Hervé Javelot

Antidepressant-like effects of a cocoa polyphenolic extract in Wistar-Unilever rats.

Abstract Depression is a major public health problem affecting about 12% of the world population. Drugs exist but they have many side effects. In the last few years, natural substances (e.g. flavonoids) have been tested to cure such disorders. Cocoa polyphenolic extract is a complex compound prepared from non-roasted cocoa beans containing high levels of flavonoids. The antidepressant-like effect of cocoa polyphenolic extract was evaluated using the forced swimming test in rats. Cocoa polyphenolic extract significantly reduced the duration of immobility at both doses of 24 mg/kg/14 days and 48 mg/kg/14 days, although no change of motor dysfunction was observed with the two doses tested in the open field. The results of the forced swimming test after a subchronic treatment and after an additional locomotor activity test confirm the assumption that the antidepressant-like effect of cocoa polyphenolic extract in the forced swimming test model is specific. Further, it can be speculated that this effect might be related to its content of active polyphenols.

Enhanced physician adherence to antibiotic use guidelines through increased availability of guidelines at the time of drug ordering in hospital setting.

Some studies have shown that making practice guidelines accessible to physicians when they are making clinical decisions could improve prescribing practices. The aim of the study was to assess the benefit of impact on physician adherence of the intervention that consisted of embedding previously paper‐based antibiotic guidelines in the computerized physician drug order entry system of a teaching hospital in order to make these guidelines available to physician at the time of antibiotic ordering. Before the intervention, these guidelines were available in booklet form in all the wards of the hospital.

Efficacy of Chronic Antidepressant Treatments in a New Model of Extreme Anxiety in Rats

Animal models of anxious disorders found in humans, such as panic disorder and posttraumatic stress disorder, usually include spontaneous and conditioned fear that triggers escape and avoidance behaviors. The development of a panic disorder model with a learned component should increase knowledge of mechanisms involved in anxiety disorders. In our ethological model of extreme anxiety in the rat, forced apnea was combined with cold water vaporization in an inescapable situation. Based on the reactions of vehicle controls, behaviors involved in paroxysmic fear were passive (freezing) and active (jumping) reactions. Our results show that subchronic fluoxetine (5 mg/kg, IP, 21 days) and imipramine (10 mg/kg, IP, 14 days) administration alleviated freezing and jumping behaviors, whereas acute fluoxetine (1 mg/kg, IP) provoked opposite effects. Acute low dose of diazepam (1 mg/kg, IP) was not effective, whereas the higher dose of 3 mg/kg, IP, and clonazepam (1 mg/kg, IP) only had an effect on jumping. Paroxysmic fear generated in this experimental condition may therefore mimic the symptomatology observed in patients with anxiety disorders.

Unilateral mydriasis due to scopolamine patch

Case We report the case of a patient who presented with unilateral mydriasis after a scopolamine patch application. The specific clinical context (cancer) reported here may have led to the misinterpretation of the etiology of mydriasis. Conclusion Our case description warns against diagnostic mistakes related to this side effect and highlights the advantages of pilocarpine test in the differential diagnosis of unilateral mydriasis.

Benzodiazepines Withdrawal: Initial Outcomes and Long-Term Impact on Falls in a French Nursing Home

Long-term use of benzodiazepines (BZDs) is known to induce tolerance and dependence, and increase the risk of falls-related injuries in older adults. We present a study carried out in a French nursing home that concerns the implementation of a BZD withdrawal program reassessed at one year. BZD deprescription was achieved by gradual cessation of doses. A secondary benefit of this program was assessed by comparing the number of falls among residents before and after withdrawal. The number of falls was recorded over a six-month period prior to the onset of withdrawal (T1) and then over a six-month period after reassessment at one year (T2). At the beginning, 31 (28.7%) of the patients were under BZD. Total deprescription was obtained for 11 patients. The number of falls per patient over the T1 period was not different between the two groups (future non-withdrawn and withdrawn patients in BZD): 2.1 ± 1.3 and 2.3 ± 0.6 falls per resident, respectively. Conversely, the number of falls per patient was significantly decreased in the population completely withdrawn in BZD between the T1 and T2 periods (2.3 ± 0.6 vs. 0.5 ± 0.2 falls, p = 0.01). The results show that BZD deprescription, through a gradual reduction of doses, is possible to achieve.

The anticholinergic impregnation scale: Towards the elaboration of a scale adapted to prescriptions in French psychiatric settings

PURPOSE Some drugs have anticholinergic activity and can cause peripheral or central side effects. Several scales exist to evaluate the potential anticholinergic effect of prescribed drugs but: (i) they are validated in the elderly and mainly assess the cognitive side effect of treatments; (ii) they do not concern some of the drugs frequently used in clinical psychiatry in France. The aim of our study is to develop a new scale, the anticholinergic impregnation scale (AIS), with drugs used in France and based on an assessment of the drugs used against peripheral anticholinergic adverse effects. METHODS We assigned a score, ranging from 1 to 3, to a list of 128 drugs with a consensus approach obtained via literature data and expert opinions. We collected data from 7278 prescriptions in 34 French psychiatric facilities: age, sex, atropinic drugs, laxatives and treatments of xerophthalmia and xerostomia, in order to evaluate the association between AIS score and the prescription of drugs aiming to reduce peripheral anticholinergic side effects. RESULTS The most frequently prescribed drugs were cyamemazine (n=1429; 20%) and tropatepine (n=1403; 19%), two drugs marketed almost exclusively in France and with a score of 3. The frequency of patients with a high AIS score, greater than 5, was significantly higher in patients who received laxatives and treatments of xerostomia. AIS score represents the first validated solution to evaluate anticholinergic load in psychiatry settings in France. CONCLUSION The anticholinergic problem remains underevaluated in mental health settings. In order to rule out the confounding factor of mental disease, assessment of peripheral side effects can be considered more objective than the evaluation of cognitive function in psychiatric patients. Building scales appropriate for each state also appear essential to obtain an useful and effective tool in clinical practice.

Inappropriate drug combinations in adult versus geriatric patients in a psychiatric setting

Introduction The objective of this study was to assess the reliability of drug–drug interaction software in monitoring prescriptions in psychiatric settings. Method A 1 day cross sectional analysis of the ongoing drug regimens in the inpatient population was carried out. Results This study showed a relatively high prevalence of hazardous or contraindicated drug combinations (approximately 15%). Three major categories of interactions were found: (1) those requiring diagnostic tests; (2) those requiring dosage adjustments, an appropriate drug choice or pharmacological class; and (3) those whose risk–benefit ratio was positive in the treatment indication. Discussion The findings demonstrate that without access to biological test results and indications, the most prevalent interactions cannot be validated by the pharmacist. These results suggest that the availability of these data is essential, and that interactions with prescribers should be facilitated in order to increase the quality of clinical pharmacy in psychiatry.

High-dose quetiapine and therapeutic monitoring

Quetiapine is an atypical antipsychotic with a good safety profile permitting its administration beyond the maximum dose of 800 mg/day. We report the case of a patient with a resistant schizophrenia treated with high doses of quetiapine (up to 2000 mg/day) combined with drug monitoring and with favourable therapeutic response and tolerance.

Angiotensin Converting Enzyme Inhibitors and Sartans in a Geriatric Setting: Impact of Therapeutic Interchange

Background: Therapeutic interchange is widely used in geriatric settings, such as angiotensin enzyme converting inhibitors and angiotensin II receptor antagonists and angiotensin receptor blockers (sartans). Objective: we evaluate the clinical impact (efficacy and tolerance) of a therapeutic interchange program for noncomplicated hypertension. Method: 13 patients receiving angiotensin enzyme converting inhibitors and 7 patients under sartans were followed-up during 6 months after a therapeutic interchange to a first line drug: Ramipril and valsartan, respectively. Results: all the substitutions were well tolerated and no significant difference was observed for diastolic and systolic pressure after therapeutic interchange. Conclusion: therapeutic interchange on angiotensin enzyme converting inhibitors and sartans in the context of hypertension seem safe based on our clinical data.

Apparition d’œdèmes périphériques lors d’un switch de la buprénorphine seule vers l’association buprénorphine–naloxone : à propos d’un cas ☆

of clopidogrel in healthy subjects: randomized, placebocontrolled, crossover comparison studies. Clin Pharmacol Ther 2011;89(1):65—74. [12] Frelinger 3rd AL, Lee RD, Mulford DJ, Wu J, Nudurupati S, Nigam A, et al. A randomized, 2-period, crossover design study Apparition d’œdèmes périphériques lors d’un switch de la buprénorphine seule vers l’association buprénorphine—naloxone : à propos d’un to assess the effects of dexlansoprazole, lansoprazole, esomeprazole, and omeprazole on the steady-state pharmacokinetics and pharmacodynamics of clopidogrel in healthy volunteers. J Am Coll Cardiol 2012;59(14):1304—11. [13] Johnson DA, Chilton R, Liker HR. Proton-pump inhibitors in cas