Showing papers by "Thierry Christiaens published in 2021"

Approaches for discontinuation versus continuation of long‐term antidepressant use for depressive and anxiety disorders in adults

Abstract: Background Depression and anxiety are the most frequent indication for which antidepressants are prescribed. Long-term antidepressant use is driving much of the internationally observed rise in antidepressant consumption. Surveys of antidepressant users suggest that 30% to 50% of long-term antidepressant prescriptions had no evidence-based indication. Unnecessary use of antidepressants puts people at risk of adverse events. However, high-certainty evidence is lacking regarding the effectiveness and safety of approaches to discontinuing long-term antidepressants. Objectives To assess the effectiveness and safety of approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults. Search methods We searched all databases for randomised controlled trials (RCTs) until January 2020. Selection criteria We included RCTs comparing approaches to discontinuation with continuation of antidepressants (or usual care) for people with depression or anxiety who are prescribed antidepressants for at least six months. Interventions included discontinuation alone (abrupt or taper), discontinuation with psychological therapy support, and discontinuation with minimal intervention. Primary outcomes were successful discontinuation rate, relapse (as defined by authors of the original study), withdrawal symptoms, and adverse events. Secondary outcomes were depressive symptoms, anxiety symptoms, quality of life, social and occupational functioning, and severity of illness. Data collection and analysis We used standard methodological procedures as expected by Cochrane. Main results We included 33 studies involving 4995 participants. Nearly all studies were conducted in a specialist mental healthcare service and included participants with recurrent depression (i.e. two or more episodes of depression prior to discontinuation). All included trials were at high risk of bias. The main limitation of the review is bias due to confounding withdrawal symptoms with symptoms of relapse of depression. Withdrawal symptoms (such as low mood, dizziness) may have an effect on almost every outcome including adverse events, quality of life, social functioning, and severity of illness. Abrupt discontinuation Thirteen studies reported abrupt discontinuation of antidepressant. Very low-certainty evidence suggests that abrupt discontinuation without psychological support may increase risk of relapse(hazard ratio (HR) 2.09, 95% confidence interval (CI) 1.59 to 2.74; 1373 participants, 10 studies) and there is insufficient evidence of its effect on adverse events (odds ratio (OR) 1.11, 95% CI 0.62 to 1.99; 1012 participants, 7 studies; I-2 = 37%) compared to continuation of antidepressants, without specific assessment of withdrawal symptoms. Evidence about the effects of abrupt discontinuation on withdrawal symptoms (1 study) is very uncertain. None of these studies included successful discontinuation rate as a primary endpoint. Discontinuation by "taper" Eighteen studies examined discontinuation by "tapering" (one week or longer). Most tapering regimens lasted four weeks or less. Very low-certainty evidence suggests that "tapered" discontinuation may lead to higher risk of relapse (HR 2.97, 95% CI 2.24 to 3.93; 1546 participants, 13 studies) with no or little difference in adverse events (OR 1.06, 95% CI 0.82 to 1.38; 1479 participants, 7 studies; I-2 = 0%) compared to continuation of antidepressants, without specific assessment of withdrawal symptoms. Evidence about the effects of discontinuation on withdrawal symptoms (1 study) is very uncertain. Discontinuation with psychological support Four studies reported discontinuation with psychological support. Very low-certainty evidence suggests that initiation of preventive cognitive therapy (PCT), or MBCT, combined with "tapering" may result in successful discontinuation rates of 40% to 75% in the discontinuation group (690 participants, 3 studies). Data from control groups in these studies were requested but are not yet available. Low-certainty evidence suggests that discontinuation combined with psychological intervention may result in no or little effect on relapse (HR 0.89, 95% CI 0.66 to 1.19; 690 participants, 3 studies) compared to continuation of antidepressants. Withdrawal symptoms were not measured. Pooling data on adverse events was not possible due to insufficient information (3 studies). Discontinuation with minimal intervention Low-certainty evidence from one study suggests that a letter to the general practitioner (GP) to review antidepressant treatment may result in no or little effect on successful discontinuation rate compared to usual care (6% versus 8%; 146 participants, 1 study) or on relapse (relapse rate 26% vs 13%; 146 participants, 1 study). No data on withdrawal symptoms nor adverse events were provided. None of the studies used low-intensity psychological interventions such as online support or a changed pharmaceutical formulation that allows tapering with low doses over several months. Insufficient data were available for the majority of people taking antidepressants in the community (i.e. those with only one or no prior episode of depression), for people aged 65 years and older, and for people taking antidepressants for anxiety. Authors' conclusions Currently, relatively few studies have focused on approaches to discontinuation of long-term antidepressants. We cannot make any firm conclusions about effects and safety of the approaches studied to date. The true effect and safety are likely to be substantially different from the data presented due to assessment of relapse of depression that is confounded by withdrawal symptoms. All other outcomes are confounded with withdrawal symptoms. Most tapering regimens were limited to four weeks or less. In the studies with rapid tapering schemes the risk of withdrawal symptoms may be similar to studies using abrupt discontinuation which may influence the effectiveness of the interventions. Nearly all data come from people with recurrent depression. There is an urgent need for trials that adequately address withdrawal confounding bias, and carefully distinguish relapse from withdrawal symptoms. Future studies should report key outcomes such as successful discontinuation rate and should include populations with one or no prior depression episodes in primary care, older people, and people taking antidepressants for anxiety and use tapering schemes longer than 4 weeks.

Regulatory reliance to approve new medicinal products in Latin American and Caribbean countries

Abstract: Objective. To describe the current status of regulatory reliance in Latin America and the Caribbean (LAC) by assessing the countries’ regulatory frameworks to approve new medicines, and to ascertain, for each country, which foreign regulators are considered as trusted regulatory authorities to rely on. Methods. Websites from LAC regulators were searched to identify the official regulations to approve new drugs. Data collection was carried out in December 2019 and completed in June 2020 for the Caribbean countries. Two independent teams collected information regarding direct recognition or abbreviated processes to approve new drugs and the reference (trusted) regulators defined as such by the corresponding national legislation. Results. Regulatory documents regarding marketing authorization were found in 20 LAC regulators’ websites, covering 34 countries. Seven countries do not accept reliance on foreign regulators. Thirteen regulatory authorities (Argentina, Colombia, Costa Rica, Dominican Republic, Ecuador, El Salvador, Guatemala, Mexico, Panama, Paraguay, Peru, Uruguay, and the unique Caribbean Regulatory System for 15 Caribbean States) explicitly accept relying on marketing authorizations issued by the European Medicines Agency, United States Food and Drug Administration, and Health Canada. Ten countries rely also on marketing authorizations from Australia, Japan, and Switzerland. Argentina, Brazil, Chile, and Mexico are reference authorities for eight LAC regulators. Conclusions. Regulatory reliance has become a common practice in the LAC region. Thirteen out of 20 regulators directly recognize or abbreviate the marketing authorization process in case of earlier approval by a regulator from another jurisdiction. The regulators most relied upon are the European Medicines Agency, United States Food and Drug Administration, and Health Canada.

Harmonizing and improving European education in prescribing : An overview of digital educational resources used in clinical pharmacology and therapeutics

Abstract: Aim: Improvement and harmonization of European clinical pharmacology and therapeutics (CPT) education is urgently required Because digital educational resources can be easily shared, adapted to local situations and re-used widely across a variety of educational systems, they may be ideally suited for this purpose Methods: With a cross-sectional survey among principal CPT teachers in 279 out of 304 European medical schools, an overview and classification of digital resources was compiled Results: Teachers from 95 (34%) medical schools in 26 of 28 EU countries responded, 66 (70%) of whom used digital educational resources in their CPT curriculum A total of 89 of such resources were described in detail, including e-learning (24%), simulators to teach pharmacokinetics and/or pharmacodynamics (10%), virtual patients (8%), and serious games (5%) Together, these resources covered 235 knowledge-based learning objectives, 88 skills, and 13 attitudes Only one third (27) of the resources were in-part or totally free and only two were licensed open educational resources (free to use, distribute and adapt) A narrative overview of the largest, free and most novel resources is given Conclusion: Digital educational resources, ranging from e-learning to virtual patients and games, are widely used for CPT education in EU medical schools Learning objectives are based largely on knowledge rather than skills or attitudes This may be improved by including more real-life clinical case scenarios Moreover, the majority of resources are neither free nor open Therefore, with a view to harmonizing international CPT education, more needs to be learned about why CPT teachers are not currently sharing their educational materials

EurOP2E – the European Open Platform for Prescribing Education, a consensus study among clinical pharmacology and therapeutics teachers

Abstract: Sharing and developing digital educational resources and open educational resources has been proposed as a way to harmonize and improve clinical pharmacology and therapeutics (CPT) education in European medical schools. Previous research, however, has shown that there are barriers to the adoption and implementation of open educational resources. The aim of this study was to determine perceived opportunities and barriers to the use and creation of open educational resources among European CPT teachers and possible solutions for these barriers. CPT teachers of British and EU medical schools completed an online survey. Opportunities and challenges were identified by thematic analyses and subsequently discussed in an international consensus meeting. Data from 99 CPT teachers from 95 medical schools were analysed. Thirty teachers (30.3%) shared or collaboratively produced digital educational resources. All teachers foresaw opportunities in the more active use of open educational resources, including improving the quality of their teaching. The challenges reported were language barriers, local differences, lack of time, technological issues, difficulties with quality management, and copyright restrictions. Practical solutions for these challenges were discussed and include a peer review system, clear indexing, and use of copyright licenses that permit adaptation of resources. Key challenges to making greater use of CPT open educational resources are a limited applicability of such resources due to language and local differences and quality concerns. These challenges may be resolved by relatively simple measures, such as allowing adaptation and translation of resources and a peer review system.

Potential negative impact of reputed regulators’ decisions on the approval status of new cancer drugs in Latin American countries: A descriptive analysis

Abstract: Background Many new cancer drugs are being approved by reputed regulatory authorities without evidence of overall survival benefit, quality of life improvement, and often based on clinical trials at high risk of bias. In recent years, most Latin American (LA) countries have reformed their marketing authorization (MA) rules to directly accept or abbreviate the approval process in case of earlier authorization by the European Medicines Agency (EMA) and the US Food and Drug Administration, mainly. This study assessed the potential impact of decisions taken by EMA regarding the approval of new cancer drugs based on no evidence of overall survival or in potentially biased clinical trials in LA countries. Design Descriptive analysis. Setting Publicly accessible marketing authorization databases from LA regulators, European Public Assessment Report by EMA, and previous studies accessing EMA approvals of new cancer drugs 2009-2016. Main outcome and measures Number of new cancer drugs approved by LA countries without evidence of overall survival (2009-2013), and without at least one clinical trial scored at low risk of bias, or with no trial supporting the marketing authorization at all (2014-2016). Results Argentina, Brazil, Chile, Colombia, Ecuador, Panama and Peru have publicly accessible and trustful MA databases and were included. Of the 17 cancer drugs approved by EMA (2009-2013) without evidence of OS benefit after a postmarketing median time of 5.4 years, 6 LA regulators approved more than 70% of them. Of the 13 drugs approved by EMA (2014-2016), either without supporting trial or with no trial at low risk of bias, Brazil approved 11, Chile 10, Peru 10, Argentina 10, Colombia 9, Ecuador 9, and Panama 8. Conclusions LA countries keep approving new cancer drugs often based on poorly performed clinical trials measuring surrogate endpoints. EMA and other reputed regulators must be aware that their regulatory decisions might directly influence decisions regarding MA, health budgets and patient's care elsewhere.

European List of Essential Medicines for Medical Education: a protocol for a modified Delphi study.

Abstract: Introduction Junior doctors are responsible for a substantial number of prescribing errors, and final-year medical students lack sufficient prescribing knowledge and skills just before they graduate. Various national and international projects have been initiated to reform the teaching of clinical pharmacology and therapeutics (CPandT) during undergraduate medical training. However, there is as yet no list of commonly prescribed and available medicines that European doctors should be able to independently prescribe safely and effectively without direct supervision. Such a list could form the basis for a European Prescribing Exam and would harmonise European CPandT education. Therefore, the aim of this study is to reach consensus on a list of widely prescribed medicines, available in most European countries, that European junior doctors should be able to independently prescribe safely and effectively without direct supervision: The European List of Essential Medicines for Medical Education. Methods and analysis This modified Delphi study will recruit European CPandT teachers (expert group). Two Delphi rounds will be carried out to enable a list to be drawn up of medicines that are available in ?80% of European countries, which are considered standard prescribing practice, and which junior doctors should be able to prescribe safely and effectively without supervision. Ethics and dissemination The study has been approved by the Medical Ethics Review Committee of VU University Medical Center (no. 2020.335) and by the Ethical Review Board of the Netherlands Association for Medical Education (approved project no. NVMO-ERB 2020.4.8). The European List of Essential Medicines for Medical Education will be presented at national and international conferences and will be submitted to international peer-reviewed journals. It will also be used to develop and implement the European Prescribing Exam.

And they slept happily ever after: Online interpretive repertoires on the use of benzodiazepines and z-drugs

Abstract: Drawing on a critical social-psychological framework for discourse analysis, data from a popular forum for people over 50 were analysed to study how the habitual use of benzodiazepines and Z-drugs (BZD/Z) is discursively negotiated by Flemish older adults. We present five different repertoires (risk and addiction; alternative pathways; suffering; rationalisation; cessation) that illustrate how a pharmaceutical imaginary of these medications is constructed online and how posters act as reflexive users taking on a health role. Most repertoires emerge from a tacit norm on the undesirability of medication use for sleeping problems. In the alternative pathways and cessation repertoires this norm is implicitly accepted by focussing on how to either prevent or overcome chronic use with various alternative solutions or through tapering off, while the risk and addiction repertoire is used to more openly defend and discursively magnify the idea that medication has to be avoided at all cost. We discuss how this reflects a prevailing imperative of health and ethos of healthicisation of sleep. The rationalisation and suffering repertoires on the other hand challenge this norm by defending medication use. We further explore how these repertoires are used to self-position as either ‘noble non-user’, ‘deserving and/or compliant patient’ or ‘rational user’, reflecting previously found moral positions in offline settings. Our data add another position that has thus far not been discussed extensively with regard to prescription medication use, namely that of a ‘recovered user’. As such, this study shows how this particular online community is a site for contestation of health promotion and medical/pharmaceuticalised discourses on sleep by users and non-users alike and offers a unique insight into how people in the age group that is known to use most BZD/Z discursively negotiate the use of these medications in pseudonymised online interactions.

Stopzetten antidepressieve behandeling roept vooral veel vragen op

Abstract: Het Laatste Nieuws, 27 april 2021: “Experten willen meer onderzoek naar afbouwen van antidepressiva” Er is meer wetenschappelijk onderzoek nodig naar het afbouwen van antidepressiva. Dat vindt een internationaal team onder leiding van UGent-onderzoekers. Hoewel er veel bekend is over het groeiende gebruik van antidepressiva, is dat niet het geval over veilige en effectieve methodes om ermee te stoppen.