Psychotropics and COVID-19: An analysis of safety and prophylaxis.

The use of psychotropics during the COVID-19 pandemic has raised two questions, in order of importance: first, what changes should be made to pharmacological treatments prescribed to mental health patients? Secondly, are there any positive side effects of these substances against SARS-CoV-2? Our aim was to analyze usage safety of psychotropics during COVID-19; therefore, herein, we have studied: (i) the risk of symptomatic complications of COVID-19 associated with the use of these drugs, notably central nervous system activity depression, QTc interval enlargement and infectious and thromboembolic complications; (ii) the risk of mistaking the iatrogenic impact of psychotropics with COVID-19 symptoms, causing diagnostic error. Moreover, we provided a summary of the different information available today for these risks, categorized by mental health disorder, for the following: schizophrenia, bipolar disorder, anxiety disorder, ADHD, sleep disorders and suicidal risk. The matter of psychoactive substance use during the pandemic is also analyzed in this paper, and guideline websites and publications for psychotropic treatments in the context of COVID-19 are referenced during the text, so that changes on those guidelines and eventual interaction between psychotropics and COVID-19 treatment medication can be reported and studied. Finally, we also provide a literature review of the latest known antiviral properties of psychotropics against SARS-CoV-2 as complementary information.

[Cost-effectiveness study of olanzapine pamoate: Mirror-image analysis after one year]. / Étude coût-efficacité du pamoate d'olanzapine : analyse en miroir sur un an.

INTRODUCTION: Olanzapine pamoate has a higher cost of treatment than the oral form and requires administration in a hospital setting (unlike other long-acting antipsychotics), and the cost-effectiveness of this treatment may be questioned. Many scientific societies and national health systems are increasingly interested in the pharmacoeconomic impact of health products. The search for efficacy of a treatment can be done in two ways: medico-economic modeling studies or observational studies i.e. randomized controlled trials or mirror studies. The models are based on theoretical models from published clinical data simulating the course and evolution of patient health conditions, which benefit from a particular therapeutic strategy. Even if the design of observational mirror studies makes it possible to get closer to the clinical reality by observing the patient before and after the initiation of the treatment, the majority of the pharmacoeconomic studies published on olanzapine pamoate are modeling works that do not reflect actual conditions of care. The Guillaume Régnier Hospital Center in Rennes has a large cohort of patients treated with olanzapine pamoate: 121 instauration treatments are recorded from April 1, 2010 to Mars 1, 2015. The objective of this study is to evaluate the cost-effectiveness of olanzapine pamoate in actual clinical practice. METHODS: This is a one-year cost-effectiveness retrospective observational mirror-image study of a cohort of 52 patients with schizophrenia who were treated for at least three months with olanzapine pamoate. The primary efficacy endpoint is the differential in the number of full-time hospitalizations before and after the introduction of olanzapine pamoate versus the hospital cost differential. The secondary criteria are the difference of the number of the days spent in hospital and the number of outpatient consultations between the year preceding the injection and the year following it. The results were calculated on the general cohort and within 2 subgroups: patients treated for more than one year and those receiving less than one year of treatment with olanzapine pamoate. RESULTS: Fifty-two patients were included (median age=35 years, sex ratio H/F=2.7) and only 38.5% discontinued treatment. For patients who maintained long-acting treatment, they received a dosage of 25mg oral olanzapine (min=7.5mg, max=60mg), 5mg more medially than the group having stopped the olanzapine pamoate (20mg; min=10mg, max=40mg). The majority of these patients were receiving off-label authorized marketing doses of oral olanzapine, whereas 22% of them had off-label dosages of olanzapine pamoate. The main causes of discontinuation were symptom persistence, loss of vision and the occurrence of adverse effects (including weight gain and sedation). Olanzapine pamoate significantly reduced the number of hospitalizations compared to the previous management strategy (1 less hospitalization, P<0.001 in patients treated more than one year and in the general cohort). As a logical consequence the number of hospitalization days in day care increased after the establishment of this long-acting antipsychotic with hospital reserve status (18 in median; min=0, max=159). We observed a non-statistically significant tendency of decrease in the number of days of full-time hospitalization and an increase in the number of ambulatory procedures, particularly in patients who have maintained the treatment for one year. This efficiency had a non-significant additional cost of €3361 per year. There was an average multiplication by 8,5 of the drug cost a year later in the general cohort (5.5 in the group of patients treated less than one year and 10.4 in the group of patients who maintained it a year). There was a 23,2% average increase in the cost of hospitalization in the general cohort (3.75 % in patients who maintained treatment compared to 48.9% in patients who discontinued treatment). CONCLUSION: By its mirror design, the study was placed in real conditions of care of the patient with schizophrenia. A total of 61.5% of patients maintained treatment with olanzapine pamoate for a minimum of one year. This APAP is more effective without significantly increasing the cost compared to the previous therapeutic strategy (including oral olanzapine). The additional cost is partly due to the administration restriction in a hospital setting in relation to risk of Post-Injection Delirium/Sedation Syndrom (PDSS). There is currently no acceptable efficiency limit. The results of this cost-effectiveness analysis cannot be extrapolated to the other long-acting antipsychotics since it is the only one with hospital reserve status. The current limitations of medico-economics in psychiatry derive from the heterogeneity of clinical forms and the management of mental pathologies.

Use of very-high-dose olanzapine in treatment-resistant schizophrenia.

Schizophrenia is a chronic illness with a progressive course that can be marked by resistance to antipsychotic treatment. This can make therapeutic support challenging for the practitioner, with results that are partial and unsatisfactory. In the literature, treatment with high-dose olanzapine (>20mg/day) appears to be a good alternative to clozapine, the gold standard for treatment-resistant schizophrenia. In the present observational prospective study, we studied the clinical and biological profiles of patients treated with olanzapine doses up to 100mg/day. In total, 50 patients were clinically and biologically assessed. We found a linear relationship between oral dose and serum concentration (Pearson's r=0.83, p<0.001) with effects of tobacco (p<0.05) and of coffee and tea consumption (p<0.01). Tolerance seemed to be good regardless of dose. No link was found between concentration and efficiency. Despite a nonexhaustive assessment of pharmacokinetic parameters, not least pharmacogenetic data (e.g., genotyping of cytochrome P450-1A2 or glycoprotein P Abcb1a), pharmacokinetic aspects alone cannot account for why the disease may sometimes be resistant to 20mg of olanzapine but respond to higher doses. A nuclear imaging study exploring brain occupancy by high-dose olanzapine, coupled with the abovementioned pharmacokinetic assessment, may prove a relevant experimental paradigm for studying the pathophysiological mechanisms of resistant schizophrenia.

[Hospital pharmacy residency in France in 2014: to a recognition of the specialization?]. / L'internat en pharmacie hospitalière en France à l'horizon 2014 : vers une formation reconnue ?

The current format of French residency in hospital pharmacy was created in 1983 and is a 4-year specialized training. So far, training has not been recognized as a prerequisite for hospital pharmacy practice. Since 2011, pharmacy residents and hospital pharmacists representative structures have lobbied for that recognition and the government has worked in that direction. The ideology of the concept was validated after a period of probation and the regulatory procedure began late 2012. Two key elements were initially identified as obstacles: first the European legislation on recognition of professional qualifications and then the fear that there might not be enough hospital pharmacists trained in order to complete the care missions in hospital pharmacies in France. The European legislation has now been amended in order to recognize professional qualifications and a demographic analysis of hospital pharmacists leads to the conclusion that these items are no longer obstacles. In 2014, hospital pharmacy residency, through the Specialized Studies degree, should be recognized as a prerequisite for hospital pharmacy practice.