[Psychological impact of the COVID-19 pandemic on health care professionals]. / Impact psychique de la pandémie de Covid-19 sur les professionnels soignants.

Like other pandemics, those of COVID-19 had a significant psychological impact on the general population. Nevertheless, this impact was even more acute among healthcare staff, in connection with repeated exposure to the risk of infection, the reorganization of healthcare and their specific positioning. Dispensary pharmacists, who ensured continuity of healthcare in a climate of widespread teleworking, were not spared. Psychotraumatic, anxiety and depressive symptoms were observed.

Determinants of Care Pathways for C-PTSD Patients in French Psychotrauma Centers: A Qualitative Study.

In 2018, the International Classification of Diseases (ICD-11) established a novel nosographic category within the stress-specific disorders known as complex post-traumatic stress disorder (C-PTSD). Characterized by distinctive clinical attributes and a limited response to conventional PTSD treatments, C-PTSD has prompted the reconsideration of care methods. Our study's purpose was to explore the intricate factors shaping the care pathways for individuals suffering from C-PTSD. We used a grounded theorization technique involving professionals across a range of specialized French psychotraumatology institutions. The resulting comprehensive theoretical model offers valuable insights into the constitution mechanisms of these pathways, helping elucidate the varying care options. Interestingly, we found that differences in clinical perspectives were determined by the care provider's viewpoint on clinical guidelines, screening tools, and treatment options, but also by structural and organizational factors. The distinctive dynamics and interrelationships identified in our research reveal potential areas of focus for incorporating C-PTSD care more effectively into specialized French trauma centers. This investigation offers a path toward improved understanding and management of C-PTSD, ultimately advancing patient outcomes.

A non-randomized pilot trial of the use of prazosin in the prevention of transition from acute stress disorder to post-traumatic stress disorder.

BACKGROUND: Following a traumatic event, 40-80% of the patients with acute stress disorder (ASD) will develop post-traumatic stress disorder (PTSD), 67% at 6 months. Alpha1-blockers are effective in treating some symptoms of PTSD but their usefulness in acute stress situations remains unclear. We hypothesized that reducing noradrenergic hyperactivity with an alpha1-blocker during the acute phase after a traumatic event could prevent the transition to PTSD in patients with ASD. OBJECTIVE: To investigate the efficacy and safety of a 1-month course of alpha1-blocker (prazosin) to prevent the transition to PTSD in patients with ASD at 6 months. METHOD: In a monocentric open-label prospective pilot study, 15 patients with ASD were included within 3-7 days of exposure to a traumatic event. After enrolment, they received prazosin LP at home at bedtime at 2.5 mg/day for 7 days and then 5 mg/day for 21 days. Incidence of PTSD was assessed at 6 months using the Clinician Administrated PTSD Scale (CAPS). RESULTS: At 6 months, 22% of patients who completed the study (2/9) met the diagnostic criteria for PTSD. This rate was significantly lower than that observed in previous studies (67%; p = .047). The treatment was well tolerated and there were no serious adverse events. CONCLUSIONS: These preliminary findings indicating the safety of prazosin and suggesting its potential to prevent the development of PTSD in ASD require to be replicated in large-scale randomized placebo-controlled studies.Trial registration: The study was pre-registered on a public database (www.clinicalTrials.gov identifier: NCT03045016).

Alpha1-blockers are safe and well tolerated in patients with acute stress disorder.The use of alpha1-blockers 3­7 days after traumatic exposure is worthy of study.Alpha1-blockers could prevent the transition to PTSD in ASD patients at 6 months.

Can a single session of noninvasive brain stimulation applied over the prefrontal cortex prevent stress-induced cortisol release?

INTRODUCTION: A better understanding of how the hypothalamic-pituitary-adrenal (HPA) axis can be externally regulated is of major importance, especially because hyperreactivity to stress has been proposed as a key factor in the onset and maintenance of many psychiatric conditions. Over the past decades, numerous studies have investigated whether non-invasive brain stimulation (NIBS) can regulate HPA axis reactivity in acute stress situation. As the current results did not allow us to draw clear conclusions, we decided to conduct a systematic review of the literature investigating the effect of a single NIBS session on stress-induced cortisol release. METHODS: We searched MEDLINE and Web Of Science for articles indexed through December 2021. Among the 246 articles identified, 15 fulfilled our inclusion criteria with a quality estimated between 52 and 93%. RESULTS: Of the different NIBS used and targeted brain regions, stimulating the left dorsolateral prefrontal cortex, with either high frequency repetitive transcranial magnetic stimulation or anodal transcranial direct current stimulation, seems to be the most appropriate for reducing cortisol release in acute stress situations. CONCLUSIONS: Despite the heterogeneity of the stimulation parameters, the characteristics of participants, the modalities of cortisol collection, the timing of the NIBS session in relation to the stressor exposure, and methodological considerations, stimulating the left dorsolateral prefrontal cortex can be efficient to modulate stress-induced cortisol release.

Relevance and Feasibility of Group Traumatic Episode Protocol Delivered to Migrants: A Pilot Field Study.

INTRODUCTION: Post-Traumatic Stress Disorder (PTSD) and Major Depressive Disorder (MDD) are commonly observed in migrants. Although Eye Movement Desensitization and Reprocessing (EMDR) can be helpful to treat these diseases, it remains difficult to propose EMDR as an individual intervention in help-seeking migrants. Group EMDR, like Group Traumatic Episode Protocol (G-TEP), which was built around the 8 phases of the original EMDR protocol, could offer an effective treatment to a large number of people. It may also be more resource-efficient to provide psychiatric care to migrants. METHODS: In this open-label trial, the feasibility and the effectiveness of a 6-session G-TEP intervention was investigated in a group of 10 migrants. RESULTS: The intervention was well tolerated by participants. The final attrition rate was 10%. After the intervention, there was a 28.2% significant decrease in PTSD and complex PTSD symptoms, as measured by the International Trauma Questionnaires (total_ITQ) scores (p = 0.013) and a trend towards a significant decrease in MDD symptoms, as measured with the Patient Health Questionnaire (PHQ-9) (p = 0.057). CONCLUSIONS: G-TEP may be effective in decreasing PTSD symptoms in migrants. The accessibility, low-cost, and very structured features of G-TEP may make its implementation sustainable in the field of psychiatric care for migrants.

Experiences of Inter-Hospital Transfers (IHT) by Patients and Relatives during the COVID-19 Pandemic in France: A Qualitative Study.

BACKGROUND: The first wave of the COVID-19 epidemic led to a rapid and unexpected saturation of the French ICU, forcing the health care system to adapt. Among other emergency measures, inter-hospital transfers were carried out. OBJECTIVE: To assess the psychological experience of patients and their relatives regarding inter-hospital transfers. METHODS: Semi-structured interviews were conducted with transferred patients and their relatives. A phenomenological study design was used to examine subjective experiences and their meanings for the participants. RESULTS: The analysis found nine axes pertaining to the experiences of IHT (inter-hospital transfers), grouped in three super-ordinate themes: Information about inter-hospital transfers, differences in patients' and relatives' experiences, and host hospital experience. It appears that patients felt little impacted by the transfers, unlike relatives who experienced intense anxiety when the transfer was announced. Good communications between patients and their relatives resulted in a good level of satisfaction regarding their host hospitals. COVID-19 and its somatic consequences seem to have had more psychological impact on the participants than the transfers by themselves. CONCLUSION: Our results suggest that there are limited current psychological consequences of the IHT implemented during the first wave of COVID-19, although the involvement of patients and their relatives in the organization of the IHT at the time of transfer could further limit them.

Are psychological debriefing groups after a potential traumatic event suitable to prevent the symptoms of PTSD?

Psychological debriefing is a psychotherapeutic approach developed for early intervention in civilians and professionals who have to cope with a potential traumatic event (PTE). Although initial works claimed that this approach may decrease symptoms of posttraumatic stress disorder (PTSD), some studies have concluded that the clinical benefits of psychological debriefing were limited. Several methodological variations could explain the discrepancies observed among studies. Among these variations, how the approach is administered to participants should have importance, and clinical evidence suggests that debriefing groups instead of individuals could have a beneficial clinical effect. We conducted a systematic search of the literature investigating the clinical effects of psychological debriefing groups on PTSD symptoms after a PTE according to the PRISMA guidelines. Among the 790 articles found, 11 met our inclusion criteria. Most of these articles did not support any beneficial effect of psychological debriefing groups on PTSD symptoms. A large number of methodological variations that may influence the outcomes of these studies were observed. Psychological debriefing groups did not seem efficient in alleviating PTSD symptoms. Further studies of high methodological quality are needed to elucidate the effect of psychological debriefing groups on specific PTSD symptoms and on nonspecific symptoms.

An appropriate and reactive response to the repeated waves of the COVID-19 pandemic by the national medico-psychological network (CUMP) in France.

INTRODUCTION: France has been impacted by the COVID-19 pandemic. Anxiety, depression, burn out and the high proportion of post-traumatic stress disorder proved to be the most expected troubles caused by this pandemic and the confinement. Medico-psychological emergency units (CUMP) have been solicited at the very early stage of the pandemic because CUMP units are very well known by the French government and systematically associated to emergency plans. METHODS: In this article we describe the process which has been developed to cope with the psychological needs in the general population. At a first level, platforms of volunteers specialised into listening were available. Then those platforms could directly mobilise the CUMP in case of psychiatric disorders. It ran over the whole first wave and it has been reactivated because of the second confinement in France. RESULTS: During the first wave, approximately 1% of all the calls made on the national Covid number required to be redirected to the listening platforms. Of this group, 4% were related to reactive pathology or a psychiatric decompensating that required adapted and specialised care. CONCLUSION: The high rates of psychological distress detected in the general population in recent scientific literature seem discrepant with our findings of relatively low reorientation towards the CUMP. Nevertheless, our study highlights that the response of the CUMP network in France during the first wave was supportive. The second wave displays its adaptability to the public health policies.

Impaired Modulation of Corticospinal Excitability in Drug-Free Patients With Major Depressive Disorder: A Theta-Burst Stimulation Study.

Impaired neural plasticity may be an important mechanism in the pathophysiology of major depressive disorder (MDD). Coupled with electromyography (EMG), repetitive transcranial magnetic stimulation (rTMS) is a useful tool to evaluate corticospinal excitability and cortical neuroplasticity in living humans. The goal of this study was to compare rTMS-induced cortical plasticity changes in patients with MDD and in healthy volunteers. In this single-blind controlled study, 11 drug-free patients with MDD and 11 matched healthy controls were analyzed. Cortical excitability, measured by the amplitude of motor evoked potentials (MEPs) evoked by single-pulse TMS, was assessed before and repeatedly after (for 30 min) participants received a single session of intermittent theta-burst stimulation (iTBS) and continuous TBS (cTBS). rTMS was applied over the left motor cortex using a neuronavigation system. Intensity was set at 80% of the active motor threshold (AMT). A large interindividual variability was observed after both iTBS and cTBS in the two groups. At the group level, we observed impaired iTBS-induced neuroplasticity in patients with MDD compared to that in controls. No differences were observed between the groups regarding cTBS-induced neuroplasticity. Our results suggest impaired long-term potentiation (LTP)-like mechanisms in MDD. Clinical Trial Registration: www.Clinicaltrials.gov, identifier #NCT02438163.

Clinical Effects of Mindfulness-Based Intervention in Patients With First Episode Psychosis and in Individuals With Ultra-High Risk for Transition to Psychosis: A Review.

Objectives: Recent clinical studies and meta-analyses have reported the clinical effects of mindfulness-based interventions as a complementary treatment for patients with schizophrenia, but their possible efficacy in patients with first episode of psychosis (FEP) and in individuals with ultra-high risk (UHR) of transition to psychosis is less clear. Here, we investigated the current evidence on the usefulness of mindfulness-based interventions in these two populations. Methods: We conducted a systematic search of the literature according to the PRISMA guidelines. Results: Among the 102 references retrieved, 9 responded to the inclusion criteria (8 in FEP patients and 1 in UHR individuals). In FEP patients, mindfulness interventions are well-tolerated and have a satisfactory level of adherence. The clinical benefits consist primarily of reduced anxiety and sadness and improved quality of life. None of the studies reported any increase in positive symptoms. Conclusion: Future sham-controlled studies with large sample sizes are needed to definitively conclude on the clinical interest of mindfulness-based interventions in FEP patients and UHR individuals as well as to understand their underlying mechanisms of action.

Neural effects of mindfulness-based interventions on patients with major depressive disorder: A systematic review.

Growing evidence has suggested that mindfulness-based interventions (MBIs) could have beneficial effects on the acute phase of depression and on the prevention of depressive relapse or recurrence. Despite growing clinical interest, the effects of MBIs on brain functioning in patients with MDD remain unclear. The aim of this systematic review was to assess the changes in brain functioning associated with MBIs in patients with MDD. A systematic search was conducted, and of the 56 articles found, 8 were eligible. MBIs have modulatory effects on several brain regions implicated in the pathophysiology of MDD, such as the prefrontal cortex, the basal ganglia, the anterior and posterior cingulate cortices, and the parietal cortex. These regions have been implicated in self-awareness, attention and emotion regulation. Some of these findings were consistent with the effects of MBIs observed in healthy subjects and patients with other psychiatric disorders, especially enhanced activity in the frontal and subcortical regions related to the improved somatosensory awareness. Further studies are needed to elucidate the mechanisms of MBIs in MDD.

Duration but not intensity influences transcranial direct current stimulation (tDCS) after-effects on cortical excitability.

Recent studies have shown heterogeneous results regarding the influence of intensity and duration of motor transcranial direct current stimulation (tDCS) on cortical excitability. In this pilot crossover study including 14 healthy participants, we compared the effects of a single session of anodal-tDCS set with two commonly used durations (20 and 30minutes) and intensities (1 and 2mA) on short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). Regardless of the current intensity, 20minutes of tDCS increased SICI (3ms inter-stimulus interval ISI) and decreased ICF (7ms ISI); 30minutes of tDCS did not affect cortical excitability.

Significant Need for a French Network of Expert Centers Enabling a Better Characterization and Management of Treatment-Resistant Depression (Fondation FondaMental).

BACKGROUND: Major depression is characterized by (i) a high lifetime prevalence of 16-17% in the general population; (ii) a high frequency of treatment resistance in around 20-30% of cases; (iii) a recurrent or chronic course; (iv) a negative impact on the general functioning and quality of life; and (v) a high level of comorbidity with various psychiatric and non-psychiatric disorders, high occurrence of completed suicide, significant burden along with the personal, societal, and economic costs. In this context, there is an important need for the development of a network of expert centers for treatment-resistant depression (TRD), as performed under the leadership of the Fondation FondaMental. METHODS: The principal mission of this national network is to establish a genuine prevention, screening, and diagnosis policy for TRD to offer a systematic, comprehensive, longitudinal, and multidimensional evaluation of cases. A shared electronic medical file is used referring to a common exhaustive and standardized set of assessment tools exploring psychiatric, non-psychiatric, metabolic, biological, and cognitive dimensions of TRD. This is paralleled by a medico-economic evaluation to examine the global economic burden of the disease and related health-care resource utilization. In addition, an integrated biobank has been built by the collection of serum and DNA samples for the measurement of several biomarkers that could further be associated with the treatment resistance in the recruited depressed patients. A French observational long-term follow-up cohort study is currently in progress enabling the extensive assessment of resistant depressed patients. In those unresponsive cases, each expert center proposes relevant therapeutic options that are classically aligned to the international guidelines referring to recognized scientific societies. DISCUSSION: This approach is expected to improve the overall clinical assessments and to provide evidence-based information to those clinicians most closely involved in the management of TRD thereby facilitating treatment decisions and choice in everyday clinical practice. This could contribute to significantly improve the poor prognosis, the relapsing course, daily functioning and heavy burden of TRD. Moreover, the newly created French network of expert centers for TRD will be particularly helpful for a better characterization of sociodemographic, clinical, neuropsychological, and biological markers of treatment resistance required for the further development of personalized therapeutic strategies in TRD.

Exploring venlafaxine pharmacokinetic variability with a phenotyping approach, a multicentric french-swiss study (MARVEL study).

BACKGROUND: It is well known that the standard doses of a given drug may not have equivalent effects in all patients. To date, the management of depression remains mainly empirical and often poorly evaluated. The development of a personalized medicine in psychiatry may reduce treatment failure, intolerance or resistance, and hence the burden and costs of mood depressive disorders. The Geneva Cocktail Phenotypic approach presents several advantages including the "in vivo" measure of different cytochromes and transporter P-gp activities, their simultaneous determination in a single test, avoiding the influence of variability over time on phenotyping results, the administration of low dose substrates, a limited sampling strategy with an analytical method developed on DBS analysis. The goal of this project is to explore the relationship between the activity of drug-metabolizing enzymes (DME), assessed by a phenotypic approach, and the concentrations of Venlafaxine (VLX) + O-demethyl-venlafaxine (ODV), the efficacy and tolerance of VLX. METHODS/DESIGN: This study is a multicentre prospective non-randomized open trial. Eligible patients present a major depressive episode, MADRS over or equal to 20, treatment with VLX regardless of the dose during at least 4 weeks. The Phenotype Visit includes VLX and ODV concentration measurement. Following the oral absorption of low doses of omeprazole, midazolam, dextromethorphan, and fexofenadine, drug metabolizing enzymes activity is assessed by specific metabolite/probe concentration ratios from a sample taken 2 h after cocktail administration for CYP2C19, CYP3A4, CYP2D6; and by the determination of the limited area under the curve from the capillary blood samples taken 2-3 and 6 h after cocktail administration for CYP2C19 and P-gp. Two follow-up visits will take place between 25 and 40 days and 50-70 days after inclusion. They include assessment of efficacy, tolerance and observance. Eleven french centres are involved in recruitment, expected to be completed within approximately 2 years with 205 patients. Metabolic ratios are determined in Geneva, Switzerland. DISCUSSION: By showing an association between drug metabolism and VLX concentrations, efficacy and tolerance, there is a hope that testing drug metabolism pathways with a phenotypical approach would help physicians in selecting and dosing antidepressants. The MARVEL study will provide an important contribution to increasing the knowledge of VLX variability and in optimizing the use of methods of personalized therapy in psychiatric settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT02590185 (10/27/2015). This study is currently recruiting participants.