Marie Tournier

Benzodiazepine use and risk of Alzheimer’s disease: case-control study

Objectives To investigate the relation between the risk of Alzheimer’s disease and exposure to benzodiazepines started at least five years before, considering both the dose-response relation and prodromes (anxiety, depression, insomnia) possibly linked with treatment. Design Case-control study. Setting The Quebec health insurance program database (RAMQ). Participants 1796 people with a first diagnosis of Alzheimer’s disease and followed up for at least six years before were matched with 7184 controls on sex, age group, and duration of follow-up. Both groups were randomly sampled from older people (age >66) living in the community in 2000-09. Main outcome measure The association between Alzheimer’s disease and benzodiazepine use started at least five years before diagnosis was assessed by using multivariable conditional logistic regression. Ever exposure to benzodiazepines was first considered and then categorised according to the cumulative dose expressed as prescribed daily doses (1-90, 91-180, >180) and the drug elimination half life. Results Benzodiazepine ever use was associated with an increased risk of Alzheimer’s disease (adjusted odds ratio 1.51, 95% confidence interval 1.36 to 1.69; further adjustment on anxiety, depression, and insomnia did not markedly alter this result: 1.43, 1.28 to 1.60). No association was found for a cumulative dose <91 prescribed daily doses. The strength of association increased with exposure density (1.32 (1.01 to 1.74) for 91-180 prescribed daily doses and 1.84 (1.62 to 2.08) for >180 prescribed daily doses) and with the drug half life (1.43 (1.27 to 1.61) for short acting drugs and 1.70 (1.46 to 1.98) for long acting ones). Conclusion Benzodiazepine use is associated with an increased risk of Alzheimer’s disease. The stronger association observed for long term exposures reinforces the suspicion of a possible direct association, even if benzodiazepine use might also be an early marker of a condition associated with an increased risk of dementia. Unwarranted long term use of these drugs should be considered as a public health concern.

Troubles cognitifs, syndrome extrapyramidal et hyperammoniémie sous traitement thymorégulateur par divalproate de sodium : à propos d'un cas

Resume Nous rapportons le cas d’un homme de 58 ans traite depuis 7 mois par divalproate de sodium pour trouble bipolaire de l’humeur de type I et ayant presente des troubles cognitifs et une hypertonie extrapyramidale s’aggravant de facon progressive depuis 3 a 4 mois. Les examens paracliniques montrerent une hyperammoniemie, un trace ralenti a l’electroencephalogramme, et une atrophie cerebrale sus- et sous-tentorielle avec dilatation des cavites ventriculaires au scanner cerebral. Les concentrations plasmatiques d’acide valproique etaient dans les valeurs therapeutiques attendues. Le bilan hepatique etait normal. Un mois apres l’arret du divalproate de sodium, les symptomes cliniques et les anomalies paracliniques avaient disparu. Bien que les effets neurologiques sous acide valproique aient ete largement decrits, aucun cas n’avait encore rapporte la survenue concomitante de troubles cognitifs, syndrome extrapyramidal et hyperammoniemie avec le divalproate de sodium. Il convient d’evoquer une origine medicamenteuse lors de la survenue de manifestations extrapyramidales et de troubles cognitifs chez tout patient traite par valproate de sodium et ses derives.

Antidepressant treatment patterns in younger and older adults from the general population in a real-life setting

The treatment of depression in real‐life settings appears to be influenced by health care systems. Antidepressant drugs have been found to be underused in the older population relative to younger adults when refunding of such drugs is poor. No study assessed the pattern of antidepressant use according to age in a universal health care system. The objective is to assess whether the pattern of antidepressant drug use differs between younger and older adults with respect to treatment duration, adherence to treatment, coprescription of other psychotropic drugs, switch, or combination of antidepressant drugs.

Depressed older adults may be less cared for than depressed younger ones

The aim of the study was to investigate depression treatment use, either psychotherapy (PT) or antidepressant drugs (ADT) in the older and younger depressed population. Cohorts of 6316 elderly (≥65 year-old) and 25,264 matched non-elderly (25-64 year-old) depressed patients were created from a large national claims database of managed care plans from 2003 to 2006. Factors associated with ADT or PT were assessed using multivariate logistic models. During the 120 days following the depression diagnosis, the elderly persons were less often treated than the younger adults either by ADT (25.6% vs. 33.8%) or by PT (13.0% vs. 34.4%). ADT dispensing occurred later in the elderly group (51 vs. 14 days). ADT was associated with comorbid chronic conditions or polypharmacy in the elderly and younger adults. The selection of treatment (ADT or PT) was associated with the history of treated depression using the same type of treatment, in both groups. Thus, depression goes commonly untreated. Comorbidity was associated with higher ADT dispensing rates. However, although depressed elderly commonly presented with comorbidity, this age group was at higher risk of untreated illness or later treatment.

Transition in care in persons with antidepressant prescription in naturalistic conditions

BACKGROUND Few studies have explored transition to psychiatric care in persons treated by antidepressants in primary care. OBJECTIVE To assess the rates of transition in care after a dispensing of antidepressant and the characteristics associated with transition from primary to psychiatric care. METHODS A follow-up study of persons (n = 19 975) starting antidepressant treatment was carried out on a representative sample of the 2005-07 French Social Security Insurance national database. Prescribers were categorized as GPs, hospital practitioners (as a proxy for public psychiatrist), private psychiatrists and other private specialists. Transition in care was defined as a prescription of psychotropic drugs by a prescriber belonging to a category different from that of the index antidepressant prescriber. RESULTS Eighty per cent of incident antidepressant treatments were initiated by a GP and 28% of persons transited in care. The most frequent pattern was transition from a GP to a hospital practitioner (8%) or to a private psychiatrist (5%). Transition to psychiatric care was independently associated with younger age and markers of illness severity (psychiatric chronic illness status, duration of the index antidepressant treatment >6 months and prescription of other classes of psychotropic drugs). Almost all treatments with antipsychotics or mood stabilizers were initiated after the transition to a specialist. CONCLUSIONS Transition to psychiatric care seemed coherent with distribution of tasks between primary and secondary care according to illness severity. Further studies using detailed clinical information are required to assess not only the clinical appropriateness of psychiatric referral but also lack of referral in antidepressant users.

Compliance of psychotropic drug prescription with clinical practice guidelines in older inpatients

Several practice guidelines were published by French regulatory agencies between 2006 and 2009 to improve psychotropic drug use in older patients. The objectives of the study were to assess compliance with these guidelines in older patients hospitalized in psychiatric units and to identify characteristics associated with compliance. A cross‐sectional study was conducted in 117 patients aged 65 years and older hospitalized in two psychiatric departments of a public hospital, at three dates randomly chosen between January and May 2014. Medical and sociodemographic characteristics were collected from electronic medical records. In all, 8% of psychotropic prescriptions were compliant with guidelines. A total of 98% of antidepressant prescriptions complied with guidelines for product selection (no tricyclics) and 72% for initial dosage (half of that recommended for younger adults). Regarding benzodiazepines, short half‐life drugs were chosen in 73% of treatments, low maintenance dosage was found in 64% of treatments, and a discontinuous administration rhythm was noted in 33% of treatments. Regarding antipsychotics, initial dosage was a quarter of the allowed initial dosage for younger adults in 39% of prescriptions and metabolic blood testing was performed in 17% of prescriptions. Neurological and cognitive tolerance was monitored in 41% and 61% of prescriptions, respectively. Few clinical factors were found to be associated with compliance or noncompliance with guidelines in older psychiatric inpatients. Practice guidelines on psychotropic drug prescription were partially respected in older inpatients. Practitioners should take into account the risks associated with non‐recommended patterns of psychotropic drug use in this vulnerable population.

Effectiveness of risk communication interventions on the medical follow-up of youth treated with antidepressants

Following reports of a potential association between antidepressants (ADs) and suicidal behaviour in youth, regulatory warnings were issued in May 2004, and clinical recommendations on medical follow-up were published in November 2007. Our study aimed at assessing the association between these communication interventions and medical follow-up of children (age 10-14) and adolescents (age 15-19) who initiate an AD treatment. A retrospective cohort study (1998-2008) was conducted among youth members of the Quebec public drug plan. Study outcomes consisted of adequate follow-up practice, defined as at least 1 medical visit per month during the first 3 months of treatment. The effect of each intervention on follow-up practices was determined through multivariate logistic regression analysis. The cohort included 4576 children and 12,419 adolescents. Two thirds of both children and adolescents had at least one medical visit during the first trimester of treatment, but only 20% had a frequency of at least one visit per month (i.e. adequate). The occurrence and frequency of visits did not change after either the warning nor the publication of the guidelines. Further interventions designed to optimize monitoring practices should be envisaged.

P02-125 Choice of psychotropic drugs used for intentional drug overdose

Objectives To assess with which frequency subjects with intentional overdose of psychotropic drugs ingest their own psychotropic drug treatment, and whether prescription of a drug may be a factor influencing the choice of drugs used for the IDO. Methods Demographic characteristics, psychiatric history, and currently prescribed psychotropic drug treatment were collected for all the patients (n=1654) admitted to an emergency department (ED) for IDO with psychotropic drugs (anxiolytics, hypnotics, antidepressants, antipsychotics and mood stabilizers) over a period of 18 months. Results Two-thirds of the patients ingested during the IDO at least one of their own prescribed psychotropic drugs. Compared with the subjects who had ingested psychotropic drugs not prescribed for them, they were more likely to have a history of psychiatric hospitalization (OR 4.2; 95%CI 3.1-5.5), of parasuicide (OR 2.5; 95%CI 1.9-3.3), to be a psychiatric outpatient (OR 3.9; 95%CI 3.0-5.1), and to present with a serious IDO (OR 2; 95%CI 1.4-2.9). Independently from age and psychiatric hospitalization history (i.e. the seriousness of psychiatric disorder), they ingested during the IDO more often antidepressants (OR 4.4; 95%CI 3.0-6.4), antipsychotics (OR 2.9; 95%CI 1.7-4.8) and mood stabilizers (OR 4.1; 95%CI 1.6-10.7). No association was found with prescription for overdose of benzodiazepine or paracetamol. Conclusion Prescription of the psychotropic drugs plays an important role in the choice of the drugs ingested for the IDO. It might make potentially “dangerous” drugs available for the patient. Physicians have always to balance the benefit of the treatment against the risk of drug overdose.