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Received A ug . 22 , 1 989 ; rev is ion rece ived Jan . 2 5 , 1991 ; accep tedF eb . 15 , 1991 . F rom the D ep ar tm en t o f P sych ia try , D epartm en t o fN euro log y , and M ovem ent D iso rders U nit, M assachuse tts G enera lH osp ital, B os ton ; and the P sychoph arm aco log y P rogram , M cL eanH osp ital, B e lm ont, M ass . A ddress rep rin t requ es ts to D r. F a lk , C lin -ica l P sych opharm aco logy U nit, 15 P ark rn an S t.-W ACC 815 , B os-ton , M A 02114 .

C opyr ig h t 1991 A m erican Psych ia tric A ssoc ia tion .

Am J P sych ia try 148:8 , A ugust 1991 l o s s

A R ev iew of 32 C ases o f T ard ive D yston ia

Joanne D . W ojc ik , R .N ., M .S ., C .S ., W illiam E . F a lk , M .D .,J . S teph en F ink , M .D ., P h .D ., J onathan 0 . C o le , M .D ., and A lan J . G elenberg , M .D .

O b jec tive : T ard ive d yston ia , h is to r ica lly comb ined w ith ta rd ive d ysk inesia , is now v iew edas p robab ly having a differen t pa thophysio log y, course, ou tcom e, and trea tm en t responsethan tard ive d ysk in esia . In add itio n , pa tien ts w ith tard ive d yston ia a re repo rted to b eyounger , a nd m ost a re m en . This s tu dy eva lua tes chara cte r is tic s o f 32 patien ts w ith tard ived yston ia and com pa res resu lts to o th er reports . M e thod : Tw enty -fou r pa tien ts had beenre fe rred for resea rch purposes and w ere video taped , w hile e igh t had been fo llow ed clin ica lly .Tw o ofth e authors review ed a ll a va ila b le video tapes and c lin ica l repo rts to assess th e courseo fsym p tom s over tim e . F o r g lobal ra tin gs and ra ting s o fa ffected body parts , tw o sca le s w ereu sed : the Abnorm al In vo lun ta ry M ovem ent S ca le (A IM S ) for tard ive d ysk inesia and a sim ilarsca le for ta rd ive dyston ia . Th e m e thod of case fin d ing does no t prov id e inc idence or prey -a lence d a ta fo r ta rd ive dy ston ia . R esu lts: F ifty -n ine pe rcen t o f th e pa tien ts expe rienced on setof ta rd ive dyston ia sym ptom s w ith in 6 yea rs o f an tipsychotic d rug expo sure; w om en had asho rter exposure tim e . N o patien t had comp le te rem iss ion o fta rd ive dyston ia sym p tom s, and22 w ere m odera te ly o r severe ly im paired w hen th eir m ovem ents w ere m ost p rom inen t.C onc lusio ns: W hile ep idem io log ica l s tud ie s o f ta rd ive d yston ia have yet to b e p erfo rm ed ,these resu lts support th e observa tio ns o f o thers tha t m o st pa tien ts w ith tard ive d yston ia a rem en , have a sho rt h is to ry o fexpo sure to antip sycho tic drug s , a nd m ay in itia lly presen t w ithb lepha rosp asm . T ard ive dy ston ia rare ly rem its com p le tely , ca n cause no tab le d isab ility , an dm ay p artia lly r esp on d to an ticho line rg ic a gen ts .

(A m J P sych ia try 19 91 ; 1 48 :10 55 -1 059)

T ard ive d ys to n ia is a d iso rd er o f ab no rm a lly sus-tam ed po s tu rin g assoc ia ted w ith th e use o fd op am ine -re cep to r b lo ck ing ag en ts such a s an tip sy -cho tic d ru gs . A lth ou gh ch ron ic dys to n ia w as firs t re c-o gn ized in the 19 60 s , pa tien ts w ith ta rd ive d ys to n iaw ere com b ined w ith those w ho h ad ta rd ive d ysk in es ia ,w ith a ll ab no rm a l m ov em en ts ra ted com posite ly onth e A bno rm a l Inv o lu n ta ry M ov em en t S ca le (A IM S )(1 ). S ev era l rep o rts su gg es t th at ta rd ive d ys to n ia gen -e ra lly affe c ts a d iffe ren t p op u la tio n o f psych ia tric pa -t ien ts and m igh t h ave a d iffe ren t pa tho phys io log y ,cou rse , ou tcom e, and trea tm en t re spo nse than ta rd iv edysk ine s i a (2-5) . Th is p ap er ad ds to th e g row in g lit-ena tu re o n ta rd iv e d ys to n ia by pre sen tin g d ata o n 32sys tem atica lly a sse ssed p atien ts .

METHODW e iden tified 32 p atien ts w ith ta rd iv e d ys to n ia w ho

w ere fo llow ed at tw o m a jo r h osp ita ls . T h e m a jo rity o fthe pa tien ts (N = 24) w ere refe rred fo r re sea rch pun-po ses and w e re v ideo tap ed a s pa rt o f re sea rch p ro to -co ls . T h e rem a in in g e igh t w e re se le cted from hosp ita lreco rd s as p atien ts w ith cle a r de scrip tiv e h is to rie s o fta rd iv e dy ston ia . T h ese p a tien ts w ere no t v id eo tap ed .O ur se le ct ion criteria do n o t p rov ide inc iden ce o r p rey -alen ce da ta fo r th is d iso rd er; the se p atien ts d o n o t rep -resen t a ll ca ses o f tand iv e dy s ton ia seen a t th ese in s ti-tu t ion s b u t o n ly tho se fo r w hom video tape s o r c lea rc l in ic a l d esc rip t ion s to m ak e a d iag nos is o f tard ive dy s-ton ia w e re av ailab le . In a ll c ase s, t im e of on set o f th em ovem en t d iso rde r w as de te rm ined by m ed ical h is to ryo r re co rd rev iew .

D iagn os is o f ta rd iv e d ys to n ia w as con firm ed by aneu ro log is t w ho u sed the fo u r e ssen tia l criteria e stab -lished by Bu rke et a l. (2 ): 1 ) th e p re sen ce o f d ys ton icm ovem en ts o r po stu re s, 2 ) deve lo pm en t d u rin g tre at-m en t w ith neu ro lep tic s o r w ith in 2 m on ths o f d rugcessat ion , 3 ) exc lu sion o f o th e r cause s o f secon da rydy s ton ia by clin ic a l an d lab o ra to ry eva lu ation , and 4 )no fam ily h isto ry o f dy ston ic m ov em en t d iso rde r. T he

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WOJCIK , FALK , FINK , ET AL .

Am J P sych ia try 148:8 , A ugu st 1991 1057

TAB LE 2. R atin gs o f 32 P atien ts W ith T ard ive D ys to niaGlob a l

A bn orm al G lob a l

Patien t S exA ge

a t O nse t(y ears ) Psych ia tric D iagnos is

.Du ra tion ofTard iveDys ton ia(years )

Invo lun ta ryMovemen tS ca le S coreF irst L as t

Tard iveDyston ia

S ca le S co reF irst L ast

.Clin ica lImpress iono f C ha ng es

1 M 22 S ch izophren ia 4 3 2 3 3 W orse2 M 22 M ood d iso rder 8 0 0 3 2 B ette r3 F 22 S ch izophren ia S 0 2 2 2 B ette r4 M 24 S ch izoaffec tiv e d iso rder 6 3 0 2 3 Wo r s eS F 24 M ood d isord er S 0 0 3 3 S am e6 M 25 Sch izophren ia 9 2 2 2 2 B ette r7 M 26 M ood d isord er - 2 - 3 - -8 M 26 S ch izophren ia , ob sessive -

com puls iv e d iso rder10 0 0 2 3 W o rse

9 M 26 M ood d isord er , ob sess ive -com puls iv e d iso rder

14 2 2 4 4 B etter10 M 27 M ood d iso rder 12 3 2 3 2 B ette r1 1 M 27 M ood d iso rder 12 2 0 3 2 Bet te r12 F 27 M ood d iso rder 3 1 0 3 3 S am e13 M 28 S ch izophren ia 6 3 2 3 4 S ame14 M 30 Sch izophren ia 1 2 0 3 3 S am eis M 3 1 M ood d isord er 12 2 3 3 3 W orse16 F 32 M ood d iso rder 4 3 2 3 1 B ette r1 7 M 32 M ood d isord er 2 2 2 2 3 S am e18 M 32 S ch izophren ia 6 0 0 3 2 B ette r19 F 33 M ood d iso rder 6 0 0 4 3 B ette r20 F 36 M ood d iso rder 6 4 2 4 4 W orse21 M 38 S ch izoaffec tiv e d iso rder 6 3 2 3 3 B ette r22 F 40 M ood d isord er 10 3 4 3 4 W orse23 M 43 M ood d iso rder 8 3 2 3 1 Bet te r24 M 43 Sch izoph ren ia 1 1 3 3 4 4 W orse25 M 44 P sy chosis 10 3 3 3 3 Sam e26 F 44 M ood d iso rder 3 3 3 4 2 B ette r27 F 45 M ood d isord er 4 3 - 4 - -28 M 49 M ood d isord er 14 3 0 3 1 B etter29 M 58 Toxic psychos is 3 3 3 4 3 Bet te r30 F 64 M ood d iso rder - 2 - 3 - -31 M 68 M ood diso rder 12 2 3 3 4 W orse32 F 69 A nx ie ty d iso rder 8 2 1 3 2 Bet te r

aC hang e in ta rd ive dysk ines ia and ta rd ive dys to n ia . R a tin g based on overa ll clin ica l im p ress ion and no t th e g loba l sco res a lone .

TABLE 3 . M ed ica tio ns Taken a t F irs t and Las t E va lua tion s by 32P atie nts W ith T ard ive D ysto nia

Medica t ionN um ber of P a tien ts

F ir st E va lu at io n L as t E va lu at io nA ntipsy ch o tics 2 5 1 6B en zod ia zep ines 12 25L ith ium 7 12Anticho l ine rg ics S 8Antidep ressan ts 4 9Antih istamines 3 4n-b lo ck ers 1 2A nticonvu lsan ts 0 3B ac lo fen 0 2L ec ith in 0 1

cho tic m ed ica tio n , fo u r w ere tak ing h ig he r do ses , th reew e re tak in g low e r do se s , an d m ed ica tio n d ose w as un -k now n fo r on e. Fo r th e un chang ed on w o rse g rou p ,fou r w ere no lon ge r tak ing an tip sy ch o tic d ru gs , fo u rw e re tak ing h ig he r do ses , o ne w as tak in g a low e r d ose ,th ree rem a ined at th e sam e do se, and th e do se w as

TAB LE 4 . E ffe c t o f M ed ica tions Adm in is te red A fte r th e Deve lop -m ent o f T ard ive D ys to nia in 32 P atien ts

Medica t ionDef in i te lyImproved

Poss ib lyImproved

Unimprovedor W orse

A n ticho line rg icsa 6 7 iOChol ine rg ics 2 4 10B enzod iazep ines 12 4 7R eserp ine 1 2 2D iph enhydram ine 1 3 1L ith ium 1 1 4H alop erid o l 2 0 2Carb ama z ep in e 1 0 0Proprano lo l 0 3 2C lozap ine 1 0 0Baclofen 2 1 2N eural g row th fac to r 0 0 1aA mitrip ty line , ben ztro pine , trih exyphen id yl.

unknow n fo r tw o . T h irte en (87% ) o f th e im p rov edpa tien ts (N = 15 ) d id h av e sh o rte r ex po su re to an tip sy -ch o tic d rugs (le ss th an 6 years ) b efo re o nset o f ta rd iv edy s ton ia . F o r the un chang ed o r w orse g rou p (N = 14 ),

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TARD IV E DYSTON IA

1058 Am J P sych ia try 148 :8 , A ugust 1991

TAB LE 5. C lin ica l R epo rts o f T a rd iv e D y st on iaM ean A ge N um ber ofa t O nse t Pa tien ts in

Item N S ex (years ) D iag no sis C lin ica l R em iss ionK ang e t al . (5 ) 67 35 M

32 F3444

2 2 S ch iz o ph re ni a28 M ood d iso rder8 Anxiety d iso rder7 O ther (aggressive , m ultip le

som atic com pla in ts , ch ron icg as tro in te stin al c om plain ts )

2 U n s p ec i fi e d

S

Y assa e t a l. (6 ) 7 S M2 F

356 1

S Sch izophren ia1 M en ta l reta rda tion1 S en ile dem entia

0

Y assa e t a l. (7 ) 8 6 M2 F

46 .8a 5 Sch izophren ia3 O rgan ic m en ta l d iso rder

-G ard os et a l. (8 ) 10 6 M

4 F3432

4 S c h iz o p hr e ni aS M ood d iso rder

0

G im enez-R o ld an e t al . (9 ) 9 S M4 F

3438

1 O bsessive -com pulsive d iso rder6 Sch izophren ia2 Ch ron ic psychos is1 S ch izo af fective d iso rder

0

L ieb erm an e t a l. (10 ) S 4 M1 F

2829

3 S c h iz o p hr e ni a2 M ood d iso rder

0L ieb erm an et a l. (ii) S S M 32 2 Sch izophren ia

3 M ood d iso rder-

Y assa e t a l. (12 ) 9 7 M2F

44.la

Y ada lam et a l. (13 ) 4 3 M1 F

2638

2 S c h iz o p hr e ni a2 M ood d iso rder

1b

W ojc ik (p resen t s tu dy) 32 21 M1 1 F

3440

8 S c h iz o p hr e ni a2 S ch izo af fective d iso rder

20 M ood d isord er2 O th er

0

To t a l 156 9 7MS9 F

3 3Mc44Fc

6

aG roup m ean . t ha l amotomy .CExc lu d in g da ta from Y assa e t a l. (7 , 12 ).

n ine (6 4% ) had m o re than 6 yea rs exp osu re to an ti-p sy cho tic d rug s .

T ab le 3 show s th e num ber o f p atien ts tak ing m cd i-c an on s (b ro ken dow n by class ), bo th w h en th ey w erefirs t seen an d a t th eir la st ev alu a tion . T h e m ed ica tio nstaken a t la st eva lua tio n m igh t b e v iew ed as th osew h ich co n tro lled ta rd ive dy s ton ia be s t on a t le as t d idn o t ap pea r to w orsen it . B enzod iazep ine s w e re m ostfreq uen tly p re sc rib ed (N =25), fo llow ed by an tip sy -cho tic d rug s (N = 16) an d lith ium (N = 12 ). T o tre atta rd iv e d ys to n ia , a v arie ty o f m ed ica tio ns w e re tried ,bu t no c lea rcu t resp onse to an y sin g le c lass o f d rugw as ev id en t (tab le 4 ).

Twen ty - two p atien ts (69% ) w e re m od era te ly o r se -v en ely d isab led w hen the ir m ov em en t d iso rde r w asm ost p rom inen t. Im p a irm en ts o f sp eech , v is ion , s it-tin g , and w a lk in g occu rred , w h ich in terfe red w ith ac -tiv itie s o f da ily liv in g an d w e re soc ia lly em ba rrass in g .P a tien ts o ften foun d the se m ov em en ts to be pa in fu l;f iv e pa tien ts had fix ed ab no rm a l po s tu re s d ue to atro -p hy . E igh t pa tien ts (25% ) rep o rted m ild in te rfe rencew ith fu nc tion ing ; o n ly tw o p atien ts had no com pla in tso f d isab il ity . T en d isab led pa tien ts s top ped th eir an ti-

p sy cho tic m ed ica tio n ; s ix im p rov ed , on e w as un -chang ed , and th re e w o rsened .

N ine te en o f the 24 p a tien ts firs t ev alua tion v id eo -tape s w e re rera ted w ith th e A IM S and th e ta rd iv e d ys-to n ia ra t ing sca le . T h eir sco re s w ere com pa red to c i-th en th e ir las t eva lu atio n o r las t v ideo tap e (m eandura tio nS338 m on ths). F o r the se 19 pa tien ts , th erew as m in im a l im pro vem en t in th e A IM S sco ne ov entim e (from a m ean scon e o f 5 .64 .8 to 4 .74 .0 ) an dm in im a l ch an ge in th e tard ive d ys to n ia ra ting scon e(from a m ean sco re o f 7 .0 4 .2 to 6 .14 .6 ).

D ISCUSS IONTh is p ap er de scribe s 32 pa tien ts d iagn osed w ith ta r-

d ive dy s ton ia , con sid e red a sub typ e o r an aty p ic a lfo rm of tard ive dysk ine s ia (3 , 4 ). W hen w e add ourp atien ts to p rev iou s rep o rts (5 -13 ), th ere a re now 156w e ll-de scribed ca se s o f tard iv e d ys to n ia : 97 m en and59 w om en (tab le 5 ). M en ten d to b e y ounge r th anw om en . A m a jo rity o f o u r p a tien ts h av e m ood d iso r-dens , w h ile in o th er se rie s 4 0% are sch izop hren ic , 4S%have m ood d iso rd ers , and the rem a in ing 1 5% have a

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W OJC IK , FALK , F INK , ET A L .

Am J P sych ia try 1 48:8 , A ugust 1991 10S9

va rie ty o f d iagn ose s in clu d in g anx ie ty d iso rd e rs , on -gan ic b rain syn drom es , an d g as tro in tes tin al d iso rde rs .Whi l e m ost ta rd iv e dy sk ine s ia p a tien ts are o ld e r(9 0% are o ve r th e ag e o f 40 ) (4 ), in ta rd iv e dy ston iathe op po site is fo un d : 6 3 % (N = 87 o f 13 9) a re u nd erag e SO . C asey (4 ) sug ge sts tha t th e inc idence o f tard ivedy sk ine s ia m ig h t v ary w ith ag e a t firs t exp osu re ;yo unge r p atien ts m ay h av e a linear cu rv e , w ith a 3% -4% new case inc id en ce each yea r, w h ile the e ld erly(o ve r age 60 y ears ) sh ow a s igm oid do se re spo nsecu rve w ith larg e risk (5 0% ) occu rrin g in th e firs t 3yea rs o f d rug trea tm en t. T o d ate , s im ila r ep idem io lo g -ica l s tu d ie s o f ta rd iv e dy s ton ia have n o t b een p er-fo rm ed , so th at its inc id en ce ra te an d risk g rou ps a rest ill to be de fin ed . H ow eve r, it does seem th at tard ivedy ston ia p atien ts , e spec ia l ly the yo ung , d o h av e a sho rtex po su re h isto ry (1 4 ).Whi l e w ithd raw a l dy sk ine s ia s a re com m on , w ith -d raw a l dy ston ia ap pea rs to be un comm on and rem is-sion rare (14 ). O n ly s ix w e re con s ide red to haveach iev ed com ple te rem iss ion , on e o f tho se a fte r ath alam otom y . F urth erm ore , u n lik e ta rd iv e dy sk in es ia ,ta rd iv e dy s ton ia frequ en tly cause s pa in an d d isab ility .

B leph a rospa sm , rep ea ted con trac tio ns o f the o rb icu -lan is ocu li m uscle , m ay rang e from in creased b lin k rateto p ro lo ng ed ey e closu re . B lep ha rospa sm can be id io -pa th ic o r cau sed b y n eu ro lo g ic a l d iso rde rs su ch as en -cep ha litis o r se izu re s (15 , 1 6 ), bu t it is o ften assoc ia tedw ith neu no lep tic d ru g use . Som e au th o rs have co ns id -en ed it a s ign o f ta rd ive d ysk ine s ia , b u t, d ue to itsdy s ton ic n atu re , w e su gg es t tha t it is m ore app rop n i-a te ly g ro up ed w ith d ys ton ia . B o th th e p resen t s tu dyan d tha t o f G andos e t a l. (8 ) no ted an in cre a se in b linkrate a s a com m on early sym p tom o f tard ive m ovem en td iso rde rs . If a pa tien t w ith b lep hano spa sm is psy ch ia t-n ica lly s tab le , it m ay be ad v isab le to tape r neu ro lep ticdo se and lo ok fo r em e rg in g m ovem en ts.

A re la ted d iso rd er, tand ive m yo clonu s (17 ), w ithb rie f, inv o lu n tary m usc le con tra ctions and jerk ingm ovem en ts , h as b een de sc rib ed . T w o o f o u r p atien tsdeve lo ped tard ive m yo clon us in ad d itio n to tard iv edy s ton ia . It is un clea r if th e re cen t inc re ase in repo rtso f o th e r ta rd iv e m ov em en ts is th e resu lt o f in cre asedreco gn itio n , m ore care fu l exam in a tion , o r o the r a s y etu nk now n facto rs .

T he re spo nse s o f ta rd ive dy sk in es ia and tan d iv e dy s-to n ia to tre a tm en t h av e s im ila ritie s and d ifference s.B o th type s o f m ov em en t d iso rde r im p rov e, a t le a sttem pora rily , w ith do pam ine b lo ck ing an d dopam ined ep le t ing agen ts . K ang et a l. (5 ) fo un d te tra be na zin em ost he lp fu l fo r tan d iv e dys to n ia , w h ile L ieb erm an sg roup (10 , 1 1 ) rep o rted b rom ocn ip tin e bene fic ia lw ith in a the rap eu tic w indow . B o th g rou ps o f inv es ti-

g ato ns ob se rved tha t an ticho lin en g ic agen ts, w h ich u su -a lly tem pora rily agg rav ate o r unco ve r tard iv e d ysk ine -s ia (8 , 1 2 ), p ro v id ed som e b en e fit fo r ta rd iv e dy s ton ia .O ur fin d in gs su pport the con ten tio n th a t a t lea s t som ep atien ts w ith tand ive d ys ton ia a re b en e fi ted by an ticho -lin eng ic ag en ts (10 ). G iven th e p ers is ten t and po ten -tia lly d isab ling na tu re o f ta rd iv e d ys to n ia , neu ro lep tic ssho u ld b e jud ic iou s ly p resc ribed . A ltho ugh ind ica teda t tim es in the tre atm en t o f m ood d iso rde rs, neu ro lep -tic use sh ou ld be avo ided , if a t a l l po ss ib le , w ith th isd iag no s tic g rou p .

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