Electroencephalography based systems and methods for selecting therapies and predicting outcomes

• US 20030135128A1
• Filed: 07/11/2002
• Published: 07/17/2003
• 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.
• Granted Patent: US 7,177,675 B2
• Time in Patent Office: Days
• 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 a first treatment based on neurophysiologic information from a subject independent of a behavioral mental disease diagnosis of or behavioral data from the subject, the method comprising the steps of:

scaling the neurophysiologic information to enable comparison with stored neurophysiologic information obtained from a data source;

computing at least one indicative variable from the neurophysiologic information; and

evaluating the at least one indicative variable with aid of at least one rule to predict the outcome of the first treatment prior to actually administering the first treatment.

2. The method of claim 1 wherein neurophysiologic information comprises electroencephalogram recordings recorded by electrodes placed in accordance with the International 10/20 system.

3. The method of claim 1 further including the step of identifying the at least one indicative variable by screening a response database comprising pre-treatment neurophysiologic information and response to the first treatment in the form of active-treatment neurophysiologic information from a plurality of subjects.

4. The claim of method 3 further including the step of identifying clusters of pre-treatment neurophysiologic information associated with subjects having similar responses to the first treatment as part of the screening step.

5. The method of claim 4 further including the steps of identifying a cluster by identifying a region in a multidimensional space defined by a range of values of unitary variables such that a threshold number of subjects having a common response to the first treatment are included in the region;

and identifying the range of values of unitary variables describing the region.

6. The method of claim 5 wherein the threshold number is 80% whereby 80% of subjects having a common response to the first treatment are included in the cluster.

7. The method of claim 5 further including the step of combining the set of unitary variables having values shared by subjects within a cluster to form a multivariable and employing the multivariable as the at least one indicative variable.

8. The method of claim 5 wherein each of the similar responses is a clinical global improvement score selected from the set consisting of an integer in the range [−

1to 3] such that ‘

−

1’

indicates adverse therapeutic entity effect, ‘

0’

indicates no improvement, ‘

1’

indicates minimal improvement, ‘

2’

indicates moderate improvement and ‘

3’

indicates complete absence of symptoms.

9. The method of claim 5 wherein each of the similar responses is a measure of the difference between the active-treatment neurophysiologic information and a distribution of neurophysiologic information of age-matched reference subjects.

10. The method of claim 1 further including the step of including the outcome of the first treatment in a report.

11. The method of claim 1 further including the steps of applying a plurality of rules associated with a plurality of indicative variables to the neurological information from a first data source;

evaluating whether the rules indicate substantial agreement with one of a plurality of outcomes following the-first treatment; and

including, in response to such an indication, the one of a plurality of outcomes following the first treatment in a report.

12. The method of claim 1 wherein the first treatment is specified in response to a traditional diagnosis of mental disease.

13. The method of claim 12 wherein the first treatment is in a list of treatments specified in response to the traditional diagnosis of mental disease whereby effective treatments in the list are rapidly identified.

14. The method of claim 13 further including the steps of comparing a result of applying at least one rule to the neurological information from the subject to at least one expected result associated with a second treatment, the second treatment not in the list of treatments based on the neurological information from the subject;

and identifying, in response to detecting a similarity between the at least one expected result and the result, the second treatment as a possible treatment in a report.

15. The method of claim 14 wherein the traditional diagnosis is major depressive disorder and the second treatment is selected from the group consisting of glutamine, phenylalanine, and tyrosine.

16. The method of claim 14 wherein the traditional diagnosis is psychological factors affecting medical condition, atypical asthma and the second treatment is selected from the group consisting of glutamine, phenylalanine, tyrosine, bupropion, pamate, moclobemide, phenalzine, seligeline, venlafaxine, carbamazapine, gabapentin, lamotrigine, ginko biloba, dexedrine, methapmphetamine, methylphenidate, and pemoline.

17. The method of claim 14 wherein the traditional diagnosis is one of anxiety disorders and the second treatment is selected from the group consisting of gaba, glutamine, phenylalanine, tyrosine, buproprion, citalopram, fluvoxamine, citalopramine, clomipramine, moclobemide, parnate, phenalzine, seligeline, carbamazapine, divalproex, gabapentin, lamotrigine, guanfacine hcl, clonidine, atenolol, metopolol, propranolol, lithium, ginko biloba, kava kava, st. john'"'"'s wort, amantadine, phototherapy at 10000 lux, adderall, dexedrine, methapmphetamine, methylphenidate, modafinil, and pemoline.

18. The method of claim 14 wherein the traditional diagnosis is one of psychological factors affecting medical condition, disorders usually first diagnosed in infancy, childhood, or adolescence and the second treatment is selected from the group consisting of gaba glutamine, phenylalanine, tyrosine, donepezil, buproprion, citalopram, clomiprimine, doxepin, fluoxetine, fluvoxamine, moclobemide, parnate, phenalzine, seligeline, trazodone, venlafaxine, carbamazapine, diphenylhydantoin, divalproex, gabapentin, lamotrigine, guanfacine hcl, clorazepate, diazapam, oxazepam, quazepam, atenolol, metopolol, propranolol, lithium, ginko biloba, kava kava, st. john'"'"'s wort, silbtrimin, amantadine, phototherapy at 10000 lux, adderall, dexedrine, methapmphetamine, methylphenidate, modafinil, and phentermine.

19. The method of claim 14 wherein the traditional diagnosis is one of eating disorders and the second treatment is selected from the group consisting of gaba, glutamine, phenylalanine, tyrosine, donepezil, buproprion, moclobemide, pamate, phenalzine, seligeline, venlafaxine, carbamazapine, diphenylhydantoin, divalproex, gabapentin, lamotrigine, diazapam, lorazepam, atenolol, metopolol, propranolol, lithium, ginko biloba, kava kava, st. john'"'"'s wort, amantadine, phototherapy at 10000 lux, zolipidem, adderall, dexedrine, methapmphetamine, methylphenidate, modafinil, pemoline, and phentermine.

20. The method of claim 14 wherein the traditional diagnosis is one of delirium, dementia and amnestic and other cognitive disorders and the second treatment is selected from the group consisting of glutamine, phenylalanine, tyrosine, donepezil, amitriptyline, buproprion, fluxotine, moclobemide, parnate, phenalzine, seligeline, venlafaxine, carbamazapine, divalproex, gabapentin, lamotrigine, atenolol, metopolol, propranolol, lithium, ginko biloba, silbtrimin, amantadine, phototherapy at 10000 lux, zolipidem, adderall, dexedrine, methapmphetamine, methylphenidate, modafinil, pemoline, and phentermine.

21. The method of claim 14 wherein the traditional diagnosis is impulse control disorders not elsewhere classified and the second treatment is selected from the group consisting of glutamine, phenylalanine, tyro sine, donepezil, buproprion, citalopram, clomiprimine, desipramine, moclobemide, nefazodone, parnate, phenalzine, seligeline, venlafaxine, carbamazapine, diphenylhydantoin, divalproex, gabapentin, lamotrigine, guanfacine hcl, clonidine, atenolol, metopolol, propranolol, ginko biloba, kava kava, silbtrimin, amantadine, phototherapy at 10000 lux, adderall, dexedrine, methapmphetamine, methylphenidate, and pemoline.

22. The method of claim 14 wherein the traditional diagnosis is one of mood disorders and the second treatment is selected from the group consisting of glutamine, phenylalanine, tyrosine, moclobemide, parnate, phenalzine, seligeline, diphenylhydantoin, lamotrigine, guanfacine hcl, clonidine, lorazepam, oxazepam, quazepam, temazepam, trizolam, atenolol, metopolol, propranolol, ginko biloba, kava kava, st. john'"'"'s wort, phototherapy at 10000 lux, adderall, dexedrine, methapmphetamine, methylphenidate, pemoline, and phentermine.

23. The method of claim 14 wherein the traditional diagnosis is one of other codes and conditions and the second treatment is selected from the group consisting of gaba, glutamine, phenylalanine, tyrosine, donepezil, buproprion, citalopram, clomiprimine, fluvoxamine, moclobemide, notriptyline, parnate, phenalzine, seligeline, trazodone, venlafaxine, carbamazapine, divalproex, gabapentin, lamotrigine, guanfacine hel, clonidine, atenolol, metopolol, propranolol, ginko biloba, kava kava, st. john'"'"'s wort, amantadine, phototherapy at 10000 lux, zolipidem, adderall, dexedrine, methapmphetamine, methylphenidate, pemoline, and phentermine.

24. The method of claim 14 wherein the traditional diagnosis is one of personality disorders and the second treatment is selected from the group consisting of gaba, glutamine, phenylalanine, tyrosine, donepezil, buproprion, moclobemide, pamate, phenalzine, seligeline, venlafaxine, carbamazapine, diphenylhydantoin, divalproex, gabapentin, lamotrigine, diazapam, atenolol, metopolol, propranolol, lithium, ginko biloba, kava kava, st. john'"'"'s wort, phototherapy at 10000 lux, adderall, dexedrine, methapmphetamine, methylphenidate, pemoline, and phentermine.

25. The method of claim 14 wherein the traditional diagnosis is hypoactive sexual desire disorder and the second treatment is selected from the group consisting of buproprion, buspirone, moclobemide, pamate, phenalzine, and seligeline.

26. The method of claim 14 wherein the traditional diagnosis is one of sleep disorders and the second treatment is selected from the group consisting of gaba, glutamine, phenylalanine, tyrosine, donepezil, buproprion, buspirone, citalopram, clomiprimine, desipramine, fluoxetine, fluvoxamine, moclobemide, parnate, phenalzine, seligeline, sertraline, venlafaxine, carbamazapine, diphenylhydantoin, divalproex, gabapentin, lamotrigine, guanfacine hcl, clonidine, atenolol, metopolol, propranolol, lithium, ginko biloba, kava kava, st. john'"'"'s wort, silbtrimin, phototherapy at 10000 lux, adderall, dexedrine, methapmphetamine, methylphenidate, pemoline, and phentermine.

27. The method of claim 14 wherein the traditional diagnosis is one of somatoform disorders and the second treatment is selected from the group consisting of gaba, glutamine, phenylalanine, tyrosine, donepezil, buproprion, citalopram, fluvoxamine, moclobemide, parnate, phenalzine, seligeline, carbamazapine, diphenylhydantoin, divalproex, gabapentin, lamotrigine, atenolol, metopolol, propranolol, ginko biloba, kava kava, st. john'"'"'s wort, amantadine, phototherapy at 10000 lux, zolipidem, adderall, dexedrine, methapmphetamine, methylphenidate, modafinil, pemoline, and phentermine.

28. The method of claim 14 wherein the traditional diagnosis is one of substance-related disorders and the second treatment is selected from the group consisting of gaba, glutamine, phenylalanine, tyrosine, donepezil, fluvoxamine, moclobemide, parnate, phenalzine, seligeline, , venlafaxine, carbamazapine, diphenylhydantoin, divalproex, gabapentin, lamotrigine, guanfacine hcl, atenolol, metopolol, propranolol, ginko biloba, kava kava, st. john'"'"'s wort, silbtrimin, phototherapy at 10000 lux, adderall, dexedrine, methapmphetamine, methylphenidate, and pemoline.

29. A method for identifying a treatment for a subject based on pretreatment neurophysiologic information from the subject and a desired outcome, the method comprising the steps of:

scaling the pretreatment neurophysiologic information to enable comparison with stored neurophysiologic information obtained from a data source;

constructing clusters of pretreatment neurophysiologic information in a treatment-response database comprising pre-treatment neurophysiologic information and associated response score and active-treatment neurophysiologic information for each of a plurality of subjects by considering pretreatment neurophysiologic information associated with the desired outcome;

identifying at least one cluster to which the pretreatment neurophysiologic information of the subject belongs, the at least one cluster defining a range of neurophysiologic information; and

identifying at least one treatment associated with the at least one cluster.

54. A method for identifying a treatment for a subject based on pretreatment neurophysiologic information from the subject and a desired outcome, the method comprising the steps of:

transmitting information from a first site, the transmitted information comprising the pretreatment neurophysiologic information and the desired outcome; and

receiving information at a second site, wherein the received information comprising an indication of at least one treatment that was determined by the method of claim 29 from the transmitted information.

55. The method of claim 54 wherein the information is transmitted to and received from a processing site performing the method of claim 29.

56. The method of claim 55 wherein the processing site is remotely located from the first and the second site.

57. The method of claim 55 wherein the processing site is colocated with the first or with the second site.

58. The method of claim 54 wherein the first and the second site are colocated.

59. The method of claim 54 wherein the first and the second site are remotely located.

60. The method of claim 54 further comprising

transmitting at least part of the received and at least part of the transmitted information to a reviewing site;

and

reviewing the quality of the transmitted information in view of the received information.

61. A system for identifying a treatment for a subject based on pretreatment neurophysiologic information from the subject and a desired outcome, the method comprising:

a transmitting device at a first site, for transmitting information comprising the pretreatment neurophysiologic information and the desired outcome; and

a receiving device at a second site, for receiving information comprising an indication of at least one treatment that was determined by the method of claim 29 from the transmitted information.

62. A program product comprising a computer-readable medium having encoded instructions for causing a computer system to perform the methods of claims 29 or 54.

30. A method of building a treatment-response database to facilitate predicting treatments having a desirable outcome, avoiding ineffective or harmful treatments, and defining treatment-based conditions, the method comprising the steps of:

storing initial neurophysiologic information associated with a subject in association with a treatment administered to the subject, a active-treatment neurophysiologic information associated with the subject and a magnitude-outcome of the treatment associated with the subject, the magnitude-outcome reflecting the extent of change rather than change in a particular feature whereby effect of the treatment on different mental diseases having various distinct features can be compared; and

obtaining such information from at least a specified number of subjects.

31. A treatment-response database comprising:

initial neurophysiologic information for each of a plurality of subjects;

treatment information for the each of a plurality of subjects; and

indicator of clinical treatment outcome for the each of a plurality of subjects.

32. A method for identifying a condition for which a treatment is available, the method comprising the steps of:

obtaining initial neurophysiologic information from a plurality of subjects;

obtaining active-treatment neurophysiologic information for the plurality of subjects following administration to each of the plurality of subjects a treatment;

obtaining an outcome for each of the plurality of subjects following the treatment;

clustering initial neurophysiologic information from subjects exhibiting a desirable outcome following the treatment to obtain at least one cluster, wherein a cluster is bounded by values of neurophysiologic information; and

identifying a range of values of neurophysiologic information defining the at least one cluster as a condition precedent to be satisfied by a new initial neurophysiologic information of a new subject prior to administration of the treatment.

33. A method of estimating a function of a therapeutic entity on a subject of interest, the method comprising the steps of:

receiving a neurophysiologic information of the subject;

identifying clusters of neurophysiologic information, each of the clusters defined by a range of values for neurophysiologic information, in a treatment-response database comprising neurophysiologic information and the effect of treatments thereon, such that the neurophysiologic information of the subject satisfies respective ranges of the identified clusters;

identifying treatments associated with the identified clusters;

determining whether any of the treatments is similar to an administration of the therapeutic entity; and

inferring the function of the therapeutic entity based on the function of the identified treatments.

34. A method of reevaluating therapeutic entity testing data, that does not reveal a desired effect of a therapeutic entity on subjects, to identify at least one condition for using the therapeutic entity on at least one subset of subjects, the method comprising the steps of:

identifying subjects having initial neurophysiologic information and a desired response to the therapeutic entity in the therapeutic entity testing data;

clustering initial neurophysiologic information corresponding to the subjects having a desirable response to administration of the therapeutic entity;

identifying at least one cluster that satisfies at least one of the set consisting of a prescribed threshold;

identifying a range of a parameter defining the at least one cluster; and

specifying the range of the parameter as a condition for pre-screening subjects for administration of the therapeutic entity whereby ensuring that subjects for administering the therapeutic entity also have neurophysiologic information belonging to the at least one cluster.

35. A method of generating rules for predicting suitability of a treatment for a subject based on the subject'"'"'s neurophysiologic information as opposed to a traditional diagnosis of a mental disorder, the method comprising the steps of:

clustering initial neurophysiologic information from a plurality of subjects such that each cluster is associated with at least one treatment outcome;

evaluating neurophysiologic information in a cluster to determine at least one feature of the neurophysiologic information that is common to the cluster; and

generating a rule based on the at least one feature to determine whether a new initial neurophysiologic information from a new subject belongs to the cluster whereby predicting the same outcome for the treatment as that associated with the cluster.

36. The method of using a treatment-response database comprising a treatment, initial neurophysiologic information, active-treatment neurophysiologic information and an outcome of the treatment, the method comprising the steps of:

converting into univariate measures;

extracting multivariables of interest from the univariate measures; and

storing multivariables in the treatment-response database whereby facilitating subsequent database searches.

37. A portable device for evaluating and suggesting a treatment, the device comprising:

an input module for receiving neurophysiologic information from a subject;

a rule module for providing rules for a specific variables in the neurophysiologic information;

a correspondence module to detect a match between a result of applying rules to variables in the neurophysiologic information and the expected result for a treatment; and

an output module for indicating an outcome for at least one treatment.

38. A method of establishing an approved use of a therapeutic agent in treating patients having a disorder, wherein said agent has not heretofore been approved for treatment of said disorder in approved clinical practice, the method comprising:

indicating said agent for treatment of said disorder where neurophysiologic information obtained from one or more patients having said condition indicates that said agent has therapeutic effectiveness in reference patients, whether or not the reference patients have been diagnosed with said disorder.

39. A method of treating a patient having a behaviorally diagnosed psychiatric disorder other than an attention-deficit/hyperactivity disorder, comprising:

administering a therapeutically effective dose of methylphenidate.

40. A method of recommending treatment for a patient having a behaviorally diagnosed psychiatric disorder, comprising:

indicating one or more therapeutic agents in dependence on neurophysiologic information obtained from said patient, wherein the therapeutic agents are indicated independently of the identity of said disorder, and

recommending one of more of the indicated therapeutic agents wherein said patient is without externally observable anatomic pathology.

41. A method of recommending treatment for a patient having a behaviorally diagnosed psychiatric disorder, comprising:

indicating therapeutic agents by comparing quantified neurophysiologic information obtained from the patient with quantified neurophysiologic information obtained from individuals in one or more reference populations of individuals, wherein the information from at least one reference population includes treatment modalities for individuals with behaviorally diagnosed psychiatric disorders, and

recommending one or more of the indicated therapeutic agents.

42. A method of recommending treatment for a patient having a behaviorally diagnosed psychiatric disorder, comprising:

determining the effects of one or more therapeutic agents on quantified neurophysiologic information obtained from individuals in one or more reference populations of individuals, and

recommending one or more therapeutic agents independence on a comparison of quantified neurophysiologic information obtained from said patient with said determined effects of one or more therapeutic agents, wherein therapeutic agents are recommended independently of the identity of said disorder.

43. A method of correlating patient with therapeutic agents, wherein said patients have behaviorally diagnosed psychiatric disorders, the method comprising:

for each said patient and each said agent, determining a level of correlation between said patient and said agent by;

indicating a relatively high level of correlation between said patient and said agent if quantified neurophysiologic information obtained from said patient correlates with quantified neurophysiologic information obtained from at least one reference individual of one or more reference populations of individuals, wherein the information from at least one reference population includes treatment modalities for individuals, and wherein information for at least one treatment modality for said reference individual indicates said reference individual was relatively effectively treated with said agent, and

indicating a relatively low level of correlation between said patient and said agent if quantified neurophysiologic information obtained from said patient correlates with quantified neurophysiologic information obtained from at least one reference individual of one or more reference populations of individuals, and wherein information for at least one treatment modality for said reference individual indicates said reference individual was relatively ineffectively treated with said agent.

44. A method for classifying physiologic brain imbalances, comprising:

comparing quantified neurophysiologic information from a patient with neurophysiologic information from a reference population of individuals to produce a group of differences for the patient,

organizing said differences by neurophysiologic output measurements to provide a differences profile of the physiological state of the patient'"'"'s brain function,

comparing said differences profile of the patient with neurophysiologic information from a second reference population who are symptomatic for physiologic brain imbalances to produce a group of similarities for the patient,

organizing said similarities by neurophysiologic output measurements to provide a similarities profile of the physiological state of the patient'"'"'s brain function,

correlating said similarities profile of the patient with a series of treatment modalities for the second reference group to produce a treatment recommendation.

45. A method for classifying physiologic brain imbalances, comprising:

comparing quantified neurophysiologic information from a patient with neurophysiologic information from a reference population of individuals to produce a group of differences for the patient, and

organizing the differences by neurophysiologic output measurements to provide a differences profile of the physiological state of the patient'"'"'s brain function.

46. A method for analyzing physiologic brain imbalances of a patient, comprising:

comparing quantified neurophysiologic information from the patient with neurophysiologic information from a reference population of individuals who are symptomatic for physiologic brain imbalances to produce a group of similarities for the patient, and

organizing the similarities by neurophysiologic output measurements to provide a similarities profile of the physiological state of the patient'"'"'s brain function.

47. A method for classifying physiologic brain imbalances, comprising:

comparing quantified neurophysiologic information from a patient with neurophysiologic information from a reference population of individuals to produce a group of differences for the patient; and

organizing the differences by neurophysiologic output measurements to provide a differences profile of the physiological state of the patient'"'"'s brain function.

48. A method for the classification, diagnosis, and treatment of a physiologic brain imbalance of a patient at a remote location, comprising:

sending the neurophysiologic information of the patient from the remote location to a central processing location,

comparing the sent information at the central processing location with multivariate neurophysiologic output measurements collected from a reference population of individuals to obtain a brain profile,

associating at the central processing location the brain profile to brain profiles indicative of brain pathologies to produce an association, and

sending to the remote location a treatment recommendation based on the association.

49. A method suitable for determining the effect of a new or known drug on the CNS system of a patient, comprising:

selecting at least one patient,

administering the drug to the patient,

obtaining the patient'"'"'s post administration, neurophysiologic information,

analyzing the patient'"'"'s post administration, neurophysiologic information to determine the effect of the drug on the CNS system of the patient.

50. A method for treating physiologic brain imbalances, comprising:

obtaining neurophysiologic information from a patient,

quantifying the neurophysiologic information, and

correlating the neurophysiologic information to therapy responsivity profiles.

51. A method of prescribing multiple treatments to a subject with the aid of a treatment-response database, the method comprising the steps of:

obtaining neurophysiologic information from the subject;

identifying at least one treatment option with the aid of the treatment-response database;

selecting a first treatment, in response to identification of multiple treatment options, one treatment;

administering the first treatment to the subject;

adjusting the first treatment in accordance with an effect of the treatment on neurophysiologic information of the subject; and

selecting a second treatment in accordance with an effect of the treatment on neurophysiologic information of the subject.

52. A method of generating a report reflecting a prospective estimate of a response to a treatment, the method comprising the steps of:

reporting a class of an agent along with specific agents within the class such that the specific agents are indicated for a treatment of a subject based on a neurophysiologic information of the subject and a treatment-response database;

ordering multiple classes in order of significance;

representing responsivity to at least one treatment in the report by a responsivity code; and

ordering multiple agents in order of the responsivity code.

53. A method of establishing an approved use of a therapeutic agent in treating patients having a disorder, said agent has not heretofore been approved for treatment of said disorder in approved clinical practice, the method comprising:

indicating said agent for treatment of said disorder where EEG information obtained from one or more patients having said condition indicates that said agent has therapeutic effectiveness in reference patients, whether or not the reference patients have been diagnosed with said disorder.