Research Article The Investigation of Tramadol Dependence with …downloads.hindawi.com/journals/bmri/2013/283425.pdf · 2019-07-31 · of tramadol in USA was -/, and then declined

Hindawi Publishing CorporationBioMed Research InternationalVolume 2013 Article ID 283425 6 pageshttpdxdoiorg1011552013283425

Research ArticleThe Investigation of Tramadol Dependence withNo History of Substance Abuse A Cross-Sectional Survey ofSpontaneously Reported Cases in Guangzhou City China

Haoran Zhang12 and Zhimin Liu2

1 School of Public Health Peking University Beijing 100191 China2National Institute on Drug Dependence Peking University 38 Xueyuan Road Haidian District Beijing 100191 China

Correspondence should be addressed to Zhimin Liu zhiminliubjmueducn

Received 10 April 2013 Revised 14 July 2013 Accepted 14 August 2013

Academic Editor Eiichi Kumamoto

Copyright copy 2013 H Zhang and Z LiuThis is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

The studywas to survey and assess the drug dependence and abuse potential of tramadolwith no history of substance abuse Subjectsof tramadol dependence with no prior history of substance abuse were surveyed by interview Physical dependence of tramadolwas assessed using 10 items opiate withdrawal scale (OWS) and psychological dependence was assessed by Addiction ResearchCenter InventorymdashChinese Version (ARCI-CV) Twenty-three male subjects (the median age was 234 plusmn 41 years) referred to theaddiction unit in Medical Hospital of Guangzhou with tramadol abuse problems were included in this cross-sectional study Thecontrol group included 87 heroin addicts 60methamphetamine (MA) abusers and 50 healthymenThe scores of OWS of tramadolwere 083ndash230 the mean scores of identifying euphoric effectsndashMBG sedative effectsndashPCAG and psychotomimetic effectsndashLSDof ARCI were 896 plusmn 308 652 plusmn 325 and 665 plusmn 250 respectively F = 4927 119875 lt 0001 Scores of MBG scale in tramadol did notdiffer from those in heroin and MA groups (119875 gt 005) but were higher than those in healthy men (119875 lt 005) Tramadol with nohistory of substance abuse has a clear risk of producing high abuse potential under the long-term infrequent abuse and the highdoses

1 Introduction

Tramadol marketed in Germany by Grunenthal since 1977 isa centrally acting analgesic with weak 120583-opioid agonist prop-erties and inhibition of norepinephrine (NA) and serotoninreuptakeThe drug is most widely used in moderate to severeacute and chronic pain It has been postulated that tramadolachieves its analgesic activity from an M1 metabolite withpotent opioid properties and through inhibition of reuptakeof monoamines [1] Prior to its United States (US) approvalin 1995 tramadol was marketed in Europe for approximately20 years with little evidence of abuse The abuse probabilityof tramadol in USA was 2-3100000 and then declined to1100000 [2] World Health Organization (WHO) attachedgreat importance to the abuse and dependence of tramadoland four estimates were done From 1992 to 2006 tramadoldependence was evaluated for four times by Expert Com-mittee on Drug Dependence (ECDD) [3ndash6] Because the

available informationwas still not enough it could not decideto control tramadol internationally Although tramadol abuseis a low-level worldwide the nonmedical purpose abuse oftramadol was popular in China since its first marketingin China in the early 1990s as a noncontrolled analgesicespecially in opiate addicts and adolescents In order toprevent the abuse of tramadol and manage the clinicalapplication of tramadol in 2007 the State Food and DrugAdministration of China issued the newest version of mea-sures for psychotropic drugs administration and tramadolwas controlled as the second category of psychotropic drugs[7] After that the incidence of tramadol abuse has declinedto a low level According to the report of National DrugAbuse Monitoring the proportion of tramadol use amongdrug abusers increased from 02 in 2004 to 160 in 2006the trend of tramadol use varied very smoothly from 2007to 2009 however the proportion of tramadol use amongdrug abusers declined sharply from 133 in 2009 to 34

2 BioMed Research International

in 2011 [8ndash11] However it is worth noting that tramadolabuse was still prevalent in some regions and tramadol abuseshows a property of regional distribution Among thosethe percentage of tramadol use was highest in South China(51) and tramadol popular use in Guangdong provincewas still relatively high [11] According to statistics of DrugMonitoring Center of Guangdong Province the number oftramadol abusers increases from 11 persons in 2004 to 4492persons in 2006 in Guangdong province [12] Based on thesereasons all tramadol patients were recruited in Guangzhoucity Guangdong Province

Tramadol is generally considered to be safe and thoughtto have minimal potential for abuse Despite a range ofstudies still no consensus data exist on the dependencepotential of tramadol Studies from animal experiment holdcontroversial finding one is that tramadol was not likely toinduce tolerance and physical dependence in mice [13] andthe other is that conditioned place preference (CPP) in ratswas produced [14 15] Though tolerance and dependencewere not described after repeated administration of tramadolin human [16 17] case reports that tramadol can lead todependence continue to emerge [18 19] It was suggested thatthe abuse liability of tramadol may be greater than hithertoassumed [20]

Hence data for the dependence and abuse potentialof tramadol are conflicting and important information isstill missing regarding cases of tramadol dependence andabuse in China The objective of this study was to evaluatedrug dependence and abuse potential of tramadol usingtramadol abusers spontaneously referred to the addictionunit ofMedical Hospital inGuangzhou city between July 2012and December 2012

2 Methods

21 Ethical Statement The study was approved by the eth-ical committee of Peking University Health Center (Grantnumber IRB00001052-10026) Before the interviews wereconducted subjects were informed about the purpose ofthis study and confidentiality of all information they wouldprovide Respondentsrsquo consent was gathered The survey wasconducted in an isolated room and the survey procedureswere designed to protect privacy of subjects by allowing foranonymous and voluntary participation Participants in thestudy could stop at any time if they desired

22 Subjects Identification and collection of relevant caseswere conducted from 1 July 2012 to 1 January 2013 Allavailable information in the included tramadol cases wasregistered age sex occupation marital status educationalstatus concomitant medication prescribed and ingesteddoses of tramadol duration of tramadol abuse and otherimportant information Subjects reported to have a history ofcontinuous tramadol abuse for 7 days in a week or those whohad life-time used tramadol for 6months at least were furtherreviewed by theAmerican PsychiatricAssociationDiagnosticand Statistical Manual of Mental Disorders fourth revision(DSM-IV) Only subjects who fulfilled these criteria were

finally included in the final analysisThough the identificationof tramadol dependence in this study was conducted basedon DSM-IV criteria the diagnosis in the detoxification unithas no such information Generally patients in the drugdependence agencies may require tramadol detoxification ordose reduction

The inclusion criteria were (1) male (2) 18 years old orabove (3) the primary abused drug of choice was tramadol(4) willing to sign an informed consent and (5) adhered suf-ficiently to the study protocol Meanwhile the exclusionarycriteria were made (1) unwilling to participate or could notprovide written informed consent (2) could not discriminatethe primary drug of abuse (3) severe psychotic disorders(4) severe body diseases (eg prostrate disease of liver orkidney) (5) be apt to drop out and (6) deficiency in or lackof language and comprehensive problems The criteria forcontrols were (1) men aged 18 and above (2) for healthycontrols without a history of drug abuse before the studyand no evidence of drug abuse during study (3) for heroinaddicts and methamphetamine abusers predominate drugsof choice were heroin and methamphetamine in the baselinesurvey respectively (4) provided informed consent Overalla total of 23 eligible tramadol addicts 85 heroin addicts60 methamphetamine addicts 45 smokers and 50 healthycontrols were recruited

23 Data Collection and Measures The study was a cross-sectional survey Before the formal survey a pilot trial wasadministrated Researchers participated in the investigationwere trained by empirical experts on specific aspects of surveytechniques Each sample was briefly informed about thepurposes of the investigation in order to seek their supportand cooperation After that a written informed consent wasobtained from all participants A questionnaire with detailedbaseline variables was offered by National Institute on DrugDependence Peking University Current sociodemographiccharacteristics history of substance use and informationof ARCI were obtained from a face-to-face interview Allfinished questionnaires were reviewed by researchers forcompleteness and consistency

Physical dependence of tramadol was assessed using 10items opiate withdrawal scale (OWS) which composed of10 symptomssigns A 4-point scale was used to rate eachsymptomssigns zero (0) mild (1) moderate (2) and severe(3) Subjects were asked to rate their symptoms accordingto severity of previous experienced tramadol withdrawalPsychological dependence was assessed by association testof Addiction Research Center InventoryndashChinese Version(ARCI-CV) [21] The 40-item ARCI is a true-false question-nairewith three empirically derived scales that are sensitive tothe effects of a variety of classes of abused drugs The derivedscales were the MBG (morphine-benzedrine group) a mea-sure of drug-induced euphoria the PCAG (pentobarbital-chlorpromazine group) scale which measured sedationand the LSD (lysergic diethylamide) scale which measuresdysphoria and somatic symptoms The same method whichpriority evaluated drug dependence of dihydroetorphine andbuprenorphine was used in this study

BioMed Research International 3

Table 1 Characteristics of demographic and history of drug use

VariablesTramadol(119899 = 23)n ()

Heroin(119899 = 85)n ()

MA

(119899 = 60)n ()

Healthy men(119899 = 50)n ()

1198651205942

119875

Age (years)119909 plusmn 119904 234 plusmn 41 257 plusmn 916 236 plusmn 81 229 plusmn 31 1148 0267Range (18ndash34) (18ndash61) (20ndash56) (19ndash29)

EducationJunior high school 9 (391) 28 (329) 19 (317) 16 (320) 1941 0115Senior high school and above 14 (609) 57 (671) 41 (683) 34 (680)

Marital statusSingle 15 (652) 56 (659) 31 (517) 43 (860) 1252 0207Otherslowast 8 (348) 29 (341) 29 (483) 7 (140)

EthnicityHan ethnicity 21 (913) 70 (824) 59 (983) 49 (980) 1094 0236Others 2 (87) 15 (176) 1 (17) 1 (20)

OccupationUnemployed998787 7 (304) 31 (365) 19 (317) 30 (600) 0289 0591

Employed 16 (696) 54 (635) 41 (683) 20 (400)998787Including studentslowastIncluding married divorced and othersMethamphetamine

24 Statistical Analysis Statistical analysis was completedusing the SPSS computer software for Microsoft Windows(SPSS Inc Chicago IL USA) Quantitative symmetricallydistributed variables were described by using the mean andstandard deviation whereas quantitative variables with askewed distribution were described by using the medianNonparametric statistical tests were undertaken when thedistribution was not normal Descriptive statistics were usedto examine distributions of demographic and history of drugabuse Differences among subgroups of ARCI were exploredusing 119905-test or one-way analysis of variance (ANOVA) Alltests of statistical significance were two-tailed and used analpha level of 005

3 Results

31 Characteristics of Demographic and History of Drug UseDemographic characteristics and history of drug use weresummarized in Tables 1 and 2 At baseline no significant dif-ferencewas observed in respondentrsquos average age educationalstatusmarital status ethics and occupation (119875 gt 005) acrossgroups

Of the 23 tramadol patients the median age was (234 plusmn41) years and ranged between 18 and 34 years and 739(1723) of cases were lower than 25 years 870 (2023) ofthe sample had no previous history of drug abuse beforetramadol abuse and 900 (2123) were on tramadol aloneor 100 on poly drugs The drugs most frequently used incombination with tramadol were cough syrup (5 subjects)and methamphetamine (MA) (3 subjects) The median dosewas 750mgper time at frequency and 2000mgper timeat most The median duration of tramadol use was 618 plusmn

302 months (ranged from 5 months up to 112 months) Themedian age of first tramadol use was 183 plusmn 40 years All 23tramadol users reported that the route of administration wasoral method Instigating by friends or other acquaintanceswas the most reason of tramadol use for 23 cases whichaccounts for 609 (1423) and there were 391 reportedthat the reason of tramadol use was curiosity or simulatingAs for the source of tramadol the top three were private clinicor pharmacy (1223) normal pharmacy (623) and blackmarket (623) 696 (1623) of subjects have at least one timeor above admission to detoxification or drug reduction

32 Measure of Physical Dependence As mentioned in themethods physical dependence was rated by scores of 10 itemsopiate withdrawal scale (OWS) In total the range of meanscores of OWS scale was 083ndash230 Of those 957 (2223) ofthe patients had at least one seizure Ratings on the insomnia(230 plusmn 093) yawning (183 plusmn 098) and runny eyes (161 plusmn123) were the top three increased by tramadol Howeverthe differences of ratings of each signsymptom betweentramadol and heroin did not reach statistical significance(119875 gt 005)

33 Measure of Psychological Dependence Table 3 detailsthe measure of psychological dependence of tramadol andcomparators The mean scores of three scales in identify-ing euphoric effectsmdashMBG sedative effectsmdashPCAG andpsychotomimetic effectsmdashLSD of ARCI were 896 plusmn 308652 plusmn 325 and 665 plusmn 250 respectively One-way analysis ofvariance indicated that the variation in 3 scaleswas significant(119865 = 4927 119875 lt 0001) On the all three scales of ARCI


Table 2 History of drug abuse of 23 tramadol abusers

Variables 119873

Duration of tramadol abuse (month)119909 plusmn 119904 618 plusmn 302Median (minndashmax) 630 (5ndash112)

Age of first tramadol use (year)119909 plusmn 119904 183 plusmn 40Median (minndashmax) 180 (13ndash28)

Purpose of first tramadol useInstigating by friends or otheracquaintances 14

Curiosity or simulating 9Medical purpose 2Experienced the spiritual effects of drugs(euphoria) 2

Relieving negative emotions 2Influence of family members 1

Route of administrationOral 23

Median dose of tramadol use (mgper time)At the outset (range) 2500 (50ndash1000)Regular dose (range) 7500 (100ndash5000)Maximum (range) 20000 (250ndash10000)

Source of tramadolPrivate clinic or pharmacy 12Normal pharmacy 6Black market 6Relatives or friends 1Internet 1

Voluntary detoxification for one time orabove 16

measures tramadol produced a significantly greater effectthan healthy placebo (119875 lt 005) On the ARCI-MBGmeasures tramadol scores were lower than heroin but higherthan MA whereas the differences were not significant (119875 gt005) On the ARCI-PCAGmeasures the scores produced byheroin were higher than those produced by tramadol (119875 lt005) However the comparison with MA did not On theARCI-LSD measures the scores of tramadol did not differfrom other two active drugs (119875 gt 005)

4 Discussion

Using spontaneous data from the addiction unit we foundthat tramadol dependence fulfilling DSM-IV criteria occursin 23 males with no known history of substance abuse Thefindings indicated that tramadol appeared to produce highabuse liability within the long-term infrequent abuse by thosewithout preexisting substance abuse and the high doses

Tramadol is thought to have low potential for abusebut the cases with no reported prior history of substanceabuse became dependent on tramadol in our study This may

suggest that tramadol dependence in patients with no priorhistory of drug abuse differed from those of opiate addicts[21] The results did not support the previous findings fromexperimental [22] and surveillance studies [23] One of thepossible reasons of conflicting results is the different studysample included in the study As far aswe know this is the firststudy to evaluate the dependence and abuse liability of tra-madol with no drug abuse history usingmultiple placebo as apreference Thus we have no comparable studies to interpretand support our results However a wide abuse of tramadoldoes not largely appear to occur in other countries andsome controversy is driven by uncertainty in subpopulationvulnerable to tramadol dependence Chinese tramadol abuseseems to be a growing problem and a unique phenomenonWe claimed that it may be due to a complex and polymor-phic pharmacokinetic or pharmacodynamics characteristicsor patient characteristics The work of further exploringthe effect of those factors in tramadol dependence is theguarantee for scientific and reasonable tramadol use Anotherexplanation may be a discrepancy between doses used incontrolled studies and doses used in real life The actualproblem is that most tramadol abusers have a long durationof abusing drugs rather than short period in controlled studyDoses of tramadol in our sample extremely exceed the dosesprescribed by the physician Results from our study suggestthat high dosage with a long abused time probably increasethe ability of tramadol to induce dependence

In this study we examined the subjective effects oftramadol compared with multiple controls using ARCI-CVThere was good concordance between tramadol in generalpopulation in our study and the findings for this drugin opiate addicts [21] regarding its subjective effects Inparticular in the results of this study particularly those forthe comparison between tramadol and heroin no statisticallysignificant results were found on measures of MBG scalewhich suggests that the euphoria effects of tramadol issomewhat qualitatively equal to heroin As an example ofthe severity of tramadol dependence this study implies thatdependence of tramadol has led to admission to drug depen-dence clinic of hospital for detoxification or dose reductionThe proportion of subjects having at least one time or abovedetoxification treatment is 696 (1623) Otherwise neitheranimals experiment nor volunteer self-administration testhas been associated with reports of actual abuse Tramadolwhich did not produce a significant dependence effect andno abuse potential in the laboratory did not translate intoactual abuse in the marketplace Actual abuse of drugs isinfluenced by a number of factors that are not assessed inhuman laboratory studies of abuse potential including theavailability of other abused drugs the cost or difficulty ofobtaining the drug expectations regarding social roles andthe potential consequences of abuse [24 25] In our study itis possible that the doses much higher than the therapeuticrange have contributed to its actual abuse However theassociation between higher dose and tramadol dependenceshould be further explored

There were several factors that limit the interpretationregarding the significance of the results First we were notable to evaluate whether a dose response existed for the


Table 3 Comparison of scores of ARCI scales across groups

Comparison Mean value of difference 95 CI 119875

TramadolMBG versus PCAG 243lowastlowast 069 418 0007MBG versus LSD 230lowast 056 405 0010PCAG versus LSD minus013 minus187 161 0882

MBGTramadol versus heroin minus027 minus191 137 0745Tramadol versus MA 087 092 minus097 0348

Tramadol versus healthy 258lowastlowast 088 428 0004

PCAGTramadol versus heroin minus218lowastlowast minus369 minus068 0005Tramadol versus MA minus019 minus177 138 0807

Tramadol versus healthy 202lowast 047 357 0012

LSDTramadol versus heroin minus058 minus179 062 0334Tramadol versus MA minus214 minus147 104 0733

Tramadol versus healthy 150lowast 025 275 0020LSD test lowast119875 lt 005 and lowastlowast119875 lt 001

observed effects Our results were limited to evaluating thehigher doses of tramadol which were higher than prescribeddoses exceedingly Second as with any study of this typeconclusions drawn regarding the assessment of relative abusepotential for drugs depend on the patientsrsquo recollection Andthe methodology is the major limitation of our study Wewould improve and amend it in the following researchThirdthe population tested in this study would not necessarily beexpected to be representative of all tramadol abusers Fourththe sample is smallThe reasons and its importance have beendiscussed above

In conclusion these results add further support totramadol dependence data indicating that tramadol has ahigh risk of producing dependence potential A history oftramadol abuse with a long period andor high doses maybe one of important risk factors for those with no priordrug abuse history To further strengthen the surveillance andadministration of tramadol would be necessary

Conflict of Interests

All authors declare that they have no conflict of interests

Acknowledgments

The authors would especially like to thank the staff atMedicalHospital of Guangzhou City of Guangdong province anddetoxification center in Beijing The survey would not havebeen possible without their hard work Also we gratefullythank the participants for agreeing to take part in theinvestigation This study was funded by a Grant from theMajor State Basic Research Project (973 Program Grant no2009CB522007) and the National ldquoTwelfth Five-Yearrdquo Planfor Science and Technology Support Program (Grant no2012BAI01B07) of China

References

[1] C Gillen M Haurand D J Kobelt and S Wnendt ldquoAffin-ity potency and efficacy of tramadol and its metabolites at

the cloned human 120583-opioid receptorrdquo Naunyn-SchmiedebergrsquosArchives of Pharmacology vol 362 no 2 pp 116ndash121 2000

[2] L Radbruch S Grond and K A Lehmann ldquoA risk-benefitassessment of tramadol in the management of painrdquo DrugSafety vol 15 no 1 pp 8ndash29 1996

[3] WHOExpert Committee onDrugDependence Twenty-EighthReport WHO Geneva Switzerland 1992

[4] WHO Expert Committee on Drug DependenceThirty-SecondReport WHO Geneva Switzerland 2000

[5] WHO Expert Committee on Drug Dependence Thirty-ThirdReport WHO Geneva Switzerland 2002

[6] WHO Expert Committee on Drug Dependence Thirty-FourthReport WHO Geneva Switzerland 2006

[7] SFDA ldquoNarcotic drugs and psychotropic drugs directoryrdquo 7thversion 2008

[8] SFDA ldquoNational drug abusemonitoring centerrdquo Annual Reportof National Drug Abuse 2009




[12] Center for ADR Monitoring of Guangdong ProvinceldquoIt is more terrable for analgesic addictionrdquo 2006httpnewssinacomcnch2006-09-19162511050122shtml2006-09-19

[13] H F Miranda and G Pinardi ldquoAntinociception toleranceand physical dependence comparison between morphine andtramadolrdquo Pharmacology Biochemistry and Behavior vol 61 no4 pp 357ndash360 1998

[14] J E Sprague M Leifheit J Selken M M Milks D H Kinderand D E Nichols ldquoIn vivo microdialysis and conditioned placepreference studies in rats are consistent with abuse potential oftramadolrdquo Synapse vol 43 no 2 pp 118ndash121 2002

[15] M Zhang L Jing Q Liu et al ldquoTramadol induces condi-tioned place preference in rats interactions with morphine andbuprenorphinerdquo Neuroscience Letters vol 520 no 1 pp 87ndash912012

[16] K L Preston D R Jasinski and M Testa ldquoAbuse potential andpharmacological comparison of tramadol andmorphinerdquoDrugand Alcohol Dependence vol 27 no 1 pp 7ndash17 1991


[17] M D Vickers D OrsquoFlaherty S M Szekely M Read andJ Yoshizumi ldquoTramadol pain relief by an opioid withoutdepression of respirationrdquo Anaesthesia vol 47 no 4 pp 291ndash296 1992

[18] R J Leo R Narendran and B Deguiseppe ldquoMethadonedetoxification of tramadol dependencerdquo Journal of SubstanceAbuse Treatment vol 19 no 3 pp 297ndash299 2000

[19] S Shadnia K Soltaninejad K Heydari G Sasanian andM Abdollahi ldquoTramadol intoxication a review of 114 casesrdquoHuman and Experimental Toxicology vol 27 no 3 pp 201ndash2052008


[21] Z-M Liu W-H Zhou Z Lian et al ldquoDrug dependence andabuse potential of tramadolrdquo Acta Pharmacologica Sinica vol20 no 1 pp 52ndash54 1999

[22] E C OrsquoConnor and A N Mead ldquoTramadol acts as a weakreinforcer in the rat self-administration model consistent withits low abuse liability in humansrdquo Pharmacology Biochemistryand Behavior vol 96 no 3 pp 279ndash286 2010

[23] T J Cicero E H Adams A Geller et al ldquoA postmarketingsurveillance program to monitor ultram (tramadol hydrochlo-ride) abuse in the united statesrdquo Drug and Alcohol Dependencevol 57 no 1 pp 7ndash22 1999

[24] B Dew K Elifson and M Dozier ldquoSocial and environmentalfactors and their influence on drug use vulnerability andresiliency in rural populationsrdquo Journal of Rural Health vol 23no 1 supplement pp 16ndash21 2007

[25] A Fletcher C Bonell and J Hargreaves ldquoSchool effects onyoung peoplersquos drug use a systematic review of intervention andobservational studiesrdquo Journal of Adolescent Health vol 42 no3 pp 209ndash220 2008

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in 2011 [8ndash11] However it is worth noting that tramadolabuse was still prevalent in some regions and tramadol abuseshows a property of regional distribution Among thosethe percentage of tramadol use was highest in South China(51) and tramadol popular use in Guangdong provincewas still relatively high [11] According to statistics of DrugMonitoring Center of Guangdong Province the number oftramadol abusers increases from 11 persons in 2004 to 4492persons in 2006 in Guangdong province [12] Based on thesereasons all tramadol patients were recruited in Guangzhoucity Guangdong Province

Tramadol is generally considered to be safe and thoughtto have minimal potential for abuse Despite a range ofstudies still no consensus data exist on the dependencepotential of tramadol Studies from animal experiment holdcontroversial finding one is that tramadol was not likely toinduce tolerance and physical dependence in mice [13] andthe other is that conditioned place preference (CPP) in ratswas produced [14 15] Though tolerance and dependencewere not described after repeated administration of tramadolin human [16 17] case reports that tramadol can lead todependence continue to emerge [18 19] It was suggested thatthe abuse liability of tramadol may be greater than hithertoassumed [20]

Hence data for the dependence and abuse potentialof tramadol are conflicting and important information isstill missing regarding cases of tramadol dependence andabuse in China The objective of this study was to evaluatedrug dependence and abuse potential of tramadol usingtramadol abusers spontaneously referred to the addictionunit ofMedical Hospital inGuangzhou city between July 2012and December 2012

2 Methods

21 Ethical Statement The study was approved by the eth-ical committee of Peking University Health Center (Grantnumber IRB00001052-10026) Before the interviews wereconducted subjects were informed about the purpose ofthis study and confidentiality of all information they wouldprovide Respondentsrsquo consent was gathered The survey wasconducted in an isolated room and the survey procedureswere designed to protect privacy of subjects by allowing foranonymous and voluntary participation Participants in thestudy could stop at any time if they desired

22 Subjects Identification and collection of relevant caseswere conducted from 1 July 2012 to 1 January 2013 Allavailable information in the included tramadol cases wasregistered age sex occupation marital status educationalstatus concomitant medication prescribed and ingesteddoses of tramadol duration of tramadol abuse and otherimportant information Subjects reported to have a history ofcontinuous tramadol abuse for 7 days in a week or those whohad life-time used tramadol for 6months at least were furtherreviewed by theAmerican PsychiatricAssociationDiagnosticand Statistical Manual of Mental Disorders fourth revision(DSM-IV) Only subjects who fulfilled these criteria were

finally included in the final analysisThough the identificationof tramadol dependence in this study was conducted basedon DSM-IV criteria the diagnosis in the detoxification unithas no such information Generally patients in the drugdependence agencies may require tramadol detoxification ordose reduction

The inclusion criteria were (1) male (2) 18 years old orabove (3) the primary abused drug of choice was tramadol(4) willing to sign an informed consent and (5) adhered suf-ficiently to the study protocol Meanwhile the exclusionarycriteria were made (1) unwilling to participate or could notprovide written informed consent (2) could not discriminatethe primary drug of abuse (3) severe psychotic disorders(4) severe body diseases (eg prostrate disease of liver orkidney) (5) be apt to drop out and (6) deficiency in or lackof language and comprehensive problems The criteria forcontrols were (1) men aged 18 and above (2) for healthycontrols without a history of drug abuse before the studyand no evidence of drug abuse during study (3) for heroinaddicts and methamphetamine abusers predominate drugsof choice were heroin and methamphetamine in the baselinesurvey respectively (4) provided informed consent Overalla total of 23 eligible tramadol addicts 85 heroin addicts60 methamphetamine addicts 45 smokers and 50 healthycontrols were recruited

23 Data Collection and Measures The study was a cross-sectional survey Before the formal survey a pilot trial wasadministrated Researchers participated in the investigationwere trained by empirical experts on specific aspects of surveytechniques Each sample was briefly informed about thepurposes of the investigation in order to seek their supportand cooperation After that a written informed consent wasobtained from all participants A questionnaire with detailedbaseline variables was offered by National Institute on DrugDependence Peking University Current sociodemographiccharacteristics history of substance use and informationof ARCI were obtained from a face-to-face interview Allfinished questionnaires were reviewed by researchers forcompleteness and consistency

Physical dependence of tramadol was assessed using 10items opiate withdrawal scale (OWS) which composed of10 symptomssigns A 4-point scale was used to rate eachsymptomssigns zero (0) mild (1) moderate (2) and severe(3) Subjects were asked to rate their symptoms accordingto severity of previous experienced tramadol withdrawalPsychological dependence was assessed by association testof Addiction Research Center InventoryndashChinese Version(ARCI-CV) [21] The 40-item ARCI is a true-false question-nairewith three empirically derived scales that are sensitive tothe effects of a variety of classes of abused drugs The derivedscales were the MBG (morphine-benzedrine group) a mea-sure of drug-induced euphoria the PCAG (pentobarbital-chlorpromazine group) scale which measured sedationand the LSD (lysergic diethylamide) scale which measuresdysphoria and somatic symptoms The same method whichpriority evaluated drug dependence of dihydroetorphine andbuprenorphine was used in this study




Heroin(119899 = 85)n ()

MA

(119899 = 60)n ()

Healthy men(119899 = 50)n ()

1198651205942

119875








3 Results








Variables 119873











4 Discussion




















Acknowledgments


References

































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















Heroin(119899 = 85)n ()

MA

(119899 = 60)n ()

Healthy men(119899 = 50)n ()

1198651205942

119875








3 Results








Variables 119873











4 Discussion




















Acknowledgments


References

































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


















Variables 119873











4 Discussion




















Acknowledgments


References

































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of






























Acknowledgments


References

































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















Documents

Research Article The Investigation of Tramadol Dependence with …downloads.hindawi.com/journals/bmri/2013/283425.pdf · 2019-07-31 · of tramadol in USA was -/, and then declined