Anne Roussin

Misuse and Dependence on Non-Prescription Codeine Analgesics or Sedative H1 Antihistamines by Adults: A Cross-Sectional Investigation in France

Background Given the growing worldwide market of non-prescription drugs, monitoring their misuse in the context of self-medication represents a particular challenge in Public Health. The aim of this study was to investigate the prevalence of misuse, abuse, and dependence on non-prescription psychoactive drugs. Method During one month, in randomly solicited community pharmacies, an anonymous questionnaire was offered to adults requesting paracetamol (control group), codeine combined with paracetamol in analgesics, or sedative H1 antihistamines. Responses about misuse (drug use not in agreement with the Patient Information Leaflet) abuse (excessive drug use having detrimental consequences), and dependence (established according to questions adapted from the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria) on psychoactive drugs were compared to those of the paracetamol control group. Results 295 patients (mean age 48.5 years, 68.5% of women) having used one of the studied drugs during the previous month were included. Misuse and dependence to codeine analgesics concerned 6.8% and 17.8% of the patients exposed to these drugs, respectively, (n = 118), which was significantly higher than for paracetamol. 19.5% had used codeine analgesics daily for more than six months. Headache was the most frequent reason for persistent daily use. A high prevalence of persistent daily users of sedative H1 antihistamines was also observed. Whereas these drugs are recommended only for short treatment courses of occasional insomnia, 72.2% of the participants having taken doxylamine (n = 36) were daily users, predominantly for more than six months. Conclusions Results on misuse and dependence on non-prescription codeine analgesics suggest that chronic pain, in particular chronic cephalalgia, requires better medical care. In addition, as for hypnotics on prescription, persistent use of doxylamine for self-medication is not justified until an acceptable benefit-risk ratio for chronic sleep disturbance is shown by clinical data.

Evaluation of abuse and dependence on drugs used for self-medication: a pharmacoepidemiological pilot study based on community pharmacies in France.

AbstractBackground: Drugs that can be obtained without a medical prescription in community pharmacies are used to treat minor pathologies that can easily be diagnosed by the patient. Some of these drugs contain psychoactive substances with a potential for abuse and dependence. However, there is a lack of data concerning their problematic use in a wide population. Objective: To explore the feasibility of a pharmacoepidemiological method to investigate misuse, non-medical use, abuse and dependence on drugs used for self-medication. Methods: This cross-sectional pilot study, conducted during a 2-month period (from 15 January to 15 March 2007), was based on the participation of community pharmacies in the Midi-Pyrénées region of France to collect patient data. Patients requesting one drug from a list of available drugs used for self-medication and containing psychoactive substances (codeine in analgesics, pseudoephedrine, dextromethorphan and histamine H1 receptor antagonists [antihistamines]) were included in the study. A control group was set up that consisted of patients requesting antacid drugs. The pharmacy staff proposed to the patients that they filled in an anonymous questionnaire. The questionnaire was designed to investigate patterns of drug use and the harmful consequences of overuse (abuse). In addition, questions on lack of control over drug use were adapted from the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for evaluation of dependence. Results: Thirty-two percent (n = 74) of the solicited pharmacies participated in the survey. Only 4.8% of the solicited patients (n = 817) refused to complete the questionnaire distributed by the pharmacy staff. The questionnaire was completed inside the pharmacy by 53.3% of the patients. The other patients took the questionnaire away from the pharmacy and 31.7% of them returned it in a prepaid envelope. The patient participation rate was 64.9%, and was higher for the psychoactive substance groups than the control group. Statistically significant differences on misuse (and/or non-medical use), abuse and dependence were obtained between the codeine and antacid groups. In the codeine group, among the patients having used the product in the previous month (n= 53), 15.1% misused the drug and/or used the drug for a non-medical reason, 7.5% were cases of abuse and 7.5% presented criteria of lack of control over drug use related to dependence on the substance for the psychoactive effects or for pain relief. Conclusion: The results obtained in this pilot study indicate that using anonymous self-administered questionnaires offered to patients by pharmacy staff is a reliable method to obtain information on the problematic use of drugs con-taining psychoactive substances purchased in a pharmacy for self-medication.

Evaluation of abuse and dependence in addiction monitoring systems: tramadol as an example.

The objective of this paper is to present an evaluation of the potential for abuse of and dependence on a drug from the data obtained from the different pharmacoepidemiological tools used by the French network for evaluation and information on pharmacodependence and addiction monitoring taking the example of tramadol. Comparison of the data from spontaneous reports with surveys in specific populations and with evaluations of indicators of diverted uses does not highlight a major problem of tramadol abuse and dependence in terms of public health, but stresses the importance of paying attention to the signal. This example of addiction monitoring of tramadol illustrates the interest of comparing results obtained from different validated sources. The implementation of repeated observational programs of abuse of and dependence on psychoactive drugs is an important aid to health authorities to define the content of the information to be delivered or regulatory decisions to reduce these problematic uses.

Withdrawal syndrome after co-medication of opioid maintenance therapy with nalmefene: unrecognized interaction

To the editor: We read with interest the recently published paper reporting two cases of severe opioid withdrawal syndrome due to the drug interaction between the recently approved opioid antagonist nalmefene and opioids [1]. Since the end of 2014, the French network of the addictovigilance centers received several notifications of withdrawal syndrome after prescription of nalmefene in patients receiving opioid maintenance therapy (OMT) [2]. Up to March 2015, 7 cases of withdrawal syndromewere identified (5 men and 2 women, mean age 40 years [range 31–49]). Methadone was mentioned in 3 cases, buprenorphine in 3 cases, and buprenorphine/ naloxone in 1 case. When documented, the delay of onset of withdrawal syndrome was between 1 and 2 h. The withdrawal syndrome was sometimes severe (hallucinations, convulsions, and cardiac disorders), leading to hospitalization in 71 % of cases (not specified in 2 cases). The outcome was favorable in the majority of cases (1 case unknown), but with symptoms that lasted until 10–12 h with buprenorphine and buprenorphine/naloxone. At the time of the events, this pharmacologically expected interaction was not clearly mentioned in the nalmefene summary of product characteristics (SPC) [3]. It was stated that the use of nalmefene was contraindicated in patients taking opioid analgesics, in those with a recent history of opioid dependence and in those for whom a recent opioid consumption is suspected [3]. The specific interaction with methadone and buprenorphine was not mentioned. Accordingly, in the report of its March 2015 meeting, the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency recommended clarifying the contraindication [4]. However, cases of withdrawal syndrome were also reported with the association between OMT and naltrexone, another opioid antagonist used in alcohol dependence despite a clear mention in SPC [5,6]. This association was observed in 1.8 % of patients treated with OMT [7]. Another explanation could be close consonance between nalmefene and baclofen, another drug authorized for the treatment of alcohol dependence but with different pharmacological properties (RTU Baclofène; http://ansm. sante.fr/var/ansm_site/storage/original/application/ 5478accaf69e1a0f97987c9eeb9b9347.pdf). Prescribers should be aware of this interaction, as the alcoholic comorbidity is common in patients under OMT. Vigilance is also needed for nalmefene in combination with other opioid analgesics or antitussives. * Hélène Peyrière h-peyriere@chu-montpellier.fr

Comment on: "Social Media Mining for Toxicovigilance: Automatic Monitoring of Prescription Medication Abuse from Twitter"

We read with great interest the article entitled ‘‘Social Media Mining for Toxicovigilance: Automatic Monitoring of Prescription Medication Abuse from Twitter’’ by Sarker and colleagues, published in a recent issue of Drug Safety [1]. It is an interesting research article dealing with the problem of monitoring abuse and addiction with prescription drugs in the real-life context. Sarker et al. are right to point out the crucial need for discovering new monitoring sources and methods to identify and better characterize the patterns of use of drugs with an abuse potential and the complications related to this use. This is indeed a critical point in the field of drug abuse and addiction as the knowledge on this topic is solely based on the collection of abuse/addiction cases reported by health professionals, published as case reports or case series, or reported to pharmacovigilance systems [2, 3]. Unfortunately, the high proportion of unreported cases limits these systems [4]. Therefore, spontaneous reporting systems must not be the only source of data [5] and need to be completed, as has been done in a few countries. For example, in the US, several complementary monitoring systems have been developed to survey the harmful consequences of drugs with an abuse potential [6, 7]. In France, the national surveillance system relies on the crossing of multiple data sources, including several original pharmacoepidemiological programs that have been specifically set up to complement the information provided by spontaneous notification and to improve the assessment of psychotropic medication misuse [8, 9]. Computerized data coming from the hospital database, or even the national reimbursement system database, are also explored [10, 11]. Combined with pharmacological data, all of these are useful for identifying addiction signals and launch alerts. Sarker et al. propose to explore the data collected by Twitter to raise data about prescription medication abuse. Furthermore, they provide a standardized method to automatically detect these data for future research. Nowadays, surveillance of the Internet seems essential as the Internet provides considerable information on the use of psychoactive substances. For example, online discussions have been explored to characterize the modalities of administration and the effects described by users of various licit or illicit psychoactive substances [12, 13]. As Twitter is a very popular social media platform, it appears to be a valuable data source to explore for addictovigilance purposes. This letter refers to the article available at doi:10.1007/s40264-0150379-4.

Weak Opioid Analgesics Abuse and Addiction: A Comparison of the Pharmacology and Pharmacoepidemiology of Codeine, Dihydrocodeine, and Tramadol

Abuse and addiction to weak opioids (codeine, dihydrocodeine, and tramadol) are less expected than with strong opioids. However, some metabolites, agonists of mu-opioid receptors with much higher affinity, are produced from weak opioids, depending on genetic variability. Updated pharmacoepidemiological data on abuse and addiction to weak opioids obtained from death-related registries, population-based studies, and studies performed in specific populations were analyzed in relation to the evolution of exposure of European populations to these substances. Even if the magnitude of abuse and addiction issues could differ between countries, it will always be related to the extent of use of these substances. While abuse and addiction to codeine, dihydrocodeine, and tramadol are observed in users of psychoactive substances, further studies in the general population are required. These studies should investigate whether persistent use of weak opioid analgesics, or individual genetic characteristics impacting their metabolism and transport through membranes, can lead to abuse and addiction.