Template for GEMP 4 EBM Assignment (2012)

Title: Antipsychotics s Ben!o"ia!epines or moo" sta#ilisers for rapi" tran$%ili!ation of a manic episo"e&

't%"ent "etails:
Name (optional): Student number: 0210648g Email address: 0210648g@student.wits.a .!a

Patient (etails:
"atient#s name: "re ious $ag%ar &'gbar (utpatient)*ospital number: +,00-.2./1 0ard or unit w*ere seen: S*ort sta1 in ward 260 2ospital: 3*arlotte 4a5e6e 7o*annesburg 8 ademi 2ospital 9ate o% 8dmission) onsultation: 2.t* 8ugust 2012

(epartment (rotation)
Psychiatry

EBM Assignment mar)ing sheet

(:ea;e page blan6 < %or use b1 mar6er onl1) *inal Mar): ,riteria 3*oi e o% ,opi "resentation ++++ ,omponents (riginalit1 (2) =ele;an e to blo 6 (2) 3ompleted all se tions (1) Neatness (1) Spelling *e 6 ompleted (1) +rammar *e 6 ompleted (1) S*ort des ription o% t*e lini al situation =ele;ant and interesting 3lear? on;in ing "atient)&nter;ention)3omparison)(ut ome =esour es used (2) Sear * terms used (2) 2its %ound (1) 2its rele;ant? details o% w*1 ot*er *its e5 luded (-) E5planation o% w*1 4<6 papers sele ted %or re;iew *osen (-) 3ompleteness o% sear * (1) &9 (2) "atients (4) Stud1 design and le;el (2) (ut omes (4) Stud1 results (.) 0ea6nesses (6) Summation o% t*e e;iden e Strengt*s and wea6nesses o% e;iden e 3on lusion)s 3lear? on ise? orre t =ele;an e o% e;iden e sear * to inde5 (1our) patient 9id t*e e;iden e ma6e a di%%eren eA 3ited orre tl1 in te5t (1) Ban ou;er s1stem %ollowed (4) MaMar) 4 4 't%"ent Mar)

S enario E5planation %or *oi e o% topi Stru tured 3lini al @uestion Sear * strateg1

> > 4 12

Summar1 o% =ele;ant papers

2>

3ommentar1 3lini al bottom line)s 8ppli abilit1 to patient "atient out ome =e%eren es Total Mar)er name: ,omments:

20 > 6 > > 100

'cenario
Short description of the clinical situation. Relevant and interesting. 4rs. $ag%ar? a 6nown bipolar mood t1pe & patient was broug*t in at nig*t b1 poli e o%%i ers a%ter s*e be ame aggressi;e at *ome and t*reatening to 6ill *er *usband %or w*om s*e *ad perse utor1 delusions. ,*is was %ew wee6s a%ter s*e stopped ta6ing *er medi ations. S*e ;erbalised t*at s*e wanted to di;or e *er *usband be ause *e did not want to support *er %inan iall1 and also mentioned t*at s*e was seeing gu1s around w*o ould ta6e are o% *er better. 2er promis uit1 was %ed b1 t*e grandiosit1 w*ereb1 s*e belie;ed t*at e;er1 man wanted to go out wit* *er. S*e ould not remember sleeping %or t*e past t*ree wee6s and w*ile awa6e s*e would be wandering around t*e *ouse and ame a ross as unusual a ording to ollaterals. S*e lost weig*t due to diminis*ed appetite and s*e *ad %lig*ts o% ideas. 2er insig*t was none5istent and to *er? li%e was not wort* it an1more. S*e was %lambo1ant? wit* *ea;1 ma6eup on *er %a e and s*e was ;er1 tal6ati;e. S*e was o;er %amiliar b1 t*e time o% inter;iew. 2er mood s1mptoms toget*er wit* ps1 *oti %eatures as well as poor insig*t were t*e reasons %or *er admission. S*e was later admitted to t*e ps1 *iatri ward under t*e mental *ealt* are a t %or a .2 *our obser;ation. 0*ile in t*e ward? s*e be ame more disin*ibited w*ereb1 s*e would lo 6 *ersel% in t*e bat*room wit* male patients. ,*is was t*e reason %or *er re%erral to ,8=8 *ospital. Ce%ore t*e re%erral s*e de;eloped a urinar1 tra t in%e tion %or w*i * s*e re ei;ed treatment.

E-planation for choice of topic

&n a ute mania? t*e aggressi;e be*a;iour *as to be ontained. &n ;er1 agitated patients? a pro ess o% de<es alation as well as me *ani al and *emi al restrains *as to be deplo1ed to ontain t*e user. 8 simple guideline suggests t*e use o% antips1 *oti as well as ben!odia!epines %or rapid tran'uilisation o% t*e patient. &n t*is e5er ise? & as6ed w*i * o% t*ese two is t*e most e%%e ti;e wit* t*e least side e%%e ts and better o;erall prognosis. &%? & were t*rown in a rural setting? w*i * o% t*e two would & pre%er usingA

'tr%ct%re" ,linical .%estion

"atient &nter;ention 3omparison (ut ome /n an ac%te #ipolar manic episo"e 0ith psychotic feat%res 1o%l" the a"ministration of 2aloperi"ol As oppose" to gi ing a Ben!o"ia!epine or moo" sta#ilisers ,arry a #etter prognosis3

'earch 'trategy
Primary an" secon"ary reso%rces "ubmed

'earch terms %se" ((D4entall1 &ll "ersonsDE4es*F 8N9 D2aloperidolDE4es*F) (= DCen!odia!epinesDE4es*F) 8N9 DCipolar 9isorderDE4es*F 8N9 (Dloattr%ree %ull te5tDEsbF 8N9 D2002)0/)10DE"9atF : D2012)0/)06DE"9atF 8N9 D*umansDE4eS2 ,ermsF 8N9 =andomi!ed 3ontrolled ,rialEpt1pF 8N9 Englis*ElangF) 4%m#er of hits fo%n" 11 2its rele ant5 "etails of 0hy others e-cl%"e" 4 o% t*em were rele;ant. & e5 luded t*e %irst arti le be ause it loo6ed at t*e management o% depressi;e episodes b1 ansenarine instead o% loo6ing at main tran'uili!ation o% a ute mani ases. &t in luded mood stabilisers and not Gust *aloperidol ompared to ben!odia!epines. ,*e ot*er arti les were e5 luded be ause t*e eit*er loo6ed at t*e relapse inter;al or remission instead o% t*e a ute management o% t*e mani episode. (t*er arti les also %o used on mood stabilisers? w*i * did not answer m1 'uestion. (ne stud1 loo6ed at t*e e%%e t o% antips1 *oti s on sleep patterns w*i * did not mat * m1 sear * terms.

E-planation of 0hy 467 papers selecte" #y yo% for re ie0 chosen < < < < ,*e1 did not *a;e a s1stemati re;iew on t*e topi . ,*ese studies *ad a large population si!e. ,*e age group mat *ed m1 patient#s age. ,*e 'uestions answered were rele;ant to m1 stud1.

'%mmary of 8ele ant Papers

(escripti e "ata (e&g& age5 sample si!e5 inter ention5 "ose5 "%ration5 follo06%p perio")
1>0 patients wit* agitation se ondar1 to ps1 *oti or bipolar disorder were randoml1 assigned under double< blind onditions to re ei;e olan!apine? !iprasidone? *aloperidol plus mida!olam? *aloperidol plus promet*a!ine or *aloperidol alone. ,*e (;ert 8gitation Se;erit1 S ale? (;ert 8ggression S ale and =amsa1 Sedation S ale were applied wit*in 12 *ours a%ter t*e %irst dosage. Se ondar1 anal1sis o% a 6<wee6? double<blind? randomised stud1 o% olan!apine (>M20mg)da1) or pla ebo ombined wit* ongoing ;alproate or lit*ium open treatment %or -44 patients in mi5ed or mani episodes. ,*is anal1sis %o used on a d1sp*ori subgroup wit* baseline 2amilton =ating S ale %or

A%thor5 "ate an" co%ntry

't%"y type (le el of e i"ence)

9%tcomes meas%re"

:ey res%lts

't%"y 0ea)nesses

CaldaHara : et al 2011 Cra!il

=andomised double blind ontrolled trial. (le;el 1b) 7adad s ore: 2

,o ompare t*e e%%e ti;eness o% intramus ular olan!apine? !iprasidone? *aloperidol plus promet*a!ine? *aloperidol plus mida!olam and *aloperidol alone as t*e %irst medi ation(s) used to treat patients wit* agitation and aggressi;e be*a;iour

8 total o% 16- patients were s reened? and 1>0 underwent randomi!ation and re ei;ed at least one dose o% medi ation. Eig*t1< eig*t did not meet t*e in lusion riteria? and %i;e re%used to parti ipate. 8 two<tailed statisti al signi%i an e le;el was set at p I 0.0>. Jor t*e total patient group? t*e a;erage mean age was -2.1 (S9 K ...)? >/.>L were men? 60.6L *ad a ps1 *oti disorder and -/.4L *ad bipolar disorder. 8t t*e time o% entr1 into t*e stud1? t*e patients *ad an (8SS (mean) o% -0.8 (S9 K >.1) and an (8S o% 10.1 (S9 K 2.>). ,*e so io< demograp*i and lini al *ara teristi s o% all %i;e treatment groups were similar

6 Small sample si!e to e5 lude indi;idual di%%eren es < (nl1 in luded patient w*o ga;e in%ormed onsent to e5 lude t*ose t*at were riti all1 ill < Stud1 done in a metropolitan ps1 *iatri *ospital w*i * is bus1 t*ere%ore mig*t *a;e not ta6en detailed *istor1 and %ull e5amination due to *ealt* are wor6er burden

=obert 0? Ca6er 2004 England

=andomised double blind ontrolled trial. (le;el 1b) 7adad s ore: 2

,o e;aluate t*e e%%i a 1 o% olan!apine in ombination wit* lit*ium or ;alproate? %or treating depressi;e s1mptoms asso iated wit* mania

&n t*e d1sp*ori subgroup (nK8>) mean 2=S9 total s ore &mpro;ement was signi%i antl1 greater in olan!apine o<t*erap1 patients t*an in t*ose re ei;ing pla ebo plus lit*ium or ;alproate ("N0.001).Substantial ontributors to t*is superiorit1 in luded t*e 2=S9 4aier sub<s ale ("N0.01-) and t*e sui ide item("N0.001).,otal Ooung 4ania =ating S ale impro;ement was also superior wit* olan!apine o<t*erap1

< ,*e stud1 used post *o anal1sis o% data %rom a lini al trial w*i * e;aluated mania rating s ale s ore as t*e primar1 e%%i a 1 measure. < 8ssignment to ;alproate or lit*ium t*erap1 was not randomised but re%le ted t*e treatment pre%eren es o% lini ians and in;estigators. ,*e stud1 did not in lude a t1pi al antips1 *oti omparator.

Oa6sami N. Oat*am 200England

9epression (2=S9) total s ores o% 20 or o;er ontrasted wit* non<d1sp*ori patients. "atients ta6ing a mood stabiliser were randomised to -wee6s treatment wit* risperidone (nK.>) or pla ebo (nK.6).

=andomised double blind ontrolled trial. (le;el 1b) 7adad s ore: -

,o determine t*e e%%i a 1 o% =isperidone in ombination wit* a mood stabiliser in a ute mania

4auri io ,o*en 2008 England

=andomised? double< blind? 6<wee6 trial o% olan!apine (10P-0 mg)da1) plus arbama!epine (400P 1200 mg)da1Q nK>8) ;s pla ebo plus arbama!epine (nK60) %ollowed b1 open<label? 20<wee6 olan!apine (10P-0 mg)da1) plus arbama!epine (400P1200 mg)da1? nK86)? wit* *ange in mani s1mptoms as main out ome measure. Sa%et1 and p*arma o6ineti s were also e;aluated.

=andomised double blind ontrolled trial. (le;el 1b) 7adad s ore: 2

,o assess t*e e%%i a 1 and sa%et1 o% olan!apine plus arbama!epine in mi5ed and mani bipolar episodes.

,*e Ooung 4ania =ating S ale (O4=S) s ores impro;ed rapidl1 wit* Signi%i antl1 greater redu tions atwee61 in t*e risperidone group ompared wit* t*e pla ebo group. 8 tend<point O4=S s ores de reased b114.> and10.- points in t*e risperidone and pla ebo groups? respe ti;el1. Signi%i ant impro;ements ;. pla ebo (">0.0>) were noted in t*e risperidone group on se;eral ot*er lini all1 meaning%ul measures. 8dditionall1? a post *o anal1sis e5 luding arbama!epine<treated patients (plasma on entrations o% risperidone a ti;e moiet1 were 40L lower in t*is group) re;ealed signi%i antl1 greater redu tions ("K0.04.) in O4=S s ores in t*e risperidone group t*an in t*e pla ebo group. &n iden e o% ad;erse e;ents was similar in bot* groups. ,*ere were no signi%i ant di%%eren es (between baseline and endpoint ;alues) in e%%i a 1 measures between treatment groups? but at 6 wee6s trigl1 eride le;els were signi%i antl1 *ig*er ("K0.008) and potentiall1 lini all1 signi%i ant weig*t gain (>.L) o urred more %re'uentl1 (24.6L ;. -.4L? "K0.002) in t*e ombined olan!apine and arbama!epine group. 3arbama!epine redu ed olan!apine on entrations but olan!apine *ad no e%%e t on arbama!epine on entrations.

< ,*e primar1 e%%i a 1 measure ( *ange in s ore on t*e Ooung 4ania =ating S ale %rom baseline to end<point)was onl1 marginall1 statisti all1 signi%i ant. < ,*e post *o anal1sis o% t*e primar1 e%%i a 1 measure was not based on an a priori *1pot*esis. < 4an1 patients dropped out o% t*e -<wee6 double<blind p*ase

None re;ealed

,ommentary
CaldaHara : et al t*oug*t t*at o;er 12 *ours? olan!apine? !iprasidone? *aloperidol plus promet*a!ine? *aloperidol plus mida!olam and *aloperidol alone were e%%e ti;e in ontrolling agitation and ;iolent be*a;ior resulting %rom mental illness b1 produ ing tran'uili!ation. "atients w*o were gi;en olan!apine *ad better results %or agitation ontrol? a lower per entage o% e5 essi;e sedation and less need o% me *ani al restri tion. "atients gi;en !iprasidone *ad better results %or ontrolling aggressi;e be*a;iour? %ollowed b1 *aloperidol plus promet*a!ine. 8ll t*e drug ombinations *ad ad;antages and disad;antages? and t*e ombination o% *aloperidol plus mida!olam s*owed t*e worst results in all t*e parameters obser;ed. Cut *aloperidol alone ould be mu * e%%e ti;e. Cesides <R%rom t*eir *ig*er ost? at1pi al antips1 *oti s ma1 be *elp%ul and mig*t be an option in emergen ies. =obert 0. Ca6er on t*e ot*er *and %elt t*at in patients wit* a ute d1sp*ori mania? adding o%olan!apine to ongoinglit*ium or lproate mono t*erap1 signi%i antl1 impro;ed depressi;e s1mptom? mania and sui idalit1. 4auri io ,au*en %ound t*at t*e ombination o% olan!apine and arbama!epine did not *a;e superior e%%i a 1 ompared to arbama!epine alone. (ne o% t*e side e%%e ts is t*e in reases in weig*t and trigl1 erides obser;ed during ombination treatment. :ast but not least? Oa6sami N. Oat*am on luded t*at risperidone is superior to pla ebo w*en used in ombination wit* lit*ium or di;alproe5in a utemania. &t is important *owe;er to 6now t*at mania not managed in monot*erap1? it is better to alwa1s start low? go slow wit* t*e dose? *e 6 t*e lini al pi ture o% t*e patient and tapper w*en needed a ordingl1.

,linical Bottom line

8ntips1 *oti ? pre%erabl1 *aloperidol remains t*e drug o% *oi e in management o% an a ute mani episode wit* ps1 *oti %eatures.

Applica#ility an" rele ance to patient

Oes m1 patient was similar to t*e stud1 parti ipants e5 ept t*at s*e is not 3au asian. S*e did not *a;e o<morbidities. ,*e prognosis at t*is point will depend on our Ciops1 *oso ial approa *. S*e needs to gain insig*t into *er ondition and stop ma6ing it worse b1 de%aulting and t*e o<morbid substan e abuse.

Patient o%tcome
41 patient re ei;ed 2aloperiodol and to ta6e t*e edge o%% we added lora!epam. ,*ese are guidlines t*at we %ollow in terms o% management o% a ase li6e t*is. ,*e ben!odia!epine is mainl1 gi;en to sedate t*e patient until t*e antips1 *oti starts a ting. S*e settled 'uite well e5 ept t*at s*e de;eloped a urinar1 tra t in%e tion? w*i * we treated wit* augmentin and e5 luding an1 ot*er o<morbidities. 2owe;er be ause or *er suspi ious be*a;iour o% going into t*e toilet wit* ot*er male users? s*e was re%erred to ,8=8.

8eferences

1. :eonardo CaldaHara? 4arsal San *es? 9aniel 3ru! 3ordeiro? 8ndrea "arolin 7a 6ows6i. =apid tran'uili!ation %or agitated patients in emergen 1 ps1 *iatri rooms: a randomi!ed trial o% olan!apine? !iprasidone? *aloperidol plus promet*a!ine? *aloperidol plus mida!olam and *aloperidol alone. =e;ista Crasileira de "si'uiatria. 2011Q -- (1): 1<10. 2. =obert 0. Ca6er? Eileen Crown? 2agop S. 86is6al? 7osep* =. 3alabrese? ,eren e 8. Setter? :eslie 4? et al. E%%i a 1 o% olan!apine ombined wit* ;alproate or lit*ium in t*e treatment o% d1sp*ori mania. C7". 2004Q 18>:4.2<4.8. -. :a6sami n. Oat*am? Jred +rossman? &lse 8ugust1ns? Eduard Bieta and 8run =a;indran. 4ood stabilisers plus risperidone or pla ebo in t*e treatment o% a ute mania : &nternational? double<blind? randomised ontrolled C7". 200-Q 182:141<14.. 4. 4auri io ,o*en? 3*arles :. Cowden? 8natol1 C. Smule;i *? =i *ard Cergstrom? ,on1a @uinlan? (lawale (sunto6un? et al. (lan!apine plus arbama!epine v. arbama!epine alone in treating mani episodes.