (C-CASA).

6. The method of claim 1, wherein the subject is identified as suffering from suicidality using the Sheehan Suicidality Tracking Scale (S-STS) or Columbia Suicide Severity Rating Scale (C-CRS).

7. The method of claim 1, wherein the subject is identified as having suicidality symptoms of more than zero as measured by the Sheehan Suicidality Tracking Scale (S-STS) prior to said administering.

8. The method of claim 1, wherein the subject has an abnormally low brain-derived neurotrophic factor (BDNF), or cerebrospinal fluid (CSF) monoamine metabolite, concentration prior to said administering.

9. The method of claim 8, wherein the monoamine metabolite is 5-hydroxyinoleacetic acid (5-HIAA).

10. The method of claim 1, wherein the subject has a polymorphism in the tryptophan hydroxylase gene in intron 7.

11. The method of claim 1, wherein the subject has had a major depressive episode.

12. The method of claim 1, wherein the subject is suffering from bipolar depression.

13. The method of claim 1, wherein the subject is suffering from an anxiety disorder or anxiety symptoms.

14. The method of claim 1, wherein the subject is further suffering from a disorder selected from the group consisting of bipolar disorder, panic disorder, social anxiety, post-traumatic stress disorder (PTSD), substance dependence/abuse, eating disorder, obsessive compulsive disorder (OCD), schizophrenia, schizo-affective disorder, schizophrenoform disorder, Huntington'"'"'s disease, early Alzheimer'"'"'s disease, and Parkinson'"'"'s disease.

15. The method of claim 1, wherein the mecamylamine or TC-5214 is administered as a monotherapy.

16. The method of claim 1, wherein no mood stabilizing, antidepressant, antipsychotic, or anxiolytic medication, other than an nAChR inhibitor, is administered to the subject concurrently with the mecamylamine or TC-5214, or administered less than one week prior to administration of the mecamylamine or TC-5214.

17. The method of claim 1, wherein the subject is administered a mood stabilizing, antidepressant, antipsychotic, or anxiolytic medication at least one week, prior to administration of the mecamylamine or TC-5214.

18. The method of claim 1, wherein both mecamylamine and TC-5214 are administered to the subject.

19. The method of claim 1, wherein the mecamylamine is administered to the subject.

20. The method of claim 1, wherein the subject has not suffered a major depressive episode.

21. The method of claim 1, wherein the subject is not suffering from major depressive disorder.

22. The method of claim 1, wherein the subject is not suffering from bipolar disorder.

23. The method of claim 1, wherein the suicidality is thereby eliminated.

24. The method of claim 1, wherein the suicidality is non-drug-induced.

25. The method of claim 1, wherein the TC-5214 is administered to the subject.