Psychomotor retardation: What about the partial responders to magnetic transcranial stimulation in treatment resistant depression ?

OBJECTIVE: Psychomotor retardation is a core clinical component of Major Depressive Disorder responsible for disability and is known as a treatment response marker of biological treatments for depression. Our objective was to describe cognitive and motoric measures changes during a treatment by repetitive Transcranial Magnetic Stimulation (rTMS) within the THETAD-DEP trial for treatment-resistant depression (TRD), and compare those performances at the end of treatment and one month after between responders (>50% improvement on MADRS score), partial responders (25-50%) and non-reponders (no clinically relevant improvement). Our secondary aim was to investigate baseline psychomotor performances associated with non-response and response even partial. METHODS: Fifty-four patients with treatment-resistant unipolar depression and treated by either high frequency 10 Hz rTMS or iTBS for 4 weeks (20 sessions) underwent assessment including French Retardation Rating Scale for Depression (ERD), Verbal Fluency test, and Trail Making Test A. before, just after treatment and one month later. RESULTS: 20 patients were responders (R, 21 partial responders (PR) and 13 non-responders (NR). rTMS treatment improved psychomotor performances in the R and PR groups unlike NR patients whose psychomotor performance was not enhanced by treatment. At baseline, participants, later identified as partial responders, showed significantly higher performances than non-responders. CONCLUSION: Higher cognitivo-motor performances at baseline may be associated with clinical improvement after rTMS treatment. This work highlights the value of objective psychomotor testing for the identification of rTMS responders and partial responders, and thus may be useful for patient selection and protocol individualization such as treatment continuation for early partial responders.

Prospective acceptability of digital therapy for major depressive disorder in France: multicentric real-life study.

BACKGROUND: Major depressive disorder is one of the leading causes of disability worldwide. Recently, the WHO has highlighted the negative impact of recent crises (COVID-19 pandemic, war in Ukraine, economic crisis). Although most international guidelines recommend psychological and psychosocial interventions as a first-line treatment for mild to moderate depression, access remains limited in France due to limited availability of trained clinicians, high costs for patients in a context of non-reimbursement and fear of stigmatisation. Therefore, online blended psychological treatment such as deprexis® could improve access to care for people with depression. It has several advantages such as easy access, scalability and is supported by evidence. OBJECTIVE: This study aims to evaluate the real-life acceptability of a deprexis® for people with depression in France, outside of a reimbursement pathway. METHODS: DARE was designed as a multicentre cross-sectional study in which deprexis® was offered to any patient meeting the inclusion criteria during the fixed inclusion period June 2022-March 2023. Inclusion criteria were: 1/ depression, 2/ age between 18 and 65 years, 3/ sufficient French language skills, 4/ access to internet with a device to connect to the deprexis® platform. Exclusion criteria were previous or current diagnosis of bipolar disorder, psychotic symptoms and/or suicidal thoughts during the current episode. The primary objective is to measure the prospective acceptability of deprexis®, a new digital therapy. Secondary objectives are to examine differences in acceptability according to patient and clinician characteristics and to identify reasons for refusal. All investigators received video-based training on deprexis® prior to enrolment to ensure that they all had the same level of information and understanding of the programme. RESULTS: 245 patients were eligible (56.3% women and 56.3% single). Mean age 40.7+-14.1 years. 78% had moderate to severe depression (according to PHQ-9). More than half of the population had another psychiatric comorbidity (excluding bipolar disorder, psychotic disorders and suicidal ideation). 33.9% of patients accepted the idea of using deprexis® and the main reason for refusal was financial, at 83.3%. Multivariate logistic regression identified factors that might favour acceptability of deprexis®. Among these, being in a couple, being treated with an antidepressant or having a low severity level favoured acceptance of deprexis®. CONCLUSIONS: DARE is the first French study aiming at evaluating prospective acceptability of a Digital therapy in the treatment of depression. The main reason for refusal of deprexis® was financial. DARE will allow a better identification of factors influencing it in a natural setting. This study highlights the importance of investigating factors that may be associated with the acceptability of digital interventions, such as marital status, medication use and severity of depression.

The consequences of the new European reclassification of non-invasive brain stimulation devices and the medical device regulations pose an existential threat to research and treatment: An invited opinion paper.

A significant amount of European basic and clinical neuroscience research includes the use of transcranial magnetic stimulation (TMS) and low intensity transcranial electrical stimulation (tES), mainly transcranial direct current stimulation (tDCS). Two recent changes in the EU regulations, the introduction of the Medical Device Regulation (MDR) (2017/745) and the Annex XVI have caused significant problems and confusions in the brain stimulation field. The negative consequences of the MDR for non-invasive brain stimulation (NIBS) have been largely overlooked and until today, have not been consequently addressed by National Competent Authorities, local ethical committees, politicians and by the scientific communities. In addition, a rushed bureaucratic decision led to seemingly wrong classification of NIBS products without an intended medical purpose into the same risk group III as invasive stimulators. Overregulation is detrimental for any research and for future developments, therefore researchers, clinicians, industry, patient representatives and an ethicist were invited to contribute to this document with the aim of starting a constructive dialogue and enacting positive changes in the regulatory environment.

Differed spontaneous dissociative symptoms following the use of esketamine intranasal spray in a patient suffering from treatment-resistant depression: a case report.

Intranasal esketamine is used in France for treatment-resistant depression. Dissociative symptoms are common side effects during treatment sessions. We report a case of delayed spontaneous dissociative symptoms following esketamine administration. A 20-year-old female with treatment-resistant depression received esketamine treatment. Dissociative symptoms occurred during sessions and persisted at a distance, often accompanied by anxiety. Delayed dissociative phenomena disappeared within the fourth week of treatment by esketamine. The literature mainly discusses dissociation during esketamine treatment sessions, with limited data on differed spontaneous episodes. Three hypotheses are discussed concerning the mechanism of occurrence of these dissociative phenomena, including esketamine's direct effect, central nervous system sensitization, and anxiety-induced dissociation. We present the first case of differed spontaneous dissociative effects after intranasal esketamine administration for treatment-resistant depression. Our main hypothesis suggests that esketamine may act as a 'pattern' for dissociative experiences, heightening the patient's ability to discern these phenomena during other instances of dissociation, such as acute anxiety attacks. Further research is needed to validate this hypothesis.

Esketamine-induced post-traumatic stress disorder flashbacks during treatment-resistant depression indication: is it just a side effect?

Background: Posttraumatic stress disorder (PTSD) is a severe and frequent affection that is highly comorbid to major depressive disorder. Comorbid PTSD and depression are usually treatment-resistant, with a high risk of functional impairment and suicide. Esketamine nasal spray is a recent validated treatment for treatment-resistant depression (TRD), but its efficacy on comorbid TRD-PTSD remains insufficiently documented. In particular, flashbacks can occur during esketamine administration and their influence on clinical outcomes is unknown. Objectives: Our main objective was to describe esketamine-induced traumatic flashbacks and their impact on clinical trajectories within a sample of patients with comorbid TRD-PTSD. Methods: We retrospectively collected clinical data of patients receiving esketamine nasal spray for TRD with comorbid PTSD who experienced at least one flashback of their trauma during esketamine sessions across 11 psychiatric departments. Results: Between February 2020 and March 2023, 22 adult patients with TRD met inclusion criteria. In sixteen patients (72.7%) flashbacks disappeared as the sessions progressed. In six patients (27.3%), esketamine treatment was stopped because of persistent flashbacks. When esketamine was continued, clinical response was observed both for depression and PTSD (depression response rate: 45.5% and remission rate: 22.7%; PTSD response rate: 45.5% and remission: 18.2%). Limitations: The retrospective design of the study and the absence of a comparator group are the main limitations of our study. Conclusions: Our results suggest that the occurrence of esketamine-induced traumatic flashbacks does not hinder clinical response. On the contrary, when managed appropriately and combined with targeted psychotherapy, it could even contribute to positive outcomes.

Development of the PREMIUM computerized adaptive testing for measuring the access and care coordination for patients with severe mental illness.

Severe mental illness (SMI) patients often have complex health needs, which makes it difficult to access and coordinate their care. This study aimed to develop a computerized adaptive testing (CAT) tool, PREMIUM CAT-ACC, to measure SMI patients' experience with access and care coordination. This multicenter and cross-sectional study included 496 adult in- and out-patients with SMI (i.e., schizophrenia, bipolar disorder, or major depressive disorder). Psychometric analysis of the 13-item bank showed adequate properties, with preliminary evidence of external validity and no substantial differential item functioning for sex, age, care setting, and diagnosis, making it suitable for CAT administration. A post-hoc CAT simulation demonstrated that the tool was efficient and accurate, with an average of seven items, compared to the full item bank administration. Its use by clinicians can contribute to optimizing patient care pathways and transitioning towards more person-centered healthcare.

Transcranial Direct Current Stimulation for Depression in Transgender Patient.

Transgender and gender-diverse (TGD) individuals experience higher rates of mood and anxiety disorders than the general public. Transcranial direct current stimulation (tDCS) is an effective and well-tolerated treatment for major depressive disorder, in cisgender patients. With the very recent exception of electroconvulsive therapy (ECT), neuromodulation in TGD patients is not addressed in the literature. We described here the efficacy and tolerability of tDCS in a 22-year-old Caucasian female-to-male transgender individual (hereafter referred to as a male) suffering from a severe non-treatment-resistant major depressive disorder. This case report suggests that combined tDCS and antidepressant therapy have the potential to treat depressive disorders in patients of all gender identities.

Dynamics of Depressive and Psychomotor Symptoms During Electroconvulsive Therapy in Older Depressive Patients: A Case Series.

OBJECTIVE: Electroconvulsive therapy (ECT) is an effective treatment for patients experiencing a major depressive episode, especially older ones. Identification of specific responses within early ECT sessions remains an issue of debate, however. Hence, this pilot study prospectively examined the outcome in terms of depressive signs, symptom by symptom, throughout a course of ECT, concentrating particularly on psychomotor retardation symptoms. METHODS: Nine patients were clinically evaluated several times during the ECT course, before the first session and then weekly (over 3-6 weeks, according to their evolution), by completing the Montgomery-Åsberg Depression Rating Scale (MADRS), the Mini-Mental State Examination test, and the French Retardation Rating Scale for Depression for assessing the severity of psychomotor retardation. RESULTS: Nonparametric Friedman tests showed significant positive changes in mood disorders during ECT in older depressive patients (mean, -27.3% of initial MADRS total score). Fast improvement in French Retardation Rating Scale for Depression score was observed at t1 (ie, after 3-4 ECT sessions), whereas a slightly delayed improvement in the MADRS scores was found at t2 (ie, after 5-6 ECT sessions). Moreover, the scores for items linked to the motor component of psychomotor retardation (eg, gait, postural control, fatigability) were the first to significantly decrease during the first 2 weeks of the ECT course compared with the cognitive component. CONCLUSIONS: Interestingly, participants' concentration on daily functional activities, their interest and fatigability, and their reported state of sadness were the first to progress, representing possible precursor signs of positive patient outcomes after ECT.

A Call to Immediate Action to Support Management of Long COVID Related-Symptoms.

No Abstract Available.

EMDR for symptoms of depression, stress and burnout in health care workers exposed to COVID-19 (HARD): A study protocol for a trial within a cohort study.

Background: Stressful events during a pandemic are a major cause of serious health problems, such as burnout, depression and posttraumatic stress disorder (PTSD) among health care workers (HCWs). During three years, HCWs, on the frontline to fight the COVID-19 pandemic, have been at an increased risk of high levels of stress, anxiety, depression, burnout and PTSD. Regarding potential psychological interventions, Eye Movement Desensitization & Reprocessing (EMDR) is a structured, strongly recommended therapy based on its well-known efficacy in reducing PTSD symptoms and anxiety.Objectives: This study, designed as a trial within a cohort (TwiC), aims to 1) estimate the prevalence of depression, burnout and PTSD in a sample of HCWs after experiencing the COVID-19 emergency (cohort part) and 2) assess the efficacy and acceptability of 'EMDR + usual care' for HCWs from the cohort who report significant psychological symptoms (trial part).Methods: The study, designed as a TwiC, consists of a prospective cohort study (n = 3000) with an embedded, pragmatic, randomized open-label superiority trial with two groups (n = 900). Participants included in the trial part are HCWs recruited for the cohort with significant symptoms on at least one psychological dimension (depression, burnout, PTSD) at baseline, 3 months or 6 months, determined by using the Patient Health Questionnaire (PHQ-9), Professional Quality of Life (ProQOL) scale, and PTSD Checklist for the DSM-5 (PCL-5). The intervention consists of 12 separate EMDR sessions with a certified therapist. The control group receives usual care. The trial has three primary outcomes: changes in depression, burnout and PTSD scores from randomization to 6 months. All participants are followed up for 12 months.Conclusions: This study provides empirical evidence about the impact of the COVID-19 pandemic and the mental health burden it places on HCWs and assesses the effectiveness of EMDR as a psychological intervention.Trial registration NCT04570202.

Health care workers are at increased risk of stress, anxiety, depression, burnout and PTSD following the COVID-19 pandemic.In this study, the effectiveness of EMDR in reducing depression, burnout and PTSD in health care workers exposed to COVID-19 is investigated.In this study, an original 'trial within a cohort' (TwiC) design that consists of a cohort study with an embedded pragmatic randomized trial is used.The study is fully web-based, including online screening, consent and assessments.

Psychotropic drugs consumption during 2020 COVID-19 pandemic and lockdowns: Evidence of a surprising resilience of the drugs delivery system in France.

The COVID-19 pandemic imposed two lockdowns of eight and six weeks in France. While access to care was reduced during lockdown periods, these stressful situations with the pandemic and lockdown periods may have a negative impact on mental health, especially in vulnerable subgroups. Monitoring of psychotropic drugs consumption in France is a comprehensive and reliable tool for indirectly analyzing the mental health of French people. This historical cohort study (n = 767 147) investigated the short-term and long-term evolution of the weekly trend of psychotropic drugs users in 2020 by performing a Seasonal Trend decomposition time series analysis. Rate of progression of consumers per week increased from 186 in the last week of 2019 to 261 per week in the last week of 2020 (+40.3%). Our results did not show a significant break in psychotropic drugs consumption trends during the year 2020 and its two lockdowns. The increase in trend regarding psychotropic drugs consumptions was greatest in young people (<15 years) and patients not being socially deprived. Despite the increase in consumers with restrictive health measures, the French drugs delivery system has been able to adapt with the support of government and pharmacy network. This point should be kept in mind as the necessary reforms to the health care system are undertaken. The COVID-19 pandemic has a negative impact on mental health and two lockdowns occurred in France with reduced access to care. In this context, monitoring of psychotropic drugs consumption is a comprehensive and reliable tool for analyzing the mental health of French people. We hypothesized that the psychotropic drugs consumption has increased during the 2020 COVID-19 pandemic, testifying to French people mental health deterioration, with psychotropic drugs consumption breaks during lockdowns, especially during the first "grand national lockdown", due to the closure or difficulties for accessing to health care structures. By carrying out a historical cohort study among Pays de la Loire residents (n = 767 147), we investigated evolution of the weekly trend of psychotropic drugs users in 2020 compared to 2019 by performing a Seasonal Trend decomposition time series analysis. Between 2019 to 2020, we found a + 40.3% rate of progression of consumers per week. During the year 2020, changes in trend regarding psychotropic drugs consumptions was observed in various sub-groups, e.g. greater in the youngest (< 15 years), which may indicate a vulnerable group strongly impacted by COVID-19 negative consequences, and patients not being socially deprived, which may indicate a group with probably an easier access to care. Lockdown periods were not associated with a significant change in psychotropic drug use, suggesting a form of resilience in the French health care system to maintain its capacity to deliver psychotropic treatments. We mainly discussed that despite the increase in consumers and the policies of restricting access to care during lockdown periods, the French drugs delivery system has been able to adapt thanks to supportive policy actions (extension of the prescriptions validity without the need for a renewal by a physician during periods of lockdowns), an efficient pharmacy network with a collaborative practice of health actors that need to be developed and/or conserved to face potential future health crises.

Impact of response shift effects in the assessment of self-reported depression during treatment: Insights from a rTMS versus Venlafaxine randomized controlled trial.

PURPOSE: Patient-Reported Outcomes are essential to properly assess treatment effectiveness in randomized clinical trial (RCT) for Major Depressive Disorder (MDD). MDD self-assessment may vary over time depending on change in the meaning of patients' self-evaluation of depression, i.e. Response Shift (RS). Our aim was to investigate RS and its impact on different depression domains in a clinical trial comparing rTMS versus Venlafaxine. METHODS: The occurrence and type of RS was determined using Structural Equation Modeling applied to change over time in 3 domains (Sad Mood, Performance Impairment, Negative Self-Reference) of the short-form Beck Depression Inventory (BDI-13) in a secondary analysis of a RCT on 170 patients with MDD treated by rTMS, venlafaxine or both. RESULTS: RS was evidenced in the venlafaxine group in the Negative Self-Reference and Sad Mood domains. CONCLUSION: RS effects differed between treatment arms in self-reported depression domains in patients with MDD. Ignoring RS would have led to a slight underestimation of depression improvement, depending on treatment group. Further investigations of RS and advancing new methods are needed to better inform decision making based on Patient-Reported Outcomes.

The update of self-identity: Importance of assessing autobiographical memory in major depressive disorder.

Major depressive disorder is a leading global cause of disability. There is a growing interest for memory in mood disorders since it might constitute an original tool for prevention, diagnosis, and treatment. MDD is associated with impaired autobiographical memory characterized by a tendency to overgeneral memory, rather than vivid episodic self-defining memory, which is mandatory for problem-solving and projection in the future. This memory bias is maintained by three mechanisms: ruminations, avoidance, and impaired executive control. If we adopt a broader and comprehensive perspective, we can hypothesize that all those alterations have the potential to impair self-identity updating. We posit that this update requires a double referencing process: (1) to internalized self-representation and (2) to an externalized framework dealing with the representation of the consequence of actions. Diagnostic and therapeutic implications are discussed in the light of this model and the importance of assessing autobiographical memory in MDD is highlighted. This article is categorized under: Psychology > Memory Psychology > Brain Function and Dysfunction Neuroscience > Clinical.

Real world transcranial magnetic stimulation for major depression: A multisite, naturalistic, retrospective study.

BACKGROUND: In 2008, the U.S. FDA approved rTMS as a treatment against medication-resistant depression. However, real-world rTMS outcomes remain understudied. This study investigates how rTMS for depression is delivered in routine clinical practice in France, and measures its effectiveness as well as its moderators. METHODS: Five centers provided retrospective data on patients who were treated with rTMS for treatment-resistant depression from January 2015 to December 2020. Patients were assessed twice using a hetero-questionnaire, with baseline and immediate post-treatment assessments. We conducted univariate analyses to study which factors were significantly associated with rTMS effectiveness. We then included age, gender, and significant factors in a multivariate model. RESULTS: We collected data from 435 patients with a mean age of 51.27 (14.91): 66 % were female, and 26 % suffered from bipolar depression. Stimulation was delivered using four different stimulation parameters: 1 Hz (7 % of the individuals), 10 Hz (43 %), 20 Hz (12 %), and 50 Hz (intermittent Theta Burst Stimulation, iTBS) (38 %). The mean improvement of depressive symptoms was 33 % (p < 0.001, effect-size: 0.79). Response and remission rates were of 31 % and 22.8 %, respectively. In the multivariate analysis, improvement in depressive symptoms was associated with higher baseline symptoms. CONCLUSION: This is one of the largest studies that investigates, with careful clinician-rated scales by trained psychiatrists, the effect of rTMS in naturalistic settings. Repetitive TMS appears to be effective in routine clinical practice, although its efficacy could be improved by analyzing predictors of response, as well as personalized targeting of specific brain areas.

ECT: An essential therapy in psychiatry.

At a time when innovations in psychiatry are booming, particularly in the field of medical devices, we thought it necessary, as members of French Society for Biological Psychiatry and Neuropsychopharmacology (AFPBN), to reconsider one of the oldest medical devices in psychiatry: the ECT apparatus. First, we recall the regulatory aspects of ECT. National guidelines define means of implementation and conditions of administration of ECT. Second, we remind of the indications and levels of evidence of ECT in the main psychiatric disorders, including catatonia. Then, we synthetize the place of ECT alongside other brain stimulation therapies, especially repetitive Trancranial Magnetic Stimulation (rTMS). Furthermore, we explain the general effects of ECT: increased neuronal plasticity and neurogenesis, enhancement of the stress axis, resistance to oxidative stress, improved vascular endothelial function, activation of microglia and astrocytes, decrease in inflammatory events by upregulation of neuroinflammatory cytokines, and production of mitochondrial ATP. These effects appear from the first sessions and continue during the course of ECT treatment, suggesting activation of endogenous neuroprotection. Finally, we remember that most patients perform as well or better on neuropsychological assessments after ECT, relative to pre-ECT results, and this improvement continues over the following months. Memory disorders reported post-ECT are not all attributable to ECT. They may be subjective in nature or linked to residual depressive (and possibly comorbid neurogenerative) symptoms later attributed to ECT, on the basis of preexisting negative representations. We urgently need to reemphasize the crucial role of ECT in psychiatric treatment strategies as well as the need to update ECT recommendations.