'"1

Tartlive DvskinesiaNeurolepties :

in Patients Treated with MajorA Review of the Literature

B \

Slric 'c, I 9 59 u grttr ' ' ing ruttrtber of report, \lnve descrihed a ttev' tvpe tt f ncurologiculdi.srtrdcr ir t tr tenral patient.s. Tlt i .s dinrder,kncnln tt .s turt l iva t l t .skint, .si t t , l ru.s' bt 'en ttb-.s' trved in apTtro-r i tr tatelt ' 500 cuscs but,iudging lront the acc'nrate ohservctt ions nrudeh.r ' t lvet ' s(parutL, groups ol invt,.st igatttrs,t l te svtaJrrttnt, is l ikely to be ntorL, ' t ' requent

t l t t tr t orte tru\ ' su.\pect. Alt futugh ntani lestct-t iott .r of turdivt ' r /r ' rArrrc. i iu ot ' t 'ur in et numhert t i t l i saascs o l t l t t ' t ' t ,n t ru l narvoLt .s s lJ tc ,n l ,tltt're is cttttsiderablt, evidenct' thut the large-.\'cttlt' use ()t' phenotlict:ine,.s ttr .sirrtilctr drug.sit t r t 'ct,Ltt-\ ' r ,drJ i .s rt ,s.. t t t t t .sihle lor l l tc grt,utrt t t trrber of pati t ,r t t .s ' i r t tr tental ln.;pital.s erhib-i t i t tg t t t t ' tx ' l t t t t i t t urtd clt t trco-i l t l rct() i t l .st ' rr tp-l ( ) l l l . \ .

( \ .qtNCE l9-s9.. tq l - ldpers including 23 re-U ports b1' 18 authors have appeared inthe scient i f ic prcss descr ib ine an unusualneurological syndrome in pat ients t reated'uvith phenothiazines and other ner-rroleptics.This syndromc, which has been cir l led tardivedvsk ines ia by Faurbye( 12 . 34) . o r te rnr ina lextrapyranridal insufficiency svndrome byHaddenbrock( 14) i s charac ter ized by : I )inv 'o luntarv nrovr 'nrents; 2) late occurrencein tlre course of treatnrent and often afterdiscont inuat ion of drug adr l in istrat ion; 3)persistence of d isabl in-s nrani festat ions fornronths and years in a higll percentage ofcases; and 4) poor response to any typeof ther;rpv.

Sigwald and associates(30. 3l ) rvere thefirst to report such syniptorns; the tl ireeauthors rvho have contr ibuted the largestnunrber of c l in ical cascs are Faurbve and

D r . C r a n e i s w i t h t h esearch Br rnch , Na t iona l- s4 -54 Wiscons in , { l ' enue ,

-10

Psychopharnracology Re-Inst i tute of lVlental Heal th.Chevy ' Chase , IUd . 20203 .

assoc ia tes( 12. 34 ) o f ' Rosk i lde. Denmark:Degkw i t z (7 . 8 ) o f F rank fo r t . Ge rmany ; andHun te r ( 18 . l 9 ) o i London . Eng land .

The increas ins nunrber o f cases of dys-kinesias reported in the l i terature of thelast tw'o years. as well as reports of othertypes of contpl icat ions attr ibuted to neuro.lcpt ics . has been a sourcc o f cons iderab leconcern. par t icu lar l " ' " in regard to the r isksin l c r lved in long- tcrnr therap y ( 11, 20 ) .

The Sl 'nclronre

The nrost conspicuous and frequent dis-order is local ized in the oral region andnray be suff icicntly severe to affect the iunc-t ions o f speech and deglu t i t ion. S igwald(31)described the syrnptomatology of his f irstp u t i c n t a s f o l l o u s :

The tongue permanentl l ' projected for* 'ardand backw'ard fol lowing a rapid rhythm; att imes the project ion is to the side. sometimesto the r ight. sometinres to the left l a torsionmotion, or rotat ion on i ts axis complicates iuincessant conr inq and go ing mot ion. Thcmouth is half open and l ip movements ac'

company this continuous dyskinesia. The pr '

t ient is sl ightly bothered by this. and trr

speech is s l ight ly t roub led, but remains cof tprehensible. Besides, the act of speaking or o{

swallowin-e temporari ly suspends these rnc

tions u'hich resume immediately afteru'ardrAsking the patient to execute a hand mottof l

considirably accentuates the seriousness of dr

l insual-facial rJvskinesia. . The l ips rari lo'

pate in this d1'skinesia in the form crf sterct>

ivped suction motions, pursing, rol l ing rnd

incessant champing in synergy with rh. ' thmrcontractions of t t . jaw. Sometimes. on th'

other hand. there is a rhythmic opening d

the mouth which faci l i tates protrusion of dr

tongue.

Other authors who observed this sF

drome had l i t t le to add to this dramrs

Atner . J . Psych ia t .

I

OEORCE E. CRANE

oresentation by Sigwald. Disturbances of

ooti l i ty in other regions of the body were

1so descr ibed. Hunter (19) repor ted dysp-

oca and cyanosis in two patients, which he

rnributed to the lack of coordination of

ge respiratory muscles and spaslns of the

glott is. He also observed a pecul iar gait with

abduct ion o f thc arms. Faurbye( 12) . Had-

denb rock ( 14 ) . D ruckn ran ( 10 ) . and o the rs

cal led attention to continlrous jerky nlove-

ments of the upper and lorver extrel l l i t ics.

part icularl l ' of the f ingers. ankles. and toes.

Tonic cont ract ion o f the tnusc les o f the

neck and back were frequcntly encountc-rcd.

As to the character is t ics o f such d isorders .

Degkwi tz lS) sunrntar ized h is ar rd o ther au-

thors' observations as fol lows:

Termina l ex t rapvramida l h l 'perk ines ia hasbeen described predominantl l ' as a choreifornt.and in some cases also as an athetoid andball ist ic motor disorder. However, obserl 'at ionshave shown that myoclonia ( as i t had beennoted already' during the great encephali t isepidemic) was involved in a large numberof cases: we noted brief. more or less markedrhythmical twitches of individual, or frequentl-vof symmetrical muscle groups having more orless marked motor effect of vary' ing frequen-cies . . . in sporadic cases we have noted m\,o-clonia of the ocular muscles. When pa-t ients are observed while they' are pursuingtheir act ivi t ies. or u'hi le thev are gett ingdressed or undressed. hvperk ines ia is notedmuch more f requent l 'u , than under the condi -t ions customarv to neuro-psvch ia t r ie exanr ina-t ions.

Wertheinrer( 35 ) reviewed part of the l i t -erature and found sirnple btrcco-lingual-nras-t icatory dyskinesia in 14 cases. the santesyndrome associated rvith trenror in twclcases, buccel ingual-mast icatory syndronte inassociat ion wi th involuntary nroventents ofthe l imbs in three cases. dvskinesia of theneck and l imbs in one case. parkinsonisntin one case. and akathis ia and tasik inesiain two cases. Al though this c lassi f icat ion ofsymptoms is not ent i re ly c lear. i t is qui teobvious that oral dyskinesia is by far them,ost f requent manifcstat ion.'* 'Movenrents

of thc l ips and tongue aregrotesque. often socially objectionable. andthus are a source of considerable enrbarrass-ment to the pat ient and his fanr i ly . / lAs i rru le. however. pat ients do not complain of

Anter. J. P.r1 'chiut . 124: 8, Feb. 1968 Srtpp.

these svnrptonts. part icular ly i f they aredenrented. The neurological svndrontc nlaycause a nunrber of compl icat ions. such ashypertrophy of the tongue and ulcerat ionsof t l re nrouth( 10). The specch nlay' beconledlsarthr ic to the point of being inconrpre-hensible( l9 ) . [n cxtrert ]e- c i tses. swal lorv ingmay beconre difirctrlt and this rnay' ctl l lse acons iderab le loss o f ue igh t (29) . Scvere dvs-tonia invoh'ing nruscles controll ing the bal-ance of thc- bodv and of t l ie hc'ad nra,v be-painful and thus great ly reduce the pat ient 'sact iv i t r , . Standard ncurological exattr inat i r )nsrevcal essent ia l lv nc-gat ive f indings other thangross nro tor d isorc le r (35 ) .

Prevalence

Dt--gkw' i tz(8) in a rcvie* ' of the l i teraturereported 232 cases of u 'hat he ternts " l ( r -minctla extroptranidul<' Ht'perkinc.t( '." Tothese should bc irdded 272 patients includedin his art ic le and 17 addi t ional pat ientsrcported in papers not ntentirrned by Degk-rl ' i tz. Er,'en if alloil 'anccs are nrade for dr-r-pl icat ions and inclusion of some ci lses ofquest ionable svnrptontatoloty. the nuntberof pat ients publ ished thus far is or. 'er 500.This nunrbc-r is far f ront being i r r tpressiveconsider inq the nrany rni l l ions of hospi ta l -ized and arrtbulatory patic-nts u'ho \\ 'erctreated or are being treatcd rvith lteLlro-lep t ics .

Hclwever. there are tu 'o disconcert ingfacts about th is l i t t le-know'n sr , 'ndronre. [nthe first place. more than 90 percent of the'cases of dyskinesia have been reported since1964, in the second place. the f requencyof this syndrome in santples of chronicpat icnts appears to be considerable. accord-ing to three groups of invest igators. Hunter( l9 ) . who focr-rse'd onlv on severe i r revcrs-ib le symptoms found that l3 of 250 \ \ 'onrenwere af t l ic ted by th is disorder. Faurbye( l2)di i ignosed drug- induce'd d1'skinesia in 103otr t of 417 chronic pat ients. and. f inal ly.Degku ' i t z (8 ) repor ted 137 cases in a pcrp-r . r lat ion of 817 in onc hospi ta l and approxi-rrratelv 100 cascs in a populat ion of 443in another ins t i tu t ion .

Characteristics of Patients

,{g<'. Detailed inforntatic-rn as to age \\ 'asavai lablc for 279 pat icnts. and the agc

t l+ l

T A R D I \ E D Y S K I N E S I A I N P A T I E N T S I ' R E A T E D \ \ ' I T H N T A J O R N E L ' R O I - E P T I (I ' ( ) R G E E . (

distribution \\ 'as as follon's: 20-29 years ofage. seven: 30-39 . l8 ; 40-49 . 29 ' , 50-59 .90; 60-69 . 92 and over 70. 41. The ,r 'oung-est pat ient w'as 2l and the oldest 82 ycarsold. l t seenrs that the highcst incidenceof dvskinesia occurs between the ages of50 and 70. although no conclusir-rn can bedrawn fronr the data at hand since the agedistr ibut ions of the pat ient populat ions arenot knon'n. Hou'ever. the age distributionof Faurbye's sample ( 12) is typical of achronic hospi ta l izcd populat ion.

.le'.r. The ratio of wornen to nren \\'asapproximately three to one, excluding thetwo large series of patients reported byFaurbye, w'ho obtained his data f ronr fenraleservices only. Hunter( l9 ) found that thepercentaee of pat ients exhibi t ing dyskinesiawas five pcrcent for wonten and zero per-cent for nren. On the other hand. in the firstser ies of Dcgkw' i tz ( 8 ) . 2 l percent were\ \ 'onren and ten percent \ \ 'ere rren: in hissecond series. the percentage of \\ 'onlenrvas 27 and that of nren. 19. Thus. i t secmsthat women are nlore f requently affectedthan men, although the rnarked disparitybetw'een Hunter's and sonre of Degkr.l, i tz'data is di f f icul t to cxplain.

Principal and secontlart' diugrutses. Thernajority of patients had diagnoses of chronicdeter iorat ing schizophrenia. which is not sur-pr is ing s ince the bulk of pat ients were stud-ied in chronic hospi ta l wards. A nunrber ofpat ients n,ere di i rgnosed as hal ' ing orsanicbrain disorder ( seni le cerebral ar ter ia l scle-rosis. general paresis. etc. ) and an evenlarscr nuntber of pat ients. such as those ofHunter( I 8 ) . had a history of . having re-ceived var ious types of physical therapy. in-c luding leukotomy. This has led to the opin-ion that brain damaqe nrav predispose tod y s k i n e s i a ( 4 . 2 6 , 2 8 ) .

This is probably correct, but there is alsoconsiderable cvidence that young pat ientsu' i thout a history of brain danra-ee ntay beaffected by this disorder. In Degkwitz'ser ies(8) . SS out o f 137 pa t ien ts had vas-cular disease. diabetes, brain in jury. andior a histon, of having received EST andinsul in. I t is not c lear whether some of thepat ients had nrore than one of these poten-t ia l ly t raunrat ic factors. but at least 52patients did not have a history of braininjurv. [n Uhrbrand and Faurbye's paper

. 1 1

15 of 29 had sone evidence of brain r lanr.age. but in Faurbye's second repon thcrcwere only l8 ot- 103 pat ients who appL.Jrr ;to have sross neurological d isorders.

An ana lys is o f 12 separa te s tud ic r r .p o r t i n g a d e q u a t e h i s t o r i e s ( 1 0 . I l . l t . ' (

2 1 . 2 2 . 2 - 5 . 2 7 . 2 9 . 3 1 . 3 3 . 3 5 r r c r c , r , ,tha t 15 o f 43 pa t ien ts had c r idcncc o i f . r . , , .dan iage due to scn i l i t y . a lcoho l isnr . ( r r r r , : . .degenerat ive disease. The renraindcr oi t i rc, , .pat ients did not seent to havc' Icufr) l t , r ; r . .d isorders nor d id the i r pas t h is t ( )nc \ r f \ i - ;the adnr in istrat ion of an excessir c nunr i \ .of ESTs. Dement ia. which concciurhlr : : :be associated lv i th sonre ortanrc . i , , , r .was absent in a large nunrber of c;lrc, Iins tance. in S igwa ld 's (30) sc r ies . thdrc , , , , 'two pzi t ients who had no appi l rcnt nr( : r .d isease. bu t were rece iv inq nc ' r r ro lcp t r , . , rthe rc l ief of neuralc ic pain.

The ro le o f EST is a lso o [ p i l r i r t , , ; 'interest s ince this type of t rcatnrcnt r : , , ' '

ma) ' cause dyskinesia (reportcd in [ t \ur it ients ) according to Faurble( I J ) . T hc ' i -author also found that 4-1 pcrccnl , ' ipat ients who ht id previouslr ' 11'gg1r{d I r

showed dyskinet ic symptot t ts. ar t lPF' \22 percent who had not tc 'ccircd . t r r 'of convuls ive therapv. In thc r . t t r r ithe author stated that lcukotont izc. . i ; 'were no t more prone t t r d r . l r t t c 'subjects u 'ho had not hld 1g111'1)st l l ' . . "

T1'pes of Drugs

Faurbyc( l 2 ) t rbscr rc t l t j *k t t te : 'tat ions in pat ients t reatc 'd ui th t i rc '

drucs: chlorpromazi t le . pcrpl t ' . ' r ' ' ' '

r idaz ine . p roch lo rpcr l t z inc . . r r r ' i ;

ln an ear l ie r PaPcr (3- l t t l r t \ ' j

repor ted tha t o f 2v Pr t l c t r [ \ ' \ '

k ines ia . 15 had been t rc l i t l i l t t i t r '

z ine . t en u i t h ch lo rp r ( ) l ' l l i l l l t l L ' : ' r ' i

r ese rp ine , and t he [ c -S t \ \ i t h t ' t r ; . ' " ' '

t i o n s o f d r u g s . F l t u r b r c r r t ' p ' ; i '

phcnaz inc mav bc l l l ( ) r c [ t i \ r t l i " i '

p romaz ine i nasn luch l r s t l r c l ' t l t c r ' 1 r I

been usec l n l o re ex tens i r c l r t h ' r n l \ " . ' u

i n t hc Sanc t H lns Hosp i t l l l t r f R ' ' r l ' i ' '

H a d d e n b r o c k ( l 4 ) i s o i t h c ( f ; r " ' h r " '

high doses of perphcn:tzrnc ' t{ -1^.* l

pr"ophenoncs. the usc o[ pltcntrt ir l ' "r ' Iiowed bv EST' and thc' d()t l lhrr 'r ' f r

rr

phenoth iaz incs and barb i tur ' r tc l tn{ r r f i

Arrter ' J. Psychiat ' I ]1' 'q ' l r i i* ' f ' r#

-..riods of t i, terdive dy.nbed by E. . 'n rz ine in <, r . S o m e p i

. ; r r i t i v e t o c;r l r r tcd b! [

' . r l svndronri , changedthioproper

, n t s ( 3 5 ) h il rsc ' of hal tI hc generr

, , c lop only.c . o f pher t i c u l a r l y t l' . t invest i -g irl l t r 'rntore.' 1 , h a d r e c.' lr lorpronr

. i l l tvpica' ' r r tc-d fc l rr r r l c p t i c (r i r c r p a t i. r s i r r r i l u

' . . i t l n c n t ,

. f h i s p, ' l l \ C ( ) L l l

. t l r r r g s .

" ' . , . t a r r r l F

\ r t r r t fug l y ,, i r r k i n c s i

. ' t D t i l ' I U O U' ' r c r r r t c r ( 3

r rcl tc.d 1'. e lr rs bc-l 'I l u n t e r . :

' r ( ) l l l I 8

l r ; r n d . (i l ) a n d

: I . ' n q - l a S l

t h r c c o' . , , c r I 2 )' , p h r c n i c

, . r . a f t e r' r h r ce p i

r r r l c , sS t l, ; . r l f l r nd (

I l i r rcc ) -ear' . ; , r n r f cs ta t i

. rPparen, " : t l r , r n t host o - , t

J p s y c l

OEORGE E. CRANE,

6riods of t ime are particularly conducivc

iu tardive dyskinesia. All three patients de-

rribed by Evans( I I ) had recc'ived trif luo-

6razine in doses varying front 3-4 ntg. a

day. Sonre patients seented to be particularly

sensi t ive to certain types of drugs: a pat ientreported by Rodov6(27) developed a nrarked

oral syndrome five day's after her medicationwas changed fronr conventional neurolepticsto thioproperazine; one of Wertheimer's pa-dents(35) had a s imi lar response to a br iefcourse of haloperidol.

The general impression is that dyskinesiasdevelop only in patients treated with largedoses of phenothiazines. yet rrrany patients,particularly the elderly, received doses u'hichmost investigators would consider moderate.Furthermore. one of Sigrvald 's pat ients(30)who had received daily doses of 7 5 mg.of chlorpromazine for threc nronths devel-oped a typical bucco-lingual syndronre whichpersisted for at least ten nronths after allneuroleptic drugs had been discontinued.Another patient described by' Er,'ans( 1 I )had a similar reaction after four nronthsof treatntent with 3-4 nrg. of trif luoperazinea day. This pat ient . however. rnay have hadprevious courses of treatrnent u'ith psycho-tropic drugs.

Oneet and Evolution of Syrnptorns

Another widel l ' held opinion is that tar-dive dyskinesia occurs onlv af ter man)/ \ /earsof continuous medication. According toWer the imer (35) . one o f h is pa t ien ts hadbeen treated for eight years and another fornine years before the syndrome becanle ntan-ifest. Hunter's cases had been on medica-tion from 18 ntonths to five years. On theother hand. one patient reported b-v Sig-wa ld(31 ) and another b ) , Evans( 11) deve l -oped long-lasting extrapy'ramidal s1'nrptonrsafter three or four ntonths of treatntent.Faurbye( 12 ) found that only ' 34 of 7 5schizophrenic patients first nranifested dys-kinesias after thrce or ntore vears of treat-ment. three pat ients having exhibi ted symp-toms in less than one-half year, six betw'eenone-half and one year, and 32 bctw,een oneand three years. In an1' event. the neurcllogi-cal manifestations discussed in this paper bc-come apparent in the course of treatmentlater than those of classical parkinsonism or

Amer. l . PsS'chiat . 124: 8, Feb. 1968 Supp.

akathis ia (ntaxiniunr 73 days according toAyd l l l ) t rnd cons iderab l l ' l a tc r than thoscof acute d1, 'stonia ( less than one u'eek) '

Hr-rnter. Faurbye. and Degkr,r' i tz i i ,trec that

in nranv cases dyskinesia nlakes its f irst ap-

Dearance or bc-comes inte nsificd follou'ing

iernrination of drug administration or

nrarked reduct ion of dosage. The last-

nanred author( I ) ternr inated drug admin-

istrat ion in 35 \ \ 'ot l len and. of these. 12

developed "extrapl ' rar l idal hyperkinesis"n ' i th in one to 14 days. He postulated thatternr inal cxtrapyranr idal insuff ic iencv l l lavbc present but c l in ical ly not apparent dur ingdrug therapy' ; he proposed that drug- inducccJmuscular r ig id i ty ntav control synlptonts of

nrotor hyperactivity' caused bf irreversiblechanges in the central nervous systent. Faur-bve( l2 ) feels that th is nrav be true in sonleinstances. but not in cases exhibi t ing normalntuscular tone.

Outconre and Treatment

A nurnber of case histor ies suggest a rat l r -

er rapid otrset of the ntore distressin,g synlp-tonrs of dyskinesia and a gradual spreadingto t 'arious areas of the body rvithin a

short t ime, Hou'ever. nrost authors adnr i tthrit they first noticed the syndrome u'heni t u 'as fu l ly establ ished and that thel ' mayhave over looked ear lv and insidious nlani-festations. ln ntost instances treatnlent w'as

discont inued as soon as syn'rptonts bccanleapparent. or nredicat ion u 'as nranipulat t - 'd inan effort tc-r reduce hyperkinesia.

Of the 29 patients reported by Ulirbrandand Faurbyc ' (341. l2 cont inucd on drugsdespi te the presence of d1'skinesia and ofthese trvo becanre svntptol t t - f ree upon re-duct ion of dosage. In thc other tcn cases.d1'skinesia persisted. Of the l7 pat ientsw'hose treatntent \\ 'as discontinucd. 12 nolonger exhibited abnormal s\Ilttptonlatcllogyafter per iods extending front tcn days to s ixrnonths. and five continued to exhibit symp-tonts despi te terminat ion of t reatnrent. Sim-i la r l y , in Haddenbrock 's ser ies(14) , fourof ten patients becante symptonr-free.

According to three separate reports(21,2 '7, 35 ) s.vmptoms disappeared upon with-drawal of the drug. to reappear when treat-ment was reinst i tuted. ln a case descr ibedbv Schnr idt and Jarcho(29 ) , dyskinesia was

.13

T A R D I \ E D Y S K I N E S L A l \ P A ' l ' l h N ' I S I R E A T E T ) \ \ ' l - l H 1 \ I r \ . i O R N F - L R O t t : t ' l i r

rcvcrs ib le L lpon d iscont inuat ion o f thc drug fur ther repor ts on the ef l icacv o f th i . l r t . . r :dur ing the f i rs t four vears t - r f t reatnrent . but n tent l loda l i tv \ \ 'e re recc i rec l f ropr t5r . .becan re pe rn lL l nen t nhen the agen t \ \ ' a s re - s t i t u t i on . uhe re r csea rch on dvsk inc r i . r i r . ,a d n t i n i s t e r e d i n 1 9 6 2 . T h c - f a c t t h a t s y m p - b c c n r c r v i n t e n s i v c d u r i n s t h e I a s t t j r d \ ( , ; . .tc lnrs l r ra \ r appear dur ing t reat rnent . a f ter t t - ' r -I t t inat ion t t f t rc -a tn tent . t l r L lpon re inst i tu t ion Relat iq l 9 f l l vo l t r l tas- l l6 r .enr r . r r t .o f t r cu t rncn t i s i nd i c l t i r e o f t hc con rp l r - r i t ) t o f ) r ug Ac t i ono t ' t l t c p t ' oh l c ru .

- f hc nuntber o f pat ients u 'ho l rar , 'e ex- A cause- t rnd-ef fec t r r - la t ionshrp hr '1 . , , -

h i b i t ed i r r c r c r s i b l c c l vsk ines ia i s cons ide r - t he ac t i on o f neu ro lep t i c ascn t s i u r t l . , , :ab l c . A l l 16 cases o f Hun tc r ' s ( l 8 ) ex - t o rns o f pa rk i nson ia t r t r en ro r . d \ \ t ( ) n r . r , : :h ib i tcd dy, 'sk inet ic symptonrs for per iods akath is ia rvas estab l ished car l r in rhcr arv ins f ronr three to I .9 nronths a f ter d is - torv o f psychopharmacologr ' . s incccont inuat ion o f t reatnrent . One of h is pa- nran i fes ta t ions c ' rccurred shor t l r u l t t . r l rt ients has been af l l i c ted b1r th is d isordcr for rnent \ !as ins t i tu ted and suhr : ideJ : .a t l eas t s i x vea rs . Schn r i d t (2c ) ) n i ade s i r n i l a r t e r rn i na t i on o f d rue adn r i n i s t r a t i r r r r I 'observat ions in h is l i r . ' c cases. w ' i th one pa- condi t ions do not obta in in thc crsr 't i en t e rh ib i t i ng seve re dvsk ines ia 44 mon ths d i vc dvsk ines ias . To co rnp l i c l t c : . ; "a f tc r drugs \ \ 'e re d iscont inued, Rodor ' ; ' r t27 ) . r \ nont rcatcd pat ients w 'ho nt i . rv hc r r ' . , jD ruck r ran (10 ) . and Fau rbve ( 12 ) r epo r te { \ on t ro l g roL rp a rc r i r t ua l l r i r r r p , , ' . "pat ients u 'hose s \ nrp tonrs pers is ted for over t rnd.

tu o vears . N{ost authors . how'ever . a-gr r -e The rc is . how'er er " cons ide r lh lc : : , :that the srvmptonrato logy decreases over a cv idence that the druss urc r r ' ' [ ' , 'per iod o f nronths a f ter cessat ic t t t o f neuro- for the neuro log ica l c f fec ts undcr ! i , i " ,l cp t i c t rca tnrcn t . t i on . Tcx tbooks o f ps1 ' ch ia t r t . r t t e l t , , ' r '

The re i s l i t t l e i n fo r rna t i c - rn abou t t hc evo lu - dc rson and G i l l esp ie ( 16 ) . d t , r r r \ lt i on o f svn rp ton rs i n pa t i en t s r vho con t i nue s \n l p ton t s o f cho rea . a thc t ( ) \ i \ . n ) \ , \t o r ece i ve neu ro lep t i cs . I n tw 'o cases o f S i_e - e t c . . i n sch i zoph ren i c pa t i en t \ . r ' \ r ' r ' i '* ' a l d ' s (30 ) . t r ea tn ren t \ \ 'AS con t i nued a f t c r w 'ho have reached a s ta t c t r t r r r l \ . , r \

the i lppearance of d ; - 'sk ines ia because of ter iora t ion. Yet thc greu l n l i . t j ( ,n t \ , ' r , .

t he exce l l en t t he rapeu t i c r esu l t ach ie l ed exh ib i t i ng t a rd i vc d1 ' sk i ncs i l h . r , l . : . '

r i i t h t hc cond i t i on f o r r i ' h i ch t he c l r ug h i r d o f sch i zoph ren ia . On the t r t l t r r i ' . '

been prcscr ibed. i rnd the dysk ines ia seenred svrnptc tnrs u ' i th vnh ich th is p . r f j :

unchanged af ter sc 'vera l nronths or \ rears . ce rned do occu r i n o thc r P l t t i t , r l ' ' - '

Trcatn tcnt o f ser ,ere fornrs o f dysk ines ia d i t ions o f the cent ra l ncr \ ( )L l \ r \ r l i ' r '

has been unsa t i s f ac to r v . Hun te r ( 18 . l 9 ) co rd in .u t o a su r \ev t t t adc h r \ 1 . "

fec ls that d iscont inr , ra t ion o f drug therapy is Crandel l ( 24 ) in l9-s5 ( j t r ' t l ' . "

csscnt ia l even thoLrgh one ntay cxpect on lv were in t roduced in thc . ( i rc ts l , . ' r te r :

pa r t i a l r ecove rv f r on r neu ro log i ca l co rnp l i - p i t a l o f Ne 'n l ' Je rsc r ' ) . t hc ' d . ' t r ' l

ca t ions. In more severe cases a paradox ica l ex t rcmelv rare and l t l i . l \ c ( ) t l ' l r l ' : '

con t ro l o f svn tp t c l n t s n tav bc ach ie l ' ed by t i on o f one pe rccn t t r t t l t t ' i " '

the t re i i tn rent u i th l i r rge doses of the same poprr la t ion.

d rug ( l 4 ) . A chanse o f n red i ca t i on ( f r o r r r Recen t l y a " ch ro r t i c p \ \ e i r ' :

ha lopcr ido l to pcrphcnaz ine) seemed to a thetos is" w ' i rs obserrcd t ' ) I ) r r " "

he- lp one pat icn i l 2S I . Scc la t ives and h l ' 'p - a f a i r propor t ion o f h t r rp t t ' r l , ' ' ' r

not ics mav be of sonre he lp in that they in- Frc lnr the pcrcept ive r tnd d . r r t ' l ( r r '1" -

c i r - rce s lecp. anc l dur ing s leep s l 'n rp tonrs d is- o i such neuro loq ica l t t t l tn t tc ' l ' r l r " ' '

appea r . t ha t t h i s "new n ro rb id r r l t r l \

P rac t i ca l l v eve ry ,au tho r ag rees t ha t an t i - r v i t h t he i J ruc - i nduc . ' t l t ' t r ( J r \ . ' I ' r

pa rk i nson ian med i ca t i on i s e i t he r use less o r I nvo lun ta r r - r t t o r cn l cn t s t ' l l : r ' " : '

i rarnr fu l to the svndronrc . Branc l rup(6) . in scr ibed in th is papcr r r r i r \ t \ r \ ! '

thc n tcnta l hosp i ta l in Rosk i lde. s l lcccss- sen i le . pr . -scn i le . parc t ic . ' l r r " r r "i u l l 1 , usec l t c t r abenaz inc i n f ou r pa t i cn t s ex - and b ra in - i n j u r cd i n t l i r r d r r ; r l ' I l :

' ;

h i b i t i ng c l ass i ca l dvsk ines ia . Hou ,eve r , no t o son re d iagnos t i c c l i f l i c r r l t r r t t l l : c " : ' '

At t r c r . J . Ps ' t ' c l t i a t t ) ' l ' r / ' ^ d . I

t .ORGE E . CRANE

' svntptoms, particur . ;o rd ing to Faur, .k ine's ias may occ, ,p i ta l populat ion"

. rrt of patients treat,. rn i festat ions areirnccd and dist incr

' . ' i thev do not disaI t has been ment:. 'si;. i develops u,r t l1 ' af ter wi thdr:rrcdiately af ter re' i : t inre relat ionshi l. r r r r racotherapy an|ptoms provides' r . r ' t h a t d r u g s a r ,' r r s ib le for tardi 'n t \ .

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' - l l ( ) r l 1 n lOvemen,r rcd to g ive wayr) rd t ) 'pc . patho lc, i p r cdon r i nan t l y' . , r r r r l gang l i& .i r f n t s r ece i v i ngI \ pcs t : f s yn rp t cr r . r i l cc se-cnts toj , r t l f r c n r such

. r n t hc nea r f u t' : ] t c t t f t h i s w r i t i, ' . , , t ' t . , a any i n fo

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: " r c J r r n e 1 9 6 6 i r. . ' , : '

' , 1 1 t \ . \ ' ( , l t . . t / C f t C r ., , r r r r cd f x )s tmone

, l n i r p r o v i s i o n ,. l r r rg_ induced

. c i l.s q ere founr. r \ c \ . "

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, t iJ \ d( ) nr ) t d l \ l lppe i . t r \ \ i t l t ; . t t tc t l t io t t .. . , . bccn nr r ' r t t i ( ) t t r ' t i c l r r l i c r t t ra t t11 's-

d r - r c l t r p : r i i t h s r c i l t r r f r equc -nc r. i : r f tc r u i thdr l ru l t l o f t t tcd ic l t t i r r t - t ( ) r

" . . : ; . r t c i i a i t c r r c i ns t i t u t i t l n o f t r ca t l t ' l c l l t ., . i r i l lu rc l l t ionsh ip bc- t r i ecn thc evcnts o i

. i . : :)rc()thcrtp) ' and the cle'r 'elopntent t t f

. f t r , i l ) f pror idcs addi t iona l ind i rect c r i -^ . ; th ; r t drugs are. a t least in par t . re-

: , , f , ic for tard i r e inr , 'o luntarV nro\ c -

r t l ro : . l l t re l i t ' Cons i r lera t ions

. . i r . k i ncs ias r r ' po r t r - ' d i n t h i s r c i i c *i ' t ' d i r i ded i n t t - r t h r c r - c l i r r i c l r l c i r t c -

. ' c l t o r c a ( c h o r e o - r r t h c t f ) \ i s ) . r t r r r r C l r r t r -. . rnd the br . rcco- [ incLrr ) - l ] l l s t ic i . t tor \ t r iu t if . iu rbr r . ' ( I 2 ) .( i to r r 'a and nr lc - rc lon ias \ \ ' r - rc a lso dc-

. : ihcd as car lv n t i rn i fes ta t i r rns o1 r t tn Ect ln-' : r t r ' s d i sease ( 3 . 23 ) : t l r e s i cn i f i c i r n t pos t -

" , ' r lL 'nr f inc l ings r - r f pat ients u 'ho d icd in: ' r \ s tagc of the d iseasc \ \c rc in the rn id-' : . i r n und b ra in s te rn (35 ) . l n p t r t i en t s r l ho. . r r i r cd t hc acu te - s taqes o f encepha l i t i s ." , , r c r l ( ) nn l no \ cn ' t e n t and n t voc lon ias c l i s -: , l r l rcd to g i r c - u . ; . r \ t r r p l r rk i l i s t ,nr :n t t r f thc: , , n r c t ) ' p t - - . P l i t ho loc i c chanccs n c r c t hcn: : n d p r e d o r r r i n l r n t l v i n t h c s L r h s t a n t i l i r r i l n r

: r . t bus l l gunu l i a .P l r t i cn t s r cc r . - i r i r r g ncu r r i l cp t i c : e rh i b i t , - - t i

' \ r ) lh t \pr 's o f sv l lp t t - rn t : br r t t l re i r orc l r - r t i l '

. rppc. i l f l tDCe scc l t ls t t ' r b t - f r . \ c rse d . Postnt ( ) r -ic r i r d i t ta f r t tnr sL lch p l t icn ts i r i l l bc pL lb-i r shed i n t l i c nea r I ' u t u r c i n Eu roDc . r bu t a tthe t in re o f th is vu ' r i t ing thc l i te ra ture c loesnot provide an)' inforntat ion base-d on al l-topsies.

As regards biochcnt ica l chanses in

I I n the June 1966 i ssue o f the ln r ( rnu t i c tno lDrug Therurr . r , .NcH..sfu, t tar(2) Ayd states: "Faurbvehas perf t t rmed postmortem studies of the CNS ln30 c l r ses . In a p rov i s iona l su rvey o f the f i r s t l 8cases ( l 5 d rug - induced and th ree spon taneous)a t roph ic ce l l s were found in the c luda le nuc leustn l 3 cases . "

A m e r . J . P s y c h i a r . 1 2 1 ; 8 , F e l . l 9 6 E S u p p .

chorco-athetos is . i t i s * 'o r th rnent ior r inc theu 'ork o f tw 'o Canadian authors(32 ) r i ' l ro ob-sen cd such i rbnornr i r l n ror e t t rents i r r nr r )n-k t - 'ys u ' i th d iscret - - t les ions of the nr idbra in .Patho log ica l chanqes in t l r r - svster r . r o f thes r r bs tant i i t n igrur sce nrc-d to c l Lrsc c( ) r r rsct rcnr ( ) rs but i r e- re i l ( ) t ncccssr l r \ t t l r cht r rc0-nthcto ic i nr ( ) \ c -nr r - -n ts . On thc ' t r t l tc r h l in r l . tu r rl r t r r r n r t l s c r h i h i t i n g l c s i o t i s o i t h c c l o r s o n t c - t l i -l u l f i b t . r s t r f t hc cc rchn r l pcc lL rnc l c und t l i er r r b ro - t cgn r r ' n to - sp in l r l t r uc t . sh t r r i c ' d cho rc i -f o rn r n )o \ en rcn t s i n t l r r - c t - r n tn r l l t r ' n r l l i r n t ' ' s .SL rch l es ions \ \ e r c assoc ia t cd t t i t h l r : g l c r c l so l ' se ro ton in and n t - r r n ra l l e r c l s o i dopa rn incin t hc co r respond inu s t r i a tun r . The i n j ec -t ion r - r f har rn ine or harnra l ine a l tc rc-c l thccharact r - - r o f thcse abnorrna l nror e r l rcnts .Thc -s t ' f i nd ings . i t con f i r r nc -d by n ro r r - r ' x -t cns i r e cxpe r i n r r . n t s . c ( )u l d p ro r i d r ' i r t i po r -t l i n t c l r r c \ l \ t o t i r c n l r t L r r c r - r t d ruc - i nd r r ccdr l vsk incs ias l r r t d l i l so \ uggcs I t hcn rpe r r t i et l lC i tSL l Ie-S I t l g1t1-1- ! -g1 : i rC l t t l i : r , r t ]c fs .

T i t c l r t t c c , , - l i r t u r t t r - 1 1 1 . i . . 1 j g ; 1 l r r ; 1 t n l t l I I I t .i i i t r c l r i s i ' r e t l t r e t t l l r l ' t r L i n t l i n r r : : ( r c - i ; i . t i t r l l* i t h u t l r e t t r i d l i r r t l n t \ r r c l t r i r i C n t r ) \ c n t c n t s t r it l t r ' e r t r cn r i t r c : r l ocs t . t r r t h l t r c t h r - ' ! ' i u t f l r e t c r -i : t i c s o f c l t o r cu hL r t l l t : t hc dcsc r i p t i o r r t r fb rac l vk rnc ' s i l i . - " r . r t c r rn app l i cd t o s l t i i ir cqu la r r hv thn r i ca l mo r cn ten t s o f l l r gc un tp -l i t L rde . " Thesc rnc luc le " t i c s . t r f t cn cons i s t i ngof cornp l r - ' \ . c t )ord inatc 'd . rhv thrn ica i n tor c-nrcnts o i thr ' jau. . l ips . tonguc ur - rc i pu l i r tc"( -5 ) . Th is svnc l ronre u i rs l r lso c iescr ibr 'c l asonc o f t hc sec1 r - r r l l t c o f r t t n Econon ro ' s d i s -r ' use and r i us ca l l ed t he ' f ' i r - cu t che r ' s t ongueb r t he n .L r r ( ) l os i s t \ t r f t i t c pc r i o j r , f t t t cs r c l r t c ' p i t l cn r i c o f cnc r -ph l i i t i s . ThL ts . t i . l r L l t \ cr l r : k i ncs ia l r ppc l r r \ t r r i l r r c l n l l n \ t r - . t t L l r csi i r con r r l t o r t r i i t h t hc n r - -u r t , l t l g i c ; r i d r : o r t i c r s( r t v t t l t Ec t i r t on t t r ' s d i sc l Lsc .

( lo tnnren l

The causc-and- t - ' f fec t rc la t ionsh ip bctu er -nneuro lept ics and tard i r , ,e dvsk incs ias is d i f f i -cLr l t to estab l ish r i i th cer ta in t ' r ' and is basedonl l ' on ind i rcc t ev idence. Fronr sonte o f thenrorc deta i led c l in ica l h is tor ies i t is c learthat dysk ines ias were not prcsent in pa-t ients pr ior to thc i r t reatn tent u ' i th ncuro-

- The cho ice o f the te rm b r l rdyk ines iu i \ s ( )n re -uha t un f r l r l una te because . acco rd ing to n t ( ) s l : ru -tho rs . i t meuns genera l s lou ing o f n tovenren t : .

f f i l gtpulat ion" (as oppost- 'd to 26 pcr-

] , r p , , r i .n ts t rc l l t c t i r i i th ,d r t rgs ) bu t such

"nr ,ur t ,un, i l r r ' "qcncr l t l i r l l0 t as F) r ( ) -

] . . " - . * t r nd d i s t i nc t l t s t h t r se c l r L r s - i nduced .

;i,tII

t (

T A R D I V E t ) I ' S K I N E S I A I N P A T I E N T S T R E A T E D W I T H I v I A J O R N E U R O L E

lept ics. Thc possibi l i ty of chorea and nryo-clonias bein-rr coincidental is \ ,erv remotesince such condi t ions are rare. at least insub jec ts pas t the per iod o f ado lescence( 13 .I 4 ) . The bucco- l inguo-nrast icatory s-vn-drome is e-asi lv recognized and is so t 'u 'p icalthat . based on four cases. Sigwald r ' " 'as ableto state in 1959: "Tht- s1, 'nrptontatologr, ofsuc i r dvsk incs ias cons t i tu t r -s qLr i t c a tvp ica lc l in ica l g roup and ind i r idua l d i f fe renccs Aret r n l r i n d e t a i l s . "

- f o nrr kr torr l , - 'dge. th is sr nclrornu. l ras not

hccn t icscr ibccl i r r i . rn\ t r thcr cont ' i i t i t rn c\-c t f l t . l i l i \Cq t tC l l t i r i \ r ) n EC( ) l t ( ) l ) l ( ) s c r tCCprh -. i l i t i ' . P l i t i c r t t : e r i t i h i t i r r c t l r i ' \ c ( l L l c l t r l l u s tb e c r c c c r l r r r g l r r i r r c c t , n s i d c r i r r g t h l t t h c

- i f c l t cp ' r r r l e n r re c r t t i e t l - l ( ) r c ' . i l ' \ l l r ( ) . I u t t u l dl i k c t t r c t r n c l L r e l c t h i s r c r i c u b v p a r a p h r a s i n gE i t i ns I I I t : t l t c cu r r su l r c l u t i t r ns l r i p L r r t r i c cnt rcatn tc l l t r , , i th ncLrr t r l t .p t ics l inc l t t r l r l dys-k i n c s i r L i : p r c s u n t p t i \ c . b L r t i s l i k c - l i e r t h a nt h c o t h c r p o s s i l , r i l i t i c s .

Su nt r r rarv

I l r i r p l lL rcr rc \ iL - \ \ s duta f ront 2 l p t rb-I r c l t i t r n : d e ' c r i h i n s t a r d i v e d y s k i n e s i a i np t r t r e n f c t r c r r t cd r i i t h pheno th iaz ines andi r t l r t ' l ' l tCL r i ' r r i cn t r c l r gen ts . The l i t c ra t r , r r e re -t r \ ) r t \ i . i n i r r ( \ r i n t . r t e l \ - 500 pa t i en t s t - - xh ib i t i ng.L ' \ I r t l l ' r r n l r c i l r t ' l t c t e r iZed b ) ' , | ) cho re i -i i , l ' i t t r i l \ t r t ' l o l t i c i r nd pecu l i a r r hV th r i l i ca ln t ( ) \ r ' n l e n l \ . 1 ) l h i gh i nc i dence o f ab -l l I l ' 111 r1 n l r r \ cn te r t tS i n t he o ra l r cg ion : 3 )l l r t c r r cCu r r cncc r r f t hc svnd ron rc i n t hec( )ursc o f t rcat rnr .n t . or even af ter d iscon-t i nuu t i on o f d rugs ; 4 ) pe rs i s tencc o f symp-tonut to loq- r ' for nronths or years in a largenunrber o f pat ients l and 5 ) a pc lor rcsponseto r,rn\, tr pe of theri ipy.

Oldcr pat ients . \ \ ,onten. and ind iv idua lsr i i th organic bra in d isorders seem to bepu r t i c r r l u r l r p rone t o t h i s t ype o f dysk ines ia .l r l t h t , i r gh t hc re a re n tanV excep t i ons . The rei r n , , t lc f in i te proof that drugs are respons i -[ r lc lo r thc so-ca l led tard i l 'e dy,sk ines ia butthcrc is e . , idencc- that the syndronte is drug-rndrrce 'c l on the bas is o f the fo l lowing facts .l ) l r t i r r r c r c l a t i onsh ip bc tween even ts o fp l rarnacotherapy ' and the appearance ofsr n tp tonrs : 2 ) the ext rente rar i ty o f thesvndrome bef ore thc usc o f psvchot rop icdrugs: and 3 ) the s inr i la r i t .v betu, 'een tarc l rvedvsk ines ia and cer ta in mani festa t ions ob-

46

served dur ing the sreat epidemic ofEcononto's disease.

R E F E R E N C E S

1 . Avd . F . J . " J r . : A Survey o f Drug- IE x t r a p v r a m i d a l R e a c t i o n s . J . A . l v f . A . 1 7 5 : tr 0 6 0 . I 9 6 l .

2 . A v d . F . J . . J r . : P e r s i s t e n t D y s k i n e s i a : A N e u .ro log ic (omp l i ca t i on o f N fa jo r T ranqu i l i zcqI n t e r n a t i o n a l D r u g T h e r a p y N e u s l e t t e r . v o l . l .r t o . 6 . J t r n e 1 9 6 6 .

l , B l k c r . . { . B . : C l i r i i c l L l N e r t r r r l o g r ' . 2 n d e d\e t i Y t ' r r k : Hocber . 196 i . pp . l l - 1 -1 -8 i -1 .

J . f l r e k n c r . S . : N c - r r r t l l r r g i c S r n r p t r l n r s u r t h[ ) h c n o t ] . t i ; r z i n e s . I l r i t . \ l c ' d . J . 2 : f i l ( ' . I , l 6 J

- i . B r l i i r t . I - . : D i : e l s C s i r f t h c \ c r r ( ) u s S \ \ t ! ' m .6 t h c d . l - t r n d o n : ( l r f r r r c l L , n i " c r r i t v P r e r ' .l e 6 l . p p . - l t l 9 - , 1 9 9 .

6 . B r l rn t l n rp . F . : Te tn r [ - ,en t rc ine T re l t t n ten t i n Per -s i s t i r r s Dvsk ine .s ia Car rsed hv Ps l , chopharmaca ,, { n r c r . J . P s 1 ' c h i a t . 1 I 8 : - s 5 l - 5 - s 2 . 1 9 6 1 .

7 . Degkr r r t z . R . . an r . l Lu renburger . O . : Das te f .nr in l le er t r : rpy ' ranr idale Insuf f iz ienzbzw. Dc.fekts l 'ndrom info lge chronischer Anwendun3\ ( )n Neuro lep t i k r . Nen 'enarz t 36 : 173-17 t , ,1 9 6 - 5 .

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por ts \ \ 'as bv Schi i r recker . tvho descr ibed a

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nrcd ica l l i tc - r ; - t turc- or iu t r c ' bce n rc l rd a t

sc ien t i l i e n r ce t i ncs l ' r on t . l t r l v I 966 t o Oc to -

bL -1 t 9 l i 7 .

S L I P P I E \ I E N T , A , R Y R E F E R E N C E S

1 . , { 1 d . F . J . . J r . : P e r s i s t e n t D l s k i n e s i l r : , { F t r r -ther Rept r r t . ln tcrn l r t ion l r l Dr t tg Ther lp l ' Ne-u 's-l e t t e r . I l r y 1 q 6 7 .

l , A l d . I - . J . . J r . : Pe rs i s ten t D l sk i nes i : r : , { Nc t t -ro l t rg iu ( ontp l ic t i t i r )n o f 1 \ l l r jo r

- f r l rnc l t r i l i z , - - r . .

N le , . i i e ; r l Sc iencc - l l t : - i l - - 10 . . l une 196 ; .3 . F l e r S , r L r i g n l r n . \ 1 . . f : ( ) r l t l i n g e \ . X . . l r n r l C ' l e . 1 c t .

J , : S \ nd r ( )n rc \ e h t r r c< j f o rn tes t - t 1 r r pe rk in i ' ' i c .t l r r r . r h l c : t r u i r r c i v c r s i b t l c r l r p r c s l r l t i l r ' t l c n l p r , r -I o n ! , - i p i r r l e s l r c t l r ' ( ) l c p t i r l t t c r . . \ t t t t , \ l c r l j r ' r ' -

p - ' r e h o l . 1 l - 1 . l t ( . - I q 6 . 1 9 6 6- 1 . C h l i t e l r u , R . . F . r t t . R . . C r o : l t t l r t b c r t . I L . . . t n t i

P e r r c t . . l . A . : \ P l . ( i p ( ) \ 1 1 ' t t t t e l r s t l c t r r t ' t i e o l l i sspusnro t l i c l t t L - i r t t e ( ) l l f r d t t n l r i t i t n l r ' l l t I ) i r r t l c i l -r t r l e p t i c l u e s . , ' \ n n . \ l e t l i c , r p s r e h , ' 1 . 1 l - 1 : I l { } - l I l .I 9 6 6 .

- 5 . C o r r t u . F . : t s e g l e i t r v i r k ( ) n g e n . K o n t p l i k l t t i t r n c nr tnd r tnve r t rag l i chke r t t ' . r sche inunge 'n be i ps ) -

c h i a t r i s c h e r P h l t r n r a k o t h e r l t p i e . A r c h . P s l c h i l r t .N e r v e n k r . 2 1 0 : q 7 - l 1 2 . 1 9 6 7 .

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f i . C r l r n e . G . E . . R t r i z . P . l \ 1 . . r n d K e r n , r h l n .W'. J . : EfTc'cts of Drug lv f l rn iptr lat ion ()n Trt r -d i ve Dysk ines ia . read a t the l2 l rd annu ; t lmce t ing o f the Amer i can Psych ia t r i c Assoc i r t -t i on . De t ro i t . N { i ch . . N {a1 ' 8 -12 . 1967 .

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\ : r r n . , { . : L a t e n t P a r k i n s o n i s n t ( u , i t h C o m p u l -' t c . { c t i v i t - v and Ey ,e Spasnrs ) . Re leased by ,l . . r r ! a c t i l . P s y ' c h i a t . N e u r o l . 1 3 9 : 2 8 9 - 2 9 - 1 . 1 9 6 0 .

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