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Antipsychotics according to HESI

The population of the United States doubled between 1900 and 1950; during this time, the population in public mental hospitals quadrupled. The a erage length of confinement was usuall! !ears, and the trend was definitel! toward an annual increase in clients admitted to such institutions. "lient and emplo!ee in#uries caused b! combati e or abusi e clients led to the common use of ph!sical restraints and client isolation. $efore the de elopment of the antips!chotic agents, the treatment of mentall! ill clients consisted of either being isolated %i.e., hidden in cellars or attics in their homes& or, if the! came to the attention of local authorities, being transferred to #ails or homes for the insane. 'ctual therapies used before the ad ent of the antips!chotic agents were water or ice pac( therapies, strait#ac(ets or other ph!sical restraints, shoc( therap! with insulin or electricit!, lobotom!, and the use of a few drugs such as paraldeh!de, chloral h!drate, and the barbiturates. The era of antips!chotics was ushered in with the release of chlorproma)ine %Thora)ine& in the earl! 1950s. "hlorproma)ine belongs to a class of drugs referred to as phenothia)ines. 'ntips!chotics are also referred to b! the outmoded term *ma#or tranquili)ers.+ These agents bloc( dopaminergic receptors in the ",S and, while not curati e, for the first time, allowed adequate s!mptom control % Box 19-1& to ma(e communit! li ing a realistic opportunit! for man! with significant ps!chosis-related conditions. The use of the antips!chotic drugs pro ed to be a re olutionar! force in the ps!chiatric field. The duration of institutionali)ation has decreased from !ears to months for man! clients; other clients li e at home and are treated at communit! mental health centers. The reported incidence of in#uries has declined, and man! large public mental health facilities ha e closed. BOX 19-1

Positive and Negative Symptoms in Schizophrenia Clients with schizophrenia present with a wide variety of symptoms that are categorized as positive or negative. ost antipsychotic agents prod!ce an effect on the following positive symptoms" agitation# anxiety# hall!cinations# poor hygiene and dress# hyperactivity# del!sions# paranoia# and hostility# whereas the negative symptoms of flat affect# social inade$!acy# diminished speech patterns# %!dgment# insight# and others are !s!ally less responsive to dr!g therapy. &he target symptoms are !sed as monitoring parameters to eval!ate the individ!al's response to the medication. &he atypical antipsychotic dr!gs (e.g.# clozapine# risperidone# olanzapine) appear to *e more effective than older typical ne!roleptic agents against negative symptoms# altho!gh one analysis noted little difference in symptom control *etween the typical agent haloperidol and the atypical olanzapine (+osenhec, et al.# -../)
The antips!chotics fall into two broad categories. the earlier t!pical agents, including chlorproma)ine %Thora)ine& and haloperidol %/aldol&, and the newer at!pical agents including clo)apine %"lo)aril& and olan)apine %0!pre1a&. 'ripipra)ole %'bilif!& represents a no el approach with dopaminergic agonist-antagonist acti it! and is discussed separatel!. 2hile the newer at!pical agents ha e largel! replaced the older t!pical antips!chotics, both are discussed here. &a*le 19-1 presents selected agents.

TABLE 19-1

-- ANTIPSYCHOTICS

Typical Oral Adult Daily EPS Anticholi Cardio"ascular [*] Agent Chemical Class Dose (mg) is! TD is! nergic Sedation is! T#P$CA% A&T$PS#C'OT$CS chlorpromazine 0liphatic -..12.. oderate 3igh oderate 3igh oderately high (&horazine) phenothiazine (orthostatic hypotension) fl!phenazine Piperazine ..41-. 3igh 3igh 5ow 5ow 5ow (Prolixin) phenothiazine haloperidol B!tyrophenone 1114 3igh 3igh 5ow 5ow oderate (3aldol) loxapine 6i*enzepin 7.11.. 3igh 3igh 5ow oderate 5ow (5oxitane) mesoridazine Piperidine 1..18.. 5ow 3igh 3igh 3igh 3igh (prolonged (Serentil) phenothiazine 9& interval) molindone 6ihydroindolone 4.11.. 3igh 3igh 5ow 5ow 5ow ( o*an) perphenazine Piperazine 171-8 3igh 3igh 5ow 5ow 5ow (&rilafon) phenothiazine pimozide (:rap) 6iphenyl*!tylpip 111. 3igh 3igh oderate oderate oderate eridine (prolonged 9& interval) thioridazine Piperidine -..12.. 5ow 3igh 3igh 3igh 3igh (prolonged ( ellaril) phenothiazine 9& interval) thiothixene &hioxanthene 1.1/. 3igh 3igh 5ow 5ow oderate (Navane) hypotension) (orthostatic AT#P$CA% A&T$PS#C'OT$CS clozapine 6i*enzodiazepin /..184. 5ow 5ow 3igh 3igh 3igh (Clozaril) e

Comment

5ong-acting in%ecta*le decanoate form availa*le 5ong-acting in%ecta*le decanoate form availa*le

Controls positive and negative symptoms

Agent

Typical Oral Adult Daily EPS Chemical Class Dose (mg)[*] is!

olanzapine (=yprexa)

6i*enzodiazepin 411. e

$!etiapine (Sero$!el) risperidone (+isperdal)

6i*enzodiazepin /..14.. e Benzisoxazole 117

ziprasidone (Aeodon)

Benzisoxazole

8.11-.

Anticholi Cardio"ascular TD is! nergic Sedation is! Comment (seeBox 19-1) :ften effective in refractory cases See text for significant adverse effects# incl!ding *one marrow s!ppression# seiz!res# drooling ;very 11- wee, <BC co!nts re$!ired 5ow 5ow 3igh 3igh 3igh Controls positive and negative symptoms +is, of weight gain and development of dia*etes mellit!s 5ow 5ow oderate oderate oderate Controls positive and negative symptoms 5ow (> if 5ow (@> 5ow 5ow 5ow Controls positive and ?7 mg) if ?7 mg) negative symptoms >;PS for doses greater than 7 mg daily 5ow 5ow 5ow oderate oderate Controls positive and (prolonged 9& negative symptoms interval) 5ow 5ow 5ow 5ow oderate oderate high Controls positive and negative symptoms Partial agonistBantagonist activity may explain !ni$!e profile

&O(E% A&T$PS#C'OT$CS aripiprazole Class not yet (0*ilify) esta*lished

1.1/.

WBC, <hite *lood cell. EPS, ;xtrapyramidal side effectC TD, tardive dys,inesia.

6oses *eyond this amo!nt are of $!estiona*le *enefit *ased on maxim!m effective dose as demonstrated *y 6avis D Chen# -..8.

!T! is a 19-y"ar-o#d $a#" %ho pr"s"nts to th" "$"rg"ncy d"part$"nt &E'( %ith his $oth"r! H" ")hi*its ha##+cinations and co$*ati," *"ha,ior! According to his history- his *"ha,ior has *""n d"scri*"d as *i.arr" o,"r th" past /"% %""0s- *+t has "sca#at"d to a point that it pr"s"nts a h"a#th and sa/"ty iss+" to !T! and his /a$i#y! Th" $"nta# h"a#th crisis t"a$ at th" E' ",a#+at"s !T!1s stat+s- /inds no i##icit dr+g or a#coho# +s"- and r"co$$"nds an initia# dos" o/ ha#op"rido# &Ha#do#( 2 $g intra$+sc+#ar#y &I3(! 4hat ar" th" i$portant di//"r"nc"s a$ong th" typica# antipsychotics5 The older t!pical antips!chotics ser e as dopaminergic antagonists at both 3 1 and 34 receptors in the ",S %Eig!re

19-1&.

6ig+r" 19-1 T!pical antips!chotics act to bloc( posts!naptic dopamine receptors. T!pical antips!chotics ha e a greater affinit! to 3 4 receptors than to 31 receptors.

The t!pical antips!chotics are represented b! a number of classes, including %1& aliphatic phenothia)ines %e.g., chlorproma)ine 5Thora)ine6&; %4& piperidine phenothia)ines %e.g., thiorida)ine 57ellaril6&; %8& pipera)ine phenothia)ines %e.g., fluphena)ine 59roli1in6&; %:& the but!rophenones %e.g., haloperidol 5/aldol6&; %5& the thio1anthenes %e.g., thiothi1ene 5,a ane6&; and %;& the dih!droindolones %e.g., molindone 57oban6&. 2hile the chemical class helps predict therapeutic and ad erse effects, a more useful classification scheme for the t!pical antips!chotics is based on affinit! for 34 receptors and are stratified as low-potenc! %requiring higher doses&, moderate potenc! %midrange dosing&, and high potenc! %using lower dosing&. The basis for classification is the quantit! of medication necessar! to produce an equi alent effect when compared with other agents in the same categor!. <or e1ample, 100 mg of chlorproma)ine %Thora)ine& is considered to be appro1imatel! equi alent to 50 mg of mesorida)ine %Serentil& or 4 mg haloperidol %/aldol&. Thuschlorproma)ine is a low-potenc! agent; mesorida)ine, an intermediate-potenc! agent; and haloperidol, a high-potenc! agent %see &a*le 19-1 for t!pical adult doses&. The student is cautioned not to confuse potenc! with effecti eness; potenc! refers to the quantit! of a drug necessar! to produce an equi alent effect as compared with another drug in the same classification. =ffecti eness measures the therapeutic response to arious agents, which, depending on the indi idual drugs being studied, can range from less effecti e, to equi alent in effecti eness, to more effecti e. 'lthough the e1act mechanism of action for the t!pical antips!chotic effects is un(nown, their ma#or therapeutic and ad erse effects result from dopamine bloc(ade in specific areas of the ",S. There ma! be ariation in response to antips!chotics from client to client based in part on pharmacogenetic differences obser ed with these agents %see the Special "onsiderations for 9harmacogenetics bo1 on p. /28&. These drugs also produce an >-bloc(ing effect %h!potension&; most inhibit or bloc( dopamine at the chemoreceptor trigger )one and peripherall! inhibit the agus ner e in the gastrointestinal %?@& tract %antiemetic effect&. @n addition, the! produce an antian1iet! effect b! depressing the brainstem reticular s!stem. 's a group, the! increase the release of prolactin, which infrequentl! results in g!necomastia %breast swelling& and galactorrhea %mil( secretion&. haloperidol 5ha loe p"r i dole6 &Ha#do#- Ha#do# Lactat"- Ha#do# '"canoat"- Apo-Ha#op"rido# - No,o-P"rido# - P"rido# (

/aloperidol is among the more frequentl! used of the older t!pical antips!chotics. @ndication /aloperidol is used in the treatment of schi)ophrenia, ps!chosis, for the control of tics associated with Tourette s!ndrome % Box 19--&, in the treatment of se ere beha ioral problems in children, and for emergenc! sedation in delirium or se ere agitation. @t is also used as an antiemetic in the treatment of nausea and omiting. BOX 19-7

0ntipsychotics and &o!rette Syndrome &o!rette syndrome# a rare CNS disorder that res!lts in invol!ntary# rapid# and repetitive motor movements of m!scle gro!ps# is !s!ally accompanied *y invol!ntary vocalizations. &o!rette syndrome is more common in males# !s!ally appearing *efore age 18 years# and may present initially as tics (facial grimaces and *lin,ing). :ther symptoms incl!de vocal tics or noises (e.g.# gr!nting# *ar,ing# sho!ting# sniffing# and comp!lsive swearing FcoprolaliaG) and movement disorders (invol!ntary# p!rposeless movements). &he symptoms may pea, and wane thro!gho!t the individ!al's life. &he individ!al's intellect!al f!nctions are normal. 0ltho!gh there is no c!re for

&o!rette syndrome# antipsychotic medications have prod!ced dramatic improvement in some clients.
9harmaco(ineticsA3osing /aloperidol, li(e other t!pical antips!chotics, is well absorbed orall! and has an onset of action between 80 and ;0 minutes. The onset of action after @7 administration of the lactate %immediate-release& form is within 80 minutes. /aloperidol is metaboli)ed to pharmacologicall! inacti e compounds that are eliminated in the urine and feces. The elimination half-life of haloperidol is appro1imatel! 40 hours. The t!pical oral adult dose ranges from 0.5 mg twice dail! to 5 mg three times dail!. 3oses abo e 10 mg dail! ha e questionable efficac! for most clients, but some clients ma! require 80 mg dail! or more. Single doses of 4 to 5 mg @7 or intra enousl! %@B& of the immediate-release parenteral formulation of haloperidol lactate %/aldol Cactate& are t!picall! used for acute management. Cower doses are often used in older or debilitated clients. Use of long-acting haloperidol decanoate %/aldol 3ecanoate& b! @7 in#ection results in a prolonged duration of action of appro1imatel! 8 wee(s. This product should not be confused with the shorter-acting parenteral formulation. /aloperidol decanoate is generall! reser ed for circumstances where infrequent dosing is ad antageous, the client has tolerated shorter-acting dose forms, and a dail! dose has been established. This formulation is often used for clients who do not adhere to con entional therap!. @n such circumstances, a number of ethical issues must be addressed % Box 19-/&. The t!pical dose of the decanoate formulation is 10 to 40 times the dail! oral dose administered @7 e er! : wee(s, with the dose titrated to effect. BOX 19-8

;thical and 5egal Considerations in the Hse of Psychotropic 6r!gs &he !se of psychotropic dr!g therapy raises a n!m*er of ethical and legal considerations. &his is partic!larly tr!e for antipsychotic dr!gs# which are associated with significant adverse effects. In many circ!mstances# the client may not *e in a position to f!lly !nderstand the ris,s and *enefits of therapy. It is important for the mental health team to apply the principles of *iomedical ethics to each case. Eo!r *asic principles of *iomedical ethics are *eneficence# nonmaleficence# a!tonomy# and %!stice descri*ed *elow" )* +ene,icence-J6o good.K L 6oes the intervention help the client@ 6oes the dr!g red!ce mor*idity or mortality@ 6oes the dr!g improve symptoms@ &onmale,icence-J6o no harm#K L <hat is the ris, of the intervention to the client@ <hat are the short-term adverse effects of dr!g therapy@ <hat are the long-term adverse effects of dr!g therapy@ Autonomy-J;mpower the client.K L <ho ma,es the decision for the intervention@

.*

/*

Is the client competent to ma,e decisions@ Is the client f!lly informed of the ris,s and *enefits of therapy@ 0* 1ustice" JIs it fair for everyone@K L <hat impact does the intervention have on others@ 6oes treatment or lac, of treatment pose a ris, to the health and safety of others@ 6oes the cost of the intervention deprive someone else of care or intervention@

Balancing each of these competing aspects is often a diffic!lt# *!t necessary process in determining when dr!gs are !sed# which dr!gs are selected# how the decision is made# and what is important to monitor. In addition to the a*ove $!estions# the team m!st as, if the symptoms warrant dr!g therapy# which agents are most effective# which agents pose the least ris, for the client# how m!ch decision ma,ing is made *y the client# and what health and safety iss!es arise if the client is not treated. &he significant adverse effect profiles of antipsychotics may pose an increased legal ris, for prescri*ers and other team mem*ers. &he ris,s of these agents (e.g.# tardive dys,inesia with typical antipsychotics# *one marrow s!ppression with clozapine# ris, for dia*etes mellit!s with olanzapine) have prompted many clinicians to o*tain informed consent for !se of their !se. &he n!rse sho!ld *e an active participant in these decisions and f!nction as the client's advocate.
'd erse =ffects The t!pical antips!chotics, including haloperidol, are associated with a great number of ad erse effects, including orthostatic h!potension, e1trap!ramidal side effects %=9S& including par(insonian tremors, d!stonic reactions, and a(athisia. Dther ad erse effects include sedation, sei)ures, amenorrhea, galactorrhea, g!necomastia, se1ual d!sfunction, urinar! retention, #aundice, blurred ision, heat stro(e, and neuroleptic malignant s!ndrome. "hronic use poses the ris( for tardi e d!s(inesia. /aloperidol can also prolong ET inter al on electrocardiogram %="?& and increase the ris( of the life-threatening d!srh!thmia torsades de pointes. 7ost of these ad erse effects are discussed more completel! in the following paragraphs. T%"#," ho+rs a/t"r r"c"i,ing his /irst dos" o/ ha#op"rido#- !T! co$p#ains o/ n"c0 sti//n"ss! H" has di//ic+#ty in sp"a0ing %ith a s+*9"cti," s"nsation that his tong+" is :thic0!; On o*s"r,ation- his "y"s app"ar to ha," ro##"d *ac0 in his h"ad- his /ac" is t%ist"d to on" sid"- and his n"c0 app"ars arch"d and dra%n *ac0%ard! Ar" !T!1s sy$pto$s dr+g r"#at"d5

Special Considerations for :lder 0d!lts Psychotherape!tic 0gents 0ntipsychotics

Pharmacodynamics Mariation in dopamine receptor s!*types where antipsychotics act may *e genetically determined. Binding of atypical antipsychotics and the li,elihood for elevations in prolactin levels (a commonly o*served effect of these agents) is proportional to the genetic mar,er for the 6- receptor F6+6-G (No!ng et al.# -..8). <hether the 6+6- or other mar,ers are predictive of genetically *ased variation in response to antipsychotics remains to *e seen ( alhotra# !rphy# D Oennedy# -..8). Pharmaco,inetics Aenetic variation in meta*olism of haloperidol# thioridazine# and clozapine has *een reported (Chang D 0ltman# -..8). 0ripiprazole# which is meta*olized *y *oth cytochrome P84. -67 and /08 (5acy# 0rmstrong# Aoldman# D 5ance# -..8) is li,ely to also display varying pharmaco,inetics across pop!lations. &he clinical significance of these finding is not clear# *!t may explain the o*servation that some clients respond to lower doses of antipsychotics whereas other clients re$!ire higher doses for ade$!ate response. 0dverse ;ffects &he ris, for tardive dys,inesia (&6) has *een correlated with variations in the genetic mar,er for the 6/ receptor F6+6/G and the cytochrome P84. 10- isoenzyme# an isoenzyme responsi*le for meta*olism of some antipsychotics# incl!ding haloperidol ( alhotra et al.# -..8). It is c!rrently !nclear whether these mar,ers co!ld *e clinically !sef!l to identify individ!als at high ris, for &6. Similarly# the ris, for developing extrapyramidal side effects (;PS) with typical antipsychotic !se is related to cytochrome P84. -67 expression. Individ!als with red!ced capacity to meta*olize dr!gs via -67 appear to *e at higher ris, for ;PS (Schillevoort et al.# -..-). 0ntidepressants Pharmacodynamics Aenetic variation in central and peripheral serotonin receptors is o*served among individ!als and pop!lations (Alatt# &ampilic# Christie# 6eNo!ng# D Ereimer# -..8). Mariations in the serotonin transporter gene among different pop!lations have also *een correlated with the efficacy of the selective serotonin re!pta,e inhi*itor (SS+I) antidepressants ( alhotra et al.# -..8). Pharmaco,inetics &he polymorphic expression of cytochrome P84. -67 is highly varia*le across pop!lations# and explains the wide range of plasma and

tiss!e levels o*served with standard doses of many of the antidepressants# incl!ding the tricyclics# paroxetine# and fl!oxetine. &his may explain differences o*served in *oth therape!tic response and toxicity for these agents ( alhotra et al.# -..8). 0dverse ;ffects 0cc!m!lation of a n!m*er of antidepressants may *e secondary to the significant variation noted in -67 activity# which is genetically determined. 0mong the agents meta*olized *y this enzyme are many of the tricyclic antidepressants# incl!ding amitriptyline# desipramine# imipramine# and nortriptyline. Cardiac dysrhythmias secondary to toxic levels of desipramine have *een correlated with -67 polymorphism in exican 0mericans (Elores# 0lvarado# <ong# 5icinio# D Eloc,hart# -..8). 6ifferences in meta*olism of *!propion (<ell*!trin# =y*an) related to polymorphism of cytochrome P84. -B7 is also noted (Oirchheiner et al.# -../). &his may contri*!te to the ris, for seiz!res in clients who are display red!ced meta*olic clearance of the dr!g.
'd erse effects of the t!pical antips!chotics are significant, uncomfortable, and often ad ersel! affect ongoing adherence to therap!. ' ma#or grouping of acute ad erse effects of this class of drugs in ol es antagonistic acti it! of 3 4 receptors in the e1trap!ramidal tracts and are referred to as a group as e1trap!ramidal side effects %=9S&. Three distinct %and often o erlapping& =9S presentations include acute d!stonic reactions, a(athisia, and par(insonian s!mptoms %Box 19-8&. BOX 19-2

Ne!rom!sc!lar 0dverse ;ffects of Ne!roleptics ;xtrapyramidal Side ;ffects (;PS) 0,athisia 6escription otor restlessness is presentC client is !na*le to sit or stand still and feels an !rgent need to move# pace# roc,# or tap foot. 0,athisia may also appear as apprehension# irrita*ility# and general !neasiness# and may *e mista,en for agitation. &his condition is more common in females than malesC it !s!ally occ!rs within 4 to /. days (!p to 9. days) of starting dr!g therapy. &reatment L 5ower the dosage of the ne!roleptic agent# switch to a different dr!g# or administer an antipar,inson dr!g s!ch as *enztropine (Cogentin). L L L

6ystonia 6escription L L &his is an ac!te reaction that re$!ires immediate intervention. &he client exhi*its m!scle spasms of the face# tong!e# nec,# %aw# andBor *ac,. &here is hyperextension of the nec, and tr!n, and arching of the *ac,.&he tong!e may protr!deC also present are facial grimaces# exaggerated post!ring of the head# nec,# or %aw# and diffic!lty swallowing andBor tal,ing. &he client may have oc!logyric crisis# manifesting as a fixed !pward gaze andBor eye m!scle spasms. &his may *e accompanied *y excessive salivation.

It is !s!ally seen after large doses of ne!roleptics# typically within 1 ho!r to 1 wee, of initiation of dr!g therapy. It occ!rs more often in males than females. &reatment 6epending on the severity of the reaction# consider" 5owering ne!roleptic dosageC 0dministering either *enztropine (Cogentin) or diphen-hydramine (Benadryl) I 6r!g-Ind!ced Par,insonism 6escription Symptoms are similar to Par,inson's disease# with a sh!ffling gait# drooling# tremors# and increased rigidity (cogwheel). Brady,inesia (slow movements) and a,inesia (immo*ility) are also reported. L 6r!g-ind!ced par,insonism is often dose related# may occ!r at any time with typical antipsychotic therapy# and is seen in *oth males and females. &reatment L 0dd an antipar,inson dr!g s!ch as *enztropine (Cogentin) or diphenhydramine (Benadryl). L &he prescri*er can switch client to a ne!roleptic that is less li,ely to ind!ce this effect. &ardive 6ys,inesia (&6) L L

or IM

6escription Presenting feat!res incl!de" 2acial- grimacing or scowling expression# facial tics# arching of the eye*rows Ocular- *lin,ing# eyelid spasms (*lepharospasm) Oral34uccal- lip smac,ing# lower-lip thr!sting# s!c,ing# p!ffing of chee,s# chewing of the chee,s (the inside of the mo!th sho!ld *e chec,ed for this) %ingual3masticatory- lateral %aw movements# tong!e protr!sion or thr!sting s!ch as Jfly catching movements#K tong!e in lip or chee, res!lting in an o*serva*le *!lge in the specific area Systemic e,,ects- foot tappingC roc,ing from side to sideC arms# hands# and fingers possi*ly displaying a %er,ing andBor a writhing motion (choreoathetoid motion)C pelvic thr!sting motions L &ardive dys,inesia typically manifests after 7 months or more of typical antipsychotic therapy. Symptoms may *e mas,ed *y increased dose of typical antipsychotics# *!t the !nderlying condition will act!ally worsen over time with the !se of higher doses. L +is, of tardive dys,inesia is highest with 6- *loc,ers (typical antipsychotics) and may *e as high as -.P of those clients who receive ongoing therapy. &he ris, of ind!cing tardive dys,inesia increases with the total dose administered and the length of treatment. :lder women appear to *e at highest ris,. &reatment L Prevention is vital *eca!se the condition might *e irreversi*le. L 6ecreasing or discontin!ing the antipsychotic agent# if possi*le# is the recommended proced!re. L Mitamin ; may help# *!t there is no !niversally effective treatment for &6. Ne!roleptic alignant Syndrome 6escription L L L Client presents with very rigid m!scle tone and fever secondary to severe m!scle in%!ry. 0ltered mental stat!s# %oint pain# tachycardia# tachypnea and sweating are also commonly seen. Ne!roleptic malignant syndrome almost always presents in the first wee, to month of starting an antipsychotic or 6 -*loc,ing dr!g (e.g.# metoclopramide). L

&reatment L L L L 6iscontin!e offending dr!g. S!pportive n!rsing and medical care# often in the intensive care setting# is re$!ired. 6antrolene may *e !sed when significant fever and m!scle in%!ry is noted. Benzodiazepines# amantadine# *romocriptine# and electroconv!lsive therapy may also *e considered. +ecovery !s!ally re$!ires Q to 1. days# *!t may *e longer if long-acting agents s!ch as I haloperidol decanoate were !sed.

'cute d!stonic reactions t!picall! present within 4: to :F hours of an initial dose or dose increase and are more often obser ed in the highpotenc!Alow-dose t!pical agents. S!mptoms classicall! present as oculog!ric crisis %e!es roll bac( in the head&, trismus %facial twisting to one side&, a protruding and fi1ed tongue, and opisthotonus %nec( arching and stiffness&. G.T. presents with a classic d!stonic reaction. '(athisia usuall! presents as an internall! sensed motor restlessness, where clients feel *wound up.+ @t often appears as restlessness, with inabilit!

to focus and continuous arm and leg mo ement. @t is most commonl! obser ed in !ounger clients, and ma! appear earl! in therap! %within the first few months&. Unfortunatel!, this motor restlessness ma! be mista(en for an increase in underl!ing ps!chosis, and result in an increase in the dose of the offending agent. Such an action onl! ser es to worsen the a(athisia. ' third acute presentation of =9S is drug-induced par(insonism. This presents in a manner similar to s!mptoms seen in someone with idiopathic 9ar(insonHs disease, and includes a coarse %8 c!cles per second& tremor that worsens on acti it!, shuffling gait, drooling, a mas(ed loo( to the face, and muscle rigidit!. "ommon to drug-induced par(insonism is cogwheel rigidit! where passi e mo ement of the wrist or elbow of the affected indi idual b! an e1aminer results in ratchet-li(e or on-off-li(e mo ement. Treatment of =9S includes a oiding future use of the offending drug, if possible, and use of drugs with anticholinergic %specificall! antimuscarinic& properties. 'cute d!stonic reactions are er! distressing to clients. The! are t!picall! treated with a drug with antimuscarinic acti it! %e.g., @7 or @B administration of the antihistamine, diphenh!dramine 5$enadr!l6&. Treatment of drug-induced par(insonism includes treatments with other longeracting antimuscarinics, including ben)tropine %"ogentin& and trihe1!phenid!l %'rtane&. Unfortunatel!, these antimuscarinic agents ha e their own ad erse effects, including dr! mouth, urinar! retention, constipation, and occasionall! confusion. Iefer to Chapter -1 for a more complete discussion of antimuscarinic agents. !T! is tr"at"d %ith par"nt"ra# diph"nhydra$in" &B"nadry#( and his sy$pto$s r"so#," o,"r th" n")t /"% ho+rs! H" ")pr"ss"s conc"rn that th" h"a#th car" t"a$ %as trying to poison hi$- and h" has h"ard that dr+gs #i0" ha#op"rido# &Ha#do#( can ca+s" #ong-t"r$ $o,"$"nt pro*#"$s! Ho% #i0"#y ar" #ong-t"r$ $o,"$"nt pro*#"$s to r"s+#t /ro$ antipsychotic +s"5 9aranoid delusions are common with a number of ps!chiatric conditions, but the ad erse-effect profiles of the t!pical antips!chotics are troublesome and ma! ser e to reinforce paranoid perceptions for clients who do not !et ha e a full therapeutic response to the antips!chotics. 'lthough a number of long-term ad erse effects ma! occur with chronic use of the t!pical antips!chotics, tardi," dys0in"sia &T'( has raised the gra est concern. This is a s!ndrome of abnormal in oluntar! muscle mo ements related to long-term bloc(ade of 3 4 receptors. The e1act mechanism of how dopamine bloc(ade can lead to T3 is not clear, but ma! in ol e dopamine supersensiti it!, depletion of ?'$', neurologic o1idati e stress, or some other process %Aold*erg# -..-&. ?enetics has also been proposed as a ris( for de eloping T3 %see the Special "onsiderations for 9harmacogenetics bo1 on

p. /28&. T3 is characteri)ed b! in

oluntar! perioral mo ements such as lip smac(ing, lip puc(ering,

tongue darting, and #aw mo ements %see Box 19-8&. 'lso commonl! obser ed is difficult! swallowing, and choreoathetoid %worm-li(e& mo ements of the hands, arms, nec(, torso, legs, and feet. @t is more li(el! to occur with higher doses of t!pical agents for long periods of time %e.g., greater than ; months&. Significant =9S earl! in therap! ma! signal increased ris( for T3. Dlder women also appear to be at higher ris( for de eloping the condition. 'lthough there is some data that high-dose itamin = ma! offer some impro ement in s!mptoms, there is no reliable treatment for tardi e d!s(inesia. 's such, earl! identification and pre ention are critical.