Electroencephalography based systems and methods for selecting therapies and predicting outcomes

• US 7,177,675 B2
• Filed: 07/11/2002
• Issued: 02/13/2007
• Est. Priority Date: 02/09/2000
• Status: Active Grant

• Current Assignee: MYnd Analytics, Inc. (Emmaus Life Sciences, Inc.)
• Original Assignee: CNS Response Inc.
• Inventors: Emory, W. Hamlin, Suffin, Stephen C., Brandt, Leonard J.
• Primary Examiner(s): Nasser; Robert L.
• Application Number:
  US10/193,735
• Publication Number:
  US 20030135128A1
• Time in Patent Office: 1,678 Days
• Field of Search: None
• US Class Current: 600/544
• CPC Class Codes: A61B 5/0006 ECG or EEG signals
• CPC Class Codes: A61B 5/369 Electroencephalography [EEG] devices for psychotechnics A61B5/16
• CPC Class Codes: A61B 5/372 Analysis of electroencephalograms
• CPC Class Codes: A61B 5/386 Accessories or supplementary instruments therefor
• CPC Class Codes: A61B 5/4076 Diagnosing or monitoring particular conditions of the nervous system A61B5/4821, A61B5/4824 take precedence
• CPC Class Codes: A61B 5/411 Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance
• CPC Class Codes: A61B 5/4833 Assessment of subject's compliance to treatment
• CPC Class Codes: A61B 5/7257 using Fourier transforms
• CPC Class Codes: A61B 5/7264 Classification of physiological signals or data, e.g. using neural networks, statistical classifiers, expert systems or fuzzy systems neural networks per se G06N3/00; expert systems per se G06N5/00
• CPC Class Codes: G16H 15/00 ICT specially adapted for medical reports, e.g. generation or transmission thereof
• CPC Class Codes: G16H 20/10 relating to drugs or medications, e.g. for ensuring correct administration to patients
• CPC Class Codes: G16H 50/20 for computer-aided diagnosis, e.g. based on medical expert systems
• CPC Class Codes: G16H 50/70 for mining of medical data, e.g. analysing previous cases of other patients
• CPC Class Codes: G16H 70/60 relating to pathologies

Abstract

A method and system for utilizing neurophysiologic information obtained by techniques such as quantitative electroencephalography (QEEG), electrode recordings, MRI in appropriately matching patients with therapeutic entities is disclosed. The present invention enables utilization of neurophysiologic information, notwithstanding its weak correlation with extant diagnostic schemes for mental disorders, for safer and expeditious treatment for mental disorders, discovering new applications for therapeutic entities, improved testing of candidate therapeutic entities, inferring the presence or absence of a desirable response to a treatment, and deducing the mode of action of one or more therapeutic entities. In particular, methods for effectively comparing neurophysiologic information relative to a reference set are disclosed along with database-based tools for deducing therapeutic entity actions on particular patients such that these tools are readily accessible to remote users.

Claims

1. A method for identifying an outcome of at least a first treatment comprising:

a) providing a first electroencephalogram;

b) scaling said first electroencephalogram to enable comparison with a treatment-response database, wherein said database comprises stored electroencephalographic information obtained from a first plurality of subjects;

c) computing at least one indicative variable from said first electroencephalogram; and

d) identifying a cluster derived from said database under conditions that predict at least a first outcome of a first treatment prior to actually administering said first treatment, wherein said cluster comprises a second plurality of subjects and at least eighty percent of said second plurality of subjects have a common response to said first treatment.

2. The method of claim 1, further comprising identifying said at least one indicative variable by screening said treatment-response database.

3. The method of claim 1, further comprising identifying said at least one indicative variable within said cluster.

4. The method of claim 1, wherein said treatment-response database comprises a clinical global improvement score, said score comprising an integer selected from the group consisting of negative one (−

1) indicating an adverse therapeutic effect, zero (0) indicating no improvement, positive one (+1) indicating a minimal improvement, positive two (+2) indicating a moderate improvement, and positive three (+3) indicating a complete absence of symptoms.

5. The method of claim 1, wherein said indicative variable is calculated by the difference between said at least one treatment-response database univariate value within said treatment-response database and at least one reference database univariate value, said reference database comprising age-matched reference subjects.

6. The method of claim 1, wherein said first outcome is capable of improving at least one symptom of a traditionally diagnosed mental disease.

7. The method of claim 6, further comprising identifying a second treatment by comparing said first outcome to a second outcome, said second outcome resulting from said second treatment.

8. The method of claim 7, wherein said traditionally diagnosed mental disease is a major depressive disorder and said second treatment is selected from the group consisting of glutamine, phenylalanine, and tyrosine.

9. The method of claim 7, wherein said traditionally diagnosed mental disease comprises psychological factors affecting atypical asthma and said second treatment is selected from the group consisting of glutamine, phenylalanine, tyrosine, bupropion, pamate, moclobemide, phenelzine, selegiline, venlafaxine, carbamazapine, gabapentin, lamotrigine, ginko biloba, dexedrine, methamphetamine, methylphenidate, and pemoline.

10. The method of claim 7, wherein said traditionally diagnosed mental disease comprisies anxiety disorders and said second treatment is selected from the group consisting of gaba, glutamine, phenylalanine, tyrosine, buproprion, citalopram, fluvoxamine, citalopramine, clomipramine, moclobemide, parnate, phenelzine, selegiline, carbamazapine, divalproex, gabapentin, lamotrigine, guanfacine hydrochloride, clonidine, atenolol, metoprolol, propranolol, lithium, ginko biloba, kava kava, st. john'"'"'s wort, amantadine, phototherapy, adderall, dexedrine, methamphetamine, methylphenidate, modafinil, and pemoline.

11. The method of claim 7, wherein said traditionally diagnosed mental disease comprises psychological factors affecting disorders usually first diagnosed in infancy, childhood, or adolescence and said second treatment is selected from the group consisting of gaba glutamine, phenylalanine, tyrosine, donepezil, buproprion, citalopram, clomiprimine, doxepin, fluoxetine, fluvoxamine, moclobemide, parnate, phenelzine, selegiline, trazodone, venlafaxine, carbamazapine, diphenylhydantoin, divalproex, gabapentin, lamotrigine, guanfacine hydrochloride, clorazepate, diazepam, oxazepam, quazepam, atenolol, metoprolol, propranolol, lithium, ginko biloba, kava kava, st. john'"'"'s wort, silbtrimin, amantadine, phototherapy, adderall, dexedrine, methamphetamine, methylphenidate, modafinil, and phentermine.

12. The method of claim 7, wherein said traditionally diagnosed mental disease comprises eating disorders and said second treatment is selected from the group consisting of gaba, glutamine, phenylalanine, tyrosine, donepezil, buproprion, moclobemide, pamate, pheneizine, selegiline, venlafaxine, carbamazapine, diphenylhydantoin, divalproex, gabapentin, lamotrigine, diazepam, lorazepam, atenolol, metoprolol, propranolol, lithium, ginko biloba, kava kava, st. john'"'"'s wort, amantadine, phototherapy, zolipidem, adderall, dexedrine, methamphetamine, methylphenidate, modafinil, pemoline, and phentermine.

13. The method of claim 7, wherein said traditionally diagnosed mental disease is selected from the group consisting of delirium, dementia, amnesia, and other cognitive disorders and said second treatment is selected from the group consisting of glutamine, phenylalanine, tyrosine, donepezil, amitriptyline, buproprion, fluxotine, moclobemide, parnate, phenelzine, selegiline, venlafaxine, carbamazapine, divaiproex, gabapentin, lamotrigine, atenolol, metoprolol, propranolol, lithium, ginko biloba, silbtrimin, amantadine, phototherapy, zolipidem, adderall, dexedrine, methamphetamine, methylphenidate, modafinil, pemoline, and phentermine.

14. The method of claim 7, wherein said traditionally diagnosed mental disease comprises impulse control disorders and said second treatment is selected from the group consisting of glutamine, phenylalanine, tyrosine, donepezil, buproprion, citalopram, clomiprimine, desipramine, moclobemide, nefazodone, parnate, phenelzine, selegiline, venlafaxine, carbamazapine, diphenylhydantoin, divalproex, gabapentin, lamotrigine, guanfacine hydrochloride, clonidine, atenolol, metoprolol, propranolol, ginko biloba, kava kava, silbtrimin, amantadine, phototherapy, adderall, dexedrine, methamphetamine, methylphenidate, and pemoline.

15. The method of claim 7, wherein said traditionally diagnosed mental disease comprises mood disorders and said second treatment is selected from the group consisting of glutamine, phenylalanine, tyrosine, moclobemide, parnate, pheneizine, selegiline, diphenylhydantoin, lamotrigine, guanfacine hydrochloride, clonidine, lorazepam, oxazepam, quazepam, temazepam, trizolam, atenolol, metoprolol, propranolol, ginko biloba, kava kava, st. john'"'"'s wort, phototherapy, adderall, dexedrine, methamphetamine, methylphenidate, pemoline, and phentermine.

16. The method of claim 7, wherein said traditionally diagnosed mental disease comprises personality disorders and said second treatment is selected from the group consisting of gaba, glutamine, phenylalanine, tyrosine, donepezil, buproprion, moclobemide, pamate, phenelzine, selegiline, venlafaxine, carbamazapine, diphenylhydantoin, divalproex, gabapentin, lamotrigine, diazepam, atenolol, metoprolol, propranolol, lithium, ginko biloba, kava kava, st. john'"'"'s wort, phototherapy, adderall, dexedrine, methamphetamine, methyiphenidate, pemoline, and phentermine.

17. The method of claim 7, wherein said traditionally diagnosed mental disease comprises a hypoactive sexual desire disorder and said second treatment is selected from the group consisting of buproprion, buspirone, moclobemide, pamate, phenelzine, and selegiline.

18. The method of claim 7, wherein said traditionally diagnosed mental disease comprises sleep disorders and said second treatment is selected from the group consisting of gaba, glutamine, phenylalanine, tyrosine, donepezil, buproprion, buspirone, citalopram, clomiprimine, desipramine, fluoxetine, fluvoxamine, moclobemide, parnate, phenelzine, selegiline, sertraline, venlafaxine, carbamazapine, diphenylhydantoin, divaiproex, gabapentin, lamotrigine, guanfacine hydrochloride, clonidine, atenolol, metoprolol, propranolol, lithium, ginko biloba, kava kava, st. john'"'"'s wort, silbtrimin, phototherapy, adderall, dexedrine, methamphetamine, methylphenidate, pemoline, and phentermine.

19. The method of claim 7, wherein said traditionally diagnosed mental disease comprises somatoform disorders and said second treatment is selected from the group consisting of gaba, glutamine, phenylalanine, tyrosine, donepezil, buproprion, citalopram, fluvoxamine, moclobemide, parnate, phenelzine, selegiline, carbamazapine, diphenylhydantoin, divalproex, gabapentin, lamotrigine, atenolol, metoprolol, propranolol, ginko biloba, kava kava, st. john'"'"'s wort, amantadine, phototherapy, zolipidem, adderall, dexedrine, methamphetamine, methylphenidate, modafinil, pemoline, and phentermine.

20. The method of claim 7, wherein said traditionally diagnosed mental disease comprises substance-related disorders and said second treatment is selected from the group consisting of gaba, glutamine, phenylalanine, tyrosine, donepezil, fluvoxamine, moclobemide, parnate, phenelzine, selegiline, venlafaxine, carbamazapine, diphenylhydantoin, divalproex, gabapentin, lamotrigine, guanfacine hydrochloride, atenolol, metoprolol, propranolol, ginko biloba, kava kava, st. john'"'"'s wort, silbtrimin, phototherapy, adderall, dexedrine, methamphetamine, methylphenidate, and pemoline.

21. A method for identifying an outcome of at least a first treatment, comprising:

a) providing a first electroencephalogram;

b) scaling said first electroencephalogram to enable comparison with a treatment-response database, wherein said database comprises a plurality of first indicative variables;

c) computing at least one second indicative variable derived from said first electroencephalogram; and

d) evaluting said at least one second indicative variable using a plurality of rules associated with said plurality of first indicative variables under conditions that predict at least a first outcome of a first treatment prior to actually administering said first treatment.

22. The method of claim 21, further comprising identifying said at least one indicative variable by screening said treatment-response database.

23. The method of claim 21, wherein said treatment-response database comprises a clinical global improvement score, said score comprising an integer selected from the group consisting of negative one (−

1) indicating an adverse therapeutic effect, zero (0) indicating no improvement, positive one (+1) indicating a minimal improvement, positive two (+2) indicating a moderate improvement, and positive three (+3) indicating a complete absence of symptoms.

24. The method of claim 21, wherein said indicative variable is calculated by the difference between said at least one treatment-response database univariate value within said treatment-response database and at least one reference database univariate value, said reference database comprising age-matched reference subjects.

25. The method of claim 21, wherein said first outcome is capable of improving at least one symptom of a traditionally diagnosed mental disease.

26. The method of claim 25, further comprising identifying a second treatment by comparing said first outcome to a second outcome, said second outcome resulting from said second treatment.

27. The method of claim 26, wherein said traditionally diagnosed mental disease is a major depressive disorder and said second treatment is selected from the group consisting of glutamine, phenylalanine, and tyrosine.

28. The method of claim 26, wherein said traditionally diagnosed mental disease comprises psychological factors affecting atypical asthma and said second treatment is selected from the group consisting of glutamine, phenylalanine, tyrosine, bupropion, parnate, moclobemide, phenelzine, selegiline, venlafaxine, carbamazapine, gabapentin, lamotrigine, ginko biloba, dexedrine, methamphetamine, methylphenidate, and pemoline.

29. The method of claim 26, wherein said traditionally diagnosed mental disease comprisies anxiety disorders and said second treatment is selected from the group consisting of gaba, glutamine, phenylalanine, tyrosine, buproprion, citalopram, fluvoxamine, citalopramine, clomipramine, moclobemide, parnate, phenelzine, selegiline, carbamazapine, divalproex, gabapentin, lamotrigine, guanfacine hydrochloride, clonidine, atenolol, metoprolol, propranolol, lithium, ginko biloba, kava kava, st. john'"'"'s wort, amantadine, phototherapy, adderall, dexedrine, methamphetamine, methylphenidate, modafinil, and pemoline.

30. The method of claim 26, wherein said traditionally diagnosed mental disease comprises psychological factors affecting disorders usually first diagnosed in infancy, childhood, or adolescence and said second treatment is selected from the group consisting of gaba glutamine, phenylalanine, tyrosine, donepezil, buproprion, citalopram, clomiprimine, doxepin, fluoxetine, fluvoxamine, moclobemide, parnate, pheneizine, selegiline, trazodone, venlafaxine, carbamazapine, diphenylhydantoin, divaiproex, gabapentin, lamotrigine, guanfacine hydrochloride, clorazepate, diazepam, oxazepam, quazepam, atenolol, metoprolol, propranolol, lithium, ginko biloba, kava kava, st. john'"'"'s wort, silbtrimin, amantadine, phototherapy, adderall, dexedrine, methamphetamine, methylphenidate, modafinil, and phentermine.

31. The method of claim 26, wherein said traditionally diagnosed mental disease comprises eating disorders and said second treatment is selected from the group consisting of gaba, glutamine, phenylalanine, tyrosine, donepezil, buproprion, moclobemide, pamate, phenelzine, selegiline, venlafaxine, carbamazapine, diphenylhydantoin, divalproex, gabapentin, lamotrigine, diazepam, lorazepam, atenolol, metoprolol, propranolol, lithium, ginko biloba, kava kava, st. john'"'"'s wort, amantadine, phototherapy, zolipidem, adderall, dexedrine, methamphetamine, methyiphenidate, modafinil, pemoline, and phentermine.

32. The method of claim 26, wherein said traditionally diagnosed mental disease is selected from the group consisting of delirium, dementia, amnesia, and other cognitive disorders and said second treatment is selected from the group consisting of glutamine, phenylalanine, tyrosine, donepezil, amitriptyline, buproprion, fluxotine, moclobemide, parnate, pheneizine, selegiline, venlafaxine, carbamazapine, divalproex, gabapentin, lamotrigine, atenolol, metoprolol, propranolol, lithium, ginko biloba, silbtrimin, amantadine, phototherapy, zolipidem, adderall, dexedrine, methamphetamine, methylphenidate, modafinil, pemoline, and phentermine.

33. The method of claim 26, wherein said traditionally diagnosed mental disease comprises impulse control disorders and said second treatment is selected from the group consisting of glutamine, phenylalanine, tyrosine, donepezil, buproprion, citalopram, clomiprimine, desipramine, moclobemide, nefazodone, parnate, pheneizine, selegiline, venlafaxine, carbamazapine, diphenyihydantoin, divaiproex, gabapentin, lamotrigine, guanfacine hydrochloride, clonidine, atenolol, metoprolol, propranolol, ginko biloba, kava kava, silbtrimin, amantadine, phototherapy, adderall, dexedrine, methamphetamine, methyiphenidate, and pemoline.

34. The method of claim 26, wherein said traditionally diagnosed mental disease comprises mood disorders and said second treatment is selected from the group consisting of glutamine, phenylalanine, tyrosine, moclobemide, parnate, phenelzine, selegiline, diphenylhydantoin, lamotrigine, guanfacine hydrochloride, clonidine, lorazepam, oxazepam, quazepam, temazepam, trizolam, atenolol, metoprolol, propranolol, ginko biloba, kava kava, st. john'"'"'s wort, phototherapy, adderall, dexedrine, methamphetamine, methylphenidate, pemoline, and phentermine.

35. The method of claim 26, wherein said traditionally diagnosed mental disease comprises personality disorders and said second treatment is selected from the group consisting of gaba, glutamine, phenylalanine, tyrosine, donepezil, buproprion, moclobemide, pamate, pheneizine, selegiline, venlafaxine, carbamazapine, diphenylhydantoin, divaiproex, gabapentin, lamotrigine, diazepam, atenolol, metoprolol, propranolol, lithium, ginko biloba, kava kava, st. john'"'"'s wort, phototherapy, adderall, dexedrine, methamphetamine, methylphenidate, pemoline, and phentermine.

36. The method of claim 26, wherein said traditionally diagnosed mental disease comprises a hypoactive sexual desire disorder and said second treatment is selected from the group consisting of buproprion, buspirone, moclobemide, pamate, phenelzine, and selegiline.

37. The method of claim 26, wherein said traditionally diagnosed mental disease comprises sleep disorders and said second treatment is selected from the group consisting of gaba, glutamine, phenylalanine, tyrosine, donepezil, buproprion, buspirone, citalopram, clomiprimine, desipramine, fluoxetine, fluvoxamine, moclobemide, parnate, phenelzine, selegiline, sertraline, venlafaxine, carbamazapine, diphenylhydantoin, divalproex, gabapentin, lamotrigine, guanfacine hydrochloride, clonidine, atenolol, metoprolol, propranolol, lithium, ginko biloba, kava kava, st. john'"'"'s wort, silbtrimin, phototherapy, adderall, dexedrine, methamphetamine, methylphenidate, pemoline, and phentermine.

38. The method of claim 26, wherein said traditionally diagnosed mental disease comprises somatoform disorders and said second treatment is selected from the group consisting of gaba, glutamine, phenylalanine, tyrosine, donepezil, buproprion, citalopram, fluvoxamine, moclobemide, parnate, phenelzine, selegiline, carbamazapine, diphenylhydantoin, divalproex, gabapentin, lamotrigine, atenolol, metoprolol, propranolol, ginko biloba, kava kava, st. john'"'"'s wort, amantadine, phototherapy, zolipidem, adderall, dexedrine, methamphetamine, methylphenidate, modafinil, pemoline, and phentermine.

39. The method of claim 26, wherein said traditionally diagnosed mental disease comprises substance-related disorders and said second treatment is selected from the group consisting of gaba, glutamine, phenylalanine, tyrosine, donepezil, fluvoxamine, moclobemide, parnate, phenelzine, selegiline, venlafaxine, carbamazapine, diphenylhydantoin, divalproex, gabapentin, lamotrigine, guanfacine hydrochloride, atenolol, metoprolol, propranolol, ginko biloba, kava kava, st. john'"'"'s wort, silbtrimin, phototherapy, adderall, dexedrine, methamphetamine, methylphenidate, and pemoline.