Assessment of abuse of tianeptine from a reimbursement database using ‘doctor‐shopping’ as an indicator

Rouby, Frank; Pradel, Vincent; Frauger, Élisabeth; Pauly, Vanessa; Natali, F; Reggio, Patrick; Thirion, Xavier; Micallef, Joëlle

doi:10.1111/j.1472-8206.2010.00906.x

Cited by 38 publications

(34 citation statements)

References 42 publications

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“…The present study revealed that the transcriptional effects of tianeptine may result from a blockade of norepinephrine, serotonin and dopamine transporters; in this respect, tianpetine shares some of the dopaminergic and noradrenergic properties with its predecessor amineptine [67]. Supporting the view that tianeptine acts primarily by modulating monoaminergic function are clinical findings that the tianeptine, has moderate addictive potential comparable to diazepam [68] as well as the presently observed pattern of tianeptine-induced expression of activity-dependent genes. Importantly, the lack of tianeptine-binding molecular targets suggests that the drug indirectly influences monoamine levels [69].…”

Section: Discussionmentioning

confidence: 67%

Novel drug-regulated transcriptional networks in brain reveal pharmacological properties of psychotropic drugs

et al. 2013

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BackgroundDespite their widespread use, the biological mechanisms underlying the efficacy of psychotropic drugs are still incompletely known; improved understanding of these is essential for development of novel more effective drugs and rational design of therapy. Given the large number of psychotropic drugs available and their differential pharmacological effects, it would be important to establish specific predictors of response to various classes of drugs.ResultsTo identify the molecular mechanisms that may initiate therapeutic effects, whole-genome expression profiling (using 324 Illumina Mouse WG-6 microarrays) of drug-induced alterations in the mouse brain was undertaken, with a focus on the time-course (1, 2, 4 and 8 h) of gene expression changes produced by eighteen major psychotropic drugs: antidepressants, antipsychotics, anxiolytics, psychostimulants and opioids. The resulting database is freely accessible at http://www.genes2mind.org. Bioinformatics approaches led to the identification of three main drug-responsive genomic networks and indicated neurobiological pathways that mediate the alterations in transcription. Each tested psychotropic drug was characterized by a unique gene network expression profile related to its neuropharmacological properties. Functional links that connect expression of the networks to the development of neuronal adaptations (MAPK signaling pathway), control of brain metabolism (adipocytokine pathway), and organization of cell projections (mTOR pathway) were found.ConclusionsThe comparison of gene expression alterations between various drugs opened a new means to classify the different psychoactive compounds and to predict their cellular targets; this is well exemplified in the case of tianeptine, an antidepressant with unknown mechanisms of action. This work represents the first proof-of-concept study of a molecular classification of psychoactive drugs.

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Section: Discussionmentioning

confidence: 67%

Novel drug-regulated transcriptional networks in brain reveal pharmacological properties of psychotropic drugs

et al. 2013

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“…Indicators of abuse are typically measured either in the general population (such as in household surveys (107)) , in a population of patients (e.g. using dispensing data (11) or data on spontaneously reported suspected ADRs (102)), or in cohorts of individuals with drug abuse problems (such as subjects undergoing opioid substitution treatment or individuals undergoing forensic investigation (69)). …”

Section: Pharmacoepidemiological Methods In Studies Of Psychoactive Pmentioning

confidence: 99%

“…Measurements based on individual-level prescription or dispensing data typically aim at identifying behaviours typical of drug addiction and drug abuse, such as substance seeking behaviour (including doctor shopping) and the use of large volumes of drug (9)(10)(11)69 Thus, this research area is still in its infancy (69,70). In particular, there is a lack of validated and standardised measurements that identify and separate prescription drug misuse and abuse (69).…”

Section: Pharmacoepidemiological Methods In Studies Of Psychoactive Pmentioning

confidence: 99%

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Psychoactive prescription drug use disorders, misuse and abuse : Pharmacoepidemiological aspects

Tjäderborn

2016

Linköping University Medical Dissertations

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Background: There is a widespread and increasing use of psychoactive prescription drugs, such as opioid analgesics, anxiolytics, hypnotics and anti-epileptics, but their use is associated with a risk of drug use disorder, misuse and abuse. Today, these are globally recognised and emerging public health concerns. Aim:The aim of this thesis is to estimate the occurrence and prevalence of psychoactive prescription drug use disorders, misuse and abuse, and to investigate the association with some potential risk factors. Methods:A study using register data from forensic cause of death investigations analysed and described cases of fatal unintentional intoxications with tramadol (Study I). Based on register data on spontaneously reported adverse drug reactions (ADRs) reported cases of tramadol dependence were scrutinized and summarised (Study II). In a study in suspected drug-impaired drivers with a toxicology analysis confirming intake of tramadol, diazepam, flunitrazepam, zolpidem and zopiclone, the prevalence of non-prescribed use was assessed and associated factors were investigated (Study III). From a national cohort of patients initiating prescribed treatment with pregabalin, identified using data on prescription fills, a study investigated longitudinal utilisation patterns during five years with regards to use above the maximum approved daily dose (MAD) of the drug, and factors associated with the utilisation patterns (Study IV).Results: In the first study, 17 cases of unintentional intoxications were identified, in which tramadol was judged to have caused or contributed to the death. Of the deceased, more were men, the median age was 44 years and the majority used multiple psychoactive substances (prescription drugs, alcohol and/or illicit drugs). In the second study, 104 spontaneously vi reported cases of possible or probable tramadol dependence were identified, of which more concerned women. The median age in these cases was 45 years and in about a third of cases the person had a history of substance abuse and in 40% of cases there was documented history of psychoactive medication use. Severe addiction was reported. In the third study, more than half of the individuals suspected of drug-impaired driving used the drug without a recent prescription.Non prescribed use was most frequent in users of benzodiazepines and of tramadol compared to users of zolpidem or zopiclone, and was more likely in younger individuals and in multiplesubstance users and less likely in individuals with a recent prescription for another psychoactive medication. In the last paper, five longitudinal utilisation patterns were found in pregabalin users, with two patterns associated with a particularly high risk of use of doses above the maximum approved daily dose. The highest risk of use of daily doses above the MAD over time was associated with male sex, younger age, non-urban residency, and a recent prescribed treatment with an antiepileptic or opioid analgesic drug. Conclusions

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“…3 Previous articles noted that tianeptine use carries a potential for abuse, and can induce a withdrawal syndrome at supratherapeutic doses. 4,5 The therapeutic use of tianeptine during pregnancy has not raised any safety concerns until now. 6 However, the impact of using tianeptine at supratherapeutic doses during pregnancy has not been previously evaluated.…”

mentioning

confidence: 99%

Neonatal Abstinence Syndrome Following Tianeptine Dependence During Pregnancy

Bence

Bonord

Rebillard³

et al. 2016

Pediatrics

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Tianeptine, an atypical antidepressant, has been found to exhibit a potential for abuse. The use of therapeutic doses of tianeptine during pregnancy has never raised safety concerns. However, the impact of tianeptine abuse on the mother-child dyad has never been assessed. We report herein the case of a female patient who presented with dependence on tianeptine, with the use of >650 mg of the drug per day. She had 2 successive pregnancies with similar doses. The state of dependence remained unidentified throughout the first pregnancy, but just after delivery, her full-term newborn exhibited unexpected neonatal abstinence syndrome (NAS). The NAS was successfully treated with morphine, although both the mother’s and newborn’s urine drug screen was negative. The causality of tianeptine in inducing NAS was retrospectively assessed as “probable” by using a validated causality algorithm. During the second pregnancy, this patient sought addiction treatment and was admitted for residential detoxification treatment in her seventh month of pregnancy. Delivery occurred at full term with a low birth weight neonate. No further developmental insults or medical problems were subsequently identified in the 2 children. Maternal tianeptine dependence during pregnancy may induce a type of NAS that mimics opiate NAS. This finding appears to be consistent with a recent finding of the agonist action of tianeptine on the opiate μ-receptor.

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Assessment of abuse of tianeptine from a reimbursement database using ‘doctor‐shopping’ as an indicator

Cited by 38 publications

References 42 publications

Novel drug-regulated transcriptional networks in brain reveal pharmacological properties of psychotropic drugs

Novel drug-regulated transcriptional networks in brain reveal pharmacological properties of psychotropic drugs

Psychoactive prescription drug use disorders, misuse and abuse : Pharmacoepidemiological aspects

Neonatal Abstinence Syndrome Following Tianeptine Dependence During Pregnancy

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