TheCoexistenceofNeuropathicPain,Sleep,andPsychiatricDisordersANovelTreatmentApproachCharlesE.Argoff,MD*wAbstract:Thediagnosisandtreatmentofneuropathicpainmaybecomplicatedbycomorbidconditionssuchassleepdistur-bances,depression,andanxiety.Theinterrelationshipbetweentheindexneuropathicpainstateandthesecomorbiditiesiscomplex:comorbidconditionsexacerbatepain,andinturn,painexacerbatesthecomorbidconditions.Becausecomorbid-itiescannegativelyimpactresponsetopaintreatment,healthcareprovidersshouldassesscomorbiditiesaspartofthediagnosticwork-up,andmanagementstrategiesshouldbedesignedtotreatthewholepatient,notjustthepain.Theoretically,therapiesthatnotonlyreducepain,butalsoimprovesleepandreduceanxietyanddepressioncanprovidemultiplebenefitswithouttheriskofincreasedsideeffectsinherentincombinationtherapy.Anticonvulsantsandanti-depressantshavedemonstratedefficacyinimprovingneuro-pathicpainandpositivelyimpactingcomorbidsleepandmooddisturbances.Novelanticonvulsantsthatcanaddressoneormorecomorbiditiesinadditiontopainmayrepresentviabletreatmentoptionsforpatientswithneuropathicpain.KeyWords:neuropathicpain,sleepdisturbance,antidepres-sants,anticonvulsants,mooddisorders,comorbidities(ClinJPain2007;23:15–22)Neuropathicpainisatypeofchronicpainthatisassociatedwithaprimarylesionordysfunctionwithintheperipheralorcentralnervoussystem.1ItisestimatedthatintheUnitedStates,approximately3.75millionindividualssufferfromneuropathicpainresultingfromdiverseconditions[eg,diabeticpolyneuropathy(DPN),postherpeticneuralgia(PHN),complexregionalpainsyndrome,aswellaspainassociatedwithcancer,spinalcordinjury,lowbackpain,andHIV].2Manyinvestigatorshavenowrecognizedthatotherchronicpainstates,includingmigraineheadache,3andfibromyalgia,4mayalsohaveneuropathicfeatures.Giventhatmigraineaffectsover20millionindividualsintheUnitedStates5andthatfibromyalgiamayaffectapproximately2%oftheUSpopulation,6theprevalenceofneuropathicpainmayactuallybemuchgreaterthanestimated.Asinothertypesofchronicpain,individualswithneuropathicpaincommonlyhavecomorbidities,includ-ingsleepdisturbancesandmooddisorders(ie,depressionoranxiety),whichcancompoundtreatmentchallengesoftheindexdiseasestateandreducethelikelihoodofasuccessfulclinicaloutcome.7Becauseofthesimilaritiesinpathophysiologythatunderlieneuropathicpain,variousneuropathicpainsyndromesrespondtotreatmentwithneuroactiveagents—thatis,antidepressantsandantic-onvulsants—thatmayalsoamelioratesomecomorbidsymptoms.Therefore,thisreviewwillfocusonthecomplexinterrelationshipbetweenneuropathicpainandsleepandpsychiatricdisorders(ie,depressionandanxiety)andtheroleofantidepressantsandantic-onvulsants,especiallynovelanticonvulsants,inthemanagementofpatientswithneuropathicpain.INTERRELATIONSHIPBETWEENNEUROPATHICPAIN,SLEEPDISTURBANCE,DEPRESSION,ANXIETYDISORDERS,ANDQUALITYOFLIFEMorethan70%ofpatientswithchronicpainreportinterferencewithsleep,8,9andthemajorityofthesepatientscitepainasthesolereasonfortheirsleepdisturbance.8Patientswithchronicpainalsosufferfromdepressionandanxiety.10Comorbidsleepdisturbance,depression,andanxietydisordersinpatientswithchronicpainhaveaprofoundeffectonqualityoflife.Meyer-Rosbergetal11,12assessedhealth-relatedqualityoflifeandtheburdenofillnessin126patientssufferingfromperipheralneuropathicpainusingtheShortForm36HealthSurveyandtheNottinghamHealthProfile.Patientsshowedimpairmentinal...
