Evolution of the profiles of new psychotropic drug users before and during the COVID-19 crisis: an original longitudinal approach through multichannel sequence analysis using the French health-care database.

The COVID-19 pandemic has had a substantial impact on mental health. An increase in the use of anxiolytic, hypnotic, and antidepressant drugs has been highlighted in France, but with no information at the individual level (trajectories) or concerning patient characteristics. The objective of this study was to describe the profile of new psychotropic drug users since the beginning of the pandemic. We formed two historical cohorts using the Pays-de-la-Loire regional component of the National Health Data System (SNDS): a "COVID-19 crisis cohort" (2020-2021) and a "control cohort" (2018-2019). We analyzed reimbursements for psychotropic medications (anxiolytics, antidepressants, hypnotics, mood stabilizers, and antipsychotics) using a multichannel sequence analysis and performed clustering analysis of sequences. The proportion of new consumers of psychotropic drugs was higher in the COVID-19 crisis cohort (18.0%) than that in the control cohort (16.0%). In the COVID-19 cohort, three clusters of psychotropic drug users were identified, whereas four clusters were identified in the control cohort. A time lag in treatment initiation was observed in the COVID-19 crisis cohort (September) compared with the control cohort (July). This study is one of the first to analyze the profile of psychotropic treatment users during the COVID-19 crisis. Our analysis sheds light on changes in patterns of psychotropic drug use during the COVID-19 pandemic, possibly associated with changes in prescribing conditions and mental health conditions during the crisis. This study also provides an example of the application of an innovative longitudinal analysis methodology in the field of pharmacoepidemiology.

Drug-induced depressive symptoms: An update through the WHO pharmacovigilance database.

BACKGROUND: Depression is a highly incident condition and some drugs have been described as inducing or worsening depression. However, literature on this topic is rare and possibly outdated. METHODS: We performed disproportionality analyses using VigiBase®, the largest pharmacovigilance database worldwide to identify drugs associated with depression. Then we excluded drugs already known as depressogenic according to American Summary of Product Characteristics (SPC). We then reviewed drug mechanism of action, scientific literature and European SPC for each drug identified to assess a level of plausibility. We measured Reporting Odds Ratio (ROR) statistically significant and superior to 1, suggesting a significant association between a drug and the reporting of depressive symptoms. RESULTS: Out of the 5237 drugs extracted on VigiBase®, we have retained 89 new drugs associated with depression. More than half of drugs of interest are from nervous system. Opicapone (ROR: 20.66 95 %CI: 15.62-27.33), and gadoversetamide (ROR 18.62, 95 %CI 9.63-35.95) were the drugs with the highest ROR. Among the 89 drugs, 38 were considered already described such as suvorexant or ivacaftor, 20 likely associated such as anti-migraines drugs or new antipsychotic drugs and 31 potentially associated. LIMITATIONS: Pharmacovigilance studies have many inherent limitations, such as under-reporting bias, notoriety effect and protopathic bias. These results are not intended to establish a causal link, only a statistical association. CONCLUSION: We found a strong statistical signal and pharmacological plausibility for 58 new depressogenic drugs. This update list of suspected drugs may prove useful for doctors faced with potential cases of drug-induced depression or to stay aware in case. Other studies are needed to confirm the list.

"Naloxone? Not for me!" First cross-assessment by patients and healthcare professionals of the risk of opioid overdose.

BACKGROUND: Opioid-related mortality is a rising public health concern in France, where opioids were in 2021 implicated in 75% of overdose deaths. Opioid substitution treatment (OST) was implicated in almost half of deaths related to substance and drug abuse. Although naloxone could prevent 80% of these deaths, there are a number of barriers to the distribution of take-home naloxone (THN) among opioid users in France. This study is the first one which compares patients' self-assessment of the risk of future opioid overdose with the hetero-assessment provided by healthcare professionals in a population of individuals eligible for naloxone. METHODS: This was a multicenter descriptive observational study carried out in pharmacies across the Pays de la Loire region (France) during April and May 2022. All adult patients who visited a participating pharmacy for a prescription of OST and provided oral informed consent were enrolled in the study. Retrospective data were collected through cross-sectional interviews conducted by the pharmacist with the patient, utilizing an ad hoc questionnaire. The patient's self-assessment of overdose risk was evaluated using a Likert scale from 0 to 10. The pharmacist relied on the presence or absence of overdose risk situations defined by the French Health Authority (HAS). The need to hold THN was assessed using a composite criterion. RESULTS: A total of 34 patients were interviewed; near one third were aware of the existence of THN and a minority had THN in their possession. Out of the 34 participants, 29 assessed their own risk of future opioid overdose: 65.5% reported having zero risk, while 6.9% believed they had a high risk. Nevertheless, at least one risk situation of opioid overdose was identified according to HAS criteria in 73.5% of the participants (n = 25). Consequently, 55% of the participants underestimated their risk of experiencing a future opioid overdose. Yet, dispensing THN has been judged necessary for 88.2% of the participants. CONCLUSION: This study underscored the imperative need to inform not only healthcare professionals but also the patients and users themselves on the availability of THN and the risk situations of opioid overdose.

A revisited version of the disputatio for pharmacological training: An educational study.

OBJECTIVE: The disputatio is a pedagogical method existing since the Middle-Ages where students had to debate about a question asked by a "master", exercising their thinking and oratory skills. To move away from traditional vertical teaching methods, the disputatio has been revived by pharmacologists. Thus, for almost three successive years, several groups of young French pharmacologists and therapists confronted their ideas concerning a medical question at a therapeutic impasse. The aim here is to describe the initial feedback received from participants. METHODS: An anonymous questionnaire was sent by email in May 2023 to the participants of the different disputationes of 2019, 2022 and 2023. Participants were asked about different aspects of their feelings before, during and after the disputatio, using the 5-point Likert scale. They were also asked to describe the event in 2 to 5 words. Finally, participants could leave their comments in a free-field and were asked to give an overall satisfaction score out of 10. RESULTS: Out of the 39 participants, 27 (69.2%) answered the questionnaire. Although 50% of respondents reported a feeling of anxiety before participating, most enjoyed the expert talks as well as working with people they did not know. Besides, over 66% reported having underestimated the skills they could share with colleagues from different backgrounds. Over 55% of respondents reported progress in methodology, and over 83% in pharmacology and/or therapeutics. Participants reported an overall satisfaction score of 8.6/10, and the main terms used to describe the event were "sharing", "enriching" and "meeting". CONCLUSION: The disputatio is an innovative training program whose pedagogical and human values were underlined by most of the participants. Beyond pharmacology and therapeutics, the principle of disputatio could be extended to other disciplines, spanning the centuries.

Characterization of antipsychotic utilization before clozapine initiation for individuals with schizophrenia: an innovative visualization of trajectories using French National Health Insurance data.

AIMS: Despite recommendations to initiate clozapine after two unsuccessful trials of antipsychotics, clozapine is underprescribed and initiated too late. The aim of this study was to describe different antipsychotic treatment sequences in the 36 months before the initiation of clozapine and to characterize clusters of treatment trajectories. METHODS: Using the French National Health Insurance database, a historical cohort study of the population in an area in western France was performed. The data from all new users of clozapine with a diagnosis of schizophrenia or schizoaffective disorder in the period of 2017-2018 were evaluated. All outpatient reimbursements for antipsychotics during the 36 months before clozapine initiation were analysed. Successive reimbursements for identical treatments were grouped into treatment trials (TTs), and different trajectories were clustered using a state sequence analysis. RESULTS: The results showed 1191 TTs for 287 individuals. The mean number of TTs per individual was 3.2. Risperidone, aripiprazole and haloperidol were the main treatments delivered. The frequencies of antipsychotics used differed between monotherapies and combination therapies. A three-cluster typology was identified: one cluster (n = 133) of 'less treated' younger individuals with fewer TTs and shorter TT durations; a second cluster (n = 53) of 'more treated' individuals with higher numbers of TTs and combinations of antipsychotics; and a third cluster (n = 103) of 'treatment-stable' older individuals with longer TT durations. CONCLUSIONS: The results indicate that the median number of TTs during the 36 months before clozapine prescription was higher than the two recommended. The different trajectories were associated with individual characteristics and treatment differences, suggesting that additional studies of clinical parameters are needed to understand barriers to clozapine prescription.

Nitrous oxide: a unique official French addictovigilance national survey.

Introduction: Nitrous oxide has become over the last few years a public health problem in many countries. France has a dedicated health monitoring system dedicated to the surveillance of the abuse, dependence and consequences associated with the use of psychoactive substances coordinated by the French National Agency for the Safety of Medicines and Health Products.We present the French national survey of nitrous oxide. Materials and methods: We analyzed all the cases with nitrous oxide from 2012 to 2021: number of notifications, characteristics of the subjects and consumption, consequences reported and their evolutions over time. In addition, we have made a special focus on the four main complications reported. Results: A total of 525 cases were received with an exponential increase since 2019. We observed changes in the characteristics of the notifications with an increase in the proportion of women [42.7% in 2021 vs. 30.8% in 2020 (p = 0.02)]; an increase in the quantities consumed (use of cylinders); a negative evolution of the contexts of use with a search for self-therapeutic effects and use in violent contexts; an increasing trend of the severity of cases [78.1% in 2021 vs. 70.0% in 2020 (p = 0.07)].The main effects were substance use disorders and/or associated criteria (82.5%), neurological disorders (75.4%), psychiatric symptoms (15.4%) and cardiovascular events (8.6%). In terms of evolution, we observed a significant increase in cases with a use disorder and an increase in neurological complications. Moreover, new serious effects, notably cardiovascular events were reported. Discussion: The combination of high availability, varied effects from euphoria to relief of discomfort in a stressful global pandemic context and the development of dependence could explain the rapid growth of consumption and the seriousness of the cases.It must now be taken into account that (i) Substance use disorders are associated with nitrous oxide consumption; (ii) clinicians must consider "nitrous oxide" in young subjects presenting different types of manifestations; and (iii) stopping consumption is imperative and is the first treatment. In this context, an addictological assessment must also be carried out.

French national addictovigilance follow-up of zolpidem between 2014 and 2020: evolution of drug abuse, misuse and dependence before and after the regulatory change.

BACKGROUND: Since the appearance of zolpidem on the market, the occurrence of serious cases of abuse, misuse and dependence have come to the attention of authorities. In view of the increase in the number and severity of cases among zolpidem users and the predominant presence of zolpidem in falsified prescriptions, the French Health Authorities implemented part of the narcotics regulation for zolpidem in April 2017. The objective of this article was to describe the evolution of the abuse, dependence and misuse of zolpidem. METHODS: We used three data sources: (i) zolpidem is a reimbursable and strictly prescription drug in France. Medic'AM is a public database that indicates the number of tablets reimbursed each month in France for each reimbursable drug. This database has been analyzed as a proxy of the exposure of the French population to zolpidem; (ii) all French cases of drug dependence or abuse reported by health professionals (regulatory obligation) and (iii) an epidemiological tool based on the surveillance of falsified prescriptions over two periods: the 3-year period before the regulatory measure (2014-16) and the 3-year period after the regulatory measure (2018-20). RESULTS: This regulatory change had two immediate consequences: a sharp decline in falsified prescriptions and a decrease of ∼57% between the two study periods in the zolpidem reimbursement data. Markers of problematic consumption remained after the regulatory change with worsening cases, particularly for people who were genuinely dependent and/or had comorbidities or misusers for whom zolpidem was the substance of interest, whose proportion increased significantly in the addictovigilance notification system, from 43.6% (N = 107) to 59.3% (N = 127) (P < 0.01). CONCLUSIONS: Further monitoring is needed in light of these persistent markers of problematic consumption.

New Psychoactive Substances, New Behaviours, New Drug-drug Interactions: Pharmacology of a Slam Session.

BACKGROUND: Slamming has been increasing internationally for ten years, mostly among men who have sex with men. Slamming consists of injecting psychostimulants (including new psychoactive substances-NPS) intravenously to increase sexual performance. OBJECTIVE: The objective of our work was to analyse drug-drug interactions related to slamming. METHODS: Drawing upon a reported case of a slam session describing hour by hour the intake of substances, we performed a drug-interaction analysis using international references and a comprehensive literature review. High doses of sildenafil, GBL and 3-MMC were reported during the 40-hour session described. The specific drug-interaction research was performed using 9 references and 65 of the 209 records identified in the literature review. RESULTS: Pharmacological data regarding nonmedicated substances were scarce. Regarding pharmacodynamics, the risk was high at the cardiovascular level and was related to the vasodilatation effect of sildenafil and the adrenergic and serotoninergic properties of stimulants; this risk may increase with usual treatment (involving other vasodilators or central depressants). Regarding pharmacokinetics, the major interactions concerned metabolism by CYP3A4 and CYP2C9, leading to interactions, particularly with HIV medication. CONCLUSION: This innovative work provides pharmacological information on drugs that are commonly used in slamming, allowing the development of effective medical-management protocols and the provision of risk-reduction counselling.

Efficacy and Safety of Electroconvulsive Therapy in Patients With Deep Brain Stimulation: Literature Review, Case Report for Patient With Essential Tremor, and Practical Recommendations.

AIM: Deep brain stimulation (DBS) has proven to be an effective therapy of some treatment-resistant psychiatric disorders and movement disorders. Comorbid depressive symptoms are common and difficult to manage. Treatment with electroconvulsive therapy (ECT) may be required. There are few published cases describing the safety and efficacy of ECT for patients with DBS implants, and there are no available guidelines for administration of ECT in patients with DBS and mood disorders. The current study had 3 aims: (i) to conduct a systematic review of case reports on patients with DBS implants who received ECT; (ii) to report the case of a 69-year-old man with a DBS implant for essential tremor, who required ECT; and (iii) to provide practical recommendations for ECT in patients with DBS implants. METHODS: We conducted a systematic review, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, of existing case reports on patients with DBS implants administered ECT for psychiatric disorders. RESULTS: Our search yielded 25 cases of ECT in patients implanted with DBS systems. In addition, we here describe successful ECT management of major depressive disorder in a patient treated by DBS. We also set forth ECT management guidelines based on points of consensus. The 2 most important practical recommendations are to make sure the DBS system is set to 0 V and turned off before ECT, and to avoid sites near the DBS electrodes. CONCLUSIONS: Electroconvulsive therapy may be an effective and safe treatment for DBS patients with MDD.

Did the New French Regulation of Zolpidem Decrease the Problematic Consumption of Zolpidem? A Field Study among Users.

Background: The French national drug regulatory authority stated, in 2017, that a secured prescription pad must be used for zolpidem prescriptions. This study aimed to evaluate the evolution of the problematic consumption of zolpidem at the individual level since the new regulation. Methods: Two nationwide populations of at-risk users of zolpidem were recruited: one in general practitioner (GP) offices and one in specialized care centers dedicated to drug dependence (SCDDs). Participants were asked about their zolpidem consumption before and after the regulation change. The primary outcome was the evolution of problematic zolpidem consumption, as defined by at least one of the following criteria: overconsumption, fraudulent ways of obtaining, effects sought other than hypnotic, and modes of administration other than oral. Results: A total of 243 participants were included: 125 from GP offices and 118 from SCDDs. In the GP population, the prevalence of patients who were identified as problematic consumers decreased from 24.8% to 20.8% (p = 0.593), whereas the prevalence decreased from 73.7% to 51.7% in the SCDD population (p < 0.001). The most prevalent criteria for problematic status were overconsumption and fraudulent ways. Conclusions: The new French regulation of zolpidem had different impacts among two different populations of at-risk zolpidem consumers.

Perception of the Regulatory Change for Zolpidem Prescription by French General Practitioners and Its Relation to Prescription Behavior.

Background: To "limit the risk of abuse and misuse" and "encourage correct usage", the French drug regulatory authority stated that­from April 2017­zolpidem prescription must be performed on a secured prescription pad. This national study aims to evaluate the perception of general practitioners (GPs) towards this new regulation and its link with prescription strategies. Methods: We conducted structured interviews of GPs. Data were collected about GPs' perception of the measure and therapeutic strategies towards zolpidem. The primary outcome was the description of the GPs' strategy of prescription, based on the perception towards the new regulation for zolpidem. Results: For 206 GPs, the new regulation was mainly perceived as helpful (61%) and as a difficulty (55%). Other perceptions were the awareness of the risks of zolpidem (18%), awareness of the risks of hypnotics (13%), and nothing changed (5%). Four clusters of GPs were identified. In the clusters with the perception as a difficulty (only or associated with helpful), the GPs who applied the strategy "no modification" for >50% of their patients were more frequently compared to awareness and helpful only clusters (60.8%; 42.9%; 20.4%; 26.7%) (p < 0.001). Conclusions: We highlighted an association between the perception of the new regulation of zolpidem prescription by GPs and a strategy of prescription.

How do people who use drugs receiving Opioid Medication Therapy perceive their treatment ? A multicentre study.

BACKGROUND: The resurgence of heroin use and the misuse of pharmaceutical opioids are some of the reasons for a worldwide increase in opioid dependence. Opioid Medication Therapies (OMT) have amply demonstrated their efficacy. From a medical point of view, the main objectives of OMT concern medical and social outcomes, centred on risk reduction and the cessation of opioid use. But patient points of view can differ and few studies have explored opioid-dependent patient viewpoints on their OMT. This variable seems important to consider in a patient-centred approach. The aim of our study was to explore points of view of people who use drugs (PWUD) treated with OMT, in a large multicentre sample. METHOD: A cross-sectional multicentre study explored the points of view of PWUD with Opioid Use Disorder following OMT. Data regarding the patients' points of view were collected using a self-administered questionnaire developed by the scientific committee of the study. A descriptive analysis and an exploratory factor analysis were performed to explore the structure of items exploring patient viewpoints. RESULTS: 263 opioid dependent PWUD were included, a majority were men consuming heroin prior to being prescribed OMT. 68% were on methadone, 32% were on buprenorphine. Most PWUD identified a positive impact on their lives, with 92.8% agreeing or strongly agreeing that OMT had changed a lot of things in their lives. The exploratory factor analysis identified three factors: (F1) items related to points of views concerning the objectives and efficacy of OMT; (F2) items related to the legitimacy of OMT as a treatment compared to a drug, (F3) items related to experiences and relationships with OMT. CONCLUSION: Patient viewpoints on efficacy were correlated with the pharmacological benefits of OMT and with the associated psychosocial measures. The implications of OMT in relationships, such as the feeling of being judged, concerned a majority. Points of view were ambivalent concerning the role of OMT as a treatment or as a drug. Involving patient points of view in therapeutic strategies decisions could help enhance positive views among PWUD on OMT and help PWUD towards their recovery. TRIAL REGISTRATION: OPAL study was registered: (NCT01847729).

Did the pattern of use of zolpidem change since the enforcement of a new prescription rule? A latent class analysis using the French health insurance database.

BACKGROUND: In recent years, zolpidem has been the subject of numerous reports of misuse, abuse and dependence. In view of these risks, the French drug agency decreed the implementation of secure prescription pads in April, 2017. The objective of this study was to characterize the impact of this regulatory change on the patterns of zolpidem use. RESEARCH DESIGN AND METHODS: We included patients with at least one reimbursement for zolpidem before and/or after the regulatory change using a sample of the French health insurance database. For each period, we identified profiles of users using a latent class analysis (LCA). RESULTS: In total, 15,550 zolpidem users were identified before the measure and 8,301 after the measure. We identified the same three profiles of zolpidem users before and after the measure: non-problematic users (the most prevalent), users whose drug prescriptions suggest psychiatric disorder and potential problematic users. The profile of potential problematic users was similar after the regulatory change but represented a lower absolute number of patients. CONCLUSION: In conclusion, the regulatory change had a positive impact on the patterns of zolpidem use, but the impact should be reevaluated, because withdrawal can take a long time, especially in long-term users. TRIAL REGISTRATION: The study was registered at www.clinicaltrials.gov under the reference number NCT03584542.

Regulatory Framework Implementation for the Prescription of Zolpidem in France, What Impact in the Older People?

BACKGROUND: Zolpidem is one of the most prescribed hypnotic drugs. In 2001, the World Health Organization alerted a risk of pharmacodependence associated with zolpidem. The French health authority decided in 2017 to enforce security on the prescription of zolpidem to reduce those risks. The aim of our study was to evaluate the impact of regulatory framework implementation, secure prescription pad, on the prevalence and incidence of prescriptions of zolpidem according to the age. METHODS: This study was based on an observational study using the French healthcare data system. Two age categories were defined: "younger" and "older" (<65 years, ≥65 years); in order to study the evolution of prevalence and incidence of zolpidem use in our two groups, two periods were defined, before and after the implementation of the measure. RESULTS: The prevalence decreased in the younger population by 51% (4012 vs. 7948 consumers), while that of the older population decreased by 42% (4151 vs. 7282). This difference in our two groups, with a greater decrease in the younger people, is statistically significant compared to the older people. CONCLUSION: Our study showed that regulatory framework implementation and mandatory secure prescription pad is more effective for decreasing prevalence of zolpidem prescription for younger people compared to older people.

What about regular hematological monitoring during clozapine treatment? A compliance analysis using the French health insurance database.

BACKGROUND: The inherent risk of agranulocytosis associated with clozapine requires the realization of weekly white blood cell monitoring (WBCM) during the 18 first weeks of treatment. The aim of this study was to assess the compliance with WBCM during clozapine initiation for schizophrenia and Parkinson's disease (PD) subjects. RESEARCH DESIGN AND METHOD: The analysis was conducted using SNDS data on a cohort of new users of clozapine in 2018. We analyzed all reimbursements for WBCM from 2 weeks before the index date to 18 weeks after (optimal monitoring during hospitalization was assumed). The primary outcome was the proportion of good realization of WBCM according to different thresholds of completion (70%; 80%; 90%). Descriptive and comparative analyses with chi-squared test or Student's t-test were performed. RESULTS: Two hundred and ninety-six subjects were included. Rates of patients with WBCM realization over 70%, 80%, and 90% of WBCM expected were, respectively, 78.1%, 70.0%, and 56.9% for subjects with schizophrenia and 71.3%, 63.2%, and 47.8% for PD subjects. Only hospitalization during the follow-up period for schizophrenia subjects was significantly associated with good WBCM realization. CONCLUSIONS: We observed rather good results for compliance with clozapine initial monitoring. Other studies are needed to confirm our results.

Change in the regulatory framework for zolpidem: What is the impact on the landscape of the prescription of sedative medications? The French national ZORRO study.

AIMS: In recent years, zolpidem has been the subject of numerous reports of misuse, abuse and dependence. In view of these risks, the French drug agency (ANSM) decreed in April 2017 the implementation of secure prescription pads. The objective of this study was to evaluate the impact of this regulatory measure on the prescription of zolpidem and other sedative medications (zopiclone, benzodiazepines and antihistamines) in long-term users of zolpidem and associated factors. METHODS: We performed a historical cohort study using data from the Generalist Sample of Beneficiaries (EGB). All patients aged over 18 years old who were long-term users (at least 3 months) before the measure were enacted. We analysed the reimbursement trajectories of zolpidem, zopiclone, benzodiazepines and antihistamines (hydroxyzine and alimemazine) up to 2 years after the measure using a state sequence analysis. RESULTS: Overall, 2502 patients were analysed. A four-cluster typology was identified: continuation of zolpidem (n = 1044, 42%), discontinuation of sedative medications (n = 766, 31%), change to zopiclone (n = 537, 21%) and change to hypnotic benzodiazepines (n = 155, 6%). The most frequently prescribed hypnotic benzodiazepine was lormetazepam. We identified age, sex, treatment for psychiatric or addictive disorder and volume of zolpidem use before the measure as factors associated with different reimbursement trajectories after the regulatory change. CONCLUSION: The regulatory change for zolpidem prescriptions reduced exposure to zolpidem among long-term users and also had a broad impact on prescriptions of other sedative medications. Switching to other medications that also present a potential risk of abuse or dependence should be carefully monitored.

Are Seniors Dependent on Benzodiazepines? A National Clinical Survey of Substance Use Disorder.

Benzodiazepines and Z-drugs, zolpidem and zopiclone, (BZD/Z) are used longer than recommended in the elderly population. However, to date, very few attempts have been made to evaluate dependence on BDZ/Z among the elderly population. We conducted a national multicentric observational prospective study aimed at evaluating the prevalence of and risk factors for dependence among elderly adults. Patients aged 65 or older who were treated with BZD/Z for at least 3 months were evaluated through clinical interviews that conformed to official Diagnostic and Statistical Manual of Mental Disorders (DSM) dependence criteria. Among the 1,024 patients included in the survey, 442 of 976 (45.3%) met the dependence criteria. In the multivariate logistic regression model, dependent patients were categorized as follows: younger (odds ratio (OR) = 0.97), living mostly alone (OR = 1.45), showing psychiatric problems (OR = 2.22), having additional treatments (other than BZD/Z; OR = 1.37), having long-lasting treatment (OR = 1.04), exhibiting significant relationship difficulties (OR = 1.96), committing transgressional behaviors to procure BZD/Z (OR = 2.70), and wanting to stop their consumption of BZD/Z (OR = 7.60). A latent class analysis, which was applied to sort out subgroups within dependent patients, identified two profiles according to the prevalence of dependence items: profile 1 (73%), "withdrawal syndrome when BZD/Z is stopped" (100%) and "previous unsuccessful attempts to stop consumption" (82%); and profile 2 (27%), "tolerance" (76%) and "intake in larger amounts or over a longer period than intended" (86%). BZD/Z dependence is frequent in the elderly population, and among dependent patients, we found two profiles corresponding to positive and negative conditioning of the psychoactive effects of BZD/Z. This study is registered as NCT01920581.

Benzodiazepine withdrawal in older people: what is the prevalence, what are the signs, and which patients?

PURPOSE: Benzodiazepines (BZDs) and related drugs (Z-drugs) are mainly taken chronically, and older people are much more likely to take them on a chronic basis despite recommendations. Withdrawal symptoms could be an obstacle to stopping BZD/Z-drug administration. The main objective of this study is to estimate the prevalence of withdrawal symptoms in patients aged 65 years and older who have experience a stop of BZD/Z-drug. The secondary objectives are to describe the withdrawal symptoms and identify factors associated. METHOD: This ancillary study was based on a national observational study in patients with chronic BZD/Z-drug consumption. Patients who made at least one BZD/Z-drug stop experience were selected. Withdrawal symptoms are described, and a logistic regression was carried out to identify the variables most associated with withdrawal symptoms. RESULTS: In total, 697 patients were selected: 78% experienced at least one withdrawal symptom after a stop administering BZDs or Z-drugs; most of the withdrawal symptoms were psychological disorders. CONCLUSION: Our study identifies a specific population experiencing withdrawal symptoms and who cannot stop administering BZD/Z-drug. We assume that withdrawal symptoms in patients with chronic use play an essential role in the nonstop use of BZD/Z-drugs.

CYP1A2 and tobacco interaction: a major pharmacokinetic challenge during smoking cessation.

Smoking cessation is underestimated in terms of drug interactions. Abrupt smoking cessation is common in cases of emergency hospitalization and restrictions of movement. Tobacco is a known cytochrome P450 1A2 (CYP1A2) inducer, its consumption and withdrawal can lead to major pharmacokinetic drug interactions. Nevertheless, references do exist, but may have different results between them. The objective of our work was to establish the broadest and most consensual list as possible of CYP1A2 substrates treatments and propose a pharmacological approach. We searched the widest possible list of CYP1A2 substrates based on various international references. We compared the references and defined probability and reliability scores of our results to sort the substances based on the scores. For the 245 substances identified as CYP1A2 substrates, we focused on the 63 CYP1A2 substrates with both probability and reliability scores >50%. Our work establishes adaptive pharmacological approaches for the management of patients initiating smoking cessation which must be integrated into the management of smoking cessation. Pharmacologists can now adopt adaptive pharmacological approaches to complement patient-specific clinical information about smoking cessation by considering pharmacokinetic risk. This work establishes an unprecedented list. It should guide in the care of patients initiating smoking cessation to prevent pharmacokinetic drug interactions.