[ 0021 ] fig1 is a venn diagram showing the modulatory effects of serotonin and the activating effects of the catecholamines ( norepinephrine and dopamine ) in normal human functioning without depression . [ 0022 ] fig2 is venn diagram showing the symptoms of impaired modulation and activation secondary to reduced serotonin , norepinephrine and dopamine neurotransmission in depression . table 1 shows the serotonergic , noradrenergic and dopaminergic activity of some of the commonly available and more selective antidepressant medications . table 2 subtype reactivity energy sleep appetite demodulated increased same or decreased decreased increased deactivated decreased decreased increased same or increased mixed variable variable variable variable table 3 shows the relationship between ttdi scores and depressive subtypes . table 4 demonstrates an exemplary programming script for calculating the m and a scores on a palm pilot handheld computer utilizing a proprietary database management system for the palm operating system . alternate programs can be used for other personal digital assistants , handheld computers , laptop computers , and other computerized devices . turning now to a further description , in embodiment a of the invention , a 17 - item ( plus 2 historical or “ h ” items ) multiple choice test that identifies and quantifies two dimensions which have been found by the inventor to correlate with the need for serotonergic and catecholaminergic antidepressants , respectively . these questions are as follows , and are weighted as follows : a lot less than usual (− 2 ), somewhat less than usual (− 1 ), the same as usual ( 0 ), somewhat more than usual (+ 1 ), or a lot more than usual (+ 2 ) questions 2 - 15 have the same possible response possibilities as question 1 , and are as follows : questions 16 and 17 have a different scoring criteria , as follows 16 . if i were to take medication now , i would want it to help me feel . . . a lot calmer (+ 4 ), somewhat calmer (+ 2 ), no calmer than usual ( 0 ) 17 . if i were to take medication now , i would want it to help me feel . . . a lot more energetic (+ 4 ), somewhat more energetic (+ 2 ), no more energetic than usual ( 0 ) the dimensions are called the m score , measuring the need for central nervous system ( cns ) modulation , and the a score , measuring the need for cns activation . the scores can range as high as + 34 or as low as − 26 with 0 representing normal . positive scores tend to be directly proportional to the degree of depressive pathology present and the dosage of medication that may be required . small negative scores usually reflect better than average functioning , while large negative scores can reflect bipolar pathological states such as mania . in a typical application of the invention , a health professional administers the test to a patient in an outpatient or hospital treatment setting . when administered in its non - computerized form ( fig3 ), the test is scored by comparing the patient &# 39 ; s paper and pencil responses to a printed scoring key or by inputting the manual responses into computer containing the invention &# 39 ; s software program . when administered using a touch - screen monitor , keyboard or pda powered by that software , the patient &# 39 ; s scores and recommended treatment parameters can be provided instaneously to the treating professional . the test is divided into ten m items that measure impaired modulation and nine a items that measure reduced activation . as shown in eormulas 1 and 2 , the two items included in both series ( 11 . i &# 39 ; ve slept . . . 12 . i &# 39 ; ve eaten . . . ) affect scores in opposite directions , i . e ., sleeping excessively adds 2 to the a score and subtracts 2 from the m score and eating excessively adds 2 to the a score and subtracts 2 from the m score . when positive , the historical items 18 and 19 may add weight to the treatment recommendations , but are not included in the m or a scores , which reflect current states only . when patients first seek treatment these scores typically reflect the overall level of depression . this is quantified as the d score , which equals the total of the positive m and a scores . negative m and a scores are not permitted to lower the d score because the severity of a depressive subtype is not reduced by lack of symptoms in a non - contributory dimension . for example , a patient whose a score is elevated is no less depressed simply because his or her ability to manifest anger or irritability ( components of the m score ) is less than usual . the negative m score in such a case may actually be a function of the reduced energy associated with severe deactivation . ( a ) if m = 12 and a = 11 , then d = 23 . this would be an example of the mixed subtype . ( b ) if m =− 3 and a = 14 ; then d = 14 . this would be an example of the deactivated subtype . ( c ) if m = 15 and a =+ 1 , then d = 16 . this would be an example of the demodulated subtype . while the d score resembles the scores derived on traditional unidimensional depression tests such as the hamilton depression inventory , the m and a subscales are unique . when the m score is greater than 4 the invention classifies the patient as demodulated and recommends treatment with a serotonergic antidepressant . correspondingly , when the a score is greater than 4 the invention identifies the patient as deactivated and recommends treatment with a catecholaminergic antidepressant . when both m and a scores are above 4 the invention diagnoses a mixed state and calls for dual - mechanism antidepressant treatment . no other depression test that the inventor is aware of offers this type of pharmacological guidance . to add even more clinical usefulness , there are three levels of severity associated with each state : mild , moderate and severe . mild states are defined as those with m or a scores from 5 to 9 . moderate states are those with m or a scores from 10 to 14 . severe states have m or a scores of 15 or more . recommended treatment dosages increase with level of severity . the test is usually repeated two to four weeks after receiving treatment to assess improvement . if the medication is working , the difference between the patient &# 39 ; s present condition and his baseline “ normal ” state will have decreased , resulting in d , m and a scores approaching 0 . if that is not the case , as for example when a demodulated patient ( elevated m score only ) has become secondarily deactivated by his serotonergic medication ( decreased m score , newly elevated a score ), the invention recommends treating this effect of initial treatment with the appropriate agent ( e . g ., combining the serotonergic agent with a catecholaminergic antidepressant ), typically resulting in improvement or recovery within a few weeks . again , the five possible responses to items 1 through 15 are weighted either : − 2 , − 1 , 0 , + 1 and + 2 ( m items ) or + 2 , + 1 , 0 , − 1 , or − 2 ( a items ). for example , item 1 , an m item , is scored as follows i &# 39 ; ve been anxious a lot less somewhat less the same somewhat more a lot more than usual than usual as usual than usual than usual − 2 − 1 0 + 1 + 2 feeling a lot more anxious than usual ( the demodulated response ) raises the m score by 2 , whereas feeling a lot less anxious than usual ( the more modulated response ) lowers it by 2 . feeling the same as usual leaves the score unaffected . i &# 39 ; ve felt energetic a lot less somewhat less the same somewhat more a lot more than usual than usual as usual than usual than usual + 2 + 1 0 − 1 − 2 feeling a lot more energetic than usual ( the more activated response ) lowers the a score by 2 , while being a lot less energetic than usual ( the deactivated response ) raises it by 2 . the invention reverses the choices associated with increased pathology on the two scales in this manner to reduce false positive and negative errors caused by the repetitive selection of the same choice and to provide an immediate indication to the clinician of discrepancies between test - taking behavior and clinical manifestations of deactivation and / or demodulation . items 16 and 17 have only 3 choices , but are weighted more heavily than the other items . item 16 contributes to the m score as shown : if i were to take medication now , i would want it to help me feel somewhat no calmer a lot calmer calmer than usual + 4 + 2 0 if i were to take medication now , i would want it to help me feel a lot more somewhat no more energetic energetic more energetic than usual + 4 + 2 0 methods for calculating the total m and a scores are shown in formulas 1 and 2 , respectively , for a paper and pencil calculation , and in table 4 , which is a program script for a calculating the m and a scores on a palm pilot ® handheld computer utilizing a proprietary database management system for the palm operating system . in table 4 , the “$” symbol designates field values followed by a number equal to the item number + 3 , e . g ., “$ 4 ” is the raw score for item 1 . raw scores , which are a function of the requirements of the software used , are corrected when necessary by adding or subtracting the difference between raw and real scores , which in this example is − 15 for the m score and + 12 for the a score . ( these compensatory calculations are required in this case because the palm pilot ® database management system restricts the 5 choices per item to the integers 1 through 5 rather than − 2 through + 2 .) other programming platforms used by the invention , e . g ., on windows and macintosh computers , utilize other scoring algorithms to arrive at identical results . moreover , because of their larger screens , laptop and desktop computers can offer more detailed graphic and text - based information in connection with the invention &# 39 ; s , software , an example of which is shown in fig4 . for example , when a score of + 1 or + 2 is obtained for item 14 ( thinking about death “ somewhat ” or “ a lot more than usual ”), a warning message appears on the screen to evaluate the patient &# 39 ; s suicidal potential with language proportional to the potential danger , and color graphics are used to reinforce these warnings . the invention graphically depicts changes over time in the patient &# 39 ; s condition , permitting monitoring and modification of treatment as needed . embodiment b of the invention utilizes items 11 , 16 and 17 plus two more m and two a scale items (“ im x ”, “ im y ”, “ ia x ”, “ ia y ”) to guide treatment . im x , im y , ia x and ia y can be selected by the professional user during the software set up process . the formulas for calculating m and a scores in this version are : m = 2 ( im x + im y − i 11 + i 16 ) formula 1 a = 2 ( ia x + ia y + i 11 + i 17 ) formula 2 multiplying by 2 brings the scores derived in embodiment b into the same range as those of embodiment a . while this shorter form may be less comprehensive and accurate than the 17 item version , it can still provide useful guidance in selecting and managing antidepressant treatment . it further offers the professional an opportunity to abbreviate and customize the test to fit his own practice needs . in its psychobiological form , the invention utilizes data from physiological measures such as the q - eeg , serum platelet serotonin assay , and the urinary mhpg to derive the m and a scores . while at the present time , these methods are far more expensive and cumbersome than embodiments a and b , new developments in neuroscience suggest that more cost - effective methods will soon be available . these approaches will utilize the principle on which the invention is based , i . e ., inferring cns serotonin and catecholamine levels to determine the most effective antidepressant treatment , by measuring various physical concomitants of that neurotransmitter activity . for example , recent work in neurogenetics suggests that it may soon be possible for physicians to determine in seconds whether patients have the diathesis ( genetic tendency ) for serotonin or catecholamine impairment or both . the invention will provide a method for doctors to combine or substitute such physical data for the clinical data derived using the items in fig3 . the present invention covers the modifications and variations of this invention provided they come within the scope of the appended claims and their equivalents . in this context , equivalents mean each and every implementation for carrying out the functions recited in the claims , even those not explicitly described herein .
a method for determining the appropriate medication for a patient suffering from depression . a patient will take a questionnaire wherein the patient answers a number of questions with scaled responses concerning the degree to which the patient &# 39 ; s mental state is affected by at least one or both of impaired modulation and impaired activation . next , the patient &# 39 ; s answers will be processed to arrive at scores for the at least one impaired modulation and impaired activation . depending upon the patient &# 39 ; s scores for demodulation and deactivation , at least one medication which affects the at least one impaired modulation and impaired activation is recommended .