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Cause of death and drug use pattern in deceased drug addicts in Sweden, 2002-2003.

https://arctichealth.org/en/permalink/ahliterature80715
Source
Forensic Sci Int. 2007 Jul 4;169(2-3):101-7
Publication Type
Article
Date
Jul-4-2007
Author
Jönsson Anna K
Holmgren Per
Druid Henrik
Ahlner Johan
Author Affiliation
Department of Clinical Pharmacology, Linköping University, S-581 85 Linköping, Sweden. anna.k.jonsson@lio.se
Source
Forensic Sci Int. 2007 Jul 4;169(2-3):101-7
Date
Jul-4-2007
Language
English
Publication Type
Article
Keywords
Accidents - mortality
Adolescent
Adult
Age Distribution
Aged
Aged, 80 and over
Analgesics, Opioid - analysis - poisoning
Cause of Death
Central Nervous System Depressants - analysis
Central Nervous System Stimulants - analysis - poisoning
Child
Dopamine Uptake Inhibitors - analysis
Ethanol - analysis
Female
Forensic Toxicology
Homicide - statistics & numerical data
Humans
Male
Middle Aged
Prospective Studies
Registries
Sex Distribution
Substance Abuse Detection
Substance-Related Disorders - mortality
Suicide - statistics & numerical data
Sweden - epidemiology
Abstract
Compared with their contemporaries, individuals abusing illicit drugs suffer a higher risk of premature death. In Sweden, a simple protocol for registration of fatalities among abusers of alcohol, pharmaceuticals, illicit drugs, or other substances, has been used by the forensic pathologists since 2001. This routine was introduced to allow for an evaluation of the cause and manner of death, and patterns of abuse among different groups of abusers. We explored the data on drug abusers (i.e. abusers of illicit drugs) subjected to a forensic autopsy 2002-2003. The Swedish forensic pathologists examined 10,273 dead victims during the study period and 7% (743/10,273) of the cases were classified as drug abusers. Toxicological analyses were carried out in 99% (736/743) and illicit drugs were detected in 70% (514/736) of these. On average, 3.8 substances (legal or illegal) were found per case. The most common substances were ethanol and morphine, detected in 43 and 35% of the cases, respectively. When exploring the importance of the different substances for the cause of death, we found that the detection of some substances, such as fentanyl and morphine, strongly indicated a poisoning, whereas certain other substances, such as benzodiazepines more often were incidental findings. In total, 50% (372/743) died of poisoning, whereas only 22% (161/743) died of natural causes. Death was considered to be directly or indirectly due to drug abuse in 47% (346/743), whereas evidence of drug abuse was an incidental finding in 21% (153/743) or based on case history alone in 33% (244/743). We believe that this strategy to prospectively categorize deaths among drug addicts constitutes a simple means of standardizing the surveillance of the death toll among drug addicts that could allow for comparisons over time and between countries.
PubMed ID
16965879 View in PubMed
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Enantioselective analysis of citalopram and escitalopram in postmortem blood together with genotyping for CYP2D6 and CYP2C19.

https://arctichealth.org/en/permalink/ahliterature89899
Source
J Anal Toxicol. 2009 Mar;33(2):65-76
Publication Type
Article
Date
Mar-2009
Author
Carlsson Björn
Holmgren Anita
Ahlner Johan
Bengtsson Finn
Author Affiliation
Clinical Pharmacology, Faculty of Health Sciences, Linköping University, S-581 85 Sweden. bjorn.carlsson@lio.se
Source
J Anal Toxicol. 2009 Mar;33(2):65-76
Date
Mar-2009
Language
English
Publication Type
Article
Keywords
Adult
Aged
Aged, 80 and over
Aryl Hydrocarbon Hydroxylases - genetics - physiology
Cause of Death
Chromatography, Gas
Chromatography, High Pressure Liquid
Citalopram - blood - chemistry - pharmacokinetics
Cytochrome P-450 CYP2D6 - genetics - physiology
DNA - genetics
Female
Forensic Pathology - methods
Forensic Toxicology - methods
Genotype
Humans
Male
Middle Aged
Polymerase Chain Reaction
Stereoisomerism
Young Adult
Abstract
Citalopram is marketed as a racemate (50:50) mixture of the S(+)-enantiomer and R(-)-enantiomer and the active S(+)-enantiomer (escitalopram) that possess inhibitory effects. Citalopram was introduced in Sweden in 1992 and is the most frequently used antidepressant to date in Sweden. In 2002, escitalopram was introduced onto the Swedish market for treatment of depression and anxiety disorders. The main objective of this study was to investigate S(+)-citalopram [i.e., the racemic drug (citalopram) or the enantiomer (escitalopram)] present in forensic autopsy cases positive for the presence of citalopram in routine screening using a non-enantioselective bioanalytical method. Fifty out of the 270 samples found positive by gas chromatography-nitrogen-phosphorus detection were further analyzed using enantioselective high-performance liquid chromatography. The 50 cases were genotyped for CYP2D6 and CYP2C19, as these isoenzymes are implicated in the metabolism of citalopram and escitalopram. In samples positive for racemic citalopram using the screening method for forensic autopsy cases, up to 20% would have been misinterpreted in the absence of an enantioselective method. An enantioselective method is thus necessary for correct interpretation of autopsy cases, after the enantiomer has been introduced onto the market. The percentage of poor metabolizers was 6% for CYP2D6 and 8% for CYP2C19.
PubMed ID
19239731 View in PubMed
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Fatal unintentional intoxications with tramadol during 1995-2005.

https://arctichealth.org/en/permalink/ahliterature84912
Source
Forensic Sci Int. 2007 Dec 20;173(2-3):107-11
Publication Type
Article
Date
Dec-20-2007
Author
Tjäderborn Micaela
Jönsson Anna K
Hägg Staffan
Ahlner Johan
Author Affiliation
Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
Source
Forensic Sci Int. 2007 Dec 20;173(2-3):107-11
Date
Dec-20-2007
Language
English
Publication Type
Article
Keywords
Accidents - mortality
Adolescent
Adult
Aged
Analgesics, Opioid - blood - poisoning
Central Nervous System Depressants - blood
Ethanol - blood
Female
Forensic Toxicology
Humans
Male
Middle Aged
Substance-Related Disorders - mortality
Sweden - epidemiology
Tramadol - analogs & derivatives - blood - poisoning
Abstract
Tramadol is an extensively used centrally acting analgesic and is considered a safe drug devoid of many serious adverse effects of traditional opioids. However, recently, toxicity and an abuse potential of tramadol have been reported. This study examined fatal unintentional tramadol intoxications among Swedish forensic autopsy cases between 1995 and 2005. All fatal intoxications were selected, in which toxic concentrations of tramadol (>1 microg/g femoral blood) had been detected, and where the forensic pathologist considered the intoxication unintentional and the fatal outcome at least partly explained by tramadol. Toxicology analyses, police reports, autopsy protocols and medical records were scrutinized. A total of 17 cases (eleven men and six women) of fatal unintentional tramadol intoxications were identified. For these cases the median age was 44 years (range 18-78 years) and the median tramadol concentration was 2.0 microg/g (range 1.1-12.0 microg/g). Other pharmaceutical substances, illicit drugs or ethanol were detected in addition to tramadol in all of these cases. In fact, intoxication with multiple drugs was considered the cause of death in 10 (59%) cases. However, in seven cases tramadol was the only substance present in toxic concentrations. A history of substance abuse was identified in 14 (82%) subjects and a present tramadol abuse in 8 (47%). These results suggest that fatal intoxications with tramadol may occur unintentionally and that subjects with a history of substance abuse may be at certain risk. Precaution is therefore warranted when prescribing tramadol in such patients.
PubMed ID
17350197 View in PubMed
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Five-year update on the occurrence of alcohol and other drugs in blood samples from drivers killed in road-traffic crashes in Sweden.

https://arctichealth.org/en/permalink/ahliterature89936
Source
Forensic Sci Int. 2009 Apr 15;186(1-3):56-62
Publication Type
Article
Date
Apr-15-2009
Author
Jones Alan Wayne
Kugelberg Fredrik C
Holmgren Anita
Ahlner Johan
Author Affiliation
Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Artillerigatan 12, SE-587 58 Linköping, Sweden. wayne.jones@rmv.se
Source
Forensic Sci Int. 2009 Apr 15;186(1-3):56-62
Date
Apr-15-2009
Language
English
Publication Type
Article
Keywords
Accidents, Traffic - mortality
Adolescent
Adult
Age Distribution
Aged
Automobile Driving - legislation & jurisprudence
Central Nervous System Depressants - blood
Ethanol - blood
Female
Forensic Toxicology
Humans
Male
Middle Aged
Pharmaceutical Preparations - blood
Sex Distribution
Street Drugs - blood
Sweden - epidemiology
Abstract
According to statistics provided by the Swedish National Road Administration (Vägverket), a total of 1403 drivers were killed in road-traffic crashes in Sweden between 2003 and 2007. Forensic autopsies were performed in approximately 97% of all deaths and specimens of blood and urine were sent for toxicological analysis. In 60% of cases (N=835) the toxicology results were negative and 83% of these victims were men. The blood-alcohol concentration (BAC) was above the legal limit for driving (>0.2g/L) in 22% of cases (N=315) at mean, median and highest concentrations of 1.7 g/L, 1.7 g/L and 4.9 g/L, respectively. The proportions of male to female drivers with BAC>0.2g/L were 93% vs 7% compared with 83% vs 17% for those with drugs other than alcohol in blood. Drivers with a punishable BAC were over-represented in single vehicle crashes compared with multiple vehicle crashes (67% vs 33%). The opposite held for drivers who had taken a prescription drug (39% vs 61%) and also for drug-negative cases (31% vs 69%). Drugs other than alcohol were identified in 253 cases (18%); illicit drugs only in 39 cases (2.8%), both licit and illicit in 28 cases (2.0%) and in 186 cases (13.3%) one or more therapeutic drugs were present. Amphetamine was the most common illicit drug identified at mean, median and highest concentrations of 1.5mg/L, 1.1mg/L and 5.0mg/L, respectively (N=39). Blood specimens contained a wide spectrum of pharmaceutical products (mean 2.4 drugs/person), comprising sedative-hypnotics (N=93), opiates/opioids (N=69) as well non-scheduled substances, such as paracetamol (N=78) and antidepressants (N=93). The concentrations of these substances in blood were mostly in the therapeutic range. Despite an appreciable increase (12-fold) in number of arrests made by the police for drug-impaired driving after a zero-tolerance law was introduced (July 1999), alcohol still remains the psychoactive substance most frequently identified in the blood of drivers killed in road-traffic crashes.
PubMed ID
19232848 View in PubMed
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High re-arrest rates among drug-impaired drivers despite zero-tolerance legislation.

https://arctichealth.org/en/permalink/ahliterature93488
Source
Accid Anal Prev. 2008 Mar;40(2):534-40
Publication Type
Article
Date
Mar-2008
Author
Holmgren Anita
Holmgren Per
Kugelberg Fredrik C
Jones A Wayne
Ahlner Johan
Author Affiliation
Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Artillerigatan 12, SE-581 33 Linköping, Sweden.
Source
Accid Anal Prev. 2008 Mar;40(2):534-40
Date
Mar-2008
Language
English
Publication Type
Article
Keywords
Adult
Alcohol Drinking
Alcoholic Intoxication - complications
Automobile Driving - legislation & jurisprudence
Databases as Topic
Female
Humans
Male
Prisoners
Prisons
Risk factors
Street Drugs
Sweden
Abstract
BACKGROUND: A zero-tolerance law for driving under the influence of drugs (DUID) in Sweden led to a 10-fold increase in the number of cases submitted by the police for toxicological analysis. The statutory blood-alcohol concentration (BAC) limit for driving is 0.2 mg/g ( approximately 0.02 g%). METHODS: An in-house database (TOXBASE) was used to investigate re-arrests for impaired driving over 4 years (2001-2004), which comprised 36,799 cases. The age, gender, re-arrest rate of the offenders and the concentrations of ethanol and amphetamine in blood samples were evaluated. RESULTS: We found that 44% of individuals (N=16,277) re-offended 3.2 times on average (range 1-23 arrests). Between 85 and 89% of first-time offenders were men and there was also a male dominance among the recidivists (88-93%). The mean age of drunken drivers was approximately 40 years compared with approximately 35 years for driving under the influence of amphetamine, which was the drug identified in 50-60% of DUID cases, either alone or together with other licit or illicit drugs. The median BAC was 1.5mg/g ( approximately 0.15 g%), which suggests a dominance of heavy drinkers. The median BAC was even higher in recidivists (1.6-1.7 mg/g). The median concentration of amphetamine in blood was 1.0 mg/L in recidivists compared with 0.5mg/L in the first-time offenders. About 14% of drunken drivers re-offended 1-10 times compared with 68% of DUID suspects, who were re-arrested 1-23 times. People with only a scheduled prescription drug in blood were re-arrested much less frequently ( approximately 17%) compared with those taking illicit drugs (68%). CONCLUSIONS: The appreciable increase in number of arrests for DUID after a zero-tolerance law might reflect a heightened enthusiasm by the police authorities armed with knowledge that a prosecution is easier to obtain. Zero-tolerance laws do not deter people from impaired driving judging by the high re-arrest rates. During the sentencing of hardcore offenders, the courts should give more consideration to the underlying substance abuse problem.
PubMed ID
18329404 View in PubMed
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Predominance of illicit drugs and poly-drug use among drug-impaired drivers in sweden.

https://arctichealth.org/en/permalink/ahliterature84304
Source
Traffic Inj Prev. 2007 Dec;8(4):361-7
Publication Type
Article
Date
Dec-2007
Author
Holmgren Anita
Holmgren Per
Kugelberg Fredrik C
Jones A Wayne
Ahlner Johan
Author Affiliation
Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
Source
Traffic Inj Prev. 2007 Dec;8(4):361-7
Date
Dec-2007
Language
English
Publication Type
Article
Abstract
Objective. After Sweden's zero-tolerance law came into force (1 July 1999), the number of cases of driving under the influence of drugs (DUID) submitted by the police for toxicological analysis increased more than 10-fold. This prompted an in-depth investigation into the kinds of drugs used by DUID offenders, whether licit or illicit, and the frequency of their occurrence. Methods. All blood samples from DUID suspects sent by the police for toxicological analysis over a 4-year period (2001-2004) were investigated (N = 22,777 cases). Specimens of blood or urine were subjected to a broad screening analysis by immunoassay methods aimed at detecting amphetamines, cannabis, opiates, cocaine metabolite, and the major benzodiazepines. All positive results from the screening stage were verified by use of more specific analytical methods (e.g., GC-MS, LC-MS, GC-FID, and GC-NPD). Results. Between 80 and 85% of all the blood samples contained at least one banned substance and many contained two or more therapeutic and/or illicit drugs. About 15% of cases were negative for drugs, although these frequently (30-50%) contained ethanol above the legal limit for driving in Sweden, which is 0.20 mg/g (0.02 g%). Amphetamine was the most prominent illicit drug seen in 55-60% of cases either alone or together with other drugs of abuse. Stimulants like cocaine and/or its metabolite were infrequently encountered ( approximately 1.2% of cases). The next most prevalent illicit drug was cannabis, with positive results for tetrahydrocannabinol (THC) in blood either alone ( approximately 4%) or together with other psychoactive substances ( approximately 20%). Morphine, codeine, and/or 6-acetyl morphine were identified in approximately 2% of all DUID suspects, being indicative of heroin abuse. The major prescription drugs identified in blood were benzodiazepines (10%) as exemplified by diazepam, alprazolam, nitrazepam, and flunitrazepam. Drugs for treating insomnia, zolpidem and zopiclone, were also identified in blood samples from DUID suspects over the study period. Other therapeutic agents were encountered in only 1-2% of all cases. Conclusions. The dramatic increase in DUID after the zero-tolerance law came into force probably reflects enhanced police activity and more enthusiasm to apprehend and charge individuals for this offence. Illicit drugs, particularly amphetamine and cannabis, and poly-drug use were predominant compared with use of scheduled prescription drugs. The typical DUID offender in Sweden abuses central stimulants, particularly amphetamine, and has probably done so over many years. Options for treating offenders for their underlying substance abuse problem should be considered instead of the more conventional penalties for drug-impaired driving.
PubMed ID
17994489 View in PubMed
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Serum concentrations of antidepressant drugs in a naturalistic setting: compilation based on a large therapeutic drug monitoring database.

https://arctichealth.org/en/permalink/ahliterature90837
Source
Ther Drug Monit. 2009 Feb;31(1):42-56
Publication Type
Article
Date
Feb-2009
Author
Reis Margareta
Aamo Trond
Spigset Olav
Ahlner Johan
Author Affiliation
Department of Forensic Chemistry and Genetics, Swedish National Board of Forensic Medicine, Linköping, Sweden. margareta.reis@med.lu.se
Source
Ther Drug Monit. 2009 Feb;31(1):42-56
Date
Feb-2009
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Age Factors
Aged
Aged, 80 and over
Antidepressive Agents - blood - pharmacokinetics
Antidepressive Agents, Tricyclic - blood - pharmacokinetics
Biotransformation
Child
Chromatography, High Pressure Liquid
Databases, Factual
Dose-Response Relationship, Drug
Drug Monitoring - statistics & numerical data
Female
Humans
Male
Mass Spectrometry
Middle Aged
Neurotransmitter Uptake Inhibitors - blood - pharmacokinetics
Norway - epidemiology
Serotonin Uptake Inhibitors - blood - pharmacokinetics
Sex Factors
Young Adult
Abstract
A compilation of therapeutic drug monitoring data for 15 antidepressant drugs in a naturalistic routine clinical setting is presented. A substantial number of serum concentrations, at different daily doses, are outlined, and the intraindividual and overall serum concentration coefficient of variation for a respective substance is presented. Also, concentration comparisons between women and men, and patients older or younger than 65 years are made. The drugs included are amitriptyline (n = 394), citalopram (n = 5457), clomipramine (n = 400), escitalopram (n = 3066), fluoxetine (n = 793), fluvoxamine (n = 165), mianserin (n = 1063), mirtazapine (n = 1427), moclobemide (n = 200), nortriptyline (n = 206), paroxetine (n = 1677), reboxetine (n = 85), sertraline (n = 2998), trimipramine (n = 158), and venlafaxine (n = 1781). Of the 9 drugs exhibiting linear (first order) kinetics, all but reboxetine gave a significant negative dose-to-dose-normalized correlation with concentrations, that is an increased clearance with higher dose. When dose was correlated to the metabolite:parent substance ratio for drugs exhibiting linear kinetics, citalopram and mianserin gave a positive slope, contrary to a negative slope shown for sertraline and venlafaxine. The intraindividual variations of the serum concentrations were lower than the overall variations, and the intraindividual variation of the metabolite:parent substance ratio was lower than the intraindividual variation of respective parent substance (except clomipramine and mianserin). Women had significantly higher serum concentrations than men (significant for citalopram, escitalopram, mianserin, mirtazapine, and venlafaxine), and patients older than 65 years had higher serum concentrations than the younger ones for all drugs except amitriptyline, moclobemide, and trimipramine. By presenting a comprehensive compilation of therapeutic drug monitoring data for each drug, a reference tool is created, in addition to improved pharmacokinetic knowledge of antidepressant drugs.
PubMed ID
19077925 View in PubMed
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Suicides by violent means in individuals taking SSRIs and other antidepressants: a postmortem study in Sweden, 1992-2004.

https://arctichealth.org/en/permalink/ahliterature83786
Source
J Clin Psychopharmacol. 2007 Oct;27(5):503-6
Publication Type
Article
Date
Oct-2007
Author
Fazel Seena
Grann Martin
Ahlner Johan
Goodwin Guy
Author Affiliation
Department of Psychiatry, University of Oxford, Oxford, UK. seena.fazel@psych.ox.ac.uk
Source
J Clin Psychopharmacol. 2007 Oct;27(5):503-6
Date
Oct-2007
Language
English
Publication Type
Article
Abstract
A number of reports have linked consumption of selective serotonin reuptake inhibitors (SSRIs) with suicide by violent methods. We aimed to determine whether suicides with postmortem evidence of SSRI consumption are more likely to have used violent methods compared with suicides with no detectable antidepressants. Blood samples from all suicides in Sweden during 1992-2004 were examined. Suicides were classified into those who died by violence and nonviolent (self-poisoning) methods using information from police records and autopsy. In addition, we investigated proportions of violent suicide in individuals who died with detectable levels of tricyclic and other antidepressants.The sample consisted of 14,691 suicides. Of the 1958 suicides with detectable levels of SSRIs, 1247 were by violent means (63.7%) compared with 7835 of 11,045 suicides (70.9%) in antidepressant-free group (chi2(1) = 7.6; P
PubMed ID
17873685 View in PubMed
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Therapeutic drug monitoring of ziprasidone in a clinical treatment setting.

https://arctichealth.org/en/permalink/ahliterature91829
Source
Ther Drug Monit. 2008 Dec;30(6):682-8
Publication Type
Article
Date
Dec-2008
Author
Chermá Maria D
Reis Margareta
Hägg Staffan
Ahlner Johan
Bengtsson Finn
Author Affiliation
Department of Clinical Pharmacology, Faculty of Health Sciences, Linkoping University Hospital, Sweden. maria.dolores.cherma.yeste@lio.se
Source
Ther Drug Monit. 2008 Dec;30(6):682-8
Date
Dec-2008
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Age Distribution
Aged
Aged, 80 and over
Antipsychotic Agents - adverse effects - blood - metabolism - pharmacokinetics
Child
Drug Interactions
Drug Monitoring
Female
Humans
Male
Middle Aged
Piperazines - adverse effects - blood - metabolism - pharmacokinetics
Product Surveillance, Postmarketing
Sex Characteristics
Smoking
Thiazoles - adverse effects - blood - metabolism - pharmacokinetics
Abstract
There is limited information on the pharmacokinetics ofziprasidone (ZIP) in naturalistic clinical settings. The objective of this study was to investigate the concentrations of ZIP and its active metabolite S-methyl-dihydroziprasidone (SMDZ), and the dose-normalized concentrations, using routine therapeutic drug monitoring (TDM) data. A high-performance liquid chromatographic method for determining serum concentrations of these substances for routine clinical use was established at the TDM Laboratory in Linköping, Sweden. This analytical service was available to all physicians in Sweden. Between January 2001 and December 2004, 545 analyses, representing samples from 370 patients, were performed. The median daily ZIP dose was 120 mg (range 20 -320 mg). In all, 121 steady-state trough specimens with essential clinical information were included in the pharmacokinetic evaluation. The median (25th to 75th percentile) serum concentration of ZIP was 125 nmol/L (82-188 nmol/L). The SMDZ:ZIP ratio decreased with increasing serum concentration of ZIP. The median (25th to 75th percentile) dose-normalized concentrations (nmol L(-1) mg(-1) d(-1) forZIPand SMDZ were 1.13 (0.74-1.77) and 0.62 (0.45-0.86), respectively,with SMDZ:ZIP ratio of 0.57 (0.42-0.79). The overall coefficients of variation for dose-normalized serum concentrations of ZIP, SMDZ, andSMDZ:ZIP ratio were 62%, 56%, and 57%, respectively (n = 121). Smoking women had lower normalized ZIP concentrations than nonsmoking women. Twenty-eight patients with repeated eligible TDM analyses were studied for intraindividual variance over time. In summary, great interindividual and intraindividual differences in ZIPconcentrations were observed. TDM of ZIP maybe used for individual dose adjustments and monitoring medication adherence.
PubMed ID
18824954 View in PubMed
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Tramadol dependence: a survey of spontaneously reported cases in Sweden.

https://arctichealth.org/en/permalink/ahliterature95002
Source
Pharmacoepidemiol Drug Saf. 2009 Dec;18(12):1192-8
Publication Type
Article
Date
Dec-2009
Author
Tjäderborn Micaela
Jönsson Anna K
Ahlner Johan
Hägg Staffan
Author Affiliation
Division of Clinical Pharmacology, Linköping University, Linköping, Sweden. micaela.tjaderborn@liu.se
Source
Pharmacoepidemiol Drug Saf. 2009 Dec;18(12):1192-8
Date
Dec-2009
Language
English
Publication Type
Article
Abstract
BACKGROUND: Tramadol is a weak opioid analgesic, which is generally considered to be safe. However, conflicting data exist on the dependence potential of tramadol. OBJECTIVE: The aim of this study was to investigate occurrence of tramadol dependence and associated risk factors using spontaneously reported adverse drug reactions. METHODS: The Swedish database for spontaneously reported adverse drug reactions, Swedish Drug Information System (SweDIS), was searched for reports on tramadol dependence from 1 January 1995 until 31 December 2006. Selection was conducted based on the DSM-IV definition of dependence. Available information was scrutinised and registered and then presented descriptively. RESULTS: A total of 104 reports of tramadol dependence were identified, of which 60 (58%) concerned women. The median age (range) was 45 (15-84) years. Information on a history of substance abuse was present in 31 patients (30%) and 41 patients (39%) had a documented past or current use of a drug of abuse. Prescribed doses of tramadol ranged between 50-800 mg/day, and ingested doses between 50-4000 mg/day. Time of onset ranged from some weeks up to 4 years. In 72 (69%) cases the reaction was classified as serious, mainly due to hospitalisations for detoxification or discontinuation of tramadol. CONCLUSIONS: There is an occurrence of tramadol dependence in association with analgesic treatment within the recommended dose range. In susceptible patients a severe and serious dependence syndrome may develop. A history of abuse or use of a drug of abuse seems to be an important risk factor.
PubMed ID
19827010 View in PubMed
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10 records – page 1 of 1.