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.

Efficacy and Safety of Electroconvulsive Therapy in Patients With Deep Brain Stimulation: Literature Review, Case Report for Patient With Essential Tremor, and Practical Recommendations.

AIM: Deep brain stimulation (DBS) has proven to be an effective therapy of some treatment-resistant psychiatric disorders and movement disorders. Comorbid depressive symptoms are common and difficult to manage. Treatment with electroconvulsive therapy (ECT) may be required. There are few published cases describing the safety and efficacy of ECT for patients with DBS implants, and there are no available guidelines for administration of ECT in patients with DBS and mood disorders. The current study had 3 aims: (i) to conduct a systematic review of case reports on patients with DBS implants who received ECT; (ii) to report the case of a 69-year-old man with a DBS implant for essential tremor, who required ECT; and (iii) to provide practical recommendations for ECT in patients with DBS implants. METHODS: We conducted a systematic review, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, of existing case reports on patients with DBS implants administered ECT for psychiatric disorders. RESULTS: Our search yielded 25 cases of ECT in patients implanted with DBS systems. In addition, we here describe successful ECT management of major depressive disorder in a patient treated by DBS. We also set forth ECT management guidelines based on points of consensus. The 2 most important practical recommendations are to make sure the DBS system is set to 0 V and turned off before ECT, and to avoid sites near the DBS electrodes. CONCLUSIONS: Electroconvulsive therapy may be an effective and safe treatment for DBS patients with MDD.

Self-consciousness impairments in schizophrenia with and without first rank symptoms using the moving rubber hand illusion.

INTRODUCTION: The moving rubber hand illusion allows the evaluation both the sense of body ownership and agency using visuo-motor stimulations. METHODS: We used the moving rubber hand illusion in anatomic congruence with explicit measures to compare active asynchronous and passive synchronous movements in patients diagnosed with schizophrenia with first rank symptoms (FRS) (n = 31) versus without FRS (n = 25). RESULTS: Patients with FRS are characterized by a lack of agency in active asynchronous condition. The two groups had no sense of ownership in synchronous passive condition. Using a multivariate regression model, we found an association between agency and body ownership measures in the active asynchronous condition in two groups (OR: 1.825, p < 0.001). In the passive condition, this association was only present in the group with first rank symptoms (OR: 2.04, p < 0.001). CONCLUSION: Temporal proximity and sensorimotor information are essential in the understanding of self-consciousness disorders in schizophrenia.

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.

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.

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.

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.

The anticholinergic burden is not associated with cognitive impairments in patients treated by electroconvulsive therapy for treatment-resistant depression.

BACKGROUND: Electroconvulsive therapy (ECT) is the most effective non-pharmacological treatment for treatment-resistant depression (TRD) but can expose to transient cognitive impairments. Understanding factors underlying these cognitive side effects is important. This study investigated the impact of anticholinergic treatments on cognitive performances after ECT courses for TRD in naturalistic condition. METHODS: Impact of anticholinergic burden (Anticholinergic Impregnation Scale, AIS) on cognitive changes (Montreal Cognitive Assessment, MoCA) adjusted on depression level (Montgomery and Asberg Depression Scale, MADRS) was investigated in 42 patients who received an ECT course between 2017 and 2020 for unipolar or bipolar TRD. Collection of daily treatments given during ECT was carried out via the computerized traceability of treatments validated by nurses. RESULTS: Among the 31 treatments identified with an anticholinergic score, which represent only 38% of total treatments, the three most frequently given treatments were Lorazepam (47%), Venlafaxine (36%) and Cyamemazine (26%). Delayed recall was the most frequently impaired cognitive function after ECT courses. Using logistic regression, we found no association between the anticholinergic burden and the decrease in cognitive scores after ECT courses, adjusted on MADRS score evolution (p > 0.1). Conversely, improvement in MADRS scores were correlated with improvement in attention MoCA subscores. LIMITATIONS: This is a retrospective monocentric study with a moderate sample size using anticholinergic scales to calculate the anticholinergic burden without plasma dosage. CONCLUSION: Anticholinergic treatments did not seem to explain ECT-related cognitive impairments. This warrants further large prospective investigations including different measures of anticholinergic burden.

Intermittent theta burst stimulation (iTBS) versus 10 Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) to alleviate treatment-resistant unipolar depression: A randomized controlled trial (THETA-DEP).

BACKGROUND: Recently intermittent theta burst stimulation (iTBS) proved to be non-inferior to conventional repetitive transcranial magnetic stimulation (10 Hz rTMS) in unipolar depression after failure of one antidepressant trial, but to date no randomized control trial assessed the ability of iTBS to improve depression level and quality of life in more resistant features of depression with a long-term (6 month) follow-up in comparison to 10 Hz rTMS. OBJECTIVES/HYPOTHESIS: The aim of our study was to compare the efficacy of 10 Hz rTMS and iTBS in treatment-resistant unipolar depression on response rates (50% decrease of MADRS scores at one month from baseline) and change in quality of life during a 6-month follow-up. In addition, we investigated whether some clinical features at baseline were associated with the response in the different groups. METHOD: Sixty patients were randomized in a double-blind, controlled study at the University Hospital Center of Nantes, and received 20 sessions of either rTMS or iTBS applied to the left dorsolateral prefrontal cortex targeted by neuronavigation. Statistical analysis used Fischer's exact test and Chi-square test as appropriate, linear mixed model, and logistic regression (occurrence of depressive relapse and factors associated with the therapeutic response). RESULTS: Included patients showed in mean more than 3 antidepressants trials. Response rates were 36.7% and 33.3%, and remission rates were 18.5% and 14.8%, in the iTBS and 10 Hz rTMS groups respectively. Both groups showed a similar significant reduction in depression scores and quality of life improvement at 6 months. We did not find any clinical predictive factor of therapeutic response in this sample. CONCLUSION: Our study suggests the clinical interest of iTBS stimulation (which is more time saving and cost-effective as conventional rTMS) to provide long-lasting improvement of depression and quality of life in highly resistant unipolar depression.

Efficacy and Safety of Transcranial Electric Stimulation during the Perinatal Period: A Systematic Literature Review and Three Case Reports.

Introduction: The perinatal period is an at-risk period for the emergence or decompensation of psychiatric disorders. Transcranial electrical stimulation (tES) is an effective and safe treatment for many psychiatric disorders. Given the reluctance to use pharmacological treatments during pregnancy or breastfeeding, tES may be an interesting treatment to consider. Our study aims to evaluate the efficacy and safety of tES in the perinatal period through a systematic literature review followed by three original case reports. Method: Following PRISMA guidelines, a systematic review of MEDLINE and ScienceDirect was undertaken to identify studies on tES on women during the perinatal period. The initial research was conducted until 31 December 2021 and search terms included: tDCS, transcranial direct current stimulation, tACS, transcranial alternating current stimulation, tRNS, transcranial random noise stimulation, pregnancy, perinatal, postnatal, and postpartum. Results: Seven studies reporting on 33 women during the perinatal period met the eligibility criteria. No serious adverse effects for the mother or child were reported. Data were limited to the use of tES during pregnancy in patients with schizophrenia or unipolar depression. In addition, we reported three original case reports illustrating the efficacy and safety of tDCS: in a pregnant woman with bipolar depression, in a pregnant woman with post-traumatic stress disorder (sham tDCS), and in a breastfeeding woman with postpartum depression. Conclusions: The results are encouraging, making tES a potentially safe and effective treatment in the perinatal period. Larger studies are needed to confirm these initial results, and any adverse effects on the mother or child should be reported. In addition, research perspectives on the medico-economic benefits of tES, and its realization at home, are to be investigated in the future.

Feasibility of Combining Transcranial Direct Current Stimulation and Active Fully Embodied Virtual Reality for Visual Height Intolerance: A Double-Blind Randomized Controlled Study.

BACKGROUND: Transcranial Direct Current Stimulation (tDCS) and Virtual Reality Exposure Therapy (VRET) are individually increasingly used in psychiatric research. OBJECTIVE/HYPOTHESIS: Our study aimed to investigate the feasibility of combining tDCS and wireless 360° full immersive active and embodied VRET to reduce height-induced anxiety. METHODS: We carried out a pilot randomized, double-blind, controlled study associating VRET (two 20 min sessions with a 48 h interval, during which, participants had to cross a plank at rising heights in a building in construction) with online tDCS (targeting the ventromedial prefrontal cortex) in 28 participants. The primary outcomes were the sense of presence level and the tolerability. The secondary outcomes were the anxiety level (Subjective Unit of Discomfort) and the salivary cortisol concentration. RESULTS: We confirmed the feasibility of the association between tDCS and fully embodied VRET associated with a good sense of presence without noticeable adverse effects. In both groups, a significant reduction in the fear of height was observed after two sessions, with only a small effect size of add-on tDCS (0.1) according to the SUD. The variations of cortisol concentration differed in the tDCS and sham groups. CONCLUSION: Our study confirmed the feasibility of the association between wireless online tDCS and active, fully embodied VRET. The optimal tDCS paradigm remains to be determined in this context to increase effect size and then adequately power future clinical studies assessing synergies between both techniques.

Cost-utility analysis of curative and maintenance repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant unipolar depression: a randomized controlled trial protocol.

BACKGROUND: Depression is a debilitating and costly disease for our society, especially in the case of treatment-resistant depression (TRD). Repetitive transcranial magnetic stimulation (rTMS) is an effective adjuvant therapy in treatment-resistant unipolar and non-psychotic depression. It can be applied according to two therapeutic strategies after an initial rTMS cure: a further rTMS cure can be performed at the first sign of relapse or recurrence, or systematic maintenance rTMS (M-rTMS) can be proposed. TMS adjuvant to treatment as usual (TAU) could improve long-term prognosis. However, no controlled study has yet compared the cost-effectiveness of these two additional rTMS therapeutic strategies versus TAU alone. METHODS/DESIGN: This paper focuses on the design of a health-economic, prospective, randomized, double-blind, multicenter study with three parallel arms carried out in France. This study assesses the cost-effectiveness of the adjunctive and maintenance low frequency rTMS on the right dorsolateral prefrontal cortex versus TAU alone. A total of 318 patients suffering from a current TRD will be enrolled. The primary endpoint is to investigate the incremental cost-effectiveness ratio (ICER) (ratio costs / quality-adjusted life-years [QALY] measured by the Euroqol Five Dimension Questionnaire) over 12 months in a population of patients assigned to one of three arms: systematic M-rTMS for responders (arm A); additional new rTMS cure in case of mood deterioration among responders (arm B); and a placebo arm (arm C) in which responders are allocated in two subgroups: sham systematic M-rTMS and supplementary rTMS course in case of mood deterioration. ICER and QALYs will be compared between arm A or B versus arm C. The secondary endpoints in each three arms will be: ICER at 24 months; the cost-utility ratio analysis at 12 and 24 months; 5-year budget impact analysis; and prognosis factors of rTMS. The following criteria will be compared between arm A or B and arm C: rates of responders; remission and disease-free survival; clinical evolution; tolerance; observance; treatment modifications; hospitalization; suicide attempts; work stoppage; marital / professional statues; and quality of life at 12 and 24 months. DISCUSSION: The purpose of our study is to check the cost-effectiveness of rTMS and we will discuss its economic impact over time. In the case of significant decrease in the depression costs and expenditures associated with a good long-term prognosis (sustained response and remission) and tolerance, rTMS could be considered as an efficient treatment within the armamentarium for resistant unipolar depression. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03701724. Registered on 10 October 2018. Protocol Amendment Version 2.0 accepted on 29 June 2019.