[Which solution to functional somatic disorder: The ACSEPT program]. / Quelle réponse au trouble somatique fonctionnel : la filière ACSEPT.

BACKGROUND: Functional somatic disorder (FSD) is a prevalent disorder that can be severely disabling for the patient and is associated with major health costs. There are few formalized care programs for these disorders in the country, and their management encounters various difficulties, both in the diagnosis and its announcement and the treatment. Cognitive-behavioural and emotional therapy (CBT) is the standard on psychiatry care, and its efficacy has been demonstrated through several randomised controlled studies on the intensity of physical and psychological symptoms. INTERVENTION: At Lille's University Hospital Center, we have established the "ACSEPT" care pathway for TSF management which consists of a psychiatric consultation followed by an individual referral, including a treatment using repeated transcranial magnetic stimulation (rTMS) or the integration of a CBT-based psychoeducation group. This group had the particularity of caring for all patients presenting FSD regardless of the associated physical symptoms. Educating medical professionals and conducting FSD research were other goals of ACSEPT. DISCUSSION/CONCLUSION: ACSEPT allows an improvement in the care offered to these patients with a defined orientation and interdisciplinary, early, organized cares that are repeatable. Our goal is to study the effectiveness of these different interventions in subsequent studies, to continue the development of ACSEPT and to be able to distribute this intervention at the regional level to establish a clear care program allowing early management of these patients.

Prolonged increase in psychotropic drug use among young women following the COVID-19 pandemic: a French nationwide retrospective study.

BACKGROUND: The COVID-19 pandemic has had a significant impact on mental health, with evidence suggesting an enduring mental health crisis. Studies worldwide observed increased usage of antidepressants, anxiolytics, and hypnotics during the pandemic, notably among young people and women. However, few studies tracked consumption post-2021. Our study aimed to fill this gap by investigating whether the surge in the number psychotropic drug consumers in France persisted 2 years after the first lockdown, particularly focusing on age and gender differences. METHODS: We conducted a national retrospective observational study based on the French national insurance database. We retrieved all prescriptions of anxiolytics, hypnotics, and antidepressants dispensed in pharmacies in France for the period 2015-2022. We performed interrupted time series analyses based on Poisson models for five age classes (12-18; 19-25; 26-50; 51-75; 76 and more) to assess the trend before lockdown, the gap induced and the change in trend after. RESULTS: In the overall population, the number of consumers remained constant for antidepressants while it decreased for anxiolytics and hypnotics. Despite this global trend, a long-term increase was observed in the 12-18 and 19-25 groups for the three drug classes. Moreover, for these age classes, the increases were more pronounced for women than men, except for hypnotics where the trends were similar. CONCLUSIONS: The number of people using antidepressants continues to increase more than 2 years after the first lockdown, showing a prolonged effect on mental health. This effect is particularly striking among adolescents and young adults confirming the devastating long-term impact of the pandemic on their mental health.

Catatonia in patients with dementia: A descriptive study of clinical profiles and treatment response.

BACKGROUND: Catatonia is a highly prevalent syndrome in patients presenting with major neurocognitive disorders (dementia). In this study, we aim to provide a comprehensive description of the clinical and therapeutic aspects of catatonia in patients with dementia. METHOD: This descriptive study, conducted between September 2015 and June 2022, collected data from 25 patients diagnosed with dementia, out of 143 patients treated for catatonia in our specialized psychiatry department. We collected sociodemographic, clinical and treatment data for each patient. RESULTS: Dementia patients constituted 17% of the catatonic cases. Predominantly female, the cohort had a mean age of 65. Diagnoses included Alzheimer's (4 patients, 17%) and Parkinson's (1 patient, 4%) diseases, Lewy body dementia (5 patients, 21%), vascular dementia (4 patients, 17%) and frontotemporal lobar degeneration (10 patients, 41%). The mean Bush-Francis Catatonia Rating Scale score upon admission was 20/69. Overall, complete remission of catatonia was achieved in 75% of patients (n=18), with only 13% (n=3) responding to lorazepam alone, while others required additional interventions such as electroconvulsive therapy (ECT) and/or amantadine. Vascular dementia was predominantly observed in cases resistant to treatment. CONCLUSION: The findings indicate a frequent co-occurrence of catatonia and dementia, highlighting treatability yet suggesting a potential for resistance to lorazepam, which varies by dementia diagnosis. Investigating the mechanisms underlying this resistance and the variability in treatment response is crucial for developing more precise therapeutic strategies.

Indirect effect of impulsivity on suicide risk through self-esteem and depressive symptoms in a population with treatment-resistant depression: A FACE-DR study.

INTRODUCTION: Suicide is a major health issue. Its prevalence is particularly high in subjects presenting major depression disorder (MDD), making this a key suicide-related risk factor. Suicide attempts in severe forms of MDD were assumed to be linked to impulsivity and loss of control. Nevertheless, we failed to find data specifically investigating the link between impulsivity and suicide risk in treatment-resistant depression (TRD). This study seeks to review this relationship. METHOD: Patients were recruited for a prospective cohort. Suicide risk and impulsivity were assessed using the International Neuropsychiatric Interview and Barratt Impulsiveness Scale, Version 10, respectively, while the severity of depressive symptoms was assessed using the Montgomery-Asberg Depression Rating Scale, anxiety with the State-Trait Anxiety Inventory and childhood maltreatment using the Childhood Trauma Questionnaire. RESULTS: 220 TRD patients were enrolled in the study. The impulsivity score was correlated with self-esteem, marital status, professional status and anxiety. There was no direct link to suicide risk. However, impulsivity was associated with self-esteem (coefficient: -0.24; p value 0.043) and depressive symptom severity (coefficient: 0.; p value 0.045). The suicide risk was significantly correlated with depressive symptom severity (coefficient = 0.38, p < 0.001) and self-esteem (coefficient = -0.34, p = 0.01). Considering these correlations, we postulated that the effect of impulsivity on suicide risk could be mediated by self-esteem in terms of depressive symptom severity and we finally found a relevant mediation model within impulsivity having an indirect effect on suicide risk by impacting self-esteem and depressive symptoms with anxiety also playing a significant role as a covariable. CONCLUSION: We found that impulsivity could play an indirect role with the involvement of self-esteem and depressive symptoms and the contributing role of anxiety.

Somatic Symptom Disorder-B criteria scale (SSD-12): Psychometric properties of the French version and associations with health outcomes in a population-based cross-sectional study.

OBJECTIVE: The 12-item Somatic Symptom Disorder-B Criteria Scale (SSD-12) is a self-reported questionnaire designed to assess the B criteria of the DSM-5 somatic symptom disorder. In this cross-sectional study, we aimed to examine the psychometric properties of the SSD-12 French version and associated health outcomes. METHODS: Participants were volunteers from the population-based CONSTANCES cohort who reported at least one new symptom that occurred between March 2020 and January 2021. Depressive symptoms were measured with the Center for Epidemiologic Studies-Depression scale (CES-D). RESULTS: A total of 18,796 participants completed the SSD-12. The scree plot was consistent with a 1-factor structure, while goodness-of-fit indices of the confirmatory factorial analyses and clinical interpretability were consistent with a 3-factor structure (excluding the item 7): 'Perceived severity', 'Perceived impairment', 'Negative expectations'. The Cronbach's α coefficients of the total and factors scores were 0.90, 0.88, 0.84 and 0.877, respectively. The total score was associated with depressive symptoms (Spearmann's rho: 0.32), self-rated health (-0.46), the number of persistent symptoms (0.32), and seeking medical consultation (odds ratio [95% confidence interval] for one interquartile range increase: 1.51 [1.48-1.54]). Among participants seeking medical consultation, those with higher SSD-12 scores were more likely to have their symptoms attributed to "stress/anxiety/depression" (1.32 [1.22-1.43]) and "psychosomatic origin" (1.25 [1.20-1.29]), and less to "COVID-19" (0.89 [0.85-0.93]). CONCLUSION: While the SSD-12 French version can be used as a unidimensional tool, it also has a 3-factor structure, somewhat different from the DSM-5 theoretical structure, with high internal consistency and clinically meaningful associations with other health outcomes.

Evolution of Cognitive Impairments in Treatment-Resistant Depression: Results from the Longitudinal French Centers of Expertise for Treatment-Resistant Depression (FACE-DR) Cohort.

Previous studies set out profound cognitive impairments in subjects with treatment-resistant depression (TRD). However, little is known about the course of such alterations depending on levels of improvement in those patients followed longitudinally. The main objective of this study was to describe the course of cognitive impairments in responder versus non-responder TRD patients at one-year follow-up. The second aim was to evaluate the predictive aspect of cognitive impairments to treatment resistance in patients suffering from TRD. We included 131 patients from a longitudinal cohort (FACE-DR) of the French Network of Expert TRD Centers. They undertook comprehensive sociodemographic, clinical, global functioning, and neuropsychological testing (TMT, Baddeley task, verbal fluencies, WAIS-4 subtests, D2 and RLRI-16) at baseline (V0) and one-year follow-up (V1). Most patients (n = 83; 63.36%) did not respond (47 women, 49.47 ± 12.64 years old), while one-third of patients responded (n = 48, 30 women, 54.06 ± 12.03 years old). We compared the cognitive performances of participants to average theoretical performances in the general population. In addition, we compared the cognitive performances of patients between V1 and V0 and responder versus non-responder patients at V1. We observed cognitive impairments during the episode and after a therapeutic response. Overall, each of them tended to show an increase in their cognitive scores. Improvement was more prominent in responders at V1 compared to their non-responder counterparts. They experienced a more marked improvement in code, digit span, arithmetic, similarities, and D2 tasks. Patients suffering from TRD have significant cognitive impairments that persist but alleviate after therapeutic response. Cognitive remediation should be proposed after therapeutic response to improve efficiency and increase the daily functioning.

A pilot study investigating affective forecasting biases with a novel virtual reality-based paradigm.

A body of research indicates that people are prone to overestimate the affective impact of future events. Here, we developed a novel experimental paradigm to study these affective forecasting biases under laboratory conditions using subjective (arousal and valence) and autonomic measures (skin conductance responses, SCRs, and heart rate). Thirty participants predicted their emotional responses to 15 unpleasant, 15 neutral, and 15 pleasant scenarios (affective forecasting phase) to which they were then exposed in virtual reality (emotional experience phase). Results showed that participants anticipated more extreme arousal and valence scores than they actually experienced for unpleasant and pleasant scenarios. The emotional experience phase was characterized by classic autonomic patterns, i.e., higher SCRs for emotionally arousing scenarios and greater peak cardiac acceleration for pleasant scenarios. During the affective forecasting phase, we found only a moderate association between arousal scores and SCRs and no valence-dependent modulation of cardiac activity. This paradigm opens up new perspectives for investigating affective forecasting abilities under lab-controlled conditions, notably in psychiatric disorders with anxious anticipations.

Opening the black box of hospitalizations in French high-secure psychiatric forensic units.

INTRODUCTION: Basic epidemiological data are rare concerning the activity of specialized forensic psychiatric facilities in France. Here, we investigated the activity of the ten (640 beds) French "units for difficult patients" (unités pour malades difficiles [UMDs]). METHOD: We used the Programme de médicalisation des systèmes d'information (PMSI) database to describe the characteristics and evolution of psychiatric hospitalisations in UMDs between 2012 and 2021, as well as the age, sex, and principal diagnoses of the patients hospitalized in these facilities. RESULTS: Between 2012 and 2021, 4857 patients were hospitalized in UMDs (6082 stays). Among them, 897 (18.5%) had more than one stay. The number of admissions ranged from a minimum of 434 to a maximum of 632 per year. The number of discharges ranged from a minimum of 473 to a maximum of 609 per year. The mean length of stay was 13.5 (SD: 22.64) months with a median of 7.3 months (IQR: 4.0-14.4). Among the 6082 stays, 5721 (94.1%) involved male patients. The median age was 33 (IQR: 26-41) years. The most frequent principal psychiatric diagnoses were psychotic disorders and personality disorders. CONCLUSION: The number of individuals hospitalized in specialized forensic psychiatric facilities has been stable for 10 years in France and remains lower than in most European countries.

Long-term benzodiazepine prescription in treatment-resistant depression: A national FACE-TRD prospective study.

BACKGROUND: Benzodiazepine long-term use (BLTU) is a public health challenge. We lack data on the consequences of LBTU on the trajectory of treatment-resistant depression (TRD). OBJECTIVE: To determine the prevalence of BLTU in a nationwide non-selected population of patients with TRD, to determine the rate of patients succeeding at withdrawing benzodiazepines at one year and to determine if persistent BLTU is associated with poorer mental health outcomes. METHOD: The FACE-TRD cohort is a national cohort of TRD patients recruited in 13 resistant depression expert centers between 2014 and 2021 and followed-up at one year. A standardized one-day long comprehensive battery was carried out, including trained-clinician and patient-reported outcomes, and patients were reevaluated at one year. RESULTS: At baseline, 45.2% of the patients were classified in the BLTU group. In multivariate analysis, compared to patients without BLTU, patients with BLTU were more frequently classified in the "low physical activity" group (adjusted odds ratio (aOR) = 1.885, p = 0.036), and had higher primary healthcare consumption (B = 0.158, p = 0.031) independently of age, sex and antipsychotic consumption. We found no significant difference for personality traits, suicidal ideation, impulsivity, childhood trauma exposure, earlier age at first major depressive episode, anxiety and sleep disorders (all p > 0.05). Despite recommendations for withdrawal, <5% of BLTU patients withdraw benzodiazepines during the one-year follow-up. Persistent BLTU at one-year was associated with higher depression severity (B = 0.189, p = 0.029), higher clinical global severity (B = 0.210, p = 0.016), higher state-anxiety (B = 0.266, p = 0.003), impaired sleep quality (B = 0.249, p = 0.008), increased peripheral inflammation (B = 0.241, p = 0.027), lower functioning level (B = -0.240, p = 0.006), decreased processing speed (B = -0.195, p = 0.020) and verbal episodic memory (B = -0.178, p = 0.048), higher absenteeism and productivity loss (B = 0.595, p = 0.016) and lower subjective global health status (B = -0.198, p = 0.028). CONCLUSION: Benzodiazepines are over-prescribed in TRD (in almost a half of the patients). Despite recommendations for withdrawal and psychiatric follow-up, <5% of patients successfully stopped taking benzodiazepines at one-year. Maintaining BLTU may contribute to the worsening of clinical and cognitive symptoms and of daily functioning in TRD patients. Progressive and planed withdrawal of benzodiazepines seems therefore strongly recommended in TRD patients with BLTU. Pharmacological and non-pharmacological alternatives should be promoted when possible.

Persistent physical symptoms after COVID-19 infection and the risk of Somatic Symptom Disorder.

OBJECTIVE: Evidence shows that many patients with COVID-19 present persistent symptoms after the acute infection. Some patients may be at a high risk of developing Somatic Symptom Disorder (SSD), in which persistent symptoms are accompanied by excessive and disproportionate health-related thoughts, feelings and behaviors regarding these symptoms. This study assessed the frequency of persistent physical symptoms and SSD and their associated factors in patients with confirmed COVID-19. METHODS: We conducted a longitudinal retrospective study after the first two French lockdowns at the Lille University Hospital (France), including all patients with confirmed COVID-19. Persistent physical symptoms and excessive preoccupations for these symptoms were measured 8 to 10 months after the onset of COVID-19. The combination of the Patient Health Questionnaire-15 and the Somatic Symptom Disorder-B Criteria Scale was used to identify the individuals likely to present with SSD. Two linear regression models were performed to identify sociodemographic and medical risk factors of SSD. RESULTS: Among the 377 patients with a laboratory-confirmed diagnosis, 220 (58.4%) completed the questionnaires. Sixty-five percent of the 220 included patients required hospitalization, 53.6% presented at least one persistent physical symptom and 10.4% were considered to present SSD. Female sex, older age, infection during the second wave and having probable PTSD were significantly associated with the severity of SSD and SSD was associated with a significantly higher healthcare use. CONCLUSIONS: The identification of SSD should encourage clinicians to move beyond the artificial somatic/psychiatric dualism and contribute to a better alliance based on multi-disciplinary care.

Diurnal symptoms of sleepiness and dysfunction predict future suicidal ideation in a French cohort of outpatients (FACE-DR) with treatment resistant depression: A 1-year prospective study about sleep markers.

BACKGROUND: Patients suffering from treatment-resistant depression (TRD) are at risk of suicide. Sleep and circadian rhythm alterations are widely recognized as core symptoms of major depressive disorder and are associated with suicidal ideation. Thus, sleep and circadian rhythm alterations may be targeted to prevent suicide. METHODS: Patients were recruited from a prospective cohort of the French network of TRD expert centers. Mood, sleep and circadian rhythms were assessed at baseline; suicidal risk was assessed both at baseline and during a one-year follow-up with standardized subjective questionnaires. RESULTS: Excessive daytime sleepiness (adjusted odds ratio aOR = 1.7(1-3.3), p = 0.04) and daytime dysfunction (aOR = 1.81(1.16-2.81), p = 0.0085) increased the risk of suicidal thoughts over the one-year follow-up period in patients with TRD after adjustment on age, gender, depression, trauma, anxiety, impulsivity, current daily tobacco smoking and body mass index. Hypnotics intake is associated with a reduced risk of suicidal ideation at one-year follow-up after the same adjustments (OR = 0.73(0.56-0.95), p = 0.019). Other associations between sleep quality or circadian rhythms and suicidal ideations at either baseline or one year did not remain significant in multivariate analyses after the same adjustments. LIMITATIONS: Sleep assessments were based on self-reported questionnaires rather than objective measures. CONCLUSIONS: Daytime sleepiness and dysfunction are predictors of suicidal ideations, whereas hypnotics intake is associated with a reduced risk of suicidal ideations. Diurnal symptoms of sleep disturbances are therefore red flags to target for preventing suicide in depressed patients, and hypnotics seem efficient in preventing suicide for patients with TRD.

Mental Health Symptoms of University Students 15 Months After the Onset of the COVID-19 Pandemic in France.

Importance: The Conséquences de la pandémie de COVID-19 sur la santé mentale des étudiants (COSAMe) survey was conducted among university students in France during the COVID-19 pandemic and found that although there was a slight decrease in anxiety, depression, and stress between the first lockdown (T1) and 1 month after it ended (T2), the prevalence of suicidal ideation had increased between these periods and 1 in 5 students had probable posttraumatic stress disorder (PTSD) at T2. These results emphasize the need to explore the long-term consequences of the COVID-19 pandemic. Objectives: To measure the prevalence of mental health symptoms among university students in France 15 months after the first lockdown (T3) and to identify factors associated with outcomes. Design, Setting, and Participants: This cross-sectional study reports data from the third measurement time of the repeated COSAMe survey, which took place from July 21 to August 31, 2021, through an online questionnaire sent to all French university students. Main Outcomes and Measures: The prevalence of suicidal thoughts, PTSD (PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition] [PCL-5]), stress (Perceived Stress Scale), anxiety (State-Trait Anxiety Inventory), and depression (Beck Depression Inventory) at T3 were gender- and degree-standardized and compared with prevalence rates at T1 and T2. Multivariable logistic regression analyses identified risk factors. Results: A total of 44 898 students completed the questionnaires. They were mainly women (31 728 [70.7%]), and the median (IQR) age was 19 (18-21) years. Standardized prevalence rates of stress, anxiety, depression, suicidal thoughts, and PTSD were 20.6% (95% CI, 20.2%-21.0%), 23.7% (95% CI, 23.3%-24.1%), 15.4% (95% CI, 15.1%-15.8%), 13.8% (95% CI, 13.5%-14.2%), and 29.8% (95% CI, 29.4%-30.2%), respectively. Compared with the decreased prevalence rates at T2, there was an increase at T3 for stress (2.5% increase), anxiety (13.9% increase), and depression (22.2% increase). The prevalence of suicidal ideation continued to increase from T1 (10.6%) to T3 (13.8%), and the prevalence of probable PTSD increased from 1 in 5 students to 1 in 3 students between T2 and T3. Female and nonbinary participants; participants without children and living in an urban area; and those with financial difficulties, a chronic condition, psychiatric history, COVID-19 history, social isolation, and low perceived quality of information received were at risk of all poor outcomes at T3 (eg, stress among women: adjusted OR, 2.18; 95% CI, 2.05-2.31; suicidal thoughts among nonbinary respondents: adjusted OR, 5.09; 95% CI, 4.32-5.99; anxiety among students with children: adjusted OR, 0.68; 95% CI, 0.56-0.81; depression among students living in a rural area: adjusted OR, 0.80; 95% CI, 0.75-0.85). Conclusions and Relevance: These results suggest severe long-lasting consequences associated with the pandemic on the mental health of students. Prevention and care access should be a priority.

Psychiatric Hospitalizations of People Found Not Criminally Responsible on Account of Mental Disorder in France: A Ten-Year Retrospective Study (2011-2020).

Background: Criminal responsibility is a key concept in the criminal sanctioning of people diagnosed with mental health disorders who have committed crimes. In France, based on the recommendations of one or more expert psychiatrists, a judge can declare a person not criminally responsible on account of mental disorder (NCRMD) if, at the time of the offense, the person was presenting a psychiatric disorder that abolished or altered his/her capacity for discernment and/or ability to control his/her actions. In such a case, the judge also generally orders an involuntary psychiatric hospitalization. The objectives of this study were to (1) describe longitudinal retrospective administrative data of psychiatric hospitalizations for people found NCRMD, (2) identify the age, sex, and principal diagnoses of these individuals, and (3) characterize the trajectories of their psychiatric care before and after NCRMD psychiatric hospitalization. Methods: We used discharge reports from the French national hospital database called Programme de médicalisation des systèmes d'information (PMSI) to gather longitudinal data that describe psychiatric hospitalizations for people found NCRMD between 2011 and 2020, the age, sex, and principal diagnoses of these patients, the length of their hospitalization, and the trajectories of their psychiatric care before and after their NCRMD psychiatric hospitalization. Results: We identified 3,020 patients who were hospitalized for psychiatric care after having been found NCRMD between 2011 and 2020. The number of admissions on these grounds has remained stable over this period, ranging from 263 in 2011 to 227 in 2021. They were mostly young men diagnosed with a psychotic disorder (62%). The majority (87%) were hospitalized in general psychiatric hospitals, and only 13% were admitted to maximum-security units (Unités pour malades difficiles, UMD). The median duration of hospitalization for these patients was 13 months. Our results show that 73% of the patients had already been hospitalized prior to their NRCMD hospitalization. The rehospitalization rate within 5 years of discharge from NCRMD psychiatric hospitalization was 62%. Conclusion: We conducted the first study investigating the psychiatric hospital treatment of people declared NCRMD in France. There is an urgent need for further studies to investigate the clinical characteristics of these patients.

Psychiatric hospitalisations for people who are incarcerated, 2009-2019: An 11-year retrospective longitudinal study in France.

Background: Despite the poor mental health status of people who are incarcerated, few studies have examined the number of psychiatric hospitalisations in this population. Since 2010, France has progressively opened nine full-time inpatient psychiatric wards exclusively for people who are incarcerated, called "specially adapted hospital units" (unités hospitalières spécialement aménagées, UHSAs, 440 beds). This study aimed to present the annual rates of psychiatric hospitalisations and primary psychiatric diagnoses among people who are incarcerated in France from 2009 to 2019. Methods: We used discharge reports from the French national hospital database to describe longitudinal retrospective administrative data of psychiatric hospitalisations for people in jail and prison between 2009 and 2019, the age, sex, and principal diagnoses of these patients, the proportion of voluntary versus involuntary care, and the interactions between UHSAs and other facilities. Findings: Between Jan 1, 2009, and Dec 31, 2019, 32,228 (92.2% men, n = 29,721; 7.8% women, n = 2 507) incarcerated people were hospitalised for psychiatric care (64,481 stays). The main diagnoses were psychotic disorders (27.4%), personality disorders (23.2%), and stress-related disorders (20.2%). The annual number of incarcerated people hospitalised in psychiatric care increased from 3263 in 2009 to 4914 in 2019. The gradual increase in the activity of UHSAs (300 hospitalisations in 2010 versus 3252 in 2019) was not associated with a reduction in the rate of hospitalisation of incarcerated people in local psychiatric hospitals. Interpretation: The creation of psychiatric hospitals specifically dedicated to the prison population has not stopped the hospitalisation of people who are incarcerated at psychiatric hospitals. These findings suggest that access to psychiatric hospitalisation remains problematic for people who are incarcerated in France. Funding: There was no funding source for this study.

Recommendations of the treatment-resistant depression expert center network for promoting tobacco smoking cessation based on the results from the real-world FACE-TRD national cohort.

BACKGROUND: Tobacco smoking has been associated with suicide, impulsivity and depression in non-clinical populations with differences across sexes. OBJECTIVE: To determine the role of tobacco smoking in Treatment-Resistant Depression (TRD) according to sex in a precision-medicine approach. METHOD: The FACE-TRD cohort is a national cohort of TRD patients recruited in 13 resistant depression expert centers between 2014 and 2021 and followed-up at 6 months. A standardized one-day long comprehensive battery was carried out, including trained-clinician and patient-reported outcomes, and patients were reevaluated at 6 months on their smoking and psychiatric hospitalization outcomes. RESULTS: 355 TRD participants were included (222 women). The smoking rate was much higher in TRD women compared to the French general population (34% vs 24%) while it was comparable for men (approximately 29%). In multivariate analyses, compared to non-smoking women, female smokers had significantly increased number of lifetime psychiatric hospitalizations (standardized beta B = 0.232, p = 0.014) and electro-convulsive therapy (adjusted odds ratio (aOR) = 2.748, p = 0.005), increased suicidal ideations (aOR = 4.047, p = 0.031), history of suicide attempt (aOR = 1.994, p = 0.033), and increased impulsivity (B = 0.210, p = 0.006) and were more frequently treated by benzodiazepines (aOR = 1.848, p = 0.035) and third- or fourth-line TRD treatments (antipsychotics aOR = 2.270, p = 0.006, mood stabilizers aOR = 2.067 p = 0.044). Tobacco smoking at baseline was predictive of psychiatric hospitalization within 6 months in persistent smoking women (aOR = 2.636, p = 0.031). These results were not replicated in men, for whom tobacco smoking was only associated with increased clinician-rated and self-reported depressive symptoms (respectively B = 0.207, p = 0.022 and B = 0.184, p = 0.048). The smoking cessation rate at 6 months was higher in women than in men (12% vs. 7%). No patient was administered nicotine substitute or varenicline at the two timepoints. INTERPRETATION: Combining these results and those of the literature, we recommend that active tobacco cessation should be promoted in TRD to improve depression, suicide and impulsivity especially in women. Female smokers appear as a specific population with heavier mental health outcomes that should be specifically addressed.

Occurrence of Side Effects in Treatment-Resistant Depression: Role of Clinical, Socio-Demographic and Environmental Characteristics.

Introduction: Treatment-resistant depression (TRD) is a disabling psychiatric condition characterized by the failure of two antidepressants (ADs). Since the occurrence of side effects (SEs) appears to be one of the main determinants of early discontinuation of pharmacological treatments contributing to a pseudo-resistance, the purpose of this study was to determine the parameters associated with the occurrence of SEs under ADs in a cohort of patients with TRD. Methods: An observational, cross-sectional, multicentre study was carried out using data from the French network of Expert Centers for TRD. For the 108 patients enrolled in the study, the statistical analyses focused on the overall occurrence and on the profile of the SEs (9 categories, 32 items). Results: SEs were influenced by age and sex and were positively associated with the intensity of anxious, depressive and suicidal symptoms, a history of childhood trauma (sexual abuse, emotional abuse and neglect), and negatively associated with self-esteem, and assessment of overall functioning. Conclusion: Using variables accessible in common practice, these results fall within the dynamic of a more tailored approach to medicine that could allow, through integrated pharmacological management, the continuation of antidepressant treatments, and therefore limit the risk of therapeutic failure.