PRESCRIBING GUIDELINES FOR THE MANAGEMENT OF DEPRESSION SEPTEMBER 2016

Transcription

1 PRESCRIBING GUIDELINES FOR THE MANAGEMENT OF DEPRESSION SEPTEMBER 2016

2 Policy titl Prscribing guidlins for th managmnt of dprssion Policy rfrnc PHA51 Policy catgory Clinical Rlvant to All clinical staff Dat publishd Sptmbr 2016 Implmntation Sptmbr 2016 dat Dat last August 2016 rviwd Nxt rviw Sptmbr 2018 dat Policy lad Lucy Rvs, Chif Pharmacist Contact dtails : Accountabl dirctor Approvd by (Group): Approvd by (Committ): Documnt history Mmbrship of th policy dvlopmnt/ rviw tam Consultation Mdical Dirctor Drugs and Thraputic Committ August 2016 Quality Committ 20 Sptmbr 2016 Dat Vrsion Summary of amndmnts Spt Nw Guidlins Aug Routin Rviw Audry Cokr, Lad Pharmacist for Clinical Srvics. Dr Gina Watrs, Dr Lucinda Donaldson, Dr Josphin Morgan, Dr Ishrat Husain and Dr Mohamd Abdlghani DO NOT AMEND THIS DOCUMENT Furthr copis of this documnt can b found on th Foundation Trust intrant. 1

3 Contnts Pag 1 Introduction 4 2 Aims and objctivs 4 3 Scop of th policy 4 4 Ky points 5 5 Tratmnt of dprssion 9 I Prior to initiation of tratmnt 9 Ii Inadquat rspons 11 Iii Switching 11 Iv Combining antidprssants 13 V Augmnting antidprssants with non-antidprssants 13 Vi Combind mdicin and psychological tratmnt 15 Vii Elctroconvulsiv thrapy 15 Viii Complx and svr dprssion 16 IX Continuation of tratmnt 16 X Rlaps prvntion 16 XI Stopping and rducing antidprssants 19 6 Oldr adults 21 7 Post-strok dprssion 22 8 Sid ffcts of antidprssants 22 9 Suicidality Antidprssant inducd hyponatramia Cardiovascular disas Co-morbid Diabts Wight gain Hyprprolactinamia Prgnancy and brastfding Intractions of srotonin r-uptak inhibitors with othr mdicins Intractions of monoamin oxidas inhibitors Rfrncs 31 2

4 19 Dissmination and implmntation arrangmnts Training rquirmnts Monitoring and audit arrangmnts Rviw of th policy Appndix 1: Mdicins not rcommndd in th managmnt of dprssion Appndix 2: Antidprssants: Swapping and stopping Appndix 3: Mntal Halth Assssmnt and Advic Tam 37 3

5 1 Introduction Ths guidlins hav bn dvlopd to provid clinical staff with clar guidanc on prscribing for dprssion to nsur saf ffctiv car of patints in lin with currnt NICE and national good practic guidanc and trust formulary. In gnral, rfrral to scondary car (th Mntal Halth Advic and Assssmnt tam) should b mad whn on or mor of th following critria ar mt: 1) Psychological thrapy (ithr with IAPT (Improving Accss to Psychological Thrapis) or lswhr) is not appropriat or if trid, has not brought about significant improvmnt. 2) Thr has bn limitd or no improvmnt with adquat doss of two diffrnt antidprssants takn consistntly for mor than six wks. 3) Lack of improvmnt is also associatd with: a) Clinically significant co-morbidity with othr mntal disordrs. b) Clinically significant co-morbidity with physical illnss which complicats managmnt of disordr. c) Complx social car nds which complicat managmnt. d) Complx mdication managmnt nds, byond th rmit of primary car. ) Clinically significant risk factors or safguarding issus. 4) Thr is doubt about diagnosis. If in doubt as to whthr it is appropriat to rfr, do not hsitat to sk advic from th Mntal Halth Advic and Assssmnt tams. In Islington, considr consultation with th Primary Car/IAPT consultant psychiatrist prior to rfrral to assssmnt tam. If you ar unclar about othr pathways, plas contact your Trust link workr. 2 Aims and objctivs To nsur quality and cost-ffctiv prscribing of mdicins and provid optimal tratmnt of dprssion. 3 Scop of th policy This policy rlats to prscribing in patints with a diagnosis of dprssion. It dos not covr prscribing for dprssion in bi-polar disordr. It dos not covr ECT or psychological thrapis, othr than to mak rfrnc to whn thy should b considrd. 4

6 4 Ky points 4.1 Mdicin choic in th tratmnt of dprssion. Tabl 1: NICE: Mdicin choic in th managmnt of dprssion 1,2 Options Mdicin choic Commnts First lin Srotonin r-uptak Formulary options citalopram, fluoxtin, paroxtin, Scond lin Third lin (3a) inhibitors. Anothr srotonin ruptak inhibitor or a bttr tolratd nwr gnration antidprssant.g. mirtazapin. Vnlafaxin, a tricyclic antidprssant or moclobmid, phnlzin, vortioxtin srtralin. Nwr gnration antidprssants mirtazapin, mainsrin, vnlafaxin. Formulary options (tricyclic antidprssants) amitriptylin, clomipramin, imipramin, lofpramin. Phnlzin consultant psychiatrist should b consultd prior to initiation. Vortioxtin is rcommndd as an option for trating major dprssiv pisods in adults whos condition has rspondd inadquatly to two antidprssants within th currnt pisod, in particular for patints with tratmnt mrgnt sxual dysfunction 2. A consultant psychiatrist should b consultd prior to initiation. Third lin (3b) Bupropion (off-labl) Although not includd in th currnt NICE guidanc, bupropion may b considrd if th othr tratmnt options hav faild or ar not tolratd. Consultant psychiatrist must b consultd prior to initiation. Fourth lin (4a) Fourth lin (4b) Combination tratmnts - SSRI plus mirtazapin. Vnlafaxin plus mirtazapin. Augmntation tratmnts Antidprssant plus lithium. Antidprssant plus an antipsychotic. Combination tratmnt a srotonin ruptak inhibitor and bupropion (off-labl) A consultant psychiatrist should b consultd prior to initiation. A consultant psychiatrist should b consultd prior to initiation. Formulary antipsychotic options aripiprazol, olanzapin, qutiapin, rispridon. Rispridon is th Trust s first lin antipsychotic mdicin. With th xcption of qutiapin, atypical antipsychotics ar not licnsd for th managmnt of dprssion. Although not includd in th currnt NICE guidanc, bupropion and a srotonin ruptak inhibitor may b considrd if th othr tratmnt options hav faild or ar not tolratd. A consultant psychiatrist must b consultd prior to initiation. 4.2 Thr is littl vidnc to guid prscribing in rlation to dprssion subtyps or prsonal charactristics. Th main issus concrn th impact of physical disordrs Antidprssants should not routinly b usd to trat prsistnt sub-thrshold dprssiv symptoms unlss prsnt for at last two yars 1,3. Antidprssants should not b usd to trat sub-thrshold dprssiv symptoms /mild dprssion unlss othr intrvntions hav bn unsuccssful 1. Antidprssants should also b considrd if 5

7 thr is a past history of modrat or svr dprssion 1. Antidprssants ar a first lin tratmnt for modrat and svr major dprssion in adults Antidprssants should not b usd routinly for patints with mild dprssion with chronic physical halth problms, unlss it complicats th car of th physical halth problm Whr an antidprssant is considrd appropriat, an SSRI should b considrd as first-lin pharmacological tratmnt 1,3. If th patint has modrat to svr dprssion, a combination of an antidprssant with a high-intnsity psychological intrvntion should b givn Whn dprssion is accompanid by symptoms of anxity, th first priority should b to trat th dprssion. Whn th prson has an anxity disordr with co-morbid dprssion or dprssiv symptoms th NICE guidlin for th rlvant anxity disordr should b consultd and tratmnt of th anxity disordr should b considrd first as ffctiv tratmnt would oftn also improv th dprssiv symptoms 1. Rfr to th trust anxity disordr prscribing guidlins on th intrant. 4.7 Antidprssant options should b discussd with th patint including anticipatd advrs vnts, discontinuation symptoms and potntial intractions with mdicins or physical halth problms. S sction 6 to 17. Also th patint s prcption of th fficacy and tolrability of any prvious antidprssants takn should b considrd Patints should b advisd of: th natur of th illnss 3. gradual dvlopmnt of th full antidprssant ffct 1. th importanc of taking th antidprssant as prscribd and th nd to continu byond th dprssiv pisod 1,5. th duration of tratmnt 5. th potntial sid ffcts and intractions with concomitant mdicins or physical halth conditions 1. symptoms (usually mild and slf-limiting ovr on wk, but can b svr particularly if th mdicin is stoppd abruptly). Although antidprssants ar not associatd with dpndnc, discontinuation/withdrawal symptoms may occur on stopping or missing doss or occasionally on rducing doss (spcially mdicins with shortr half-livs.g. paroxtin and vnlafaxin) 1. th most commonly xprincd discontinuation/withdrawal symptoms ar dizzinss, numbnss and tingling, gastrointstinal, hadach, swating, anxity and slp disturbancs 1. th nd to sk mdical advic if thy xprinc discontinuation/withdrawal symptoms 1. Appropriat laflts should b providd from th Choic and Mdication wbsit:- 6

8 4.9 Th patint s prcption of th fficacy and tolrability of prvious antidprssants prscribd should b considrd Patints undr 30 yars should b warnd that ths mdicins ar associatd with an incrasd risk of suicidal thinking and slf-harm in a minority of patints Whn prscribing for oldr popl, prscrib an ag appropriat dos taking into account th ffct of physical halth and concomitant mdication. 1 Sid ffcts should b carfully monitord Patints should b advisd if th mdicins ar prscribd off-labl. Thy should b offrd patint information laflts from th Choic and Mdication link on th trust intrant Citalopram and to a lssr xtnt srtralin hav fwr propnsitis for mdicin intractions 6. Fluoxtin, fluvoxamin and paroxtin ar associatd with a highr propnsity for mdicin intractions than othr SSRIs Citalopram is associatd with a dos dpndnt risk of QT prolongation. 7 Th maximum dos in adults is 40mg and in oldr adults it is 20mg pr day 7. S sction Paroxtin is associatd with a highr incidnc of discontinuation symptoms than othr SSRIs. Vnlafaxin is also associatd with a highr incidnc of discontinuation symptoms Whn prscribing mdicins othr than srotonin ruptak inhibitors, th incrasd liklihood of th prson stopping tratmnt bcaus of sid ffcts (and th consqunt nd to incras th dos gradually) with vnlafaxin and tricyclic antidprssants should b considrd Th following should b considrd whn patints ar initiatd on vnlafaxin: Liklihood of stopping tratmnt bcaus of its sid ffct profil. Vnlafaxin is associatd with a gratr risk of dath compard with othr routinly usd antidprssants. 1 Highr doss of vnlafaxin ar associatd with xacrbation of cardiac arrhythmias and hyprtnsion. Patints blood prssur should b monitord at highr doss 1. Also s sction

9 4.18 Patints who hav bn prscribd bupropion long-trm for th managmnt of dprssion (.g. patints from abroad whr bupropion is licnsd for dprssion), may hav tratmnt continud. Patints nwly prscribd bupropion in th privat sctor should b rviwd and an altrnativ considrd if appropriat (i.. in accordanc with NICE guidanc). Bupropion alon may b considrd if patints hav not bnfitd from antidprssants rcommndd in th NICE guidlins and monothrapy is prfrabl. Altrnativly it may b considrd as an adjunctiv tratmnt for th managmnt of tratmnt rsistant dprssion if th patint has not bnfitd from othr options advisd by NICE (s tabl 1) 6,8. Thr must b clar communication with th GP rgarding th tratmnt plan and off-labl us Toxicity in ovrdos should b takn into account whn slcting an antidprssant for patints at significant risk of suicid 4. Vnlafaxin is associatd with a gratr risk of dath from ovrdos 1. Tricyclic antidprssants (xcpt for lofpramin) ar associatd with th risk in ovrdos Tricyclic antidprssants hav th potntial to caus postural hypotnsion and arrhythmias. Dosulpin should not b prscribd Oldr tricyclic antidprssants should gnrally b rsrvd for situations whn firstlin mdicin tratmnt, hav faild 3. S tabl Non-rvrsibl monoamin oxidas inhibitors such as phnlzin should normally only b initiatd by a spcialist mntal halth profssional Advis popl taking a monoamin oxidas inhibitor of th ditary and pharmacological rstrictions concrning th us of ths drugs as st out in th British National Formulary 6, 9. Patint counslling 9 :- Patints should b advisd to at only frsh foods and avoid food that is suspctd of bing stal or going off. This is spcially important with mat, fish, poultry or offal; gam should b avoidd. Th dangr of intraction prsists for up to 2 wks aftr tratmnt with MAOIs is discontinud. Patints should also avoid alcoholic drinks or d-alcoholisd (low alcohol) drinks. 8

10 4.24 Hamatological monitoring is rquird for ldrly patints prscribd miansrin Agomlatin should not b startd if srum transaminass xcd thr tims th uppr limit of th rfrnc rang. Livr function should b tstd bfor tratmnt and aftr thr, six, twlv and twnty four wks of tratmnt, and thn rgularly thraftr whn clinically indicatd. Th monitoring schdul should b rstartd whn th dos is incrasd. Agomlatin should b discontinud if th srum transaminass xcd thr tims th uppr limit of th rfrnc rang or symptoms of livr disordr. Patints should b told how to rcognis signs of livr disordr and advisd to sk immdiat mdical attntion if symptoms such as dark urin, light colourd stool, jaundic, bruising, fatigu, abdominal pain or pruritus dvlop 9. Agomlatin should b rqustd via th non-formulary rout Thr is no vidnc supporting th us of spcific antidprssants for patints with particular chronic physical halth problms 4, but som rcommndations ar mad in latr sctions It is appropriat to considr using th lowst ffctiv dos in prgnancy and brastfding. Tratmnts should not b stoppd abruptly A partial tratmnt rspons may tak up to four wks with a full rspons taking a furthr four wks Rfr to th Trust guidlins for th managmnt of insomnia if patints hav problms slping Th managmnt of bipolar dprssion is outsid th scop of this guidlin Th us of lctroconvulsiv thrapy is outsid th scop of this guidanc Patints with dprssion who ar considrd to b at significant risk of rlaps (including thos who hav rlapsd dspit antidprssant tratmnt or who ar unabl or choos not to continu antidprssant tratmnt) or who hav rsidual symptoms, should b offrd a psychological intrvntion Psychological intrvntions ar outsid th scop of this guidanc GPs in Islington can obtain furthr prscribing advic from Consultant Psychiatrist Islington icop/primary car (s appndix 3).Thr is not an quivalnt srvic in Camdn. 5 Tratmnt of Dprssion i. Prior to initiation of tratmnt 5.1 Bfor prscribing, th following factors should b considrd:- Associatd psychiatric disordr that may spcifically rspond to a particular antidprssant.g. obsssiv compulsiv disordr and srotonin ruptak inhibitors 3, 5 and gnral mdical problms 5 that mak th antidprssant lss wll tolratd 3. Patint prfrnc 3. Prvious tratmnt rspons to a particular antidprssant 3. Tolranc and advrs ffcts of a prviously prscribd mdicin 3. 9

11 Tndncy to produc a withdrawal syndrom spcially with paroxtin and vnlafaxin 1. Sid ffct profil and potntial for mdicin intractions 1.g. srotonin ruptak inhibitors and tramadol 5 sdation, sxual sid ffcts, wight gain 3. Tolrability and advrs ffcts to prvious tratmnt 5. If at a latr stag choosing btwn a tricyclic antidprssant or a monoamin oxidas inhibitor, a family history of diffrntial antidprssant rspons 3. If at a latr stag of tratmnt, th prsnc of atypical faturs (rsponds lss wll to imipramin than phnlzin) 3. Th risk of suicid and liklihood of toxicity in ovrdos if an antidprssant is prscribd (spcially with vnlafaxin or tricyclic antidprssants) or othr concurrnt mdication. If ncssary limit th amount of mdicin (s) availabl 1. Th prson s prior xprinc of tratmnt with individual mdicins spcially prvious rspons, adhrnc, ffctivnss, sid ffcts, xprinc of withdrawal syndrom and th prson s prfrnc 5,7. Considr incrasd potntial risk of suicidality in young adults lss than thirty yars of ag whn prscribing SSRIs. Ths patints should b sn within on wk of prscribing and thn frquntly thraftr until th risk is no longr considrd clinically important. Othr patints can b sn aftr two wks, thn vry two to four wks for th first thr months, thn at longr intrvals if th rspons is good If sid ffcts dvlop, provid appropriat information and considr: monitoring sid ffcts if mild and accptabl to th prson. stopping th antidprssant or changing th antidprssant to a diffrnt on if th prson prfrs. if anxity, agitation and/or insomnia is prsnt, short-trm (two wks) concomitant tratmnt with a bnzodiazpin (xcpt in popl with chronic symptoms of anxity) 1. This should usually b for no longr than two wks in ordr to prvnt th dvlopmnt of dpndnc An initial rspons to an antidprssant may bgin to occur two wks aftr commncing tratmnt In adults, if thr is symptomatic improvmnt by four wks, continu for anothr two to four wks. Considr switching to anothr antidprssant if:- th rspons is inadquat or thr ar sid ffcts th prson prfrs to chang tratmnt Som antidprssants hav modst vidnc for a dos-rspons.g. vnlafaxin and tricyclic antidprssants Whn prscribing for oldr popl, prscrib an ag appropriat dos taking into account th ffct of physical halth and concomitant mdication In oldr adults, tratmnt should b continud for six wks bfor considring a switch 9. If thr is a symptomatic improvmnt aftr six wks, thy may rquir a longr priod to furthr rspond thraftr Whn prscribing an oldr tricyclic antidprssant or an antidprssant rquiring dos titration, th dos should b incrasd vry thr to svn days to allow adjustmnt 10

12 to sid ffcts Th targt dos of a tricyclic antidprssant as an imipramin dos quivalnc of qual or mor than 125mg pr day if tolratd If a patint has rspondd to a lowr than a targt dos of an antidprssant, th dos should still b incrasd to on of stablishd fficacy if possibl to rduc th th liklihood of rlaps in continuation tratmnt. Whr this is not possibl, th mdicin should b continud at th sam dos and th patint monitord for rlaps Patints who ar startd on low dos tricyclic antidprssants and who hav a clar rspons can b maintaind on that dos with carful monitoring 1. ii. Inadquat rspons 5.11 If rspons is absnt or minimal aftr thr to four wks of tratmnt with a thraputic dos of an antidprssant, chck adhrnc to th prscribd dos and sid ffcts from initial tratmnt. Incras th frquncy of appointmnts using outcom monitoring with a validatd outcom masur. Considr wkly fac to fac contact or tlphon contact B awar that using a singl antidprssant rathr than combination mdication or augmntation is usually associatd with a lowr sid ffct burdn Also considr: Incrasing th dos within th spcification of product charactristics if thr ar no significant sid ffcts 1. Incras th dos to th rcommndd thraputic dos if only a low or a marginal dos has bn achivd 3. Switching to anothr antidprssant if thr ar sid ffcts or if th prson prfrs this option If thr is minimal improvmnt, thn a dos incras, a switch or combination/augmntation thrapy should b considrd. If patints hav faild a numbr of tratmnts, longr trials should b considrd bfor changing tratmnt Considr rintroducing prvious tratmnts that hav bn inadquatly dlivrd or adhrd to, including incrasing th dos Rviw diagnosis including th possibility of othr psychiatric or mdical diagnoss Th combination of antidprssant mdication and cognitiv bhavioural thrapy should b considrd. 1 iii. Switching 5.18 Switching antidprssants should b considrd spcially if:- thr ar troublsom or dos-limiting sid ffcts and/or thr has bn no improvmnt A switch should b mad within th class.g. from srotonin ruptak inhibitor to anothr or to anothr class (s tabl 1) 3. Whn switching to anothr antidprssant, considr switching to initially a diffrnt SSRI or a bttr tolratd nwr gnration antidprssant.g. mirtazapin. Subsquntly an antidprssant of a diffrnt pharmacological class could thn b considrd.g. vnlafaxin, a tricyclic 11

13 antidprssant or a monoamin oxidas inhibitor (s tabl 1). Dosulpin should not b initiatd du to its incrasd cardiac risk and toxicity in ovrdos An antidprssant of a diffrnt class should b considrd aftr mor than on failur with a spcific class.g. vnlafaxin should b considrd aftr mor than on failur with a srotonin ruptak inhibitor (s tabl 1) All antidprssants hav th potntial to caus withdrawal phnomna. Whn takn continuously for six wks or longr, antidprssants should not b stoppd abruptly unlss a srious advrs vnt has occurrd Switching btwn antidprssants should b don. Discontinuation syndrom, pharmacokintic (.g. lvation of tricyclic plasma lvls by srotonin ruptak inhibitors) or pharmacodynamics intractions (.g. srotonin syndrom) may b ncountrd during switching Th spd of th cross-tapring should b judgd by assssing patints tolrability 6. Thr ar no st guidlins on how to do cross tapr it is basd on pharmacological principls. It should b don and dpnds on th patint, th antidprssants usd and th doss. S appndix 2 or a currnt copy of th Maudsly prscribing guidlins In som cass cross-tapring may not b ncssary.g. whn swapping from on srotonin ruptak inhibitor to anothr Whn switching, particular caution should b takn whn switching from: fluoxtin to othr antidprssants du to its long half-lif (on wk) 1. fluoxtin or paroxtin to a tricyclic antidprssant bcaus thy both inhibit th mtabolism of tricyclic antidprssants. A lowr starting dos of a tricyclic antidprssant will b rquird particularly if switching from fluoxtin bcaus of it s long half-lif a non-rvrsibl monoamin oxidas inhibitor. A two wk washout priod is rquird (othr antidprssants should not b prscribd routinly during this priod) 1 bcaus of th dangrs of th ditary and mdicins intractions and th risk of intraction prsists for up to two wks aftr tratmnt with a monoamin oxidas is discontinud 6. S appndix 2. Whn switching to a nw srotonrgic antidprssant or a monoamin oxidas inhibitor, caution should b xrcisd bcaus of th risk of srotonin syndrom 1 (s tabl 2). Also s th Choic and Mdication link for a laflt Th following should b considrd whn patints ar initiatd on vnlafaxin: Liklihood of stopping tratmnt bcaus of its sid ffct profil 1. Vnlafaxin is associatd with a gratr risk of dath compard with othr routinly usd antidprssants 1. Highr doss of vnlafaxin ar associatd with xacrbation of cardiac arrhythmias and hyprtnsion. Patints blood prssur should b monitord at highr doss 1. Doss abov 300mg pr day should b prscribd undr spcialist suprvision

14 Vnlafaxin is contraindicatd in patints with an idntifid high risk of srious cardiac vntricular arrhythmias or in patints with uncontrolld hyprtnsion 9. Vnlafaxin has a highr propnsity for discontinuation/withdrawal symptoms if stoppd abruptly 1. Avoid co-administration of rythromicin (potnt CYP3A4) unlss strictly indicatd bcaus th possibility of clinically important intractions in patints with a poor mtabolisr phnotyp 10. Tabl 2: Symptoms of srotonin syndrom 6 Incrasing Svrity iv. Combining antidprssants Symptoms Rstlssnss Diaphorsis Trmor Shivring Myoclonus Confusion Convulsions Dath 5.28 Combination thrapy is whn two antidprssants ar usd togthr Combination thrapy should b considrd if thr is partial/insufficint rspons on th currnt antidprssant and thr is good tolrability of th currnt antidprssant or switching th antidprssant has bn unsuccssful If a prson is informd about and prpard to tolrat th incrasd sid ffct burdn, considr combining antidprssants Whn combining antidprssants, slct antidprssants known to b saf togthr and b awar of th incrasd sid ffct burdn (s tabl 1) If an unusual combination is to b usd, considr obtaining a scond opinion 1. Also rfr to th unlicnsd mdicins and unlicnsd us of licnsd mdicins (off-labl) policy Th rational for th combination should b discussd with th patint and monitor for advrs ffcts. Th rational should also b documntd 1. Also rfr to th unlicnsd mdicins and unlicnsd us of licnsd mdicins (off-labl) policy Whn combining antidprssants, th patint nds to b monitord vn mor carfully for sid ffcts 1 and for signs and symptoms of srotonin syndrom (s tabl 2). v. Augmnting antidprssants with non-antidprssants 5.35 Augmntation is whn an antidprssant is usd with a non-antidprssant Augmntation thrapy should b considrd if thr is partial/insufficint rspons on th currnt antidprssant and thr is good tolrability of th currnt antidprssant or 13

15 switching th antidprssant has bn unsuccssful If a prson is informd about and prpard to tolrat th incrasd sid ffct burdn, considr augmnting th antidprssant Whn using augmntation thrapy, slct mdicins known to b saf togthr and b awar of th incrasd sid ffct burdn (s tabl 1) Augmntation of an antidprssant with a non-antidprssant mdicin includs th following options lithium, rispridon, aripiprazol, olanzapin or qutiapin If an unusual combination is to b usd, considr obtaining a scond opinion 1. Also rfr to th unlicnsd mdicins and unlicnsd us of licnsd mdicins (off-labl) policy Th rational for th combination should b discussd with th patint and monitor for advrs ffcts. Th rational should also b documntd 1. Also rfr to th unlicnsd mdicins and unlicnsd us of licnsd mdicins (off-labl) policy Whn using augmntation thrapy, th patint nds to b monitord vn mor carfully for sid ffcts Whn prscribing lithium: Aim for a plasma lvl of 0.4 with an optimal rang mmol/l. Maximum srum lvl: 1.0mmol/l 6. Monitor rnal and thyroid function bfor tratmnt and vry six months. If thr is vidnc of rnal impairmnt, rlvant physical illnss, ldrly, intracting mdicins, monitoring should occur mor oftn. Wight should also b monitord 1, 6. Considr ECG monitoring in patints at high risk of cardiovascular disas 6. Monitor srum lithium lvls on wk aftr initiation and ach dos chang until stabl and vry thr months thraftr 1. Continu it in patints who ndd lithium augmntation of antidprssants in acut tratmnt 3. Adjunctiv tratmnt with lithium rducs th risk of rlaps or suicid 3,11. If discontinuing on mdicin, th prfrnc is lithium as it is not advisabl to prscrib lithium alon for dprssion 1,3. Lithium should b slowly rducd ovr at last on month. Incrmntal rduction in plasma lvls of gratr than 0.2mmol/l should b avoidd 6. Th patint must b givn a lithium patint information booklt:

16 5.44 Whn prscribing an antipsychotic, monitor wight, lipid and glucos lvls and for sid ffcts.g. xtrapyramidal sid ffcts and prolactin rlatd sid ffcts with rispridon For patints with dprssion with psychotic symptoms, augmntation of th antidprssant with an antipsychotic (.g. olanzapin or qutiapin 6 ) should b considrd. Th optimum dos and duration of tratmnt is unknown. 1 Tricyclic antidprssants ar probably th mdicins of first choic in psychotic dprssion 6. Initial augmntation is prfrabl to an antidprssant alon or an antipsychotic alon Th combination of an antidprssant with a bnzodiazpin for mor than two wks should not b usd routinly as thr is a risk of dpndnc 1. Vi Combind psychological and mdicin tratmnt 5.47 If a patint has not rspondd to ithr pharmacological or psychological intrvntions a combination of mdication with CBT should b considrd 1. Vii Elctroconvulsiv thrapy 5.48 Elctroconvulsiv thrapy should b considrd for acut tratmnt of svr dprssion (including psychotic dprssion 6 ) that is lif-thratning and whn a rapid rspons is rquird or whn othr tratmnts hav faild ECT should not routinly b usd for popl with modrat dprssion, unlss thy hav not rspondd to multipl mdication tratmnts and psychological tratmnts 1. 15

17 Viii Complx and svr dprssion 5.50 Patints would includ patints at significant risk of slf-harm, hav psychotic symptoms, rquir complx multiprofssional car, or whr an xprt opinion on tratmnt and managmnt is ndd For a prson whos dprssion has faild to rspond to various stratgis for augmntation and combination tratmnts, considr a rfrral to a spcialist srvic Aftr thoroughly rviwing prvious tratmnts for dprssion, th r-introduction of prvious tratmnts that hav bn inadquatly dlivrd or adhrd to should b considrd Othr tratmnt options not listd in tabl 1.g. adjunctiv tratmnt with triiodothyronin, buspiron and lamotrigin ar non-formulary and should b rqustd via th non-formulary rout. IX Continuation of tratmnt 5.54 Patints who hav bnfitd from taking an antidprssant should b supportd in taking it for at last six months. A discussion with th patint should xplain that: this gratly rducs th risk of rlaps; antidprssants ar not associatd with addiction Th prson should b rviwd for th nd for continud antidprssant tratmnt byond six months aftr rmission. Th following should b takn into account: numbr of prvious pisods, consquncs of rlaps, prsnc of rsidual symptoms, concurrnt physical halth problms and psychosocial difficultis Following rmission, th antidprssant tratmnt should b continud at th sam dos for at last six months Following rmission, oldr adult patints should continu tratmnt for at last twlv months Patints with rcurrnt dprssion should rciv maintnanc tratmnt for at last two yars 1, Following 2 yars of maintnanc antidprssant tratmnt, patints should b rassssd according to ag and co-morbidity and othr risk factors 1. X Rlaps prvntion 5.60 For patints with dprssion who ar at significant risk of rlaps or hav a history of rcurrnt dprssion a discussion should tak plac on tratmnts to rduc th risk of rcurrnc, including continuing mdication, augmntation of mdication or CBT. Tratmnt should b influncd by:- 16 prvious tratmnt history including th consquncs of a rlaps, rsidual symptoms, rspons of prvious tratmnt and any discontinuation symptoms. th patint s prfrnc 1.

18 th adquacy of tratmnt including dos and adhrnc 3. a rviw of th diagnosis including th possibility of additional psychiatric or mdical diagnoss Rlapss may b slf-limiting and thrfor caution should b xrcisd about frqunt or too-arly tratmnt changs Mdication rsponsiv patints should hav thir mdication continud at th acut tratmnt dos aftr rmission with th duration dtrmind by risk of rlaps In patints at lowr risk of rlaps.g. first pisod patints without othr risk factors, th duration should b at last six to nin months aftr full rmission If a prson is at risk of rlaps, tratmnt should b continud for at last two yars at th ffctiv dos In patints with mor than fiv liftim pisods and/or two pisods in th last fw yars, at last two yars should b advisd and for most, long-trm tratmnt should b considrd Thr is vidnc that continud antidprssant tratmnt in oldr popl halvs rlaps rats Th lvl of mdication should b maintaind at which acut tratmnt was ffctiv (unlss thr is a good rason to rduc th dos such as unaccptabl advrs ffcts) if:- thy hav had two or mor pisods of dprssion in th rcnt past during which thy xprincd significant functional impairmnt. thy hav othr risk factors for rlaps such as rsidual symptoms, multipl prvious pisods or a history of svr or prolongd pisods or of an inadquat rspons. th consquncs of rlaps ar likly to b svr (for xampl suicid symptoms, loss of functioning svr lif disruption and inability to work Whn dciding whthr to continu maintnanc tratmnt byond two yars, a rvaluation of th patint taking into account ag, co-morbid conditions and othr risk factors Patint with dprssion on long-trm maintnanc tratmnt should b rgularly rvaluatd with frquncy of contact dtrmind by:- co-morbid conditions 1. risk factors for rlaps 1 l svrity and frquncy of pisods of dprssion If a rlaps occurrd, tratmnt options ar:- If an antidprssant has bn stoppd, r-initiation of an antidprssant at an adquat dos 3. If th dos has bn lowrd, r-stablish th prvious dos 3. If th patint is on an adquat dos (with a rcnt onst rlaps), support and monitoring without dos changs should b considrd 3. Incrasing th dos subjct to th following: thr ar minimal sid ffcts and/or thr has bn som improvmnt on th antidprssant and/or th currnt antidprssant has a possibl dos rspons.g. vnlafaxin and tricyclic antidprssants 3. 17

19 Othr options ar switching th antidprssant, combination or augmntation thrapy 3. 18

20 5.71 If a prson has had a good rspons to an antidprssant and an augmnting agnt h/sh should rmain on th combination aftr rmission if sid ffcts ar accptabl. If on mdicin is stoppd, it should usually b th augmnting agnt. Lithium should not b usd as a sol agnt to prvnt rcurrnc of dprssion If a prson s dprssion has rspondd to a cours of ECT, antidprssant mdication should b startd or continud to prvnt rlaps. Considr lithium augmntation of antidprssants Patints who ar considrd to b at significant risk of rlaps (including thos who hav rlapsd dspit antidprssant tratmnt or who ar unabl or choos not to continu antidprssant tratmnt) or who hav rsidual symptoms should b offrd psychological intrvntions 1. Psychological intrvntions ar outsid th scop of this guidanc. XI Stopping and rducing antidprssants 5.74 Whn stopping antidprssant tratmnt aftr a priod of prophylaxis, th timing should b matchd to both risk and consquncs of rlaps and th patint should b warnd that th highst risk is in th six months aftr stopping it Th clinical situation should b takn into account whn dtrmining th rat of tapr.g. srious advrs ractions may warrant rapid discontinuation 3. Antidprssants should normally b stoppd ovr a four wk priod, but this may b longr if paroxtin or vnlafaxin was prscribd. Fluoxtin dos not rquir a tapring off priod du to its long half-lif 1. Rcommndations ar basd on pharmacological principls and dtails dpnd on th patint, th antidprssant usd, dos and th duration of tratmnt. A longr priod may b rquird for patints rciving monoamin oxidas inhibitors spcially tranylcypromin 6. Tranylcypromin is partly mtabolisd to amphtamin and is thrfor associatd with a tru withdrawal syndrom 6. A priod of som months may b appropriat for plannd tratmnt withdrawal aftr long-trm prophylaxis Th spcification of product charactristics for vortioxtin stats patints can stop tratmnt abruptly without th nd for for a gradual rduction in dos 3, Popl should b advisd discontinuation symptoms may occur on stopping tratmnt, missing doss or rducing doss. Symptoms ar usually mild and slf-limiting ovr on wk but can b svr particularly if th mdicin is stoppd abruptly 1. Patints should b warnd that a discontinuation raction may occur if tratmnt is abruptly stoppd aftr mor than a fw wks of tratmnt (th risk is incrasd aftr ight wks or longr) 6. In addition, patints should b advisd antidprssants ar not addictiv. Paroxtin and vnlafaxin ar mor likly to caus th symptoms Th onst of symptoms is usually within fiv days of stopping tratmnt or occasionally aftr tapring or missing doss Symptoms vary dpnding on th typ of antidprssant (s a currnt copy of th Maudsly prscribing guidlins) but may includ flu-lik symptoms, irritability, parasthsia, incrasd draming, insomnia and rarly movmnt disordrs or mania If discontinuation symptoms occur, monitor symptoms and rassur th prson if th symptoms ar mild. If svr, considr rintroducing th antidprssant or introduc an antidprssant with a longr half-lif from th sam class. Thn rduc th dos 19

21 gradually whil monitoring symptoms 1. For xampl for srotonin ruptak inhibitor or a srotonin-noradrnalin ruptak inhibitor, considr switching to fluoxtin which can thn b stoppd aftr discontinuation symptoms hav fully subsidd 3, If a patint switchs to a hypomanic stat, considration of stopping th antidprssant should b mad 13. This can b don abruptly or gradually dpnding on th patint currnt clinical nd, prvious xprinc of discontinuation symptoms and risk of discontinuation symptoms of th antidprssant in qustion. An intolrabl advrs raction may ncssitat an abrupt discontinuation 3. Rfr to th trust guidlins for th managmnt of bipolar affctiv disordr Th patint should b advisd that h/sh should sk advic from thir practitionr if thy xprinc significant discontinuation symptoms. If discontinuation symptoms occur:- symptoms should b monitord and th patint rassurd if th symptoms ar mild. considr th rintroduction of th original antidprssant at th dos that was ffctiv (or anothr antidprssant with longr half-lif from th sam class) if symptoms ar svr, and rduc th dos gradually whil monitoring symptoms 1. 20

22 5.83 A gnral laflt on Coming off mdicins is availabl on th Choic and Mdication link on th intrant: 6 Oldr adults 6.1 Thr is no idal antidprssant as all ar associatd with problms. Srotonin ruptak inhibitors ar bttr tolratd than tricyclic antidprssants, but thy do hav an incrasd risk of blds particularly thos with a history of blds or prscribd a non-stroidal mdicin, aspirin, stroids or warfarin. If a non-stroidal mdicin or aspirin is prscribd, a concurrnt prscription for a gastroprotctiv agnt should b considrd 1. Th risk of hamorrhagic strok may also b incrasd. Hyponatramia, postural hypotnsion and falls (th consqunc of which may b incrasd by srotonin ruptak inhibitor inducd ostopnia) ar also a risk An ag appropriat dos should b prscribd taking into account gnral physical halth and ffct of concomitant mdication on pharmacodynamics and pharmacokintics In oldr popl, rspons to antidprssants may tak longr 3. A minimum of six wks tratmnt should b givn bfor considring th tratmnt to b inffctiv 6, but it may b possibl to idntify non-rspondrs as arly as four wks Antidprssants should b initiatd at lowr doss than usd for youngr adults Th vidnc bas for switching antidprssants or augmnting antidprssants is smallr than for youngr patints. Ovrall 50% of patints rspond. Th bst vidnc is for lithium augmntation Thr is a poorr rspons and a high risk of rlaps in ldrly 8 with co-morbid mdical illnss Thr is vidnc that continud antidprssant tratmnt in oldr popl halvs rlaps rats Th avrag oldr adult is mor likly to b taking concurrnt mdicins 1 lading to a potntial for mdicins-mdicin and mdicins-disas intractions. Rfr to th summary of product charactristics or th British National Formulary for furthr information 9, Hyponatramia is common in th ldrly 11 and thus carful monitoring is advisd in this patint group as oldr ag is a risk factor (s sction10) Th rviw of pidmiological studis, mainly in patint ag 50 yars or oldr shows an incrasd risk of bon fracturs in patints rciving srotonin ruptak inhibitors and tricyclic antidprssants. Th mchanism lading to this incrasd risk is unclar Dprssion in oldr adults with dmntia should b prscribd according to th sam principls as oldr adults, aftr a carful risk assssmnt. Antidprssants with anticholinrgic sid ffcts should b avoidd whr possibl as thy advrsly affct cognition

23 7 Post strok dprssion 7.1 Antidprssants rcommndd in post-strok dprssion ar srotonin r-uptak inhibitors and nortriptylin. Not nortriptylin should b rqustd via th nonformulary rout. Howvr caution is indicatd if th indx strok was known to b hamorrhagic bcaus srotonin ruptak inhibitors incras th risk of hamorrhagic strok (absolut risk is low) whn combind with warfarin or othr antiplatlt mdicins. If th patint is taking warfarin, citalopram should b suggstd as it has th lowst intraction potntial. If th srotonin ruptak inhibitor is givn to an anticoagulatd or aspirin tratd patint, a prscription for a proton pump inhibitor should b considrd 6. 8 Sid ffcts of antidprssants 8.1 If possibl, sid ffcts likly to b transint should b discussd and if ncssary a dos rduction and r-titration If prsistnt, svr or distrssing sid ffcts options ar:- Dos rduction and r-titration if possibl. 3 Switching to an antidprssant with a lowr propnsity to caus sid ffcts 3. Non-mdicin managmnt of th sid ffct.g. dit and xrcis 3. Symptomatic tratmnt with a scond mdicin.g. bnzodiazpins for agitation or a hypnotic for insomnia 3. Spcialist rfrral.g. for sxual dysfunction. 9 Suicidality Antidprssant tratmnt has bn associatd with an incrasd risk of suicidal thoughts and acts particularly in young adults. All antidprssants hav bn implicatd including thos marktd for an indication othr than dprssion (.g. atomoxtin). It should b notd that:- although th rlativ risk may b lvatd abov placbo rats in som patint groups, th absolut risk rmains vry small. th most ffctiv way to prvnt suicidal thoughts and acts is to trat dprssion. antidprssant mdicins ar most ffctiv tratmnt currntly availabl 6. For th most part, suicidality is gratly rducd by th us of antidprssants. Thos who xprinc tratmnt mrgnt or worsning suicidal idation with on antidprssant may b mor likly to hav a similar xprinc with subsqunt tratmnts. Toxicity in ovrdos varis both btwn and within groups of antidprssants. For furthr information, s th sction on Psychotropics in ovrdos in th Maudsly prscribing guidlins 6. 22

24 10 Antidprssant-inducd hyponatramia 10.1 Considr hyponatramia with antidprssants spcially srotonrgic mdicins. Th onst is usually within thirty days of starting tratmnt. Symptoms includ hadach, dizzinss, nausa, vomiting, confusion, malais, rstlssnss, lthargy, cramps, disorintation and sizurs. Risk factors includ history of hyponatramia, low body wight, xtrm old ag (>80yars) or fmal patints, low baslin sodium concntration, rducd rnal function, warm wathr, mdical co-morbidity and som mdicins Mdical co-morbiditis that ar risk factors ar hypothyroidism, diabts, chronic obstructiv pulmonary disas, hyprtnsion, had injury, congstiv hart failur, crbrovascular disas and various cancrs Mdicins which may b a risk factor for dvloping hyponatramia includ carbamazpin, antipsychotics, diurtics, non-stroidal mdicins, tramadol, omprazol and trimthoprim, calcium antagonists and angiotnsin convrting nzym inhibitors Th normal rang for srum sodium is mmol/l (Whittington ICE) If th srum sodium is >125mmol/l, monitor sodium until normal. Symptoms ar listd abov. Considr withdrawing th antidprssant. If th srum sodium is < 125mmol/l, rfr to spcialist mdical car as thr is an incrasd risk of sizurs, coma and rspiratory arrst. Th antidprssant should b discontinud immdiatly 4. Discontinuation symptoms may complicat th clinical pictur Whn rstarting an antidprssant, prscrib an antidprssant from a diffrnt class ithr a noradrnrgic mdicin such as lofpramin, mirtazapin, rvrsibl monoamin oxidas inhibitor (moclobmid) 6. Nortriptylin or agomlatin ar othr options 6, but should b rqustd via th non-formulary rout Elctroconvulsiv thrapy could b considrd as an option S th Choic and Mdication link for laflt on hyponatramia: 11 Cardiovascular disas 11.1 Non-tricyclic antidprssants gnrally hav a low risk of inducing arrhythmias 4. Howvr antidprssants should b usd with caution in patints with risk factors for QT prolongation. Hypokalamia and hypomagnasmia should b corrctd prior to tratmnt. For high risk patints (.g. congnital long QT syndrom, bradycardia, ischamic hart disas, myocarditis, myocardial infarction, lft vntricular hyprtrophy, a gntic prdisposition, pr-xisting QT prolongation, old ag, fmal gndr, hypokalamia, hypomagnasmia, hypocalcamia, xtrm physical xrtion, strss or shock, anorxia nrvosa and mdicin intractions), ECG monitoring should b prformd. Considration should b givn to stopping th antidprssant or rducing th dos of th QT intrval is >500ms or incrass by 60ms. A QT > 500ms or an incras of > 60ms during tratmnt confrs a high risk of Torsads d Points QT prolongation appars to b a class ffct for all slctiv srotonin ruptak inhibitors and tricyclic antidprssants and also occurs with vnlafaxin. Thr ar no high quality data comparing th risk of QT prolongation btwn diffrnt 23

25 antidprssants (othr than citalopram and scitalopram). If QT prolongation or symptomatic arrhythmia occurs during antidprssant tratmnt, th antidprssant should b stoppd or th dos rducd and spcialist advic sought Citalopram is associatd with a dos dpndnt risk of QT prolongation 5,18. Th maximum dos in adults is 40mg and in oldr adults it is 20mg pr day 5,18. Citalopram is contraindicatd with othr mdicins that prolong QTc, patints with known QT prolongation or congnital long QT syndrom. 7,9,18 As antipsychotics can prolong th QTc intrval 6 s th tabl in th Maudsly Prscribing guidlins for th propnsity for antipsychotics to prolong th QTc intrval. Carful considration of th risk/bnfit must b givn bfor any dcision to prscrib combination thrapy with antipsychotics or if patints ar prscribd othr concurrnt mdicins that affct QTc S th trust antipsychotic guidlins for th tabl on th ffcts of antipsychotic mdicins on th QTc intrval Caution is advisd in patints with significant bradycardia or in patints with rcnt acut myocardial infarction or uncompnsatd hart failur 18. Elctrolyt disturbancs such as hypokalamia and hypomagnsamia incras th risk of malignant arrhythmias and should b corrctd bfor tratmnt with citalopram is startd. A baslin ECG is advisd prior to initiating citalopram in patints with stabl cardiac disas Srtralin is th tratmnt of choic for patints with a rcnt myocardial infarction 6 or unstabl angina 9. Othr SSRIs 5 and mirtazapin 6 ar likly to b saf Tricyclic antidprssants should b avoidd in patints at risk of srious arrhythmia du to thir arrhythmognic potntial, which is dos-rlatd. If th us of tricyclic antidprssants cannot b avoidd, th baslin blood prssur should b chckd and an ECG should b prformd at baslin on wk aftr ach incras in dos and priodically throughout tratmnt. Th frquncy is dtrmind by th stability of th cardiac disordr, th tricyclic antidprssant and th dos usd. Advic should b sought from a cardiologist. Lofpramin sms to lack th arrhymognicity of othr tricyclic antidprssants Bupropion, scitalopram (non-formulary), citalopram, moclobmid, lofpramin and vnlafaxin should b usd with caution or avoidd in thos at risk of srious arrhythmia (thos with hart failur, lft vntricular hyprtrophy, prvious arrhythmia or an MI). An ECG should b prformd at baslin and on wk aftr vry incras in dos if any of ths mdicins ar usd at risk patints Th arrhythmognic potntial of tricyclic antidprssants and othr antidprssants is dos rlatd. ECG monitoring should b considrd for all patints: prscribd doss towards th top of th licnsd rang. prscribd othr mdicins (.g. fluoxtin and diurtics) that through mdicin intractions may add to th risk posd by th tricyclic antidprssant 6. 24

26 11.10 In acut coronary syndrom, mdicins which do not incras th risk of subsqunt cardiac vnts should b considrd. Th bst vidnc is for srotonin ruptak inhibitors, mirtazapin and bupropion If possibl, tricyclic antidprssants should b avoidd in cardiac failur and cardiovascular disas Co-morbid Diabts 12.1 Fluoxtin has bn associatd with improvmnts in HbA1c lvls and rducd insulin rquirmnts. Srtralin may also rduc HbA1c. Howvr vidnc is accumulating that long-trm us of srotonin ruptak inhibitors may incras th risk of diabts to a modst xtnt Srotonin-noradrnalin ruptak inhibitors do not appar to disrupt glycamic control, but thr is limitd data with vnlafaxin Littl is known about th ffct of mirtazapin Tricyclic antidprssants ar associatd with incrasd apptit, wight gain and hyprglycamia. Long-trm us of tricyclic antidprssants sms to incras th risk of diabts Irrvrsibl monoamin oxidas inhibitors hav a tndncy to caus xtrm hypoglycamia pisods and wight gain. Moclobmid has no known ffcts Wight gain 13.1 Tricyclic antidprssants ar mor likly to caus incrasd apptit and wight gain than srotonin ruptak inhibitors. Irrvrsibl monoamin oxidas inhibitors hav a tndncy to caus wight gain. Mirtazapin commonly causs incrasd apptit and significant wight gain. Srotonin-noradrnalin ruptak inhibitors hav a minimal impact on wight 6. Fluoxtin has bn associatd with wight loss A wight gain advic laflt is availabl on th Choic and Mdication link on th intrant: Hyprprolactinamia 14.1 Long-standing incrasd plasma prolactin (with or without symptoms) is vry occasionally sn with antidprssant us. Whn it dos occur, riss of prolactin is usually small and short-livd and so symptoms ar rar. Routin monitoring is not rcommndd. Whr symptoms suggst th possibility of hyprprolactinamia thn th masurmnt of plasma prolactin is ssntial Whr symptomatic hyprprolactinamia is confirmd, a switch to mirtazapin is rcommndd Thr is a clar association obsrvd btwn vnlafaxin and prolactin lvation Thr ar som rports in association with srotonin ruptak inhibitors and tricyclic antidprssants A laflt is availabl on th Choic and Mdication link on th intrant:- 25

27 15 Prgnancy and brastfding 15.1 Patints who ar alrady rciving antidprssants and ar at high risk of rlaps ar bst maintaind on antidprssants during and aftr prgnancy Thos who dvlop a modrat or svr dprssiv illnss during prgnancy should b tratd with antidprssant mdicins Womn should b advisd on th spontanous abortion rat in arly prgnant (10-29%) and th baslin risk of congnital malformations (2-3%) 6. Risk of mdication in prgnancy and brastfding should b balancd against th risk to th fotus/baby of untratd matrnal dprssion which includs advrs ffcts on obsttric outcoms, disruptd attachmnt, dlayd infant/child dvlopmnt and vulnrability to subsqunt mntal halth problms An individualisd risk bnfit analysis should tak plac whn considring tratmnt and patints should b providd with writtn information to hlp thm mak an informd choic It is appropriat to considr using th lowst ffctiv dos in prgnancy and brastfding. Polypharmacy should b avoidd In trms of choic of antidprssant, rfr to a currnt copy of th Maudsly prscribing guidlins. Paroxtin may b lss saf than othr SSRIs. Whn taking in lat prgnancy, SSRIs and SNRIs may incras th risk of prsistnt pulmonary hyprtnsion of th nwborn 6,19. Srtralin has a low infant xposur 6. Srtralin is currntly th SSRI of choic in prgnancy Whn choosing an antidprssant, considr th woman s prvious rspons to ths mdicins, stag of prgnancy, what is known about th rproductiv safty of ths mdicins or altrnativ xplanations and th risk of discontinuation symptoms and nonatal adaptation syndrom Patints should b scrnd for alcohol us and for th dvlopmnt of hyprtnsion and pr-clampsia. Womn who tak srotonin ruptak inhibitors may b at an incrasd risk of post-partum hamorrhag For a woman with modrat or svr dprssion in prgnancy or th postnatal priod, a srotonin ruptak inhibitor, srotonin-noradrnalin ruptak inhibitor or a tricyclic antidprssant should b considrd if sh undrstands th risks associatd with mdication and sh has xprssd a prfrnc for mdication, sh dclind psychological intrvntions, hr symptoms hav not rspondd to psychological intrvntions or a combination of a high intnsity psychological intrvntion with mdication if thr was a limitd rspons to ithr intrvntion on thir own For a woman with a history of svr dprssion, prsnting with mild dprssion in prgnancy or th postnatal priod, a srotonin ruptak inhibitor, srotoninnoradrnalin ruptak inhibitor or a tricyclic antidprssant should b considrd