http://exhibits.library.stonybrook.edu/mfp/files/original/6ae8392f9c68d3b213edf8358a9597ac.pdf bdf1e6bcabb4c1d8c82905940f4f07c2 PDF Text Text REPRINTED FROM E. ROTHLIN (Editor) NEURO-PSYCHOPHARMACOLOGY VOL. 2 (1961) Proceedings of the 2nd International Meeting of the Collegium Internationale Neuro-Psychopharmacologicum IBasle 1960 ELSEVIERPUBLISHINGCOMPANY AMSTERDAM �Reprinted from: E. ROTHLIN (Editor), Neuro-Psychopharmacology, V01. 2 (1961), Proceedings of the 2nd International Meeting of the Collegium Internationale Ne'uro-Psychopharmacologicum, Basle 1960 ‘ NEUROPSYCHOLOGIC RESPONSE PATTERNS OF SOME PSYCHOTROPIC DRUGS MAX POLLACK, ERIC KARP, GEORGE KRAUTHAMER, DONALD F. KLEIN AND MAX FINK Department of Experimental Psychiatry, Hillside Hospital, Glen Oaks, L.I., N. Y. (U.S.A.) PROBLEM This study of the mode of action of some of the newer psychotropic agents was formulated within the framework of a neurophysiologic-adaptive hypothesisl. The concept, derived from earlier work on convulsive therapiesz, views clinical behavioral change as a resultant of the interaction of alterations in brain function and the personality of the subject. The present study emphasizes the question of pattern speciﬁcity of drug action and its relation to individual differences in behavioral response. The particular drugs utilized, chlorpromazine3 and imipramine“, were selected on the basis of pilot studies in this institution in which their effectiveness in altering physiologic and behavioral patterns had been demonstrated. This presentation is an interim report of a study currently in progress. METHOD Consecutive referrals for drug administration in a voluntary psychiatric hospital were assigned at random to one of the three drug regimens: (I) chlorpromazine with 1.2% procyclidine added, (2) imipramine, and a (3) placebo. Medication was administered in liquid vehicle in a ﬁxed dosage schedule, to a maximum in four weeks. Chlorproma— zine was begun at 300 mg and increased to 1200 mg daily and imipramine from 75 to 300 mg. Patients continued to be seen three times weekly in individual psychotherapeutic interviews during the period of drug treatment. Analysis of the data is limited to the ﬁrst 48 cases. These patients are not chronically ill—the majority being admitted for their ﬁrst hospitalization from the community, and a smaller percentage rehospitalized for a recurrence of their illness. Their mean age was 35.5 years, and years of schooling was 11.9 years. Approximately 57% were diagnosed in the group of schizophrenias, 28% as affective psychoses and I 5 0/5 psycho— neuroses and character disorders. Patients were examined in a four day period prior to drug administration on a ﬁxed schedule of physiological and psychological procedures which was repeated during the sixth week of drug treatment. RESULTS Group changes in some of the measures with drug treatments are shown in Table I. The EEG patterns measured quantitatively through electronic frequency analysis5 References 1). 384. �382 M. POLLACK et al. show that imipramine and chlorpromazine differ signiﬁcantly from the control group and from each other. There was a signiﬁcant reduction in the total electrical activity in the imipramine group, while there was an increase both in the amount of slow-wave activity and the slow to fast activity ratios in the chlorpromazine group. TABLE I GROUP CHANGES WITH DRUG TREATMENT EEG Slow/fast ratio Total activity Delta ratio Control I rmpramme Chlarpromazine w it h Procyc l {dine 0 0 co 0| ++ 0 ++ Perceptual Critical ﬂicker fusion 0 Motor Pursuit—rotor Tapping speed Hand steadiness Intellectual WechslerBellevue IQ O O ++ 05 01 —— + O O O + o o Behavorial rating Symptom complaint — 0 Depression + Increase p. + + Increase p. o —- — o No change — Decrease —— Decrease P P 0.05 0.01 The reduction in the critical ﬂicker—fusion (CFF) threshold is noted only for the chlorpromazine group. This test correlated with the increase in EEG slow-wave activity.The motor tests also reﬂect a differential drug effect with unsteadiness increased by the two drugs, tapping rate unaltered, and pursuit rotor improved only by the imipramine group. The greatest change in intellectual functioning was scored by the no-drug group, present to a lesser degree in the imipramine group and absent in the chlorpromazine group. The lack of equivalent changes for the drug groups may reﬂect an inhibition of the expected practice effect. In clinical behavior, all groups showed a reduction in complaints on self-rating as measured by the Johns Hopkins Scale, with the reduction being greater for the drug groups. In the Clyde Mood Scale, a Q—sort behavioralrating, there was a quantitative reduction in both the patient’s and the doctor’s ratings of “depression” in the drug group but not for the control group. While these data indicate a pattern that suggests differential drug activity, there was marked heterogeneity within each group on each measure. Table II shows the changes in CFF for each subject. The number within each box refers to the evaluation of a change in behavior, rated on a four—point scale by the evaluating psychiatrist. These are global changes in behavior ratings, and are not necessarily equivalent to References p. 384. �NEUROPSYCHOLOGIC RESPONSE PATTERNS 383 ratings of improvement. (Note that the ratings of behavioral change “3” and “4” were most often associated with changes in CFF of more than one cycle.) Although the difference in mean CFF score between imipramine and the control group was not signiﬁcant, the difference in variability (F ratio) was signiﬁcant (P = 0.05). The control group showed a narrow range of change, varying from +1 to ——2 cycles. In contrast, the imipramine group ranged from +2 to ——5 cycles, and chlorpromazine from zero to ——6 cycles. The chlorpromazine group change was in the downward direction only. The individual differences in the alterations of CFF threshold II TABLE CHANGE IN FLICKER FUSION THRESHOLD WITH DRUG TREATMENT Contrél +2 +1 o —1 —2 __3 Imipmmine 2 2 I 4 4 2 I 3 3 1 3 1 1 3 ‘ 2 2 2 I I 3 I I 1 1 3 1 4 2 4 2 ——4 —5 —6 Mean diﬂ. Change in C.P.S. Chlorpromazine Behavorial with Procyclidine change 2 1 4 4 4 4 4 3 2 3 4 4 3 2 ——o.6 ——o.4 TABLE None Mild 3 Moderate 4 Marked I 2 ——3.1 III ‘CHANGE IN EEG (SLOW/FAST/RATIO) WITH DRUG TREATMENT 1mm —.4 ——.3 ——.2 —.1 o +.1 +.2 +.3 +4 +5 2 2 I 2 1 I 4 I 1 3 2 11 1 443111 3 2 322 4 4 3 4 1 3 4 4 3 4 1 1 1 3 3 1 3:22:22“ INone 2 3 Mild Moderate 4 Marked 4 +.6 +-7 4 4 >+-7 Mean diff. Change in slow/fast ratio firearm +.026 +.or4 +.401 are also observable in the electroencephalographic indices. Table III shows the changes in the slow to fast EEG activity ratio demonstrating a wide range in changes for the controls, a similar pattern for the imipramine group, but a change in only one direc— tion—that of increased slowing for the chlorpromazine group. The mean increase in slow-wave activity for the chlorpromazine group was more than I5 times that of the References p. 384. �384 M. POLLACK et al. control and imipramine groups. There was also a signiﬁcant relation between the increase in slow-wave activity and increasing age with chlorpromazine—older patients being more susceptible to maximum change. DISCUSSION The psychological and EEG ﬁndings show that the agents studied affect these random— ly selected subjects differentially, producing drug—speciﬁc spectrums of change scores. This demonstration of drug speciﬁc proﬁles based on multiple tests supports previous statements by such workers as WIKLER“, LEHMANN7, and KLERMAN et al.8. It should be noted, however, that these test score proﬁles are contingent on population characteristics and not solely on the biochemical properties of the agents tested. While no adequate delineation of salient population characteristics is available, two general schemata are in use—the diagnostic nomenclature, and the concept of ”target symp— toms”. Neither scheme adequately reﬂects population characteristics, and further studies of multivariate behavioral, physiologic and psychologic characteristics are necessary for such delineation. It is thus imperative that drug studies utilize more detailed analyses of pretreatment physiological and psychological functioning. In the absence of such methodological reﬁnements, the present confusing and contradictory data about “drug effects”, “paradoxical reactions”, and imputed speciﬁcities will continue. CONCLUSION I. Pattern speciﬁcities in various tasks can be identiﬁed for group data. 2. Within various groups, individual differences may be great, leading to failure for some group data to achieve signiﬁcant differences. Further exploration of pattern speciﬁties for subjects is warranted, using some of the more recent statistical techniques of multivariate analysis. 3. Such pattern speciﬁcities for clusters of subjects may be a more meaningful way of ordering psychiatric subjects for evaluative studies than conventional nosological methods. 4. Group data for EEG, CFF and behavior are consistent with neurophysiologic— adaptive views of drug therapeutic efﬁcacy. REFERENCES 1 3 3 7 M. FINK, A uniﬁed theory of the action of physiodynamic therapies. ]. Hillside Hosp, 6 (1957) 197. M. FINK, Effect of anticholinergic compounds on post-convulsive EEG and behavior of psychiatric patients. Electroencephalog. and Clin. Neurophysiol., 12 (1960) 359. M. FINK, R. SHAW, G. GROSS AND F. S. COLEMAN, Comparative study of chlorpromazine and insulin coma in the therapy of psychosis. ]. Am. Med. Assoc., 166 (1958) 1846. M. FINK, Electroencephalographic and behavioral effects of Tofranil. Cari. Psychiat. Assoc. f., 4 (I959) 166 SG. A. ULET’I‘ AND R. G. LOEFFEL, A new resonator-integrator unit for the automatic brain wave analyser. Electroencephalog. and Clin. Neurophysiol., 5 (1953) 113. A. WIKLER, The Relation of Psychiatry to Pharmacology, Williams & Wilkins, Baltimore, 1957. H. E. LEHMANN AND J. CSANK, Differential screening of phrenotropic agents in man. J. Clin. Exptl. Psychopathol., 18 (1957) 222. G. L. KLERMAN, A. DIMASCIO, M. GREENBLATT AND M. RINKEL, The inﬂuence of speciﬁc per— sonality patterns on the effects of phrenotropic agents. In Biological Psychiatry, Grune & Stratton, New York, 1959, pp. 224—239. Printed in The Netherlands ��IWEGPSIGIGLMIB RESPGISB ' “runs at sons rsrczonorzc nuns Ha: Fullnek Ph.D., Erie Earp 3.1. George Krauthunor Ph.n., Donald 1. Klein Cad HI! Pink H.D. Ht”. Iran the Dapartnent or Exporinentnl Psychiutry, Hillside Helpital, Glcn Oaks, 3.1., U.I. Prouontod at the Second Meeting of the Gdllogiuu Internationale Houro~ Payehophnrnacologicun, Basal, July 1960. 1?: 7/60 �Probles: _ihis study or the node of action at soae er the never psychotropic agents was teraulated within the tranework of a neurophysielogie—adaptive hypothesis (1). The concept, derived from earlier work on oonvulsive therapies (2), views clinical behavioral change as a resultant of the interaction of alterations in brain function and the personality of the subject. the ,present study enphasises the question or pattern specificity of drug action and its relation to individual differences in behavioral response. The partieelar drugs utilised, ehler» proaasine (3) and iaipranine (h), were selected on the basis of pilot studies in this institution in which their ettectiveu nose in altering physiologic and behavioral patterns had been demonstrated. this preeentatien is currently in progress. an interil report of a study �hethed: VIGonseestiye referrals for drug adninistratien in a voluntary psychiatric hospital were assigned at render to one of the three drug regimens - (1) ohlorpronasine with 1.21 preoyelidine added, (2) inipraaine, and a (3) plaeebo. Hedioatien vas adainietered in liquid vehicle in a fixed dosage schedule, to a saxiaua in tour weeks. chlorproaasine was begun at 300 as. and increased to 1200 :3. daily and iaipraaine tree 75 to 300 as. Patients continued to be seen three times weekly in individual payohotherapeatio interviews during the period of drug treataent. Analysis of the data is liaited to the first us cases. These patients are notohrenioally ill - the majority being adaitted for their first hospitalisation free the ooaaenity, and a saaller percentage rehoepitalised for a recurrence or their illness. Their mean age was 35.5 years, and yeare of schooling was 11.9 years. Apprexiaetel! 575 were diagnosed in the group or sohisophrenias, 281 as affective psychoses and 15S psyche‘ neuroses and eharaoter disorders. Patients were exaained in a four day period prior to drug adainistration on a fixed schedule or physiological and psyche— legieal prooederee which was repeated iering the sixth week of drug treataent. �Results: in cone of the aeaeoree with drug treataente in the figure I. the EEG patterns aeaeored Group changes are shown --~----~--“-. FIGURE I ..—..'.....u. quantitatively through electronic frequency analyeie (5) show that inipranine and ohloryronaeine differ significantly from the control group and from each other. There was a eignificant reduction in the total electrical activity in the inipranine group, while there wee an increase both in the amount of slow ahd wave activity the slow to test activity ratio: in the chlorpronaeine group. -Thc reduction in the critical flickerotueien (CPI) threehold ie noted only for the chlorproxaaine group. Thin test correlated with the increase in EEG elow wave activity. The rotor tests also reflect a differential drug effect with uneteadieeee increased by the two drugs, ﬁapping rate unaltered, and pursuit rotor inproved only by the igipranine group. The the greatest change in intellectual functionihg rae scored by no-drug group, preeeut to a leeeer degree in the iaipraaine group and absent in the chlorprenaeine group. the lack of equivalent changes for the drug grounsnay reflect an inhibition of the expected practice effect. In clinical behavior, all groups showed a reduction in coupleinte on self-rating ae measured by the Johne napkins Scale, with the reduction being greater for the drug groups. �.h’ 611d. In the load 80:10, 3 Q-Iort bohuviornl rttilg, that. an. a qunatitt‘ivo iodnction in both tho pntaoat'n and tho dﬁﬂttr'. 2:11:33 a: 'dcprocttun' in tn. contrcl ﬁhc drug grvup but ‘ot (tr group. #311. than. du$t indicatc s ptttorn thnt angg-ata dittorontiul drug tcttvlﬁy, ‘horo w‘u narkad ho‘crogonuity within tuck grvup an Oneh nonairo. Fitlrc 2 pluts at. ohnngca ------”--‘ FIGURE 2 ouudunouca in ctr tar itch aubaoe‘. rho nunbtr within Ouch ban rotort. the 07:1tatton o: n «inn;- tn bahnviur, rated on t tour-point .031. by sh. ovnlnuting pnynhtutrtnt. it... ‘20 glohnl ch18... 13 bchuvior ratiuga, and gr. not uncocaarily‘oquavglnnt #0 rating. it ingrQVCIdnt. (lot. that £ho ratttan c: habnvtorul '3' tld 'h' IIII aunt often ussoctutcd with ehnngnl 1n err-o: uni. than on. cycle) Althodgh tbs d1£t¢rcnoo in 3033 err near. botviun 'tltpruutno and tho «Chiral group van tot signitiegnt, 6h: atttorcnco 1: vartthtltﬁy (1 ratio) III utgnizicgnt (p .o;). admiral It. gran; unused u narruv r.n¢c at chgngo, vnryiu; chaago Iran tron to n! 31:10:. In contrast; tut Slipranlno xrtup :;n¢od +2 tn -5 grains, and chlarpzalnsinn (ran not. to -6 cyclan. Ina chlorprunalinn stump chang- vas a: Shh downward atroction only. the 1nd£v1dnu1 dittorono¢n ta thn t1¢irtiiill If G?! tarantula 1:. .13d ohaorvahln 13 thn olaotro.ncopha10¢raph1¢ «an... run:- 3 an: tho clung“ 1a a. :1» u no «any; +1 an �-5... ﬁ.‘ﬂ---‘ﬂ“.119333 3 O‘ﬂumnabndou ratio demonstrating a wide range in changes fer the controls, a eiailar pattern tor the 1a1praaine group, but a change in enly one direction that of increaaed slewing fer the chlorpreaaaina sweep. The teen increase in elev wave activity for the ehlorpreaaaine group was more than 15 tines that or — the central and 1a1praaine groupe. there was also a aignifieant relation between the increaee in aloe wave activity and increasing age with chlorpreaaaine - elder patiente being late eneceptible te naxinna change. �Dieeeeeion: psychological and £36 findings ehoe that the agente etudied affect theee randomly eeleoted eubjecte differentially, producing drug-epocitio epoctroae or change eooree. This deeonotration or drug epocitic profiles based on multiple tests supports previoue statements by ouch The (7), and Klenaan et al (8). It ehould be noted, however, that theee toot ecore profiles are contingent on population ohareoterietioa and not eolely on the biochemical propertiee e: the agente tested. While no adeqoete delineation of eelient population oheraoterietice ie available, two general eohenata are in nee ~ the diagnoetio neaenclatore, and the concept or I"tax-got eynpteae'. leither ooheee adequately retleete population oharaoterietioe, and further otudiee of multivariate behavioral, phyeiologio end peyohelogio oharaoterietioe are neeeeeary for each delineation. It in thee imperative that drug etodiee utilise more detailed analyses or pretreataent psychological and physiological toentioning. In the abeenoe or euoh aethodological refinements, the present confueing and contradictory data about ”drug effects", "paradoxical reactions“, and iapeted epeoiiicitiee will continue. workere ao Wikler (6), Lohmann �Conclueieﬁ: (1) ~Psttern speeifieities identified for group dsts. 1n vsrieus tasks can be differencss individusl various Within groups, (2) to dsts sons for group to failure be lesding great, as: of Further explorstien differences. sehisve signifiesnt some using usrrsntsd, is for subjects psttsra speeitities of the nets recent ststistiesl techniques at nultivsrists snslysis. or clusters for Bush (3) pattern speeitieities of psychistrie ordering he nssniugful we: nsre s nsy sabjsets nsselegiesl eenventiensl thsa studies evaluative for subjects methods. . (h) ﬁreup dsts fer use, err and behsvier sre eensistent with nearephysielsgie-sdspt1ts views 9! drug therspeutic etilesey. �‘8REFEREHGES tho Action or of Thoory Enitiod Physiodynonic i Thoropioo. J. Hillaido IOIE. é; 197~206, 1957. 2. link, H: Effect of Anticholinorgio Gonpoundo on Poot~ convulsivo BEG ond Behavior of Psychiatric Potionto. E30 6113. lcurophyoiol. $3: 359-369, 1960 3. Pink, H., Show, 3., Grout, G. and Calcium, 1.8. Corporativo Study of chlorprouojino onc Insulin Geno in the therapy or Poychoéis. J. inor. nod. Aoooc. ;§gs 18h6~18§0, i958. h. rink, H: Electroencephalographic and Behavioral Effects of Torronil. Gonna. Pczch. Assoc. J. g. 166$~1718, 1. rink, K: 1959. Blott, G.A., Ind Lootfcl, 3.6. A new resonator1ntogrotor unit for the antarctic brain wave onolyaor. Clio. Houroghzaiol., g} 113-115, 1953. 6. Viklor, A.: 2&0 Relation of Pazchiotrz to Phornocologz, an. a Wilkins, Boltinoro, 1957. Lohnonn, B.E. and Crank, 3.: Bittorontioi scrocning or Phronotropic Agents in Hon. J. Olin. Razor. Pczchogothol. EEG lg: 222—235, 1957. Klornan, 0.1., Dixaccio, L., ﬁrocnblott, K. and Rinkol, H: the Influence of Specific Personality Pottcrnc on the Effects of Phrcnotropio Agents. Biological Pazchiotrz, Gruno & Strottcn, New York, 22h-239, 1959. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Published Works Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Neuropsychologic response patterns of some psychotropic drugs. In E. Rothlin (ed.), Neuro-psychopharmacology. Elsevier, Amsterdam, 1961, 2:381-4 Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-02-01-003-50-016 Date A point or period of time associated with an event in the lifecycle of the resource 1961 Creator An entity primarily responsible for making the resource Pollack, Max; Karp, Eric; Krauthamer; Klein, Donald F.; <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Published Works -- Articles and Reviews Relation A related resource The Max Fink Collection Description An account of the resource Reprint and [preprint]. REPRINTED FROM E.ROTHLIN (Editor) NEURO-PSYCHOPHARMACOLOGY VOL. 2 (1961). Proceedings of the 2nd International Meeting of the Collegium Internationale Neuro-Psychopharmacologicum Basle 1960 Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Published