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Treatment of Persistent Phenothiazine-Induced Oral Dyskinesia RECEIVED

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Treatment of Persistent Phenothiazine-Induced Oral Dyskinesia RECEIVED ,~ .- , ,\ . · : ••'. ' I. • Treatment of Persistent Phenothiazine-Induced Oral Dyskinesia RECEIVED By PETER A. ROXBURGH DEC 1 1 2006 Since the first description of persistent ora! with spasmodic movements of the lips. The dp kinesia following phenothiazine treatment tongue writhes continually, is often truly by Sigwald in 1956 a good deal of evidence has hyp ertrophied and may~ protruded between accumulated indicating the regular occurrence the lips in a 'fly catching" manoeuvre. Associ­ of this syndrome. However there is a disagree­ ated screwing up of the eyes with the other ment over its incid ence and the aetiologica1 facial movements is often evident. Choreiform role played by phenothiazine drugs. Kline movements of the neck, trunk and limbs occur (1968) in a recent review found a total of 114 to a lesser extent. The irregular spasms of leg> cases of (irreversible' oral dyskinesia and con­ and arms interfere with co-ordination and may cluded that the incidence had been misrepre­ prevent the individua! from feeding himself sented since less than two dozen ofthese recorded or walking unaided. There may be a general cases were previously non-brain damage. impression of extreme restlessness which can It seems likely that confusion has been be considered a form of akathisia. Spasm of crooted by some of the large scale hospital muscles of respiration may occur and give rise 'lUdies through th e inclusion ofcases displaying to grunting irregular respirations. Speech is fun ctional habits spasms. Three psychiatric similarly incoordinate and staccato in quality hospital surveys revealed a similar frequency and a considerable barrier to communication. of occurrence. T urunen and Achte (1967) This fully developed ora! dyskinesia syndrome found 6 per cent. in 480 patients ; Hunter, differs radically from the even well-established Earl and Thorni croft (1964.) 5 per cent. in 250 chewing habit of the institutionalized long­ fe male pati ents ; Demars (1966) 7 per cent. in tenn manneristic psychotic and cannot be 488 patients. Pryce and Edwards (1966) how­ reconciled as a functional development. These ever found a 17 per cent. incidence ofmoderate functional movements of the mouth which are and severe cases, while ignoring a further 7 so commonly seen are likely to be associated mild cases, in 120 female patients. In this latter with the edentulous state and with the range of study oral dyskinesia was associated with total psychiatric drugs, including phenothiazines, intake of phenothiazines and with female sex, which depress salivation through their anti­ but the results differed from the majority of cholinergic action. A further cause for inflation other studies in the absence of associated 'brain of the number of reported cases is the failure dam age' as indi cated by leucotomy, 'organicity' to allow a sufficient period to elapse before orlearning deficit. designating the condition persistent ; 6 months Reference to the description ofsma!l series of would seem a reasonable period (Kline). cases by various authors [Evans, 1965 ; Morphew and Barber, 1965 ; Schmidt and J archo, ' 966), Survey of treatment leaves little doubt of the occurrence, especially O nce with drawal of phenothiazine drugs has in the elderly, of a dramatic persistent oral failed to result in re mission, return to the dyskinesia in response to phenothiazines. In medication or a change of medication is (he fully established syndrome, grOSSJ irregular, reported as ineffective or at best slightly continual side to side or circular chewing effective. T his latter partial containment of movemen ts of the jaw are present, associated the movements can result from the Parkinsonian ", T 278 TREATMENT OF PERSISTENT PHENOTHIAZINE-INDUCED ORAL DYSKINESIA . ~ < sid e effects induced by higher dosage, but the vision from bilateral cataract. Following a ~~~ In patient I , movem e disability the patient experiences is com pounde d four years previously she had become confused ioo 60each minute were com by this additional interference with mus cular sequently developed a sustained paranoid "; psy be rated. In both patier control (Schmidt and Jarcho). The 'p,ycl>o,is was p:aumed to be a r..pame·ta 1Il0vements occurred in • • • • deprivation, but bra m da mage from some other Anti-parkinsonian drugs such as benztropme could not be excluded. She had received chJorp'ro • fbi s declining frequency methanesulphonate and trihexyphenidyl have but did not display abnormal movements until "" an appa rently parallel di been consistently found to be ineffective after being given trifluoperazine two yean after a » , andamplitude. (T urunen and Achte, Schmidt and Jarcho At the ti~e of investigation contin~ gross facial puring the mid-treatm fr~u ent p~t Evans). J menu ,?th Jess -considerable ioval , temporary resurgence a • .. of ~e Ilmbs effectively lttfabted the patient. Wlth ~e n ts • AntIhista~es such as orphen adrine and p~bent also.. a return to phenothiazine drugs, ina occurred, for whicl diphenhydramine have also proved ineffective trifluoperazine and perp henazine, bad not inBu I rot!bcoming. (Schmidt andJarcha). clinical picture nor bad a n month peri od of wi Other changes were I • f d h hi di . ofphenothiaaines. ..•' which could not be volun' A vanety 0 rugs, suc as c or azepoxide, ..J/ I reserpine and barbiturates, are reported as Thiopropazate dihydrochloride than momentarily, beca: having some slight beneficial effect (Druckman, reported (Bruyn, 1962) as effective in treatment phase) eve n th e Seelinger and Thulin, 1962). superficially similar syndrome of Hutitin movements ofthe tongue v Bandrup (1961) reports the only fully sue- Chorea, and on this basis the drug was '!fiial lIlovements to disappear. cessful treatment of persistent ph enothiazine both cases. It induced an unexpectedd coherent in one patient dyskinesia, using tetrabenacine, a benzochinoli- improvement in both patients, th eir mov in the other, while the zine believed to function by depleting hrain were reduced in frequ ency and in ampIi tranquillity allowed spent catechol amines, This drug is not generally before becoming entirely eliminated. ~ to occur for th e first time ir: available. A doub le blind trial of thiopropazatedin The irregular leg mo chloride was undertaken and a me"as occurred from 8 to 16 tin Presentstudy progress from the frequ ency of abnormal m d iminated in the treatm­ Two severely affected pa tien ts were en coun­ ments seem ed a reliable objective measur independent walking ar tered in surveying a population of 120 long­ patients were withdrawn from medication'.· possible. term mainly middle aged psychiatric patients . two week period, and two separa te trea Benefit from the thi A third patient with moderate ill-sustained periods of drugs and placebo were admiDi.t chloride was evident withi: interruptiO~ chewing and tongue movements was regarded separated by a seven day . 72 hours after withdraw. as functional and was excluded, as no movem ents order of presentation of drug and placelJo cases show ed conside rable beyond the mouth region were evident. Both unknown to the investigator. lower 30 mgm . daily d­ patients were severely disabled. Neither had a dihydrochloride, and pa family history of abnormal movements or RESULTS evident on the 60 mgm. da R esults were as illustrated in th e accom dementia. D ISCUSS; ing diagrams. CtlJe I-singh mnle, aged j 7, bad been hospitalized for The use of thiopropa CASE I 28 )'c:JJ"S with a schizophrenic illnessj improving suffici­ Plac.ebo in 'he treatmen t or a condi : ently to work a t gard ening until commenced on pheno­ by phenothiazine require thiazincs seven years previously, He bad developed marked l dystonia and akathisi a on trifluoperazine 5 mgm . twice fication. I ts efficie ncy wo . daily in spite of the addi tion of trihexpbenldyl . Within Iishcd by fur th er tria ls an: four or five months be bad developed abnormal move­ 1.0 or treated cases. Find ing: ments, but over a period of the na t three years further ~ 0 propazate in Hunti ngto trifluop eraz ine, chlorpromaz ine, thioridazine and halo­ 10 20 peridol were administered. At the time of investigation successful im pact on th e r. movements had become extreme and incessan t, and he CASE 2 1"hiopropazate not duplicated with the ' could not safely sit in a chair, function independently or c Dih)'drodi<lride except possibly perph r­ communica te more than his simplest needs. This patient l: Walsh, 1960), and indica ' did not respond to further doses of trifluoperazine or j6 cnti al effects of th is type 0 : perphcnaz ine, to an ti-parkinsonian drugs or to with­ o dal system disord ers might drawal of ph enothiazine drugs for a J2 month period . r_ 20 ~ Thlopropazine, althoug Case 2-T1U1rruJ female, aged j ./. suffered with long­ 0 zinc side-chain as d o standing severe deafness. and more recently impair ed 10 00 ~r:='" ".=i't · ~., j' - ...... i'5; ... .~ • (", :';' ~ .. -. 4~jir- . ... .... .:.. J ~ . •• ..~ • • r.. ""i .lo ' fl-,Fu. • ~'- • ,.. -- ..... • • :"f~ ~ . ,I . " '. .·f'" " .' s: j~ ~ ;.. ;. U !J;t .. ·"., '" tf:- i .":' I, -,.. ' . { . ....." . 3 . lIo ,"~ ~ .. ' .!- f .t:.. ~ !t:J~"':; o!.. .. ~ r; .. ... -:T"t ~ 'l-~ • j,' ~ t .. Q ..-r_:_.. :.. ~(~ ~ ~_ ~:.(.& '~ .,-~ ~...t ;.. ':3 r•• _ _: ~ . :"'; 1 "'r 1'. ... ~-}~ ...j .ttJ.r;~. 'j-::': ; ~;';lf_r. '1 : .l BY PETE ~· A ;- RO~URGH '1" 1 )~t~ !- { t ...:'. r~ ~2t '. !h" "' I. -:l~ ~ 79! ~~ ~ . • '.... '1., I .., !. ~.: tt ..., .;....r. • •.f:-" "1'".:i~. .." ..... , !, • ~ .. .i.ft ~ .. :f ;~ In patient I , movements morc 'rapid than trifluoperazine7 produces less ' parkinSoriis nt:'":' ~~· . : - . ;-;~ 60 each minute were continuous and could not In its use in Huntington's Chorea frank chorea be rated. In both patients a decline to zero is first controlled, then, ·as the optimum' dose tJl 0vements occurred in the treatment phase. is exceeded, signs of parkinsonism appear which fbis declining frequ ency was associated with are not beneficial to th e patient (Lyon).
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