GUIDELINESFORTHEUSEOF

BENZODIAZEPINESINOFFICEPRACTICEIN
THESTATEOFMAINE
Introduction:Thisisanevidencebasedguidelinefortheuseofbenzodiazepinesandrelateddrugsin
clinicaloffice practice.Attachedisabibliographyincludingearlierguidelinesonwhichthisguidelineis
partiallybasedandwebsites,reviews,andclinicalstudiesthatprovidesupportingevidence.Thisguideline
appliestobenzodiazepinesusedprimarilyasanxiolyticsandsedative/hypnotics,andto the relatedZ
drugs,suchaszolpidem,which,whilestructurallydifferentfromthebenzodiazepines,producesimilar
pharmacologiceffectsandhavesimilardependenceandabuse potential.

Thepatientandhishealthcareprovidersshouldagreeononeprovidertobethedesignated
BZDprescriberforthatpatient.Thisdesignatedprescriberwillalsoberesponsiblefor
prescribingothermedicationswithabusepotential,specificallycentralnervoussystem
stimulantsandnarcotics,keepinginmindthattheuseofBZDswithlongtermnarcotics
andstimulantsisnotrecommended..

PatientsreceivinganewprescriptionforaBZDforanxietyshouldbeadvisedonnondrug
therapies.Counselingreferralwillbestronglyrecommended.

RisksandsideeffectsofBZDsshouldbereviewed,includingtheriskofdependence.In
thepatientover65,theseincludetheriskoffalls,cognitiveimpairment,andinteractions
withothermedicationsandmedicalconditions.ThereforeBZDsshouldbeusedwith
cautioninthisagegroup.Becauseofdelayedmetabolismandincreasedriskofside
effects,BZDsshouldbeinitiatedatonehalfoftheusualadultstartingdoseintheelderly
patient.

PrescriptionBZDsareoftendiverted.Careshouldbetakenwhenprescribingtoreduce
theriskofdiversion.

WheninitiatingacourseofBZDtreatment,theclinicianshouldkeepinmindthatsome
patientswillhavedifficultydiscontinuingthemedicationattheendoftheacutetreatment
period.Attheinitiationoftreatment,thepatientshouldbeadvisedexplicitlyregardingthe
durationoftreatment.Exitstrategies,suchasashorttaperorinitiationofalternative
treatments,maybediscussed.Ifthepatientspastmedicationusepatternsorhistoryof
substanceabusesuggestthatBZDdiscontinuationmay beproblematic,thenalternatives
toBZDsshouldbeutilized.

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1.ContraindicationstoBZDs(particularlyforlongtermuse)

a) Pregnancyandthepatientatriskforpregnancy.BZDsarecategoryD.Ifa
hypnoticisnecessary,Zolpidem(Ambien),whichiscategoryB,ispreferred.
PatientswhoconceivewhileonBZDsshouldbetaperedoffcompletely orto
thelowestpossibledose.
b) Activesubstanceabuse,includingalcohol.
c) Medicalandmentalhealthproblemsthatmay beaggravatedbyBZDs.These
includefibromyalgia,chronicfatiguesyndrome,othersomatizationdisorders,
depression(exceptforshorttermusetotreatassociatedanxiety),bipolar
disorder(exceptforurgentsedationinacutemania),ADHD,kleptomania,
andotherimpulsecontroldisorders.Theymayworsenhypoxiaand
hypoventilationinasthma,sleepapnea,COPD,CHF,andother
cardiopulmonarydisorders.
d) Patientsbeingtreatedwithopioidsforchronicpainorreplacementtherapy
fornarcoticaddiction.
e)Griefreactions.BZDsareoftenusedforshorttermtreatmentofinsomniain
acutegriefbutshouldotherwisebeavoidedintreatinggriefreactions,asthey
maysuppressandprolongthegrievingprocess.

2. Indicationsforshorttermtreatmentwith benzodiazepines

a) TheprincipalindicationforBZDsisforshorttermtreatment(2to6weeks)of
anxiety disorders.Theseconditionsincludegeneralizedanxietydisorder,
phobias,PTSD,panicdisorder,andsevereanxietyassociatedwithdepression,
whilewaitingforthefulleffectoftheantidepressant.WhileBZDshavebeen
studiedandutilizedtotreattheseconditionstheyarenotfirstlinetherapy for
anyofthem. However,itisacceptabletouseBZDsasadjunctsduringinitial
treatmentwhilewaitingfordefinitivetherapy withlongtermmedicationsand/or
counselingtotakehold.ContinuingBZDsbeyond4to6weekswill resultin
lossofeffectiveness,thedevelopmentoftolerance,dependenceandpotential
forwithdrawalsyndromes,persistentadversesideeffects,andinterferencewith
theeffectivenessofdefinitivemedicationandcounseling.BZDstakenformore
than2weekscontinuouslyshouldbetaperedratherthandiscontinuedabruptly.

b) Insomnia

ThereisevidencefortheeffectivenessofBZDsandotherhypnoticsinthe
reliefofshortterm (1to2weeks),butnotlongterm,insomnia.Thetreatment
periodshouldnotexceed2weeks.Theonlysignificantclinicaldifference
betweenolderBZDhypnoticsandtheneweroneszolpidem(Ambien),
zaleplon (Sonata),andeszopiclone(Lunesta)istheshorterhalflifeof
zolpidemandzaleplon(2hours).Allthreehavesimilarrisksofdependence
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 andtolerance.Asearchforanetiologyoftheinsomniashouldbeundertaken.
Sleephygienemeasuresshouldbediscussed.

c) Musclerelaxant

BZDsorothermusclerelaxantsareindicatedfortheshorttermrelief (1to2
weeks)ofmusculardiscomfortassociatedwithacuteinjuriesorflareupsof
chronicmusculoskeletalpain. BZDsmaybecombinedwithanalgesicsand
nondrugtherapiesbutnotwithothersedatives,hypnotics,orothermuscle
relaxants.

d) OtherIndications:

Urgenttreatmentofacutepsychosiswithagitation
Aspartofaprotocolfortreatingalcoholwithdrawal
Adjunctivetreatmentof withdrawalfromotheraddictions(lessaccepted)
Singledosetreatmentofphobias,suchasflyingphobia
Seizuresandalimitednumberof otherneurologicaldisorders
Sedationforofficeprocedures

3. Indicationsforlongtermtreatmentwithbenzodiazepines.

BZDsmaybeusedforlongerthan6weeksintheterminallyill,intheseverely
handicappedpatient,incertainneurologicaldisorders(stiffpersonsyndrome),andas
analternativetoantipsychoticsintheseverelydementedpatient.

4. Approach tothepatientalreadyonlongtermbenzodiazepines.

ThereisnoevidencesupportingthelongtermuseofBZDsforanymentalhealth
indication.AtthetimeofBZDprescriptionrenewalormedicationreview,the
physicianshoulddiscusstherisksoflongtermBZDsandthebenefitsof
discontinuation(oncognition,mood,sleep,andenergylevel)andadvisethepatient
toreduceordiscontinuetheBZD. Forsomepatientsthiswillbedifficultor
impossible,buttheeffortshouldbemade.Formany areductionindose,ratherthan
discontinuation,willbethegoal.

ThosewhocanbepersuadedtodososhouldattemptataperoftheircurrentBZDor
hypnotic.Thetapershouldbeslowstartingwithofatabletevery2weeks(or10
to12%ofthedailydoseiftheBZDistakenoncedaily).Exceptionstothisare
zolpidemandzaleplon,whichmaybetaperedmorequicklyorevenstoppedabruptly
sincetheirhalflifeisshort.Eszopiclonehasahalflifeintherangeofshortacting
BZDs(6hrs)sowillneedtobetapered. Thepatientshoulddirectthetaperasmuch
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 asisfeasible.Somemayaccomplishthiswithlimitedphysicianinput.Otherswill
benefitfrom amorestructuredframeworkofperiodicphysicianvisits,with the
physician closelysupervisingthetaperingschedule.Therateoftaperingshouldbe
individualized.Theprocessmaytake3to12monthstocomplete.

Ifthisisnotsuccessfulorif itispreferred,thepatientcanbeswitchedtoanequivalent
doseofalongactingBZD(diazepamorchlordiazepoxide)orphenobarbital andthen
taperedoff..Ifaswitchismade,itshouldbestepwiseonedoseeveryonetotwo
weeksifthepatientisonmultipledailydoses.Thetaperingprocessmaybeginduring
theconversion. Seethetablebelowfordoseequivalentsthatmaybeusedforthis
conversion.

BecausetheyshareGABAnergicreceptoractivitywithBZDs,severalanticonvulsants
(carbamazepine,valproate,gabapentin)canbeusedtofacilitaterapidBZD
withdrawal.Whileonamaintenancedoseof theanticonvulsant,arapidtaperofthe
BZDcanbeundertakenoverthreedaystotwoweeks.Theanticonvulsantwillbe
continuedfor2to3monthsandthentapered.

Counselingshouldbeavailabletoassistwiththewithdrawalprocess.Thecounselor
may beutilizedtotreattheunderlyingconditionforwhichtheBZDwasprescribed,to
addresspersonalcriseswhichmayderailthetaperingschedule,andtodealwith
reboundanxiety.

Foramoredetaileddiscussionofhowtowithdrawpatientsfrom BZDs,visitthe
websitewww.benzo.org.uk.

5. SpecialConsiderations
a) Careshouldbetakennottotaperalprazolamtoorapidly,nortoswitchfromit
toanotherBZDtooabruptly,aswithdrawalseizuresaremorepronetooccur
withitthanwithotherBZDs.
b) Patientswhohavepreviousaddictionproblems,areonhighdosesofBZDs,or
whoaretakingopiatesoramphetaminesconcurrentlywill bemoredifficultto
withdrawandmaybenefitfromreferraltoanaddictionspecialist.
c) AspatientsagetheywillbecomemoresensitivetothesamedoseofaBZD
andhavehigherrisksofadverseeffects,soagingpatientsunabletodiscontinue
longterm BZDsshouldatleasthavetheirdosereduced.
d) Thereissomeriskindrivingandoperatingdangerousmachineryevenwith
stabledosesofBZDs.Thosewithincreasedrisk,includingarecentdose
increase,concomitantuseofothersedativemedications,high doses,or
observedsedatingeffectsshouldbecautionednottodrive.Occasionally itwill
benecessarytonotify thestateDivisionofMotorVehicles.

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 EQUIVALENCETABLETOBEUSEDFORSUBSTITUTIONDURING
WITHDRAWAL

Alprazolam(Xanax) 0.5mg
Chlordiazepoxide(Librium) 25mg
Clonazepam(Klonopin) 0.5mg
Diazepam(Valium)10mg
Lorazepam(Ativan)1mg
Temazepam(Restoril)20mg
Zolpidem(Ambien) 20mg
Zaleplon(Sonata)20mg
Eszopiclone(Lunesta)3mg

BIBLIOGRAPHYFORMAINEBENZODIAZEPINEGUIDELINES

PUBLISHEDGUIDELINES

www.state.ky.us/agencies/kbml/policy/benzo.pdf
AsuccinctandpracticalguidelinefromtheKentuckyMedicalLicensingBoard

www.racgp.org.au/guidelines/benzodiazepines/
GuidelinesfromAustralia

www.le.ac.uk/cgrdu/benzoct17.pdf
Thissitecontainsasetofauditcriteriaforappropriatebenzodiazepineuse

www.benzo.org.uk
Largesitethatisconsumeroriented,butofinteresttocliniciansalso.Usefulinformation
onBZDwithdrawal,linkstoothersites.
SeethepageBenzodiazepinesaroundtheworld.

www.nice.org.uk
Thissitecontainsaguidelineforanxietydisordersthatislongandcomprehensive.It
comeswithanextensive,uptodatebibliography.

www.dohc.ie/publications
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DepartmentofHealthandChildren(Ireland)August2002
ReportoftheBenzodiazepineCommittee

www.uptodate.com
Thiswidelyusedreference,availablebypaidsubscription,discussesrecommended
evaluation andtreatmentofcommonmentalhealthdiagnoses

Ashton,Heather
Guidelinesfortherationaluseofbenzodiazepines
Drugs199448(1)

AustralianandNewZealandclinicalpracticeguidelinesforthetreatmentofpanicdisorder
andagoraphobia
AustralianandNewZealandJournalofPsychiatry200337:641656

Guidelinesforthepreventionandtreatmentofbenzodiazepinedependence:Summaryofa
reportfromtheMentalHealthFoundation(UK)
Addiction(1993)88,17071708

MullerJEetal
Socialanxietydisorder:currenttreatmentrecommendations
CNSDrugs200519(5):37791

VanAmeringenMetal
WorldCouncilofAnxietyrecommendationsforthelongtermtreatmentofsocialphobia
CNSSpectrum2003Aug8(8SUPPL1)4052

PollackMHetal
WorldCouncilofAnxietyrecommendationsforthelongtermtreatmentof panicdisorder
CNSSpectrum2003Aug8(8SUPPL1)1730

REVIEWSANDMETAANALYSES

HolbrookAnne,CrowtherRenee,LotterAnn,ChengChiachen,KingDerek
TreatmentofInsomnia
CJAM 200016,162920:211225

VanLalkomAJ,BakkerA,SpinhoverP,etal
Ametaanalysisofthetreatmentofpanicdisorderwithorwithoutagoraphobia:a
comparisonofpsychopharmacological,cognitivebehavioral,andcombinationtreatments
JournalofNervousandMentalDisease1997185:8.510516

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BakkerA,vanBalkomAJ,SpinhovenPetal
Followuponthetreatmentofpanicdisorderwithorwithoutagoraphobia:aquantitative
review
JournalofNervousandMentalDisease1998186:7.414419

OttoMW etal
Empiricallysupportedtreatmentsforpanicdisorder:costs,benefitsandsteppedcare
JournalofConsultingandClinicalPsychology200068:556563

GouldRA,OttoMW,PollackMH,etal
Cognitivebehavioralandpharmacologicaltreatmentofgeneralizedanxietydisorder:a
preliminarymetaanalysis
BehaviorTherapy199728:285305

RoerigJL
Diagnosisandmanagementofgeneralizedanxietydisorder
JournaloftheAmericanPharmaceuticalAssociation199939:6.811821

DavidsonJRT,BallengerJC,LecrubierY,etal
Pharmacotherapyofgeneralizedanxietydisorder
JournalofClinicalPsychiatry200162:SUPPL.11:4652

BarkerMJ
Cognitiveeffectsoflongtermbenzodiazepineuse:ametaanalysis
CNSDrugs200418(1):3748

FurukawaTAetal
Antidepressantsandbenzodiazepinesformajordepression
CochraneDatabaseSystRev20012:CD001026

CummingsRG,LeCouteurDG
Benzodiazepinesandtheriskofhipfractureinolderpeople:areviewoftheevidence
CNSDrugs200317(11)825837

LydiardRB
Anoverviewofgeneralizedanxietydisorderdiseasestate:appropriatetherapy
ClinicalTher2000:22SUPPLA:A319

WagstaffAJetal
Paroxetineanupdateofitsuseinpsychiatricdisordersinadults
Drugs200262:4.655703

PollackMH
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OptimizingPharmacotherapyofgeneralizedanxietydisordertoachieveremission
JournalofClinicalPsychiatry200162SUPPL19:2025

ButlerAC,ChapmanJE,FormanEM,BeckA
Theempiricalstatusofcognitivebehavioraltherapy:areviewofmetaanalyses
ClinPsycholRev2005Sept29(inpress)

RELEVANTSTUDIES

Belowareafewrecentstudiesinvolvingoutcomesoflongtermbenzodiazepinetherapy,
issuesarounddiscontinuation,combiningbenzodiazepineswithpsychologicaltherapies,
andotherstudiesthatareuniqueandrelevant.AreviewofMedlinerevealsnumerous
studiesaddressingshorttermuseofbenzodiazepinesinvariousmentalhealthdisorders
andasmusclerelaxants,cognitiveeffectsofbenzodiazepines,otherproblemswith
benzodiazepinesingeriatricpatients,andeffectsofbenzodiazepinesondrivingandinjury
risk,whichwillnotbelistedhere.

PowerKG
Acontrolledcomparisonof cognitivebehaviortherapy,diazepam,andplacebo.Aloneand
incombination,forthetreatmentofgeneralizedanxietydisorder
JournalofAnxietyDisorders199044.267292VashaarRCetal

Alprazolamrevisited
MedicalLetterofDrugsandTherapeutics2005Jan1747(1208):57

Zolpidemisnotsuperiortotemazepamwithrespecttoreboundinsomnia:acontrolled
study
EuropeanNeuropsychopharmacology2004Aug14(4):301306

Thefollowingstudiesexaminethenegativeinfluenceofbenzodiazepinesonpsychological
therapies,particularlywhenusedonanasneededbasis.

VanBalkomAJ,deBeursE.LoeleP,etal
Longtermbenzodiazepineuseisassociatedwithsmallertreatmentgaininpanicdisorder
withagoraphobia
JournalofNervousandMentalDisease1997185:8.510516

WestraHA,StewartSH,ConradBE
Naturalisticmannerofbenzodiazepineuseandcognitivebehavioraltherapyoutcomein
panicdisorderwith agoraphobia
JournalofAnxietyDisorders200216:3.233246

Inthisstudyofdiazepamvs.placeboforGADdemonstratingonlyshorttermbenefitfrom
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diazepam,thediazepamgroupdoesntsuddenlyworsenafter3weeks,butratherthe
placebogroupcatchesup.

PourmotabbedT,McLeodDR,etal
Treatment,discontinuation,andpsychomotoreffectsofdiazepaminwomenwith
generalizedanxietydisorder
JournalofClinicalPsychopharmacology199616:202297ReferenceID:70

Thisstudysuggeststhatbenzodiazepinesincreasetheriskofrelapseinthealcoholic.

PoulosCX,ZackM
Lowdosediazepamprimesmotivationforalcoholandalcoholrelatedsemanticnetworks
inproblemdrinkers
BehavioralPharmacology2004Nov15(7):503512

Thefollowingstudiesaddressoutcomesofbenzodiazepinediscontinuation:

VormaHetal
Longtermoutcomeafterbenzodiazepinewithdrawaltreatmentinsubjectswith
complicateddependence
DrugandAlcoholDependence2003June570(3):309315

MorinCMetal
Longtermoutcomeafterdiscontinuationofbenzodiazepinesforinsomnia
BehavResTher2005Jan43(1)114

OconnorKPetal
Psychologicaldistressandadaptationalproblemsassociatedwithbenzodiazepine
withdrawal
AddictBehav2004May29(8)583593

ConnorKMetal
Discontinuationofclonazepaminthetreatmentofsocialphobia
JournalofClinicalPsychopharmacology1998Oct18(5)373378

Thesestudiesexaminethelongtermprognosesofanxietydisordersandthelongterm
outcomesofvarioustreatments.
AderschS,HettaJ
A15yearfollowupstudyofpatientswithpanicdisorder
EuropeanPsychiatry2003Dec18(8):401408

SwobodaH,AmeringM,etal
Thelongtermcourseofpanicdisorderan11yearfollowup
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JournalofAnxietyDisorders200317(2):223232

Durham RC,ChambersJA,MacDonaldRRetal
Doescognitivebehaviouraltherapyinfluencethelongtermoutcomeofgeneralized
anxietydisorder?An814yearfollowupoftwoclinicaltrials
PsychologicalMedicine200333:499509

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