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OfficialreprintfromUpToDate www.uptodate.com2015UpToDate
AuthorsMichaelHBonnet,PhDDonnaLArand,PhD
SectionEditorRuthBenca,MD,PhD
DeputyEditorAprilFEichler,MD,MPH
ThecontentontheUpToDatewebsiteisnotintendednorrecommendedasasubstituteformedicaladvice,diagnosis,ortreatment.Alwaysseektheadviceofyourownphysicianorotherqualifiedhealthcareprofessionalregardinganymedicalquestionsorconditions.TheuseofthiswebsiteisgovernedbytheUpToDateTermsofUse2015UpToDate,Inc.
Treatmentofinsomnia
Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.Literaturereviewcurrentthrough:May2015.|Thistopiclastupdated:Apr17,2015.
INTRODUCTIONInsomniawaspreviouslyviewedasasleepdisturbancethatwassecondarytoamedicalcondition,psychiatricillness,sleepdisorder,ormedication,andwouldimprovewithtreatmentoftheunderlyingdisorder[1].However,evidenceoverthepast20yearsindicatesthatthisviewisincorrect.
Itisnowrecognizedthatinsomniaisoftenanindependentdisorder[2,3].Insomniamayoccurintheabsenceofcoexistingconditionsand,whencoexistingconditionsexist,maypersistdespitesuccessfultreatmentofthecoexistingcondition.Treatmentdirectedattheinsomniaandthecomorbiditymaybenecessary.Sinceinsomniacanprecipitate,exacerbate,orprolongcomorbidconditions,treatmentofinsomniamayimprovecomorbidities[47].
Treatmentofinsomniaisdescribedinthistopicreview.Thedefinition,types,epidemiology,clinicalfeatures,consequences,anddiagnosticevaluationofinsomniaarereviewedelsewhere.(See"Overviewofinsomnia"and"Clinicalfeaturesanddiagnosisofinsomnia".)
GENERALAPPROACHAllpatientswithinsomniashouldreceivetherapyforanymedicalcondition,psychiatricillness,substanceabuse,orsleepdisorderthatmaybeprecipitatingorexacerbatingtheinsomnia(table1).Theyshouldalsoreceivebasicbehavioralcounselingaboutsleephygiene(table2)andstimuluscontrol(table3).
Forpatientswhocontinuetohaveinsomniathatissufficientlyburdensometowarrantotherinterventions,reasonableapproachesincludebehavioraltherapy,medication,orboth:
Theapproachshouldbeindividualizedaccordingtothepatient'svaluesandpreferences,theavailabilityofadvancedbehavioraltherapies,theseverityandimpactoftheinsomnia,andthepotentialbenefitsversustherisks,costs,andinconveniences.Giventhepotentialsideeffectsassociatedwithpharmacologictherapyandtoalesserextentwithbehavioraltherapy,thedecisiontotreatchronicinsomniamustalsofactorinthepotentialhealthrisksofnotprovidingtreatment,whichincludedecreasedqualityoflife,increasedriskforpsychiatriccomorbiditiesandsubstanceabuse,decreasedperformance,andtheassociationbetweenchronicinsomniaandriskofcardiovascularmorbidityandallcausemortality.(See"Overviewofinsomnia",sectionon'Consequences'.)
Behavioraltherapiesbeyondsleephygieneandstimuluscontrolincluderelaxation,sleeprestrictiontherapy,cognitivetherapy,andcognitivebehavioraltherapy.Thesetherapiesarenotavailableinallmedicalcenters.(See'Behavioraltherapy'below.)
Approvedmedicationsusedtotreatinsomniaincludebenzodiazepines,nonbenzodiazepinesedatives,melatoninagonists,andantidepressants.(See'Medications'below.)
Combinationtherapyinvolvesinitiallyprescribingbothcognitivebehavioraltherapyandamedication(usuallyforsixtoeightweeks),thentaperingthemedicationoffortoanasneededschedulewhilecontinuingcognitivebehavioraltherapy.(See'Combinationtherapy'below.)Theuseofmedicationpriortotheinitiationofbehavioraltherapyappearstobelesseffective[8].
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Inclinicalpractice,initialtreatmenttypicallyinvolvessleephygieneinstructionandstimuluscontrolprocedures.Iffollowupindicatesthatfurthertreatmentisneeded,thenmoreformalcognitivebehavioraltherapyaloneorincombinationwithamedicationmaybeusedforsixweeks.Forpatientswhorespondtotherapy(ie,reportbothimprovedsleepatnightandimprovementofdaytimedeficits),themedicationcanbetaperedorusedasneededwhilecontinuingthecognitivebehavioraltherapy.Patientswhosesymptomsrecurafterdiscontinuationoftherapymayrequirereevaluationforreferralforpolysomnographyoradditionalcognitivebehavioraltherapy,withorwithoutpharmacologictherapy.Anexceptiontothisapproachispatientswhohaveshortterminsomniaduetoaselflimitedstressorsuchpatientsmaybenefitfromshorttermmedicationalone.
BEHAVIORALTHERAPYBehavioraltherapiesforinsomniaincludesleephygieneeducation,stimuluscontrol,relaxation,sleeprestrictiontherapy,cognitivetherapy,andcognitivebehavioraltherapy.Patientswhoseinsomniahasbeensuccessfullytreatedbybehavioraltherapyarelikelytoreportdecreaseddaytimesymptomsandimprovementofdaytimefunction,qualityoflife,andcomorbidities.Behavioraltherapyiswelltoleratedandhasalowriskofadverseeffects,butitisnotreadilyavailableinmanyplaces.
Behavioraltherapybeyondanintroductiontosleephygieneandstimuluscontrolistypicallyimplementedoveraseriesofapproximately6to10sessions.Theevidencesuggeststhatthesuccessofthetherapyisrelatedtotheexperienceoftheindividualimplementingit[9].
SleephygieneSleephygienereferstoactionsthattendtoimproveandmaintaingoodsleep(table2)[10]:
Sleephygienecounselingalonehasnotbeendirectlycomparedwithnointerventionorashamintervention.However,numerousclinicaltrialshaveusedsleephygienecounselingaloneasthecontrolinterventionandshowedsomeimprovementinsleepbutlessthanthatseenwithpharmacotherapyorcognitivebehavioraltherapy[1214].
StimuluscontrolPatientswithinsomniamayassociatetheirbedandbedroomwiththefearofnotsleepingorotherarousingevents,ratherthanthemorepleasurableanticipationofsleep.Thelongeronestaysinbedtryingtosleep,thestrongertheassociationbecomes.Thisperpetuatesthedifficultyfallingasleep.
Stimuluscontroltherapyisastrategywhosepurposeistodisruptthisassociationbyenhancingthelikelihoodofsleep(table3)[15].Patientsshouldnotgotobeduntiltheyaresleepyandshouldusethebedprimarilyforsleep(andnotforreading,watchingtelevision,eating,orworrying).Theyshouldnotspendmorethan20minutesinbedawake.Iftheyareawakeafter20minutes,theyshouldleavethebedroomandengageinarelaxingactivity,suchasreadingorlisteningtosoothingmusic.Patientsshouldnotengageinactivitiesthatstimulatethemorrewardthemforbeingawakeinthemiddleofthenight,suchaseatingorwatchingtelevision.Inaddition,theyshouldnotreturntobeduntiltheyaretiredandfeelreadytosleep.Iftheyreturntobedandstillcannotsleepwithin20minutes,theprocessshouldberepeated.Analarmshouldbesettowakethepatientatthesametimeeverymorning,includingweekends.Daytimenapsarenotallowed.
Patientsmaynotimproveimmediately.However,accumulatingsleepinesswillfacilitatesleepduringsuccessivenights.
Sleepaslongasnecessarytofeelrested(usuallyseventoeighthoursforadults)andthengetoutofbedMaintainaregularsleepschedule,particularlyaregularwakeuptimeinthemorningTrynottoforcesleepAvoidcaffeinatedbeveragesafterlunchAvoidalcoholnearbedtime(eg,lateafternoonandevening)Avoidsmokingorothernicotineintake,particularlyduringtheeveningAdjustthebedroomenvironmentasneededtodecreasestimuli(eg,reduceambientlight,turnoffthetelevisionorradio)
Avoidprolongeduseoflightemittingscreens(laptops,tablets,smartphones,ebooks)beforebedtime[11]ResolveconcernsorworriesbeforebedtimeExerciseregularlyforatleast20minutes,preferablymorethanfourtofivehourspriortobedtimeAvoiddaytimenaps,especiallyiftheyarelongerthan20to30minutesoroccurlateintheday
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Stimuluscontroltherapyhasimprovedsleepinrandomizedtrialsanditseffectsmaybelonglasting[1618].Onestudysuggestedthatstimuluscontroltherapyismoreeffectiveamongpatientswhoarenotalreadytakingmedicationsforinsomnia[19].
RelaxationRelaxationtherapymaybeimplementedbeforeeachsleepperiod.Therearetwocommontechniquesforrelaxationtherapy:progressivemusclerelaxationandtherelaxationresponse.
Onetrialrandomlyassigned57patientswithinsomniatoreceiveprogressiverelaxationtherapyornotherapy[20].Progressiverelaxationtherapyimprovedmeasuresofsleep,butnotdaytimefunction.Anotherrandomizedtrialsimilarlyfoundimprovementinsleepmeasuresamongpatientswhoreceivedrelaxationtherapycomparedwithashamtherapy,buttheimprovementwasmodestandsmallerthanthatachievedwithcognitivebehavioraltherapy[21].Relaxationtherapyissometimescombinedwithbiofeedbacktoreducesomaticarousal.
SleeprestrictiontherapySomepatientswithinsomniastayinbedlongertotrytomakeupforlostsleep.Thiscausesacircadianshiftandareductioninthehomeostaticdrivethatmakessleeponsetthefollowingnightmoredifficultandresultsintheneedtostayinbedevenlonger.Sleeprestrictiontherapycounteractsthistendencybylimitingthetotaltimeallowedinbed,includingnapsandothersleepperiodsoutsideofbed,inordertoincreasethedrivetosleep[22].Thisconsolidatessleepandimprovessleepefficiency(thepercentageoftimeinbedthatthepatientisasleep).
Sleeprestrictiontherapybeginsbydecreasingthetimespentinbedtothesameamountoftimethatthepatientreportssleeping(usuallydeterminedfromsleepdiariesorlogscompletedbythepatient),butnotlessthanfivehourspernight(table4).Onadailybasis,thepatientreportstheamountofsleepobtainedthepreviousnightandtheamountoftimespentinbed.Theclinicianthencomputesthesleepefficiency,whichisthereportedtimeasleepdividedbythereportedtimeinbed.Thetimeinbedisincreasedby15to30minutesoncethesleepefficiencyexceeds85percent.Thisprocessisrepeateduntilthepatientreportsimprovedsleepwithoutresidualdaytimesleepiness.However,totaltimeinbedforsomepatientscanremainatsixhoursorlessforlongperiodsoftime.Napsarenotpermitted.
Toimprovecompliance,therationaleforthetherapyneedstobecarefullyexplainedtopatientsandsomecareneedstobeusedtodetermineandschedulethetimeinbedinamannerthatmaximizestheabilitytosleepandisacceptabletothepatient.Olderpatientstendtohavemoredifficultymaintainingsleepevenwhenrestrictedtherefore,theyaregivenmorelenientcriteria.
A2014systematicreviewidentifiedfourrandomizedtrialsofsleeprestrictiontherapyasastandalonetherapyversusanotherinterventionorcontrolforchronicinsomnia[23].Theweightedeffectsizesforimprovementinsubjectivesleepvariablesweremediumtolargeandcomparabletothoseachievedwithcognitivebehavioralinterventionsinothermetaanalyses[24,25].Inthelargestindividualstudy,179olderadultswithprimaryinsomniawererandomlyassignedtosixweeksofsleeprestrictiontherapy,stimuluscontroltherapy,amulticomponentbehavioralintervention,orwaitlistcontrol[26].Alltreatmentsresultedinsignificantimprovementsindiaryreportedsleepoutcomescomparedwithcontrol,andtherewasnoadvantagetoamulticomponentinterventionoverasinglecomponentintervention.Effectsizesweregenerallymoderatetolargeandmaintainedat3and12monthsposttreatment.
Potentialadverseeffectsofsleeprestrictiontherapyincludeincreaseddaytimesleepinessanddecreased
Progressiverelaxationisbaseduponthetheorythatanindividualcanlearntorelaxonemuscleatatimeuntiltheentirebodyisrelaxed.Beginningwiththemusclesintheface,themusclesarecontractedgentlyforonetotwosecondsandthenrelaxed.Thisisrepeatedseveraltimes.Thesametechniqueisusedforothermusclegroups,usuallyinthefollowingsequence:jawandneck,upperarms,lowerarms,fingers,chest,abdomen,buttocks,thighs,calves,andfeet.Thiscycleisrepeatedforapproximately45minutes,ifnecessary.
Therelaxationresponsebeginsbylyingorsittingcomfortably.Theeyesareclosedandrelaxationisallowedtospreadthroughoutthebody.Arelaxed,abdominalbreathingpatternisestablished.Thoughtsareredirectedawayfromeverydaythoughtsandtowardaneutralmentalfocusingdevice,suchasapeacefulwordorimage.
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reactiontimes,aswellaspossibleexacerbationofbipolardisorder.(See'Adverseeffects'below.)
CognitivetherapyPatientswhoareawakeatnightcommonlybecomeconcernedthattheywillperformpoorlythenextdayiftheydonotobtainadequatesleep.Thisworrycanexacerbatetheirdifficultyfallingasleep,creatingaviciouscycleofwakefulnessandconcern.Apersonmaybegintoblameallnegativeeventsintheirlifeonpoorsleep.Duringcognitivetherapy,apersonworkswithatherapisttodealwithanxietyandcatastrophicthinking,whileestablishingrealisticexpectationsrelatedtoinsomniaandtheneedforsleep.
CognitivebehavioraltherapyCognitivebehavioraltherapy(CBT)isastrategythatcombinesseveralofthepreviouslydescribedapproachesoverseveralweeks[27].AsampleeightsessionCBTprogrammayincludeanintroductorysleepeducationsession,followedbytwosessionsthatfocusonstimuluscontrolandsleeprestriction.Thesemaybefollowedbytwosessionsthatfocusoncognitivetherapyandthenasessiononsleephygiene.Finally,theremaybeasessionthatreviewsandintegratestheprevioussessionandasessionthataddressesfutureproblems,suchasstressandrelapse[28].Patientsareencouragedtocompletesleeplogsastheylearnandapplythevariousstrategies.Thisallowsimprovementtobemeasured.
TheadvantageoftheeducationalnatureofCBTisthatitprovidespatientswithtoolstoapplyinthefuture.DisadvantagesofCBTincludethedurationoftherapyandtherelativelyfewclinicianswhoareskilledatallofitscomponents.ThebenefitofCBTmaybereducedwhenitisadministeredbylessexperiencedclinicians[9].
CBThasprovenefficaciousinmoderatetohighqualityrandomizedtrials[1].AmetaanalysisofbehavioraltherapiesforinsomniathatfoundthatCBTimprovedsubjectivesleepqualityanddecreasedsubjectivewaketimeduringthenight[29].ThebenefitsofCBTappeartopersistwellbeyondtheterminationofactivetreatment[1].SmallrandomizedstudieshavealsosuggestedthatalternativedeliverymethodssuchastelephonebasedCBT[30,31]andinternetbasedCBT[3235]maybeeffectivetreatmentoptionsthatcouldovercomesomeoftheaccessandeconomicbarriersthatexistfortraditionalCBT.However,largerstudiesdirectlycomparingthesemethodswithtraditionalCBTareneeded[36].
CBTisparticularlyrecommendedforuseinsituationswheremedicationsarecontraindicatedormaybemorelikelytoproducesideeffects,suchasolderadults,pregnantwomen,andpatientswithrenal,hepatic,orpulmonarydisease.
OtherapproachesOtherbehavioraltherapiesthatmayemergeasusefulinthetreatmentofinsomniaincludemindfulnessmeditation[3740]andexercisetraining[41].However,asmallrandomizedtrialcomparingtaichiwithCBTinolderadultsfoundthatCBTwasassociatedwithgreaterandmoresustainedimprovementinsleepquality,fatigue,anddepressivesymptomsthantaichi[42].
AdverseeffectsAdverseeffectsofbehavioraltherapyhavenotbeenwelldescribed,butoneareaofcautionrelatestosleeprestriction.Sleeprestrictiondecreasessleeplatencyandincreasessleepefficiencybycausingsleepdeprivation(ie,totalsleeptimeisdecreased,notincreased).Inonestudy,subjectsreportedincreasedsleepinessandhadslowerreactiontimesduringafourweektreatmentperiodthatthenreturnedtobaselinethreemonthslater,whentimeinbedhadincreasedtoaboutsevenhours[43].Theseeffectsaresimilartothoseseenduringchronicpartialsleepdeprivationandsuggestthatpatientsusingthistherapyshouldbecarefullymonitoredandinstructedtoavoidhazardousactivityanddrivingwhentimeinbedhasbeensignificantlyreduced.Sleeprestrictionshouldbeusedwithcautioninpatientswithunderlyingbipolardisorder,sincesleepdeprivationcantriggermanicepisodes[44].
MEDICATIONSMedicationsthatarecommonlyusedtotreatinsomniaincludebenzodiazepines,nonbenzodiazepinesedatives,andmelatoninagonists.Patientswhoseinsomniahasbeensuccessfullytreatedwithpharmacologictherapyarelikelytoreportimprovementofdaytimefunction,betterqualityoflife,andfewercomorbidities(eg,depressedmood).Risksofpharmacologictherapyincludesideeffects,aswellasphysicalandpsychologicaladdictionwithlongtermuse.Theserisksmaybeincreasedincertainclinicalsettings:
PregnancySedativehypnoticsmayincreasetheriskoffetalmalformationsifusedduringthefirsttrimester.
AlcoholconsumptionSedativehypnoticsshouldnotbecombinedwithalcoholbecausethereisariskofexcessivesedationandrespiratorysuppressionwhenevercentralnervoussystemsuppressantsare
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ChoiceofanagentRandomizedtrialsdirectlycomparingtheeffectofdifferentmedicationsoninsomniaarerare.Indirectcomparisonsofbenzodiazepinesandnonbenzodiazepinessuggestthattheseclassesofmedicationhaveasimilarimpactonsleeponsetlatency(ie,theydecreaseobjectivesleeponsetlatencybyapproximately10minutesandsubjectivesleeponsetlatencyby15to20minutes)[45].However,thebenzodiazepinesaremorelikelytoprolongtotalsleeptime,perhapsbecausetheytendtohavelongerhalflives[45,46].
Inoneofthefewtrialsthatdirectlycompareddifferentmedications,382patientswithprimaryinsomniareceivedeachofsixinterventionsinrandomorderfortwonightseach,withathreetosevendaywashoutperiodinbetween[47].Theagentsincludedplacebo,eszopiclone(1,2,2.5,and3mg),andzolpidem(10mg).Comparedwithplacebo,eszopicloneatdosesof2.5and3mgdecreasedthemedianwaketimeaftersleeponset,butzolpidemandeszopicloneatdosesof1and2mgdidnot.Thewaketimeaftersleeponsetreferstotheamountoftimethatthepatientisawakebetweensleeponsetandthefinalmorningarisingtime.Therewerenodifferencesinanyoftheobjectivesleepoutcomeswheneszopiclone(2and3mg)andzolpidemwerecompareddirectly.
Mostcliniciansselectasedativehypnoticonthebasisofthetypeofinsomnia(ie,sleeponsetorsleepmaintenance)andthedurationofeffect:
Otherissuestobeconsideredwhenprescribingamedicationforinsomniaincludecostandadverseeffects.Thebenzodiazepinesandoffpatentnonbenzodiazepines(specifically,zaleplonandzolpidem)tendtobelessexpensivethantheothernonbenzodiazepinesandramelteon.Theadverseeffectsarediscussedbelow.(See'Risksandsideeffects'below.)
BenzodiazepinesBenzodiazepinesareaclassofsleeppromotingmedicationsthatbindtoseveralgammaaminobutyricacid(GABA)typeAreceptorsubtypes[48].Theyreducethetimetotheonsetofsleep,prolongstage2sleep,prolongtotalsleeptime,andmayslightlyreducetherelativeamountofrapideyemovement(REM)sleep[49].Inaddition,theydecreaseanxiety,impairmemory,andhaveanticonvulsiveproperties.
combined.
RenalorhepaticdiseaseMostsedativehypnoticmedicationsundergohepaticandrenalclearance.Metabolicclearancemaybedelayedinpatientswhohaverenalorhepaticdisease,leadingtoaccumulationandexcessivesedation.
PulmonarydiseaseorsleepapneaManysedativehypnoticsarerespiratorysuppressantsthatcanworsenobstructivesleepapneaorhypoventilation.
NighttimedecisionmakersSedativehypnoticsshouldnotbetakenbyindividualswhomaybecalledupontomakeimportantdecisionsduringthenight(eg,cliniciansoncallorsingleparentsresponsibleforthecareofyoungchildren)becausetheycancauseexcesssedationandimpairdecisionmaking.
OlderadultsTheriskofadverseeffectsisincreasedinolderadults,especiallythosewhoareolderthan75years.Thisisaconsequenceofmultiplecomorbiditiesandcentralnervoussystemchangesassociatedwithaging.(See'Olderadults'below.)
Forpatientswithsleeponsetinsomnia,ashortactingmedicationisareasonablechoiceforaninitialtrialofpharmacologictherapy.Thismayimprovetheinsomniawithlessresidualsomnolencethefollowingmorning.Examplesofshortactingmedications(durationofeffect8hours)includezaleplon,zolpidem,triazolam,lorazepam,andramelteon.
Forpatientswithsleepmaintenanceinsomnia,alongeractingmedicationispreferableforaninitialtrialofpharmacologictherapy.Examplesoflongeractingmedicationsincludezolpidemextendedrelease,eszopiclone,temazepam,estazolam,andlowdosedoxepin.However,thesemedicationsmayincreasetheriskforhangoversedationandpatientsmustbewarnedaboutthispossibility.
Forpatientswithawakeninginthemiddleofthenight,bothzaleplonandaspecificsublingualtabletformofzolpidemhavebeendevelopedforuseduringthenight,withtheconstraintthattherewillbeatleastfourhoursoftimeinbedremainingafteradministration.
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Benzodiazepinescommonlyusedforthetreatmentofinsomniaincludetriazolam,estazolam,lorazepam,temazepam,flurazepam,andquazepam.Aprimarydifferenceamongthesemedicationsistheirdurationofaction.Triazolamisshortactingestazolam,lorazepam,andtemazepamareintermediateactingflurazepamandquazepamarelongacting(table5)[49].Diazepamisalsolongacting,butisgenerallynotusedtotreatinsomniabecauseithasalongdurationofeffectandcanleadtotheaccumulationofactivemetabolites.Thelongactingbenzodiazepinesshouldbeavoidedinolderadultsbecausethereisincreasedriskforadverseeffectsinthispatientpopulation[50].
Metaanalysesofrandomized,placebocontrolledtrialsindicatethatbenzodiazepinesdecreasesleeplatencyandthenumberofawakenings,whileimprovingsleepdurationandsleepquality[45,46,51,52].Typicalchangesassociatedwiththesemedicationsincludedecreasesinthedurationtosleeponsetbyapproximately10minutesandincreasesinthetotalsleeptimeof30to60minutes[45,46].
Thesideeffectsofbenzodiazepinesaredescribedbelow.(See'Risksandsideeffects'below.)
NonbenzodiazepinesNonbenzodiazepinereceptoragonistshaveastructurethatisdifferentfromthebenzodiazepinesandincludesmoretargetedactionatoneGABAtypeAreceptor.Aconsequenceoftheirgreaterspecificityislessanxiolyticandanticonvulsantactivity.
Nonbenzodiazepinesappeartoimprovebothsubjectiveandobjectivesleepoutcomes.Specifically,metaanalysesofrandomized,placebocontrolledtrialsindicatethatnonbenzodiazepinesdecreasesleeplatencyandthenumberofawakenings,whileimprovingsleepdurationandsleepquality[45,46,5153].Nonbenzodiazepineshaveincreasedadverseeventscomparedwithplacebo.
Nonbenzodiazepinescommonlyusedtotreatinsomniaincludezaleplon,zolpidem,eszopiclone,andzolpidemextendedrelease(table6):
Zaleplonhasaveryshorthalflifeofaboutonehour.Asaresult,itiseffectiveforpatientswhohavedifficultyfallingasleep(ie,sleeponsetinsomnia),butmaynotbeeffectiveforpatientswhohavedifficultymaintainingsleep(ie,sleepmaintenanceinsomnia)[54].Duetotheveryshorthalflife,thepotentialforhangoversleepinessisminimalafternormalsleepperiods.Occasionalsideeffectsincludeheadache,dizziness,nausea,abdominalpain,andsomnolence[48].Zaleplonisnotindicatedforlongtermuse.
Zolpidemhasahalflifeofapproximately1.5to2.4hours.Itisindicatedfortheshorttermtreatmentofinsomniacharacterizedbydifficultywithsleepinitiation[55].Themostcommonsideeffectsareheadache,dizziness,andsomnolence,whichcaninturnleadtofalls.Zolpidemisnotapprovedforlongtermuse.
Zolpidemisalsoavailableinadissolvabletabletandasanoralsprayforpatientswhohavedifficultyswallowingapill.Adissolvabletablet(1.75to3.5mg)canbetakeninthemiddleofthenightforsleepmaintenanceinsomnia,withtherequirementthatatleastfourhoursbeavailabletosleepafteradministrationandatleastfivehoursbeavailablepriortodriving.InJanuaryof2013,theUSFoodandDrugAdministration(FDA)issuedasafetyannouncementrecommendinguseofalowerdoseinwomenthanhadbeenpreviouslyrecommended[56].Thisshouldalsobeconsideredinmen.(See'Dosingprecautions'below.)
Zolpidemextendedreleasealsohasahalflifeofabout1.5to2.4hours,butisreleasedoveralongerduration.Itwasdevelopedtoimprovebothsleeponsetinsomniaandsleepmaintenanceinsomniawhileavoidinghangovereffects,althoughithasneverbeendirectlycomparedwithregularzolpidem[57].Sideeffectsofzolpidemextendedreleasearerelativelyfew,withthemostcommonbeingheadache,somnolence,anddizziness,whichcaninturnleadtofalls[48].InJanuaryof2013,theFDArecommendeduseofalowerdoseinwomenthanhadbeenpreviouslyrecommended[56].Thislowerdoseshouldalsobeconsideredformen.Inafollowupsafetyannouncement,theFDAaddedawarningthatpatientsshouldnotdriveorengageinotheractivitiesthatrequirecompletementalalertnessthedayaftertakingzolpidemextendedreleasebecausezolpidemlevelscanremainhighenoughthenextdaytoimpairtheseactivities[58].
Sleepmaybeworseduringthefirstnightfollowingdiscontinuationofthismedicine.Zolpidemextended
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Mostclinicaltrialsevaluatedshorttermtherapy(eg,sevendays),althoughafewlongerclinicaltrialshavebeenperformed.Inonerandomizedtrial,patientstreatedwitheszopicloneforsixmonthshadimprovedqualityoflife,decreasedworklimitation,andimprovedsleepcomparedwithplacebo[61].Thispersistedthroughoutthetrialandthesubsequentsixmonthopenlabelextension.Inanotherrandomizedtrialof1018patientswithinsomnia,zolpidemextendedreleasetakenforuptosixmonthsimprovedsleeponset,sleepmaintenance,morningsleepiness,nextdayconcentration,andworkperformancecomparedwithplacebo[62,63].
Adverseeffectsassociatedwiththenonbenzodiazepinesaresimilartothoseassociatedwithbenzodiazepines.Thisisdiscussedbelow.(See'Risksandsideeffects'below.)
MelatoninagonistsRamelteonisamelatoninagonist.Inrandomizedtrials,shorttermuseoframelteonisassociatedwithimprovementinsomesleepparametersinpatientswithinsomnia,buttheeffectsizeisrelativelysmall.
A2014metaanalysisthatincluded11trialsandover5700patientsfoundthatramelteonwasassociatedwithsignificantimprovementinsubjectivesleeplatency(4.6minutes)andtotalsleeptime(7.3minutes)comparedwithplacebobutnosignificantdifferenceinotherparameters,includingsubjectivetotalsleeptime,numberofawakenings,andwakefulnessaftersleeponset[64].Althoughmoststudiesexaminedshorttermtreatmentandoutcomeinmiddleagedadults[64],asmallnumberofindividualtrialshavedemonstratedpersistenceofsubjectivebenefitforatleastsixmonths,andimprovementinolderadults[6569].Subjectiveefficacyextendedtooneyearinanopenlabeltrial[70].
AlthoughramelteonisapprovedintheUnitedStatesandJapan,theEuropeanMedicinesAgency(EMA)concludedin2008thattherewasinadequateevidencethatthedrugwaseffectiveforinsomnia[71].Itdidnotapproveramelteonforuse.TasimelteonisasecondmelatoninagonistthathasbeenapprovedintheUnitedStatesfortreatmentofnon24hoursleepwakedisorder,acircadiansleepwakerhythmdisorderthatoccursprimarilyinblindindividuals[72].
Ramelteonbindstomelatoninreceptorsexpressedinthesuprachiasmaticnucleuswithmuchhigheraffinitythanmelatoninitselfandhasahalflifeof1.5to5hours[73,74].Ramelteonismetabolizedbytheliverandshouldbeusedwithcautioninpatientswithhepaticinsufficiency.Itiscontraindicatedinpatientstakingfluvoxamine,sincefluvoxaminemaydecreasethemetabolismoframelteon[75].Ramelteonismoreeffectiveintreatingsleeponsetinsomniacomparedwithsleepmaintenanceinsomnia.
Adverseeffectsassociatedwithmelatoninagonistsaregenerallymilderthanthoseassociatedwithbenzodiazepinesandnonbenzodiazepines.Themostcommonadverseeffectissomnolence.(See'Adverseeffectsofmelatoninagonists'below.)
OrexinreceptorantagonistsOrexinreceptorantagonistsareanovelclassofdrugsindevelopmentforthetreatmentofinsomnia.OrexinAandorexinBarehypothalamicneuropeptidesthatplayakeyroleinpromotingwakefulnessandregulatingthesleepwakecycle[76].Suvorexant,anoraldualorexinreceptorantagonistwitha12hourhalflife,wasapprovedbytheFDAinAugust2014[77].
Theefficacyofsuvorexantwasdemonstratedinamulticenterinternationaltrialof781patientswithprimary
releaseisnotlimitedtoshorttermuseandthereislittleevidenceforabuseordependenceinmostpatients.Intheory,however,suchmedicationscouldbehabitformingwithlongtermuse.(See'Adverseeffectsofnonbenzodiazepines'below.)
Eszopiclonehasthelongesthalflifeoftheapprovednonbenzodiazepines,approximatelyfivetosevenhours.Thismayextendtoninehoursinolderadultpatients.Eszopicloneiseffectiveforbothsleeponsetinsomniaandsleepmaintenanceinsomnia[59].Patientstakingeszopiclonemayreportanunpleasantmetallictaste.Otherreportedsideeffectsaresharedwithnonbenzodiazepinesasaclass(headache,dizziness,parasomnias,nextdayimpairmentinsomepatients)[48,60].(See'Adverseeffectsofnonbenzodiazepines'below.)
Sleepmaybeworseonthefirstnightafterdiscontinuationofthismedication.Eszopicloneisnotlimitedtoshorttermuseandthereislittleevidenceforabuseordependenceinmostpatients.Intheory,however,suchmedicationscouldbehabitformingwithlongtermuse.
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insomniawhowererandomlyassignedtoreceivenightlysuvorexantorplaceboina2:1ratioforoneyear,followedbyatwomonthrandomizeddiscontinuationphase[78].Thedoseofsuvorexantusedwas40mgforpatients
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constipation,andincreasedintraocularpressure[1].Routineuseofdiphenhydraminetotreatinsomniaisnotrecommended.
AntipsychoticsAntipsychoticshavebeenusedtotreatinsomnia.However,therearefewtrialsthatdemonstrateeffectivenessofthesemedicationsandallhavepotentiallysignificantadverseeffects.Theroutineuseofantipsychoticstotreatinsomniainpatientswithoutpsychosisisnotrecommended[1].
BarbituratesBarbiturateshavesimilarlybeenusedtotreatinsomnia.However,thereislittleevidencethatthesemedicationsimproveinsomniaandallhavepotentiallysignificantadverseeffects.Routineuseofbarbituratestotreatinsomniaisnotrecommended[1].
OverthecounterHerbalproducts,hormones,andalcoholicbeverageshavebeenusedassleepaidsbypatientswithinsomniabuttherearesparsedatauponwhichtoevaluatetheirefficacy.TheseagentsarenotregulatedbytheFDA.
Risksandsideeffects
CommontoallhypnoticsThemostcommonadverseeffectsassociatedwiththebenzodiazepinesandnonbenzodiazepinesareresidualdaytimesedation,drowsiness,dizziness,lightheadedness,cognitiveimpairment,motorincoordination,anddependence[1,45,46,51].Inaddition,mosthypnoticsarerespiratorysuppressantsthatcanworsenobstructivesleepapneaorhypoventilation.
Longtermusemaybehabitformingandreboundinsomniamayoccurwhensomeshortactingmedicationsarediscontinued.Lesscommonadverseeffectsincludecomplexsleeprelatedbehaviors(eg,sleepwalking,driving,makingtelephonecalls,eating,orhavingsexwhilenotfullyawake),anterogradeamnesia(particularlywithtriazolamorwhenusedwithalcohol),aggressivebehavior,andsevereallergicreaction[49,92].Lethaloverdoseisrare[93],unlessthereisconcurrentuseofalcoholoranothercentralnervoussystemdepressant.
AdverseeffectsofnonbenzodiazepinesGenerallyspeaking,theadverseeffectsassociatedwiththenonbenzodiazepinesaresimilartothoseassociatedwiththebenzodiazepines,buttheirfrequencyandseveritymaybeless[45,46].Thisisprobablyrelatedtotheirshorterhalflives,althoughasdiscussedbelow,nextmorningimpairmenthasbeenincreasinglyrecognizedwithhigherdosesandincertainpatientpopulations.(See'Dosingprecautions'below.)
Mostofthecomplexsleeprelatedbehaviorsthathavebeenreportedinpatientstakingnonbenzodiazepineswererelatedtozolpidem,butitisunknownwhetherthisreflectsthewidespreaduseofzolpidemoranassociationbetweentheagentandthesideeffect[49].Inonestudy,zolpidemaccountedfor12percentofall
HerbalproductsAvarietyofherbalproductsarepurportedtobeusefulforinsomnia.Thereislittleevidencefromrandomizedcontrolledtrialsabouttheefficacyofmanyherbals,however,andforthosethathavebeenwellstudied(eg,valerian),thereislittleevidenceofbenefit.Ametaanalysisthatincluded14randomizedtrialsinover1600patientsfoundnosignificantdifferencebetweenanyherbalmedicineandplaceboonanyof13clinicalefficacymeasuresofinsomnia[84].Themajorityofthetrials(11outof14)studiedvalerianchamomile,kava,andwulingwerestudiedinonetrialeach.Unliketheotherherbalsstudied,valerianwasassociatedwithagreaternumberofadverseeventsperpersoncomparedwithplacebo.Valerianmayalsoproducehepatotoxiceffects[1].Contaminationwithundesirablesubstancesposesaproblemformanysuchnaturalremedies.
MelatoninMelatoninisahormonethatisnormallysecretedbythepinealgland.Itdoesnotappeartobebeneficialasatreatmentforinsomniainmostpatientswithtwoexceptions:itmaybeusefulinpatientswhohavedelayedsleepphasesyndromeandinasubgroupofpatientswithlowmelatoninlevels[1,8590].Itappearstobesafewhenusedshortterm(threemonthsorless)[87].(See"Classificationofsleepdisorders",sectionon'Circadianrhythmsleepwakedisorders'.)
AlcoholAlcoholiscommonlyselfprescribedasasleepaidbecauseitdecreasesthetimerequiredtofallasleep,atleastintheshortterm.However,alcoholcanpromotesleepdisturbanceslaterinthenightandpromotesupperairwayinstabilityandsleepapnea.Thesenegativeeffects,coupledwiththesignificantriskofdependenceandinteractionwithothermedications,precludetheuseofalcoholtotreatinsomnia[91].
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emergencydepartmentvisitsforadversedrugeventsrelatedtopsychiatricmedicationintheUnitedStatesovertheperiodof2009to2011,and21percentofallsuchvisitsinvolvingadults65yearsofage[94].Othersideeffectsthathavebeenreportedinpatientstakingnonbenzodiazepinesincludeanunpleasanttaste(eszopiclone)andhallucinations(zolpidem).
Theincidenceofinfection(eg,upperrespiratory,otitismedia,urinarytract,conjunctivitis,others)mayalsobeincreasedamongpatientstakinganonbenzodiazepine,accordingtoonemetaanalysis[95].Twosubsequentstudies,oneinhumansandoneinmice,havealsoreportedanincreasedriskofpneumoniaassociatedwithbenzodiazepinesandthenonbenzodiazepinezopiclone,possiblyrelatedtomodificationofGABAtypeAactivityduringinfection[96,97].Astudyinmicesuggestedthatthisriskcouldextendtoallhypnoticsthatactatthissite[97].
DosingprecautionsDosingrecommendationsforhypnoticmedicationshavetraditionallybeenbasedongroupstatisticaleffectsratherthanindividualresponses.However,therehasbeenincreasingrecognitionthatvariabilityinnonbenzodiazepinemetabolismmayaffectnextmorningdruglevelsandsideeffects.Thesafetyannouncementsreviewedbelowsuggestthatcliniciansshouldhaveincreasedsensitivitytonextdayresidualeffectswhenprescribinganyofthedrugsinthisclassandshouldeducatepatientsaccordingly.
AdverseeffectsofmelatoninagonistsRamelteonhasfewersideeffectsthanthenonbenzodiazepinesorbenzodiazepines[99].Itisnotassociatedwithhypnoticsideeffects(eg,nextdayresidualperformancedeficits),withdrawal,orreboundinsomnia,anditdoesnotappeartobehabitforming[69,99].RamelteonhaslittleabusepotentialandisnotascheduledsubstancewiththeUnitedStatesDrugEnforcementAdministration(DEA),unlikemostotherdrugsusedtotreatinsomnia.Themostcommonsideeffectsaresomnolence,dizziness,nausea,fatigue,andheadache[1,49].Elevatedprolactinlevelsanddecreasedtestosteronelevelsmayoccur,butroutinemonitoringofeitherisnotindicatedintheabsenceofotherclinicalindications.
OlderadultsOlderadultshaveaparticularlyhighriskofadverseeffects,includingexcessivesedation,cognitiveimpairment,delirium,nightwandering,agitation,postoperativeconfusion,balanceproblems,fallandfractures,andimpairedperformanceofdailyactivities[100102].Inametaanalysisof24randomizedtrials(2417patients)thatevaluatedtheimpactofpharmacotherapyinadultsolderthan60yearswithinsomnia,therewasanimprovementofsleepquality,totalsleeptime,andfrequencyofnighttimeawakening[103].However,themagnitudeofthesebenefitswasrelativelysmallcomparedwiththetwotofivefoldincreaseinadversecognitiveorpsychomotorevents.Thissuggeststhatadditionalcautionisnecessarywhendecidingwhetherpharmacotherapyisindicatedforanolderpatientwithinsomnia.
MortalitySeveralobservationalstudieshavefoundanassociationbetweenuseorprescriptionofhypnoticdrugsandallcausemortality,withadjustedhazardratiosrangingfrom1.1to4.5[104109].Theassociationhasbeenobservedinthegeneraladultpopulation[104106,108,109],postmenopausalwomen
In2013,theFDApublishedasafetycommunicationthattherecommendeddoseforzolpidembesetatthelowestdose(5mgforallexceptzolpidemextendedrelease,whichisnow6.25mg)forwomenandalsobeconsideredformen[56].Inaddition,anewwarningwasissuedforzolpidemextendedrelease,advisingthatindividualsrefrainfromdrivingorotheractivitiesthatrequirementalalertnessthedayaftertakingthedrug[58].Theserecommendationswerebasedonstudiesshowingthatbloodlevelsofzolpidemaboveabout50ng/mLappearedcapableofimpairingdrivingsufficientlytoincreasetheriskofanaccident.Thisbloodlevelwasfoundinabout15percentofwomenand3percentofmeneighthoursafteradministrationof10mgofzolpidem.Eighthoursafteruseoftheextendedreleaseformulationofzolpidem,33percentofwomenand25percentofmenstillhadthiselevatedbloodlevel.
Additionalrecommendationswerenotmadeforolderadults,whohavepreviouslybeenadvisedtousethelowestdosesofthesemedications,butadditionalcareiswarrantedforthesepatients.(See'Olderadults'below.)
In2014,asimilarsafetycommunicationwasissuedforeszopiclone,basedondatathatthe2and3mgdosesmaybeassociatedwithimpairmentofdrivingskills,memory,andcoordinationlastingmorethan11hourswithoutsubjectiveawarenessinsomepatients[98].Astartingdoseof1mgisnowrecommendedinallpatients.
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[107],andinpatientswithschizophrenia[110].Otherstudiesinolderadultshavefailedtofindasignificantassociationbetweenhypnoticuseandmortalityafteradjustingforpotentialconfounders[111,112].
Oneofthelargerstudiessuggestedthathypnoticdrugs(includingfrequentlyprescribedagentssuchaszolpidemandtemazepam)wereassociatedwithanincreasedriskofbothcanceranddeath,evenatprescriptionlevelsoflessthan18dosesperyearovera2.5yearduration[104].Anotherlargeretrospectivecasecontrolstudyincludedover34,000patientsage16yearsandolderfirstprescribedananxiolyticorhypnoticdrugorbothbetween1998and2001,matchedbyage,gender,andprimarycarepracticewithnearly70,000controls[109].Overanaveragefollowupperiodof7.6years,prescriptionofanxiolyticandhypnoticdrugswasassociatedwithatwofoldincreasedhazardofdeathafteradjustingforawiderangeofpotentialconfounders,includingmedicalandpsychiatriccomorbidities,sleepdisorders,andotherdrugs.Afterexcludingdeathsduringthefirstyearoffollowup,thiseffecttranslatedtofourexcessdeathsper100peoplefollowedoverasevenyearperiod.
Itisimportanttoemphasize,however,thatthisevidenceisobservationaland,therefore,doesnotindicatecausality.Chronicinsomniahasbeenassociatedwithavarietyofmedicalandpsychiatriccomorbidities,manyofwhichareassociatedwithprematuremortality,anditisdifficulttoexcluderesidualconfoundingbyindicationorotherunmeasuredfactors.Aprospectiveinvestigationoflongtermhypnoticusecomparedwithplaceboandbehavioraltreatmentisneeded.
DruginteractionsConcurrentuseofanysleepingmedicationandalcohol(oranothercentralnervoussystemdepressant)increasestheriskofcentralnervoussystemdepressionand,therefore,iscontraindicated.
Mostbenzodiazepines(exceptlorazepam,oxazepam,andtemazepam)andnonbenzodiazepinesaremetabolizedbytheCYP3A4system[49].InhibitorsoftheCYP3A4system(eg,clarithromycin)increasetheriskoftoxicityrelatedtobenzodiazepinesandnonbenzodiazepines,whileinducersoftheCYP3A4system(eg,rifampin)maydecreasetheeffectivenessofbenzodiazepinesandnonbenzodiazepines.
RamelteonismetabolizedbytheCYP1A2systemand,toalesserextent,theCYP2C9andCYP3A4systems[49].FluvoxamineisapotentinhibitoroftheCYP1A2systemandshouldnotbeusedwithramelteonbecauseitmarkedlyincreasesserumconcentrationsoframelteon.OtherinhibitorsoftheCYP1A2(eg,ciprofloxacin),CYP2C9,orCYP3A4systemsmayalsoincreasetheriskoframelteontoxicity,whileinducersoftheCYPsystems(eg,rifampin)maydecreasetheeffectivenessoframelteon.
COMBINATIONTHERAPYCombinationtherapyinvolvesprescribingbothcognitivebehavioraltherapy(CBT)andamedication,usuallyforsixtoeightweeks.Themedicationisthentaperedoffortoanasneededschedule,whilecontinuingtheCBT.
Twotrialsfromthesameinvestigatorsillustratetheeffectsofcombinationtherapy:
Thefirsttrialrandomlyassigned78patientswithpersistentinsomniatoreceiveCBTalone,temazepamalone,CBTplustemazepam,orplaceboforeightweeks[113].Attheendofthetreatmentphase,allofthetherapieshadsignificantlydecreasedthewaketimeaftersleeponsetcomparedwithplacebo,althoughtherewerenosignificantdifferenceswhenthetreatmentgroupswerecomparedwitheachother.Twoyearsfollowingthecompletionoftreatment,onlytheCBTalonegrouphadmaintaineditsreductioninthewaketimeafterinitialsleeponset.
Thesecondtrialrandomlyassigned160patientswithpersistentinsomniatoreceiveCBTpluszolpidemorCBTaloneforsixweeks[114].Bothgroupshaddecreasedsleeponsetlatency,decreasedwaketimeaftersleeponset,andincreasedsleepefficiencywhencomparedwithbaselineaftersixweeks.However,therewasnosignificantdifferenceintheremissionratewhenthegroupswerecomparedwitheachother(44versus39percent).Thepatientsthenunderwentsecondaryrandomization.PatientsintheCBTalonegroupwererandomlyassignedtonotreatmentormaintenanceCBT,whilepatientsintheCBTpluszolpidemgroupwererandomlyassignedtoeithermaintenanceCBTormaintenanceCBTplusasneededzolpidem.Theimprovementofsleeplatency,waketimeaftersleeponset,andsleepefficiencywasmaintainedinallgroupsatsixmonths,whencomparedwithbaseline.TheremissionratewashigheratsixmonthsamongthegroupsthathadreceivedCBTpluszolpidemduringtheinitialsixweeksofthetrial,thanamongthegroupsthathadinitiallyreceivedCBTalone(56versus43percent).
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Takentogether,theevidenceindicatesthatCBTalone,drugtherapyalone,andcombinationtherapyallimprovemeasuresofinsomnia(eg,waketimeaftersleeponset)withinweeksofinitiatingthetherapy.ContinuingCBTaloneafterthecompletionofinitialtherapyappearstobethebestoptionformaintainingimprovementlongterm.CBTalsoincreasesthelikelihoodthatthemedicationcaneventuallybetapered[115].
Ifsleeprestrictiontherapyiscombinedwithhypnoticmedication,cliniciansshouldbeawarethatthecombinationofchronicpartialsleepdeprivationandmedicationhangovercouldsignificantlyincreasedaytimesleepinessandbehavioralrisk.(See'Adverseeffects'above.)
Theevidenceisinsufficienttojustifycombinationtherapyasroutineinitialmanagementforinsomniapatients.ManypatientswillimprovewithCBTalone,withoutpharmacologictherapy.
FOLLOWUPIfthetreatmentissuccessful,patientswillreportbothimprovedsleepatnightandimprovementofdaytimedeficits.Discontinuationofthemedicationshouldbeconsideredinanypatientwhoisreceivingpharmacologictherapyaloneorcombinationtherapy.
Patientswhohavelittleimprovementduringtheinitialtrialofcognitivebehavioraltherapy,pharmacologictherapy,orcombinationtherapymayhaveothercausesofpoorsleep.Adherencewiththeprescribedtherapyshouldbeconfirmedandthenadditionaldiagnosticevaluationperformed.Suchpatientsoftenrequirereferraltoasleepdisorderscentertobeevaluatedforsleepapneaorotherunderlyingcauses.Suchanevaluationisindicatedearlier(ie,priortothefailureofroutinetherapy)ifthereisclinicalsuspicionthatsleepapneaoranotheretiologyexists.(See"Clinicalfeaturesanddiagnosisofinsomnia",sectionon'Othersleepdisorders'.)
Otherpatientsmayrespondinitiallytopharmacologictherapybutlaterrelapsewhilestilltakingthesamedrug.Insuchcases,clinicalreevaluationiswarrantedtodeterminewhethertherearelifestylechangesorothernewfactorsthatmaybeexacerbatingtheinsomnia.Therearelimiteddataontoleranceandcrosstoleranceamongvariousmedicationsusedtotreatinsomnia,butsomeamountoftolerancelikelyexistsforthebenzodiazepinesandnonbenzodiazepinereceptoragonists[116118].Treatmentdecisionsinpatientswithpossibletolerancemustbeindividualized,takingintoaccountfactorssuchassideeffects,durationoftherapy,priortherapies,andavailabilityofalternativeoptions,suchasbehavioraltherapy.Iflifestylechangesandotherexacerbatingfactorshavebeenruledout,weconsiderthefollowingapproaches:
INSOMNIARELATEDTOCIRCADIANRHYTHMDISORDERSPatientswhohaveinsomniaassociatedwithacircadianrhythmdisordermaybenefitfromphototherapyorchronotherapy.
PhototherapyExposuretobrightlightwhenawakeningisaneffectivetherapyforpatientswhosesleeponsetinsomniaisduetodelayedsleepphasesyndrome,aconditioninwhichtheonsetofsleepisdelayedbecausetheindividual'ssleepwakerhythmislongerthan24hours[83].(See"Classificationofsleepdisorders",sectionon'Circadianrhythmsleepwakedisorders'.)
Patientsundergoingphototherapysitinfrontof5000to10,000luxlightbox(oroutdoorsorinfrontofawindowwithsunlight)for30to40minutesuponawakening(averageindoorlightingis300to500lux,averagesunnysummerdayis100,000lux).Inaddition,theymarkedlyreducetheirexposuretobrightlightintheevening(eg,theymaykeeptheirshadesdownandindoorlightsdim).Aresponsetotherapyisgenerallyevidentaftertwotothreeweeks[119].Indefinitetreatmentisfrequentlynecessarytomaintainthebenefits.Inlessseverecases,consistentawakeningatagiventimeinthemorning,followedbyphysicalactivitywithexposuretooutdoorlight(eg,awalkoutside,sittingnexttoawindowwiththeshadesandcurtainsopen),maybesufficientevenonacloudyday.
Inapatientwhocomplainsoflossofefficacyfromashortactingnonbenzodiazepine,suchaszolpidem,wesuggestatrialofalongeractingdrug,suchaseszopiclone,orswitchtomedicationfromadifferentclass,suchaslowdosedoxepin.
Somepatientsmaybenefitfromadrugholiday,afterwhichtimetheymayagainrespondtotheinitialdrugtherapy.
Institutionofbehavioraltherapycanhelptransitionsomepatientsawayfromlongtermuseofabenzodiazepineornonbenzodiazepinereceptoragonist.(See'Behavioraltherapy'above.)
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Phototherapymayalsobebeneficialtopatientswhoseinsomniaisduetoadvancedsleepphasesyndrome,aconditioninwhichtheindividualdesiressleepearlyandawakensearlybecausetheirsleepwakerhythmhasshiftedearlier.Inthissituation,exposuretobrightlightintheeveningcanhelpdelaysleeponset.
ChronotherapyChronotherapyisabehavioralstrategythatcanbeusedinpatientswithdelayedsleepphasesyndrome.Itreferstotheintentionaldelayofsleeponsetbytwotothreehoursonsuccessivedaysuntilthedesiredbedtimeisreached.Afterthis,thepatientstrictlyenforcesthissleepwakeschedule.Onestudyreportedahighsuccessrateamongpatientswithdelayedsleepphasesyndrome,evenwhenthedisorderhadbeenpresentformanyyears[120].
Chronotherapyrequiresclosemonitoringofschedules.Patientsmustcontinuetodelaytheirsleeptimesuntilthedesiredbedtimehasbeenreached,whichmeansadheringtoseveralafternoonandeveningbedtimes.Thisisanarduousscheduleandpatientsgenerallydonotadheretotheirscheduleafteradjustmentandlapseintotheiroriginalsleephabits.Insomeindividuals,chronotherapycanresultinafreerunningcircadianrhythmandshouldthereforebeusedwithcaution.
JETLAGJetlagisacommoncauseofinsomniathatisdiscussedseparately.(See"Jetlag".)
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,"TheBasics"and"BeyondtheBasics."TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5 to6gradereadinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.Thesearticlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.BeyondtheBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewrittenatthe10 to12 gradereadinglevelandarebestforpatientswhowantindepthinformationandarecomfortablewithsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthesetopicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon"patientinfo"andthekeyword(s)ofinterest.)
SUMMARYANDRECOMMENDATIONS
th th
th th
Basicstopic(see"Patientinformation:Insomnia(TheBasics)")
BeyondtheBasicstopics(see"Patientinformation:Insomnia(BeyondtheBasics)"and"Patientinformation:Insomniatreatments(BeyondtheBasics)")
Allpatientswithinsomniashouldreceivetherapyforanymedicalcondition,psychiatricillness,substanceabuse,orsleepdisorderthatmaybeprecipitatingorexacerbatingtheinsomnia.Theyshouldalsoreceivegeneralbehavioralsuggestions,particularlyadviceregardingsleephygiene(table2)andstimuluscontrol(table3).(See'Generalapproach'above.)
Forpatientswhocontinuetohaveinsomniathatissevereenoughtorequireanintervention,wesuggestcognitivebehavioraltherapy(CBT)astheinitialtherapy(Grade2B).AnalternativetypeofbehavioraltherapyisreasonableifCBTisnotavailable.(See'Generalapproach'aboveand'Behavioraltherapy'above.)
ForpatientswhoseinsomniacontinuestobesevereenoughtorequireaninterventiondespiteCBT,wesuggesttheadditionofamedicationtoCBTratherthanchangingtoastrategyofmedicationalone(Grade2B).(See'Generalapproach'aboveand'Medications'above.)
Forpatientswhorequiremedicationforsleeponsetinsomnia,wesuggestashortactingmedicationratherthanalongeractingagent(Grade2C).(See'Choiceofanagent'above.)
Forpatientswhorequiremedicationforsleepmaintenanceinsomnia,wesuggestalongeractingmedicationratherthanashortactingagent(Grade2C).Alternatively,anewformulationofzolpidemhasbeenapprovedforuseinthemiddleofthenight.Patientsshouldbewarnedabouttheriskfordaytimedrowsiness,impaireddriving,dizziness,andlightheadedness.(See'Choiceofanagent'above.)
Patientsgivenbehavioralpluspharmacologictherapyshouldcontinuebehavioraltherapyforsixtoeight
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UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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Disclosures:MichaelHBonnet,PhDNothingtodisclose.DonnaLArand,PhDConsultant/AdvisoryBoards(spouse):Merck[insomnia(suvorexant)].RuthBenca,MD,PhDGrant/Research/ClinicalTrialSupport:Merck(Insomniaresearch[suvorexant]).Consultant/AdvisoryBoards:Merck(Insomnia[suvorexant])JazzPharmaceuticals[Hypersomnia(sodiumoxybate)].AprilFEichler,MD,MPHEquityOwnership/StockOptions:Johnson&Johnson[Dementia
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