This document summarizes three studies on the risks and efficacy of opioids for chronic non-cancer pain (CNP). The first study finds that while opioids were associated with small improvements in pain and physical functioning compared to placebo, they also increased the risk of vomiting. Comparisons to other medications found similar benefits to pain and functioning. The second study finds no difference in pain-related function between opioid and non-opioid groups over 12 months, and higher rates of adverse effects and pain intensity in the opioid group. The third study finds limited effectiveness of opioids for CNP, as opioid users did not report improvements in outcomes after 2 years. Regarding risks, higher opioid doses are associated with increased overdose risk across several patient groups in

1. Efficacy of Opioids for CNP
Busse,J.W., etal. (2018). "OpioidsforChronicNoncancerPain:A SystematicReviewandMeta-
analysis."Jama320(23): 2448-2460.
Importance:Harmsand benefitsof opioidsforchronicnoncancerpainremainunclear.
Objective:Tosystematicallyreviewrandomizedclinical trials(RCTs) of opioidsforchronicnoncancer
pain.Data Sourcesand StudySelection:The databasesof CENTRAL,CINAHL,EMBASE,MEDLINE, AMED,
and PsycINFOwere searchedfrominceptiontoApril 2018 for RCTs of opioidsforchronicnoncancerpain
vs anynonopioidcontrol.DataExtractionandSynthesis:Pairedreviewersindependentlyextracteddata.
The analysesusedrandom-effectsmodelsandthe Gradingof RecommendationsAssessment,
DevelopmentandEvaluationtorate the qualityof the evidence.MainOutcomesandMeasures:The
primaryoutcomeswere painintensity(score range,0-10cm on a visual analogscale forpain;loweris
betterandthe minimallyimportantdifference [MID] is1 cm),physical functioning(score range,0-100
pointsonthe 36-itemShortForm physical componentscore [SF-36PCS];higherisbetterandthe MID is
5 points),andincidence of vomiting.Results:Ninety-six RCTsincluding26169 participants(61% female;
medianage,58 years[interquartilerange,51-61 years]) were included.Of the includedstudies,there
were 25 trialsof neuropathicpain,32 trialsof nociceptive pain,33trialsof central sensitization(pain
presentinthe absence of tissue damage),and6trialsof mixedtypesof pain.Comparedwithplacebo,
opioiduse wasassociatedwithreducedpain(weightedmeandifference [WMD], -0.69cm [95% CI, -0.82
to -0.56 cm] ona 10-cm visual analogscale forpain;modeledriskdifference forachievingthe MID,
11.9% [95% CI, 9.7% to 14.1%]),improvedphysical functioning(WMD,2.04 points[95% CI, 1.41 to 2.68
points] onthe 100-point SF-36 PCS;modeledriskdifference forachievingthe MID,8.5% [95% CI, 5.9% to
11.2%]),and increasedvomiting(5.9%withopioidsvs2.3% withplacebofor trialsthat excludedpatients
withadverse eventsduringarun-inperiod).Low- tomoderate-qualityevidence suggestedsimilar
associationsof opioidswithimprovementsinpainandphysical functioningcomparedwithnonsteroidal
anti-inflammatorydrugs(pain:WMD, -0.60 cm [95% CI, -1.54 to 0.34 cm]; physical functioning:WMD, -
0.90 points[95% CI, -2.69 to 0.89 points]),tricyclicantidepressants(pain:WMD, -0.13 cm [95% CI, -0.99
to 0.74 cm]; physical functioning:WMD, -5.31 points[95% CI, -13.77 to 3.14 points]),and
anticonvulsants(pain:WMD, -0.90 cm [95% CI, -1.65 to-0.14 cm]; physical functioning:WMD,0.45
points[95% CI, -5.77 to 6.66 points]).ConclusionsandRelevance:Inthismeta-analysisof RCTsof
patientswithchronicnoncancerpain,evidence fromhigh-qualitystudiesshowedthatopioiduse was
associatedwithstatisticallysignificantbutsmall improvementsinpainandphysical functioning,and
increasedriskof vomitingcomparedwithplacebo.Comparisonsof opioidswithnonopioidalternatives
suggestedthatthe benefitforpainandfunctioningmaybe similar,althoughthe evidence wasfrom
studiesof onlylowtomoderate quality.
Krebs,E. E., etal.(2018). "Effectof OpioidvsNonopioidMedicationsonPain-RelatedFunctionin
PatientsWithChronicBackPainor Hipor Knee OsteoarthritisPain:The SPACERandomizedClinical
Trial."Jama 319(9): 872-882.
Importance:Limitedevidence isavailable regardinglong-termoutcomesof opioidscompared
withnonopioidmedicationsforchronicpain. Objective:Tocompare opioidvsnonopioidmedications
over12 monthson pain-relatedfunction,painintensity,andadverse effects.Design,Setting,and

2. Participants:Pragmatic,12-month,randomizedtrial withmaskedoutcomeassessment.Patientswere
recruitedfromVeteransAffairsprimarycare clinicsfromJune 2013 throughDecember2015; follow-up
was completedDecember2016. Eligible patientshadmoderate tosevere chronicbackpainor hipor
knee osteoarthritispaindespite analgesicuse.Of 265 patientsenrolled,25withdrew priorto
randomizationand240 were randomized.Interventions:Bothinterventions(opioidandnonopioid
medicationtherapy) followedatreat-to-targetstrategyaimingforimprovedpainandfunction.Each
interventionhaditsownprescribingstrategythatincludedmultiple medicationoptionsin3steps.Inthe
opioidgroup,the firststepwasimmediate-releasemorphine,oxycodone,or
hydrocodone/acetaminophen.Forthe nonopioidgroup,the firststepwasacetaminophen
(paracetamol) ora nonsteroidal anti-inflammatorydrug.Medicationswerechanged,added,oradjusted
withinthe assignedtreatmentgroupaccordingtoindividualpatientresponse.MainOutcomesand
Measures:The primaryoutcome waspain-relatedfunction(Brief PainInventory[BPI]interferencescale)
over12 monthsand the mainsecondaryoutcome waspainintensity(BPIseverityscale).ForbothBPI
scales(range,0-10; higherscores= worse functionorpain intensity),a1-pointimprovementwas
clinicallyimportant.The primaryadverse outcomewasmedication-relatedsymptoms(patient-reported
checklist;range,0-19).Results:Among240 randomizedpatients(meanage,58.3years;women,32
[13.0%]),234 (97.5%) completedthe trial.Groupsdidnotsignificantlydifferonpain-relatedfunction
over12 months(overall P= .58); mean12-month BPIinterference was3.4for the opioidgroupand3.3
for the nonopioidgroup(difference,0.1[95% CI, -0.5 to 0.7]).Painintensitywassignificantlybetterin
the nonopioidgroupover12 months(overall P= .03); mean12-month BPIseveritywas4.0 for the
opioidgroupand3.5 for the nonopioidgroup(difference,0.5[95% CI, 0.0 to 1.0]). Adverse medication-
relatedsymptomswere significantlymore commoninthe opioidgroupover12 months(overall P=.03);
meanmedication-relatedsymptomsat12 monthswere 1.8 inthe opioidgroupand 0.9 in the nonopioid
group(difference,0.9[95% CI,0.3 to 1.5]). ConclusionsandRelevance:Treatmentwithopioidswasnot
superiortotreatmentwithnonopioid medicationsforimprovingpain-relatedfunctionover12months.
Resultsdonot supportinitiationof opioidtherapyformoderate tosevere chronicbackpainor hipor
knee osteoarthritispain.Trial Registration:clinicaltrials.govIdentifier:NCT01583985.
Veiga,D.R., etal. (2018). "Effectivenessof opioidsforchronicnoncancerpain:atwo-yearmulticenter,
prospective cohortstudywithpropensityscore matching."JPain.
Opioiduse inCNCPisstill controversial regardingtheireffectivenessandsafety.We conducteda
2-yearprospective cohortstudyin4 multidisciplinarychronicpainclinics(MCPCs) toassesslong-term
opioideffectivenessinCNCPpatients.AlladultCNCPpatientsconsecutivelyadmittedtotheirfirst
consultationwere recruited.Demographicandclinical datawere collected,andpropensityscore
matchingwasusedto adjustfor differencesbetweenopioidusersandnonusers.The Brief Pain
Inventory(BPI) andthe Shortversionof TreatmentOutcomesinPainSurvey(S-TOPS) were usedto
measure painoutcomesandqualityof life.A total of 529 subjectswere matchedandincludedinour
analysis.Rate of prescriptionopioiduse was59.7% at baseline,whichincreasedto70.3% over2 years,
of which42.7% of the prescriptionswere forstrong opioids.Opioidusersreportednoimprovement
regardingpainsymptoms,physical function,emotional functionandsocial/familiardisability.Opioid
usersreportedhighersatisfactionwithcare andoutcomesat1 yearof follow-up,butat2 years,they
only reportedimprovementinsatisfactionwithoutcomes.Opioidshave shownlimitedeffectivenessin
long-termCNCPmanagement,asopioiduserspresentednoimprovementsregardingfunctional

3. outcomesandqualityof life.These findingsemphasize the needforproperselectionandoutcome
assessmentof CNCPpatientsprescribedopioids.PERSPECTIVE:Thisstudyaddsimportantadditional
evidence concerningthe controversial use of opioidsinCNCPmanagement.Opioiduserspresentedno
improvementregardingpainrelief,functional outcomesandqualityof lifeover2yearsof follow-up.
Therefore,ourresultssupportandhighlightthe limitedeffectivenessof opioidsinlong-termCNCP
management.
Risks of Opioids for CNP
Overdose
Bohnert,A.S.,et al.(2016). "A DetailedExplorationIntothe Associationof PrescribedOpioidDosage
and Overdose DeathsAmongPatientsWithChronicPain."MedCare 54(5): 435-441.
BACKGROUND:Highopioiddosage hasbeenassociatedwithoverdose,andclinical guidelines
have cautionedagainstescalatingdosagesabove 100 morphine-equivalentmg(MEM) basedon the
potential harmandthe absence of evidence of benefitfromhighdosages.However,this100 MEM
thresholdwaschosensomewhatarbitrarily.OBJECTIVE:Toexamine the associationof prescribedopioid
dosage as a continuousmeasure inrelationtoriskof unintentional opioidoverdose toidentifythe range
of dosagesassociatedwithriskof overdoseata detailedlevel.METHODS:Inthisnestedcase-control
studywithrisk-setsamplingof controls,cases(opioidoverdose decedents)andcontrolswere identified
froma populationof patientsof the VeteransHealthAdministrationwhowere prescribedopioidsand
whohave a chronicpaindiagnosis.Unintentional fatal opioidanalgesicoverdose was measuredfrom
National DeathIndex recordsandprescribedopioiddosage frompharmacyrecords.RESULTS:The
average prescribedopioiddosage washigher(P<0.001) for cases(mean=98.1 MEM, SD=112.7;
median=60,interquartilerange,30-120),than controls(mean=47.7 MEM, SD=65.2; median=25,
interquartilerange,15-45).In a ROC analysis,dosage wasamoderatelygood"predictor"of opioid
overdose death,indicatingthat,onaverage,overdose caseshadaprescribedopioiddosage higherthan
71% of controls.CONCLUSIONS:A clearcut-pointinopioiddosage todistinguishbetweenoverdose
casesand controlswas notfound.However,loweringthe recommendeddosagethresholdbelow the
100 MEM usedinmany recentguidelineswouldaffectproportionatelyfew patientsnot atrisk for
overdose whilepotentiallybenefittingmanyof those atrisk foroverdose.
Bohnert,A.S.,et al.(2011). "Associationbetweenopioidprescribingpatternsandopioidoverdose-
relateddeaths."Jama305(13): 1315-1321.
CONTEXT:The rate of prescriptionopioid-relatedoverdose deathincreasedsubstantiallyinthe
UnitedStatesoverthe past decade.Patternsof opioidprescribingmaybe relatedtoriskof overdose
mortality.OBJECTIVE:Toexamine the associationof maximumprescribeddailyopioid doseanddosing
schedule ("asneeded,"regularlyscheduled,orboth) withriskof opioidoverdosedeathamongpatients
withcancer,chronic pain,acute pain,and substance use disorders.DESIGN:Case-cohortstudy.SETTING:
VeteransHealthAdministration(VHA),2004 through2008. PARTICIPANTS:All unintentional prescription
opioidoverdose decedents(n=750) and a randomsample of patients(n= 154,684) among those
individualswhousedmedical servicesin2004 or 2005 and receivedopioidtherapyforpain. Main

4. Outcome Measure Associationsof opioidregimens(dose andschedule) withdeathbyunintentional
prescriptionopioidoverdose insubgroupsdefinedbyclinical diagnoses,adjustingforage group,sex,
race, ethnicity,andcomorbidconditions.RESULTS:The frequencyof fatal overdose overthe study
periodamongindividualstreatedwithopioidswasestimatedtobe 0.04%.The riskof overdose death
was directlyrelatedtothe maximumprescribeddailydose of opioidmedication.The adjustedhazard
ratios(HRs) associatedwitha maximumprescribeddose of 100 mg/dor more,comparedwiththe dose
category1 mg/dto lessthan20 mg/d,were asfollows:amongthose withsubstance use disorders,
adjustedHR= 4.54 (95% confidence interval[CI],2.46-8.37; absolute riskdifference approximation
[ARDA] = 0.14%); among those withchronicpain,adjustedHR= 7.18 (95% CI,4.85-10.65; ARDA =
0.25%); among those withacute pain,adjustedHR= 6.64 (95% CI,3.31-13.31; ARDA = 0.23%); and
amongthose withcancer,adjustedHR = 11.99 (95% CI, 4.42-32.56; ARDA = 0.45%). Receivingbothas-
neededandregularlyscheduleddoseswasnotassociatedwithoverdoseriskafteradjustment.
CONCLUSION:Amongpatientsreceivingopioidprescriptionsforpain,higheropioiddoseswere
associatedwithincreasedriskof opioidoverdose death.
Dunn,K. M., et al.(2010). "Opioidprescriptionsforchronicpainandoverdose:acohort study."Ann
InternMed 152(2): 85-92.
BACKGROUND:Long-termopioidtherapyforchronicnoncancerpainisbecoming increasingly
commonin communitypractice.Concomitantwiththischange inpractice,ratesof fatal opioidoverdose
have increased.The extenttowhichoverdoserisksare elevatedamongpatientsreceivingmedically
prescribedlong-termopioidtherapyisunknown.OBJECTIVE:Toestimate ratesof opioidoverdoseand
theirassociationwithanaverage prescribeddailyopioiddose amongpatientsreceivingmedically
prescribed,long-termopioidtherapy.DESIGN:Cox proportional hazardsmodelswere usedtoestimate
overdose riskasa functionof average dailyopioiddose (morphine equivalents)receivedatthe time of
overdose.SETTING:HMO. PATIENTS:9940 personswhoreceived3or more opioidprescriptionswithin
90 days forchronic noncancerpainbetween1997 and 2005. MEASUREMENTS: Average dailyopioid
dose overthe previous90 daysfrom automatedpharmacydata.Primaryoutcomes--nonfatal andfatal
overdoses--were identifiedthroughdiagnosticcodesfrominpatientandoutpatientcare anddeath
certificatesandwere confirmedbymedical recordreview.RESULTS:51 opioid-relatedoverdoseswere
identified,including6deaths.Comparedwithpatientsreceiving1to 20 mg/dof opioids(0.2% annual
overdose rate),patientsreceiving50 to 99 mg/dhad a 3.7-foldincrease in overdose risk(95% CI,1.5 to
9.5) and a 0.7% annual overdose rate.Patientsreceiving100mg/d or more had an 8.9-foldincrease in
overdose risk(CI,4.0 to 19.7) and a 1.8% annual overdose rate.LIMITATIONS:Increasedoverdoserisk
amongpatientsreceivinghigherdose regimensmaybe due toconfoundingbypatientdifferencesand
by use of opioidsinwaysnotintendedbyprescribingphysicians.The small numberof overdosesinthe
studycohort isalsoa limitation.CONCLUSION:Patientsreceivinghigherdosesof prescribedopioidsare
at increasedriskforoverdose,whichunderscoresthe needforclose supervisionof these patients.
PRIMARY FUNDINGSOURCE: National Institute of DrugAbuse.
Franklin,G.M., et al.(2012). "Bendingthe prescriptionopioiddosingandmortalitycurves:impactof the
WashingtonState opioiddosingguideline."AmJIndMed 55(4): 325-331.

5. BACKGROUND:Opioiduse anddosingforpatientswithchronicnon-cancerpainhave
dramaticallyincreasedoverthe pastdecade,resultinginanational epidemicof mortalityassociated
withunintentional overdose,andincreasedriskof disabilityamonginjuredworkers.We assessed
changesinopioiddosingpatternsandopioid-relatedmortalityinthe WashingtonState (WA) workers'
compensationsystemfollowingimplementationof aspecificWA opioiddosingguidelineinApril,2007.
METHODS: UsingdetailedcomputerizedbillingdatafromWA workers'compensation,we reportoverall
prevalence of opioidprescriptions,average morphine-equivalentdose (MED)/day,andproportionof
workersondisabilitycompensationreceivingopioidsandhigh-dose (>/=120mg/dayMED) opioidsover
the past decade.We alsoreportthe trendof unintentional opioiddeathsduringthe same time period.
RESULTS: Comparedtobefore 2007, there hasbeena substantial decline inboththe MED/dayof long-
actingDEA Schedule IIopioids(by27%) andthe proportionof workersondoses>/=120 md/dayMED
(by35%). There wasa 50% decrease from2009 to 2010 inthe numberof deaths.CONCLUSIONS:The
introductioninWA of an opioiddosingguideline appearstobe associatedtemporallywithadecline in
the meandose for long-actingopioids,percentof claimantsreceivingopioiddoses>/=120 mg MED per
day,and numberof opioid-relateddeathsamonginjuredworkers.
Garg, R. K., etal. (2017). "Patternsof OpioidUse and Riskof OpioidOverdose DeathAmongMedicaid
Patients."MedCare 55(7): 661-668.
BACKGROUND:The CentersforDisease Control andPreventionrecognizesMedicaidasa high-
riskpopulationforfatal opioidoverdose.Furtherresearchisneededtoidentifyfactorsthatput
Medicaidpatientsatincreasedrisk.OBJECTIVE:Todeterminewhetherpatternsof opioiduse are
associatedwithriskof opioid-relatedmortalityamongopioidusers.DESIGN:Thisisa retrospective
cohort study.PATIENTS:Intotal,150,821 noncancerpain patientsaged18-64 years with>/=1 opioid
prescription,April2006 to December2010, WashingtonMedicaid.MEASURES:Average dailydose
(morphine equivalents),opioidschedule/durationof action,sedative-hypnoticuse.RESULTS:Compared
withpatientsat1-19 mg/d,riskof opioidoverdosedeathsignificantlyincreasedat50-89 mg/d[adjusted
hazard ratio(aHR),2.3; 95% confidence interval (CI),1.4-4.1],90-119 mg/d(aHR, 4.0; 95% CI, 2.2-7.3),
120-199 mg/d (aHR,3.8; 95% CI,2.1-6.9), and >/=200 mg/d(aHR, 4.9; 95% CI, 2.9-8.1). Patientsusing
long-actingplusshort-actingSchedule IIopioidshad4.7 timesthe riskof opioidoverdose deaththan
non-Schedule IIopioidsalone (aHR,4.7;95% CI,3.3-6.9). Sedative-hypnoticuse comparedwithnonuse
was associatedwith6.4timesthe riskof opioidoverdosedeath(aHR,6.4; 95% CI, 5.0-8.4). Riskwas
particularlyhighforopioidscombinedwithbenzodiazepinesandskeletal muscle relaxants(aHR,12.6;
95% CI,8.9-17.9). Evenat opioiddoses1-19 mg/d,patientsusingsedative-hypnoticsconcurrentlyhad
5.6 timesthe riskthanpatientswithoutsedative-hypnotics(aHR,5.6;95% CI, 1.6-19.3). CONCLUSIONS:
Our findingssupportFederal guideline-recommendeddosingthresholdsinopioidprescribing.
Concurrentsedative-hypnoticuse evenatlow opioiddosesposessubstantiallygreaterriskof opioid
overdose.
Gomes,T., etal. (2011). "Opioiddose anddrug-relatedmortalityinpatients withnonmalignantpain."
Arch InternMed171(7): 686-691.

6. BACKGROUND:Opioidsare widelyprescribedforchronicnonmalignantpain,oftenatdoses
exceedingthose recommendedinclinical practice guidelines.However,the risk-benefitratioof high-
dose opioidtherapyisnotwell characterized.The objective of thisstudywastocharacterize the
relationshipbetweenopioiddose andopioid-relatedmortality.METHODS:We conducteda population-
basednestedcase-control studyof Ontario,Canada,residentsaged 15 to 64 yearswhowere eligible for
publiclyfundedprescriptiondrugcoverage andhadreceivedanopioidfromAugust1,1997, through
December31, 2006, fornonmalignantpain.The outcome of interestwasopioid-relateddeath,as
determinedbythe investigatingcoroner.The riskof opioid-relateddeathwascomparedamongpatients
treatedwithvariousdailydosesof opioids.RESULTS:Among607,156 people aged15 to 64 years
prescribedanopioidoverthe studyperiod,we identified498eligiblepatientswhosedeathswere
relatedtoopioidsand1714 matchedcontrols.Afterextensive multivariable adjustment,we foundthat
an average dailydose of 200 mg or more of morphine (orequivalent),wasassociatedwithanearly3-
foldincrease inthe riskof opioid-relatedmortality(oddsratio[OR],2.88;95% confidence interval [CI],
1.79-4.63) relative tolowdailydoses(<20mg of morphine,orequivalent).We foundsignificantbut
attenuatedincreasesinopioid-relatedmortalitywithintermediatedosesof opioids(50-99mg/dof
morphine:OR,1.92; 95% CI, 1.30-2.85; 100-199 mg/dof morphine:OR,2.04; 95% CI,1.28-3.24).
CONCLUSION:Amongpatientsreceivingopioidsfornonmalignantpain,the dailydose isstrongly
associatedwithopioid-relatedmortality,particularly atdosesexceedingthresholdsrecommendedin
recentclinical guidelines.
Gwira Baumblatt,J.A.,etal. (2014). "High-riskuse bypatientsprescribedopioidsforpainanditsrole in
overdose deaths."JAMA InternMed174(5): 796-801.
IMPORTANCE:FromJanuary 1, 2003, throughDecember31, 2010, drugoverdose deathsin
Tennessee increasedfrom422 to 1059 per year.More of these deathsinvolvedprescriptionopioids
than heroinandcocaine combined.OBJECTIVE:Toassessthe contributionof certainopioid-prescribing
patternsto the riskof overdose death.DESIGN,SETTING,ANDPARTICIPANTS:We performedamatched
case-control studythatanalyzedopioidprescriptiondatafromthe TennesseeControlledSubstances
MonitoringProgram(TNCSMP) fromJanuary1, 2007, throughDecember31, 2011, to identifyrisk
factors associatedwithopioid-relatedoverdosedeathsfromJanuary1,2009, throughDecember31,
2010. Case patientswere ascertainedfromdeathcertificate data.Age- andsex-matchedcontrolswere
randomlyselectedfromamonglive patientsinthe TNCSMP.MAIN OUTCOMES AND MEASURES: We
definedahigh-risknumberof prescribersorpharmaciesas4 or more per yearand high-riskdosage asa
dailymeanof more than 100 morphine milligramequivalents(MMEs) peryear. The mainoutcome was
opioid-relatedoverdose death.RESULTS:From January1, 2007, throughDecember31, 2011, one-third
of the populationof Tennesseefilledanopioidprescriptioneachyear,andopioidprescriptionrates
increasedfrom108.3 to 142.5 per100 populationperyear.Amongall patientsinTennessee prescribed
opioidsduring2011, 7.6% usedmore than4 prescribers,2.5% usedmore than4 pharmacies,and2.8%
had a meandailydosage greaterthan100 MMEs. Increasedriskof opioid-relatedoverdosedeathwas
associatedwith4 or more prescribers(adjustedoddsratio[aOR],6.5;95% CI, 5.1-8.5), 4 or more
pharmacies(aOR,6.0; 95% CI,4.4-8.3), and more than 100 MMEs (aOR,11.2; 95% CI, 8.3-15.1). Persons
with1 or more riskfactor accountedfor55% of all overdose deaths.CONCLUSIONSANDRELEVANCE:
High-riskuse of prescriptionopioidsisfrequentandincreasinginTennessee andisassociatedwith
increasedoverdosemortality.Use of prescriptiondrug-monitoringprogramdatato directrisk-reduction

7. measurestothe typesof patientsoverrepresentedamongoverdose deathsmightreduce mortality
associatedwithopioidabuse.
Paulozzi,L.J.,etal. (2012). "A historyof beingprescribedcontrolledsubstancesandriskof drug
overdose death."PainMed13(1):87-95.
OBJECTIVE:The abuse of prescriptiondrugshasincreaseddramaticallysince 1990.Personswho
overdose onsuchdrugs frequentlyconsume large dosesandvisitmultiple providers.The riskof fatal
overdose fordifferentpatternsof use of opioidanalgesicsandsedative/hypnoticshasnotbeenfully
quantified.DESIGN:Matchedcase-control study.Caseswere 300personswhodiedof unintentional
drug overdosesinNewMexicoduring2006-2008, andcontrolswere 5,993 patientsidentifiedthrough
the state prescriptionmonitoringprogramwithmatching6-monthexposure periods.OUTCOME
MEASURES: Death fromdrug overdose ordeathfromopioidoverdose.Exposureswere demographic
variablesandcharacteristicsof prescriptionhistory.Crude andadjustedoddsratios(AOR) were
calculated.RESULTS:Increasedriskwasassociatedwithmale sex (AOR2.4,95% confidence interval [CI]
1.8-3.1), one or more sedative/hypnoticprescriptions(AOR3.0,CI 2.2-4.2), greaterage (AOR1.3, CI 1.2-
1.4 for each10-year increment),numberof prescriptions(AOR1.1,CI 1.1-1.1 for eachadditional
prescription),anda prescriptionforbuprenorphine (AOR9.5,CI 3.0-30.0), fentanyl (AOR3.5,CI1.7-7.0),
hydromorphone (AOR3.3,CI1.4-7.5), methadone (AOR4.9,CI 2.5-9.6), or oxycodone (AOR1.9,CI 1.4-
2.6). Patientsreceivingadailyaverage of >40 morphine milligramequivalentshadanORof 12.2 (CI 9.2-
16.0). CONCLUSIONS:Patientsbeingprescribedopioidanalgesicsfrequentlyorathighdosage face a
substantial overdoserisk. Prescriptionmonitoringprogramsmightbe the bestwayforprescribersto
knowtheirpatients'prescriptionhistoriesandaccuratelyassessoverdoserisk.
Zedler,B.,etal.(2014). "Riskfactorsfor seriousprescriptionopioid-relatedtoxicityoroverdose among
VeteransHealthAdministrationpatients."PainMed15(11): 1911-1929.
OBJECTIVE:Prescriptionopioiduse anddeathsrelatedtoserioustoxicity,includingoverdose,
have increaseddramaticallyinthe UnitedStatessince 1999.However,factorsassociatedwithserious
opioid-relatedrespiratoryorcentral nervoussystem(CNS)depressionoroverdose inmedical usersare
not well characterized.The objective of thisstudywastoexamine the factorsassociatedwithserious
toxicityinmedical usersof prescriptionopioids.DESIGN:Retrospective,nested,case-control analysisof
VeteransHealthAdministration(VHA) medical,pharmacy,andhealthcare resource utilization
administrativedata.SUBJECTS:PatientsdispensedanopioidbyVHA betweenOctober1, 2010 and
September30,2012 (N=8,987). METHODS: Cases(N=817) experiencedlife-threateningopioid-related
respiratory/CNSdepressionoroverdose.Tencontrolswere randomlyassignedtoeachcase (N=8,170).
Logisticregressionwasusedtoexamine associationswiththe outcome.RESULTS:The strongest
associationswere maximumprescribeddailymorphine equivalentdose (MED)>/=100 mg (oddsratio
[OR]=4.1, 95% confidence interval [CI],2.6-6.5),historyof opioiddependence (OR=3.9,95% CI,2.6-5.8),
and hospitalizationduringthe 6monthsbefore the serioustoxicityoroverdose event(OR=2.9,95% CI,
2.3-3.6). Liverdisease,extended-releaseorlong-actingopioids,anddailyMEDof 20 mg or more were
alsosignificantlyassociated.CONCLUSIONS:Substantial risk forseriousopioid-relatedtoxicityand
overdose existsatevenrelativelylowmaximumprescribeddailyMED,especiallyinpatientsalready

8. vulnerable due tounderlyingdemographicfactors,comorbidconditions,andconcomitantuse of CNS
depressantmedicationsorsubstances.Screeningpatientsforrisk,providingeducation,and
coprescribingnaloxone forthose atelevatedriskmaybe effective atreducingseriousopioid-related
respiratory/CNSdepressionandoverdose inmedical usersof prescriptionopioids.
Opioid Use Disorder
Edlund,M. J.,et al.(2014). "The role of opioidprescriptioninincidentopioidabuse anddependence
amongindividualswithchronicnoncancerpain:the role of opioidprescription."ClinJPain30(7):557-
564.
OBJECTIVE:Increasingratesof opioiduse disorders(OUDs) (abuseanddependence) among
patientsprescribedopioidsare asignificantpublichealthconcern.We investigatedthe association
betweenexposuretoprescriptionopioidsandincidentOUDsamongindividualswithanew episodeof a
chronicnoncancerpain (CNCP) condition.METHODS:We utilizedclaimsdatafromthe HealthCore
Database for 2000 to 2005. The datasetincludedall individualsaged18 and overwitha new CNCP
episode (nodiagnosisinthe prior6 mo),andno opioiduse orOUD inthe prior 6 months(n=568,640).
We constructeda single multinomial variable describingprescriptiononopioiddayssupply(none,acute,
and chronic) andaverage dailydose (none,low dose,mediumdose,andhighdose),andexaminedthe
associationbetweenthisvariable andanincidentOUDdiagnosis.RESULTS:PatientswithCNCP
prescribedopioidshadsignificantlyhigherratesof OUDs comparedwiththose notprescribedopioids.
Effectsvariedbyaverage dailydose anddayssupply:low dose,acute (oddsratio[OR]=3.03;95%
confidence interval [CI],2.32,3.95); lowdose,chronic(OR=14.92; 95% CI,10.38, 21.46); mediumdose,
acute (OR=2.80; 95% CI,2.12, 3.71); mediumdose,chronic(OR=28.69; 95% CI,20.02, 41.13); highdose,
acute (OR=3.10; 95% CI,1.67, 5.77); and highdose,chronic(OR=122.45; 95% CI,72.79, 205.99).
CONCLUSIONS:Amongindividualswithanew CNCPepisode,prescriptionopioidexposurewasastrong
riskfactor for incidentOUDs;magnitudesof effectswere large.Durationof opioidtherapywasmore
importantthandailydose indeterminingOUDrisk.
Vowles,K.E.,etal.(2015). "Ratesof opioidmisuse,abuse,andaddictioninchronicpain:asystematic
reviewanddatasynthesis."Pain156(4):569-576.
Opioiduse inchronicpaintreatmentiscomplex,aspatientsmayderivebothbenefitandharm.
Identificationof individualscurrentlyusingopioidsinaproblematicwayisimportantgiventhe
substantial recentincreasesinprescriptionratesandconsequentincreasesinmorbidityandmortality.
The presentreviewprovidesupdatedandexpandedinformationregardingratesof problematicopioid
use inchronic pain.Because previousreviewshave indicatedsubstantialvariabilityinthisliterature,
several stepswere takentoenhance precisionandutility.First,problematicuse wascodedusing
explicitlydefinedterms,referringtodifferentpatternsof use (ie,misuse,abuse,andaddiction).Second,
average prevalence rateswere calculatedandweightedbysample size andstudyquality.Third,the
influenceof differencesinstudymethodologywasexamined.Intotal,datafrom38 studieswere
included.Ratesof problematicuse were quitebroad,rangingfrom<1% to 81% across studies.Across
mostcalculations,ratesof misuse averaged between21% and29% (range,95% confidence interval [CI]:

9. 13%-38%). Ratesof addictionaveragedbetween8% and12% (range,95% CI: 3%-17%).Abuse was
reportedinonlya single study.Only1difference emergedwhenstudymethodswere examined,where
ratesof addictionwere lowerinstudiesthatidentifiedprevalenceassessmentasa primary,ratherthan
secondary,objective.Althoughsignificantvariabilityremainsinthisliterature,thisreview provides
guidance regardingpossible averageratesof opioidmisuseandaddictionandalsohighlightsareasin
needof furtherclarification.
Risks of Tapering Opioids for CNP
Bohnert,A.S.B. andM. A.Ilgen(2019). "UnderstandingLinksamongOpioidUse,Overdose,andSuicide."
N Engl J Med 380(1): 71-79.
Cunningham, J. L., et al. (2016). "Opioid Tapering in Fibromyalgia Patients: Experience from an
Interdisciplinary Pain Rehabilitation Program." Pain Med 17(9): 1676-1685.
OBJECTIVE: Despite current guideline recommendations against the use of opioids for the
treatment of fibromyalgia pain, opioid use is reported in approximately 30% of the patient population.
There is a lack of information describing the process and results of tapering of chronic opioids. The
purpose of thisstudyistodescribe opioidtaperingandwithdrawal symptomsinfibromyalgiapatientson
opioids.DESIGN,SETTING,AND SUBJECTS: This retrospective researchstudyincludedabaseline analysis
of 159 patientsconsecutivelyadmittedtothe Mayo ClinicPainRehabilitationCenterfrom2006 through
2012 with a pain diagnosis of fibromyalgia completing a 3-week outpatient interdisciplinary pain
rehabilitationprogram.Opioidtaperinganalysisincluded55(35%) patientsusingdailyopioids.METHODS:
Opioid tapering was individualizedto each patient based on interdisciplinary pain rehabilitationteam
determination.Opioidwithdrawal symptomswere assesseddaily,utilizingthe Clinical OpioidWithdrawal
Scale.RESULTS:Patientstakingdailyopioidshadamorphineequivalentmeandose of 99mg/day.Patients
on < 100 mg/daywere taperedoff overameanof 10 dayscomparedwithpatientson> 200 mg/dayover
a meanof 28 days (P< 0.001). Differencesinpeakwithdrawal symptomswere notstatisticallysignificant
based on the mean equivalent dose (P = 22). Patients taking opioids for <2 years did not differ in length
of tapering (P =0.63) or peak COWS score (P =0.80) compared with >2 years duration. Patients had
significant improvements in pain-related measures including numeric pain scores, depression
catastrophizing, health perception, interference with life, and perceived life control at program
completion. CONCLUSION: Fibromyalgia patients on higher doses of opioids were tapered off over a
longer period of time but no differences in withdrawal symptoms were seen based on opioid dose.
Durationof opioiduse didnotaffectthe time tocomplete opioidtaperorwithdrawal symptoms.Despite
opioid tapering, pain-related measures improved at the completion of the rehabilitation program.
Demidenko, M. I., et al. (2017). "Suicidal ideation and suicidal self-directed violence following clinician-
initiatedprescriptionopioiddiscontinuationamonglong-termopioidusers."GenHospPsychiatry47: 29-
35.
OBJECTIVE: Little is known about patient outcomes following discontinuationof opioid therapy,
whichmayinclude suicidalideation(SI) andsuicidalself-directedviolence (SSV).The purposeof thisstudy
was to examine correlates of SI and non-fatal SSV in a sample of patients discontinued from long-term

10. opioidtherapy (LTOT).METHOD:Five hundred-nineVeteransHealthAdministration(VHA)patientswhose
clinicians discontinued them from LTOT were selected from a national cohort of VHA patients who
discontinuedopioidsin2012. The sample comprisedpatientswithasubstance use disorderandmatched
controls. Patient electronic health records were manually reviewed to identify discontinuation reasons
and the presence of SI or SSV in the 12months followingdiscontinuation.RESULTS: Forty-sevenpatients
(9.2%) had SI only, while 12 patients (2.4%) had SSV. In covariate-adjusted logistic regression models,
mental healthdiagnosesassociatedwithhavingSI/SSVincludedpost-traumaticstressdisorder(aOR=2.56,
95% CI=1.23-5.32) and psychotic disorders (aOR=3.19, 95% CI=1.14-8.89). Other medical comorbidities,
substance use disorderandpaindiagnoses,opioiddose,andbenzodiazepine prescriptionswere unrelated
to SI/SSV.CONCLUSIONS:Amongpatientswithasubstance use disorderandmatchedcontrols,there are
high rates of SI/SSV following opioid discontinuation, suggesting that these "high risk" patients may
require close monitoring and risk prevention.
Fishbain, D. A. and A. Pulikal (2018). "Does Opioid Tapering in Chronic Pain Patients Result in Improved
Pain or Same Pain vs Increased Pain at Taper Completion? A Structured Evidence-Based Systematic
Review." Pain Med.
Objective:Tosupportorrefutethe hypothesisthatopioidtaperinginchronicpainpatients(CPPs)
improvespainormaintainsthe same painlevelbytapercompletionbutdoesnotincreasepain.Methods:
Of 364 references,20fulfilledinclusion/exclusioncriteria.Thesestudieswere type3and4(notcontrolled)
but reportedpre/post-taperpainlevels.Characteristicsof the studieswere abstractedintotabularform
for numerical analysis.Studieswere ratedindependentlybytworeviewersforquality.The percentageof
studies supporting the above hypothesis was determined. Results: No studies had a rejection quality
score. Combining all studies, 2,109 CPPs were tapered. Eighty percent of the studies reported that by
taper completion pain had improved. Of these, 81.25% demonstrated this statistically. In 15% of the
studies,painwasthe same bytapercompletion.One studyreportedthatbytapercompletion,97%of the
CPPs had improved or the same pain, but CPPs had worse pain in 3%. As such, 100% of the studies
supported the hypothesis. Applying the Agency for Health Care Policy and Research Levels of Evidence
Guidelinestothis resultproducedan A consistencyrating.Conclusions:There isconsistenttype 3 and 4
study evidence that opioidtapering in CPPs reduces pain or maintains the same level of pain. However,
these studiesrepresentedlowerlevelsof evidenceandwerenotdesignedtotestthe hypothesis,withthe
evidence beingmarginal inqualitywithlarge amountsof missingdata.These resultsthenprimarilyreveal
the need for controlled studies (type 2) to address this hypothesis.
Frank, J. W., et al. (2017). "PatientOutcomesinDose Reductionor Discontinuationof Long-TermOpioid
Therapy: A Systematic Review." Ann Intern Med 167(3): 181-191.
Background: Expert guidelines recommend reducing or discontinuing long-term opioid therapy
(LTOT) whenrisksoutweighbenefits,butevidence onthe effectof dose reductiononpatientoutcomes
has notbeensystematicallyreviewed.Purpose:Tosynthesizestudiesof the effectivenessof strategiesto
reduce ordiscontinue LTOTandpatientoutcomesafterdose reductionamongadultsprescribedLTOTfor
chronic pain. Data Sources: MEDLINE, EMBASE, PsycINFO, CINAHL, and the Cochrane Library from
inception through April 2017; reference lists; and expert contacts. Study Selection: Original research

11. published in English that addressed dose reduction or discontinuation of LTOT for chronic pain. Data
Extraction: Two independent reviewers extracted data and assessed study quality using the U.S.
Preventive Services Task Force quality rating criteria. All authors assessed evidence quality using the
GRADE (Grading of Recommendations Assessment, Developmentand Evaluation) system.Prespecified
patient outcomes were pain severity, function, quality of life, opioid withdrawal symptoms, substance
use, and adverse events. Data Synthesis: Sixty-seven studies (11 randomizedtrials and 56 observational
studies) examining 8 intervention categories, including interdisciplinary pain programs, buprenorphine-
assisteddose reduction,andbehavioral interventions,were found.Studyqualitywasgoodfor 3 studies,
fair for 13 studies, and poor for 51 studies. Many studies reported dose reduction, but rates of opioid
discontinuation ranged widely across interventions and the overall quality of evidence was very low.
Among40 studiesexaminingpatientoutcomesafterdosereduction(verylowoverallqualityof evidence),
improvement was reported in pain severity (8 of 8 fair-quality studies), function (5 of 5 fair-quality
studies), and quality of life (3 of 3 fair-quality studies). Limitation: Heterogeneous interventions and
outcome measures;poor-qualitystudieswithuncontrolleddesigns.Conclusion:Verylow qualityevidence
suggeststhatseveral typesof interventionsmaybe effectivetoreduce ordiscontinue LTOTandthatpain,
function, and quality of life may improve withopioid dose reduction. PrimaryFunding Source: Veterans
Health Administration. (PROSPERO: CRD42015020347).
Vanderlip, E. R., et al. (2014). "National study of discontinuation of long-term opioid therapy among
veterans." Pain 155(12): 2673-2679.
Veterans have high rates of chronic pain and long-term opioid therapy (LTOT). Understanding
predictors of discontinuation from LTOT will clarify the risks for prolonged opioid use and dependence
among this population.All veterans with at least 90 days of opioid use within a 180-day period were
identifiedusingnational Veteran'sHealthAffairs(VHA)databetween2009and2011. Discontinuationwas
definedas6monthswithnoopioidprescriptions.We usedCoxproportionalhazardsanalysistodetermine
clinical anddemographiccorrelatesfordiscontinuation.A total of 550,616 veteransmetcriteriaforLTOT.
The sample was primarilymale (93%) and white (74%),witha mean age of 57.8 years. The mediandaily
morphine equivalentdose was26mg, and 7% receivedhigh-dose (>100mgMED) therapy.At1 yearafter
initiation,7.5%(n=41,197) of the LTOT sample haddiscontinuedopioids.Amongthose whodiscontinued
(20%, n=108,601), the mediantime todiscontinuationwas317 days.Factors significantlyassociatedwith
discontinuation included both younger and older age, lower average dosage, and having received less
than 90 days of opioidsinthe previousyear.Althoughtobaccouse disordersdecreasedthe likelihoodof
discontinuation, co-morbid mental illness and substance use disorders increased the likelihood of
discontinuation. LTOT is common in the VHA system and is marked by extended duration of use at
relatively low daily doses with few discontinuation events. Opioid discontinuation is more likely in
veteranswithmental healthandsubstance use disorders.Furtherresearchisneededtodelineate causes
and consequences of opioid discontinuation.
Changes in Pain with Tapering

12. Fishbain,D.A.and A.Pulikal (2018)."DoesOpioidTaperinginChronicPainPatientsResultinImproved
Painor Same Painvs IncreasedPainatTaper Completion?A StructuredEvidence-BasedSystematic
Review."PainMed.
Objective:Tosupportorrefute the hypothesisthatopioidtaperinginchronicpainpatients
(CPPs) improvespainormaintainsthe same painlevel bytapercompletionbutdoesnotincrease pain.
Methods:Of 364 references,20fulfilledinclusion/exclusioncriteria.These studieswere type 3and4
(notcontrolled) butreportedpre/post-taperpainlevels.Characteristicsof the studieswere abstracted
intotabularform fornumerical analysis.Studieswere ratedindependentlybytworeviewersforquality.
The percentage of studiessupportingthe above hypothesiswasdetermined. Results:Nostudieshada
rejectionqualityscore.Combiningall studies,2,109CPPswere tapered.Eightypercentof the studies
reportedthatby tapercompletionpainhadimproved.Of these,81.25% demonstratedthisstatistically.
In 15% of the studies, painwasthe same bytaper completion.One studyreportedthatbytaper
completion,97%of the CPPshad improvedorthe same pain,but CPPshadworse painin 3%. Assuch,
100% of the studiessupportedthe hypothesis.Applyingthe AgencyforHealthCare PolicyandResearch
Levelsof Evidence GuidelinestothisresultproducedanA consistencyrating.Conclusions:There is
consistenttype 3and 4 studyevidence thatopioidtaperinginCPPsreducespainormaintainsthe same
level of pain.However,these studiesrepresentedlowerlevelsof evidence andwere notdesignedto
testthe hypothesis,withthe evidence beingmarginal inqualitywithlarge amountsof missingdata.
These resultsthenprimarilyrevealthe needforcontrolledstudies(type2) to addressthishypothesis.
Frank,J. W., etal. (2017). "PatientOutcomesinDose ReductionorDiscontinuationof Long-TermOpioid
Therapy:A SystematicReview."AnnInternMed167(3): 181-191.
Background:Expertguidelinesrecommendreducingordiscontinuinglong-termopioidtherapy
(LTOT) whenrisksoutweighbenefits,butevidenceonthe effectof dose reductiononpatientoutcomes
has notbeensystematicallyreviewed.Purpose:Tosynthesizestudiesof the effectivenessof strategies
to reduce or discontinue LTOTandpatientoutcomesafterdose reductionamongadultsprescribedLTOT
for chronicpain.Data Sources:MEDLINE, EMBASE, PsycINFO,CINAHL,andthe Cochrane Libraryfrom
inceptionthroughApril 2017; reference lists;andexpertcontacts.StudySelection:Originalresearch
publishedinEnglishthataddresseddose reductionordiscontinuationof LTOTfor chronicpain.Data
Extraction:Twoindependentreviewersextracteddataandassessedstudyqualityusingthe U.S.
PreventiveServicesTaskForce qualityrating criteria.All authorsassessedevidencequalityusingthe
GRADE (Gradingof RecommendationsAssessment,DevelopmentandEvaluation)system.Prespecified
patientoutcomeswere painseverity,function,qualityof life,opioidwithdrawal symptoms,substance
use,andadverse events.DataSynthesis:Sixty-sevenstudies(11randomizedtrialsand56 observational
studies) examining8interventioncategories,includinginterdisciplinarypainprograms,buprenorphine-
assisteddose reduction,andbehavioralinterventions,were found.Studyqualitywasgoodfor3 studies,
fairfor 13 studies,andpoorfor 51 studies.Manystudiesreporteddosereduction,butratesof opioid
discontinuationrangedwidelyacrossinterventionsandthe overall qualityof evidence wasverylow.
Among40 studiesexaminingpatientoutcomesafterdose reduction(verylow overall qualityof
evidence),improvementwasreportedinpainseverity(8of 8 fair-qualitystudies),function(5of 5 fair-
qualitystudies),andqualityof life(3of 3 fair-qualitystudies).Limitation:Heterogeneousinterventions
and outcome measures;poor-qualitystudieswithuncontrolleddesigns.Conclusion:Verylow quality

13. evidence suggeststhatseveral typesof interventionsmaybe effectivetoreduce ordiscontinue LTOT
and that pain,function,andqualityof lifemayimprove withopioiddose reduction.PrimaryFunding
Source:VeteransHealthAdministration.(PROSPERO:CRD42015020347).
Withdrawal and LTOT
Coloma-Carmona,A.,etal.(2018). "Withdrawal symptomspredictprescriptionopioiddependence in
chronicpain patients."DrugAlcohol Depend195: 27-32.
BACKGROUND:The last versionof the DiagnosticandStatistical Manual of Mental Disorders
(DSM-5) includessubstantialchangesforprescriptionopioid-use disorder(POUD).Afteritsremoval asa
criterion,the goal of thisstudywas to estimate the prevalenceof withdrawalsymptomsinlong-term
usersof prescriptionopioidsanditsassociationwiththe new DSM-5POUD classification.METHODS:
Data were collectedfrom215 long-termconsumersof opioidmedicationwhowere chronicnon-cancer
painpatients.Participantscompletedsociodemographic,AdjectiveRatingScale forWithdrawal (ARSW),
opioidtreatmentcharacteristics,POUDcriteria(DSM-5),andpainintensitymeasurements.RESULTS:
26.6% of the participantswere classifiedwithmoderate toseverePOUD.Higherintensityof withdrawal
symptomswasfoundinpatientswithmoderate/severe POUD,youngerage,andhigherpainintensity(p
< .01). Anxiolytics(p<.01) and antidepressantsuse (p< .05) and percentage of smokers(p< .05) were
significantlyhigherinpatientswithseverewithdrawal.Logisticregressionanalysessuggestedmoderate
[oddsratio(OR) = 3.25] andsevere (OR= 10.52) withdrawal asthe strongestpredictorof POUD.Age,
anxiolyticsuse,andsmokingwere alsoassociatedwithPOUD,butmultilevel analysisshowedthatthese
variablesdonotmoderate the associationbetweenwithdrawal intensityandPOUD.CONCLUSION:
Escalationof withdrawal intensityduring opioidtreatmentcanbe usedto identifypatientswithPOUD.
Furtherstudiesare neededtoassessthe clinical implicationsof these findingsduringlong-termopioid
therapyforchronic pain.
Coloma-Carmona,A.,etal.(2018). "The Adjective RatingScale forWithdrawal:Validationof itsabilityto
assessseverityof prescriptionopioidmisuse."EurJ Pain.
BACKGROUND:Withdrawal symptomshave beenwidelyshowntobe auseful indicatorof the
severityof opioiddependence.One of the mostusedinstruments toassessthemisthe Adjective Rating
Scale for Withdrawal (ARSW).However,there isalack of adaptationsandvalidationsforitsuse with
prescriptionopioids,evenlessforchronicpainpatientsundertreatmentwiththese analgesics.Thus,
the aimsof thisstudywere to analyse the psychometricpropertiesandinvarianceacrossgenderof the
ARSW ina sample of chronicnoncancerpain patients.METHODS:Data were collectedfrom208
consumersof opioidmedication,chronicnoncancerpainpatients.Participantscompleted
sociodemographic,ARSW,prescriptionopioiddependence (DSM-IV-TR) andprescriptionopioid-use
disorder(DSM-5) measurements.Genderinvariancewasassessedthroughmultigroupconfirmatory
factor analysis(CFA).RESULTS:The ARSWshoweda unidimensional factorstructure andhighinternal
consistency(Cronbach'salpha=0.85). MultigroupCFA showedconfigural,metric,scalarandstrict
invariancesof ARSWacross gender.PredictivevalidityanalysesindicatedthatARSWhasgood capacity
for identifyingthe severityof prescriptionopioid-use disorder,usingbothDSM-IV-TRandDSM-5 criteria.

14. CONCLUSIONS:These findingsshowthatthe ARSWisa validand reliabletool foruse inthe assessment
of the withdrawal of prescriptionopioidsinchronicpainpatientsundertreatmentwiththese analgesics,
regardlessof theirgender.SIGNIFICANCE:Findingssupportedthe reliabilityandvalidityof the ARSWto
assesswithdrawal of prescriptionopioidsinindividualswithchronicnoncancerpain.The instrumentcan
be appliedindistinctlyinmenandwomen.Anincrease inthe ARSWscorescouldbe usedas an indicator
of potential riskof prescriptionopioid-usedisorderduringlong-termtreatments.
Juurlink,D.N.(2017). "Rethinking"doingwell"onchronicopioidtherapy."Cmaj 189(39): E1222-e1223.
Martel,M. O.,et al.(2013). "Catastrophicthinkingandincreasedriskforprescriptionopioidmisuse in
patientswithchronicpain."DrugAlcohol Depend132(1-2):335-341.
BACKGROUND:As a consequence of the substantial rise inthe prescriptionof opioidsforthe
treatmentof chronicnoncancerpain,greaterattentionhasbeenpaidtothe factors that may be
associatedwithanincreasedriskforprescriptionopioidmisuse.Recently,agrowingnumberof studies
have shownthat patientswithhighlevelsof catastrophizingare at increasedriskforprescriptionopioid
misuse.OBJECTIVE:The primaryobjective of thisstudywastoexamine the variablesthatmightunderlie
the associationbetweencatastrophizing andriskforprescriptionopioidmisuse inpatientswithchronic
pain.METHODS: Patientswithchronicmusculoskeletal pain(n=115) were askedtocomplete the SOAPP-
R, a validatedself-reportquestionnairedesignedtoidentifypatientsatriskforprescriptionopioid
misuse.Patientswere alsoaskedtocomplete self-reportmeasuresof painintensity,catastrophizing,
anxiety,anddepression.RESULTS:Consistentwithpreviousresearch,we foundthatcatastrophizingwas
associatedwithanincreasedriskforprescriptionopioidmisuse.Resultsalsorevealedthatthe
associationbetweencatastrophizingandriskforopioidmisuse waspartiallymediatedbypatients'levels
of anxiety.Follow-upanalyses,however,indicatedthatcatastrophizingremainedasignificant'unique'
predictorof riskfor opioidmisuse evenwhencontrollingforpatients'levelsof painseverity,anxietyand
depressivesymptoms.DISCUSSION:Discussionaddressesthe factorsthatmightplace patientswithhigh
levelsof catastrophizingatincreasedriskforprescriptionopioidmisuse.The implicationsof ourfindings
for the managementof patientsconsideredforopioidtherapyare alsodiscussed.
Rieb,L. M., etal. (2016). "Withdrawal-associatedinjurysite pain(WISP):adescriptive case seriesof an
opioidcessationphenomenon."Pain157(12): 2865-2874.
Withdrawal paincanbe a barrierto opioidcessation.Yet,little isknownaboutoldinjurysite
painin thiscontext.We conductedanexploratorymixed-methodsdescriptive case seriesusing aweb-
basedsurveyandin-personinterviewswithadultsrecruitedfrompainandaddictiontreatmentand
researchsettings.We includedindividualswhoself-reportedapastsignificantinjurythatwashealed
and pain-free before the initiationof opioids,whichthenbecame temporarilypainful uponopioid
cessation-aphenomenonwe have namedwithdrawal-associatedinjurysite pain(WISP).Screening
identifiedWISPin47 people,of whom34(72%) completedthe descriptive survey,including21 who
completedqualitative interviews.RecalledpainseverityscoresforWISPwere typicallyhigh(median:
8/10; interquartilerange [IQR]:2),emotionallyandphysicallyaversive,andtookapproximately2weeks

15. to resolve (median:14;IQR: 24 days).Withdrawal-associatedinjurysite painintensitywastypically
slightlylessthanparticipants'original injurypain(median:10/10;IQR: 3), and more painful thanother
generalizedwithdrawal symptomswhichalsolastedapproximately2weeks(median:13;IQR: 25 days).
Fifteensurveyedparticipants(44%) reportedreturningtoopioiduse because of WISPinthe past.
Participantsdevelopedtheoriesaboutthe etiologyof WISP,includingthatthe painisthe brain's wayof
communicatingadesire foropioids.Thisresearchrepresentsthe firstknowndocumentationthat
previouslyhealed,andpain-free injurysitescantemporarilybecomepainful againduringopioid
withdrawal,anexperience whichmaybe abarrierto opioidcessation,andacontributorto opioid
reinitiation.
Wasan, A.D., etal. (2012). "Cravingof prescriptionopioidsinpatientswithchronicpain:alongitudinal
outcomestrial."JPain13(2): 146-154.
UNLABELLED: Little isknownaboutwhetherpatientswithchronicpaintreatedwithopioids
experience cravingfortheirmedications,whethercontextual cuesmayinfluence craving,orif there isa
relationshipbetweencravingandmedicationcompliance.We hypothesizedthatcravingforprescription
opioidswouldbe significantlycorrelatedwiththe urge formore medication,preoccupationwiththe
nextdose,andcurrentmoodsymptoms.We studiedcravingin62 patientswithchronicpainwhowere
at lowor highrisk foropioidmisuse,whiletheywere enrolledinanRCTto improve prescriptionopioid
medicationcompliance.Usingelectronicdiaries,patientscompletedratingsof cravingatmonthlyclinic
visitsanddailyduringa14-day take-home period.Bothgroupsconsistentlyendorsedcraving,whose
levelswere highlycorrelated(P<.001) withurge,preoccupation,andmood.The interventionto
improve opioidcompliance inthe high-riskgroupwassignificantlyassociatedwitharate of decrease in
cravingovertime incomparisonto a high-riskcontrol group(P< .05). These findingsindicate that
cravingis a potentiallyimportant psychological constructinpainpatientsprescribedopioids,regardless
of theirlevel of risktomisuse opioids.Targetingcravingmaybe an importantinterventiontodecrease
misuse andimprove prescriptionopioidcompliance.PERSPECTIVE:Patientswith noncancerpaincan
crave theirprescriptionopioids,regardlessof theirriskforopioidmisuse.We foundcravingtobe highly
correlatedwiththe urge totake more medication,fluctuationsinmood,andpreoccupationwiththe
nextdose,andto diminishwithabehavioral interventiontoimprove opioidcompliance.
Weiss,R.D., etal. (2014). "Reasonsforopioiduse amongpatientswithdependence onprescription
opioids:the role of chronicpain."JSubstAbuse Treat 47(2): 140-145.
The numberof individualsseekingtreatmentforprescriptionopioiddependencehasincreased
dramatically,fosteringaneedforresearchonthispopulation.The aimof thisstudywasto examine
reasonsforprescriptionopioiduse among653 participantswithandwithoutchronicpain,enrolledin
the PrescriptionOpioidAddictionTreatmentStudy,arandomizedcontrolledtrial of treatmentfor
prescriptionopioiddependence.Participantsidentifiedinitialandcurrentreasonsforopioiduse.
Participantswithchronicpainwere more likelytoreportpainastheirprimaryinitial reasonforuse;
avoidingwithdrawalwasratedasthe mostimportantreasonforcurrent use inbothgroups.Participants
withchronicpainrated usingopioidstocope withphysical painasmore important,andusingopioidsin

16. response tosocial interactionsandcravingaslessimportant,thanthose withoutchronicpain.Results
highlightthe importance of physical painasa reasonforopioiduse amongpatientswithchronicpain.