Efficacy and auditory biomarker analysis of fronto-temporal transcranial direct current stimulation (tDCS) in targeting cognitive impairment associated with recent-onset schizophrenia: study protocol for a multicenter randomized double-blind sham-controlled trial.

BACKGROUND: In parallel to the traditional symptomatology, deficits in cognition (memory, attention, reasoning, social functioning) contribute significantly to disability and suffering in individuals with schizophrenia. Cognitive deficits have been closely linked to alterations in early auditory processes (EAP) that occur in auditory cortical areas. Preliminary evidence indicates that cognitive deficits in schizophrenia can be improved with a reliable and safe non-invasive brain stimulation technique called tDCS (transcranial direct current stimulation). However, a significant proportion of patients derive no cognitive benefits after tDCS treatment. Furthermore, the neurobiological mechanisms of cognitive changes after tDCS have been poorly explored in trials and are thus still unclear. METHOD: The study is designed as a randomized, double-blind, 2-arm parallel-group, sham-controlled, multicenter trial. Sixty participants with recent-onset schizophrenia and cognitive impairment will be randomly allocated to receive either active (n=30) or sham (n=30) tDCS (20-min, 2-mA, 10 sessions during 5 consecutive weekdays). The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left auditory cortex. Cognition, tolerance, symptoms, general outcome and EAP (measured with EEG and multimodal MRI) will be assessed prior to tDCS (baseline), after the 10 sessions, and at 1- and 3-month follow-up. The primary outcome will be the number of responders, defined as participants demonstrating a cognitive improvement ≥Z=0.5 from baseline on the MATRICS Consensus Cognitive Battery total score at 1-month follow-up. Additionally, we will measure how differences in EAP modulate individual cognitive benefits from active tDCS and whether there are changes in EAP measures in responders after active tDCS. DISCUSSION: Besides proposing a new fronto-temporal tDCS protocol by targeting the auditory cortical areas, we aim to conduct a randomized controlled trial (RCT) with follow-up assessments up to 3 months. In addition, this study will allow identifying and assessing the value of a wide range of neurobiological EAP measures for predicting and explaining cognitive deficit improvement after tDCS. The results of this trial will constitute a step toward the use of tDCS as a therapeutic tool for the treatment of cognitive impairment in recent-onset schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov NCT05440955. Prospectively registered on July 1st, 2022.

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.

Twice daily low frequency rTMS for treatment-resistant auditory hallucinations

Background: Repetitive transcranial magnetic stimulation (rTMS) has emerged as a therapeutic solution in patients with treatment-resistant auditory verbal hallucinations. However, the optimal stimulation parameters remain unclear, especially for patients with clozapine-resistant symptoms. Method: In an open label retrospective study, we investigated whether parameters of stimulation that were useful in patients with major depressive disorder would help schizophrenia patients with treatment-resistant auditory verbal hallucinations. Fourteen participants, including 9 under clozapine, received 30 sessions of 1 Hz rTMS over 3 weeks (360 pulses per sessions delivered with 60 s ‘on’ and 30 s ‘off’ at 110% of the resting motor threshold, 2 sessions per day). Stimulations were applied over the left temporoparietal junction (T3-P3 according to 10/20 system). Results: After rTMS, a significant decrease of auditory verbal hallucinations was observed (−38.7% ± 31.8, p = 0.003) on the Auditory Hallucination Rating Scale. The beneficial effects were also significant in the 9 patients who were also receiving clozapine (−34.9% ± 28.4, p = 0.01). Conclusions: Low frequency rTMS, 30 sessions over 3 weeks, appears to be a suitable approach to decrease treatment-resistant auditory verbal hallucinations, including in patients with clozapine-resistant symptoms. Results from the current retrospective study in the clinical settings need to be confirmed by large-scale randomized sham-controlled trials. (AU)

Twice daily low frequency rTMS for treatment-resistant auditory hallucinations.

Background: Repetitive transcranial magnetic stimulation (rTMS) has emerged as a therapeutic solution in patients with treatment-resistant auditory verbal hallucinations. However, the optimal stimulation parameters remain unclear, especially for patients with clozapine-resistant symptoms. Method: In an open label retrospective study, we investigated whether parameters of stimulation that were useful in patients with major depressive disorder would help schizophrenia patients with treatment-resistant auditory verbal hallucinations. Fourteen participants, including 9 under clozapine, received 30 sessions of 1 Hz rTMS over 3 weeks (360 pulses per sessions delivered with 60 s 'on' and 30 s 'off' at 110% of the resting motor threshold, 2 sessions per day). Stimulations were applied over the left temporoparietal junction (T3-P3 according to 10/20 system). Results: After rTMS, a significant decrease of auditory verbal hallucinations was observed (-38.7% ± 31.8, p = 0.003) on the Auditory Hallucination Rating Scale. The beneficial effects were also significant in the 9 patients who were also receiving clozapine (-34.9% ± 28.4, p = 0.01). Conclusions: Low frequency rTMS, 30 sessions over 3 weeks, appears to be a suitable approach to decrease treatment-resistant auditory verbal hallucinations, including in patients with clozapine-resistant symptoms. Results from the current retrospective study in the clinical settings need to be confirmed by large-scale randomized sham-controlled trials.

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.

Case report: accelerated cathodal HD-tDCS over the right dorsolateral prefrontal cortex in hoarding disorder.

Hoarding disorder is an under-recognized condition characterized by the excessive acquisition of possessions and difficulty in disposing of them, which can have dramatic consequences. As hoarding disorder is difficult to treat and associated with high levels of disability in all areas of functioning, there appears to be a critical need to develop novel, tailored therapeutic strategies. Non-invasive brain stimulation techniques hold promise as potential therapeutic interventions for various psychiatric conditions and as a tool to modulate impulsivity when applied over the dorsolateral prefrontal cortex (DLPFC). Therefore, we hypothesized that delivering accelerated cathodal high-definition direct transcranial stimulation (HD-tDCS) over the right DLPFC could be a suitable approach to alleviate symptoms in patients with hoarding disorder. In a case report, we observed beneficial clinical effects on acquisition and depressive symptoms after 15 sessions of three daily 20-min sessions. Accelerated cathodal HD-tDCS over the right DLPFC appears to be a safe and appropriate intervention for patients with hoarding disorder. However, randomized, sham-controlled trials are needed to further validate these encouraging findings.

High-Frequency Transcranial Random Noise Stimulation for Auditory Hallucinations of Schizophrenia: A Case Series.

Transcranial electrical stimulation has been proposed as a noninvasive therapeutic approach for reducing treatment-resistant symptoms of schizophrenia-in particular, auditory hallucinations. However, the high variability observed in the clinical response leaves much room to optimize the stimulation parameters and strengthen its benefits. We proposed to investigate the effects of high-frequency transcranial random noise stimulation (hf-tRNS), which is supposed to induce larger effects than conventional direct current stimulation. Here, we present an initial case series of ten patients with schizophrenia who underwent 10 sessions of 20 min hf-tRNS (2 mA, 100-500 Hz, 1 mA offset), with the anode placed over the left dorsolateral prefrontal cortex and the cathode over the left temporoparietal junction. Patients showed a significant reduction in auditory hallucinations after the hf-tRNS sessions (-36.1 +/- 21.8%, p = 0.0059). In this preliminary, open-label study conducted in ten patients with treatment-resistant symptoms of schizophrenia, frontotemporal hf-tRNS was shown to induce a substantial improvement in auditory hallucinations. Additional sham-controlled studies are needed to further evaluate hf-tRNS as a treatment for schizophrenia.

Association of Delayed Sleep/Wake Rhythm with Depression During the First COVID-19 Lockdown in France.

Purpose: The containment of the population during the COVID-19 pandemic led to the emergence or recurrence of psychiatric conditions and sleep disorders. The influence of sleep/wake rhythm on mental health is well known. The objective of our study was to evaluate the link between the shift in sleep/wake rhythm and the presence of depressive symptoms during the March to May 2020 lockdown in the French population. Participants and Methods: Participants (n = 2513) were recruited via newspapers and social networks in March 2020. We evaluated i) the chronotype before and during the lockdown, assessed by the change in mid-sleep time on work-free days corrected for sleep debt on workdays (delta MSFsc); ii) morningness-eveningness circadian preference (Horne & Ostberg questionnaire); iii) depressive symptoms (Patient Health Questionnaire-9, PHQ-9). The delta MSFsc and the PHQ-9 score were compared between circadian preference types. A multivariate model adjusted for age, sex, circadian preference, housing type, and marital status was used to assess the influence of delta MSFsc on the PHQ-9 score in the whole population. Results: The population consisted of 77% women, of median (IQR) age 39 (30-48) years. Compared with the pre-lockdown period, the median (IQR) MSFsc was shifted by 30 (0-66) min during the lockdown, with a significant difference between evening [60 (15-120) min], morning [15 (0-46) min] and neutral [30 (0-70) min] circadian type individuals, p < 0.001. One-third of all participants had moderate to severe depressive symptoms (PHQ-9 ≥ 10). A 1-hour shift in MSFsc was associated with a 0.50-point increase [95% CI (0.28; 0.72), p < 0.001] in the PHQ-9. Conclusion: A phase delay in the chronotype was observed in the general population during lockdown. Such disruption was associated with depressive symptoms but the direction of the relationship remains hypothetical. The impact on mental health of preventive measures targeting the sleep/wake rhythm in this context needs further evaluation.

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.

Serum Mature BDNF Level Is Associated with Remission Following ECT in Treatment-Resistant Depression.

The search for a biological marker predicting the future failure or success of electroconvulsive therapy (ECT) remains highly challenging for patients with treatment-resistant depression. Evidence suggests that Brain-Derived Neurotrophic Factor (BDNF), a protein known to be involved in brain plasticity mechanisms, can play a key role in both the clinical efficacy of ECT and the pathophysiology of depressive disorders. We hypothesized that mature BDNF (mBDNF), an isoform of BDNF involved in the neural plasticity and survival of neural networks, might be a good candidate for predicting the efficacy of ECT. Total BDNF (tBDNF) and mBDNF levels were measured in 23 patients with severe treatment-resistant depression before (baseline) they received a course of ECT. More precisely, tBDNF and mBDNF measured before ECT were compared between patients who achieved the criteria of remission after the ECT course (remitters, n = 7) and those who did not (non-remitters, n = 16). We found that at baseline, future remitters displayed significantly higher mBDNF levels than future non-remitters (p = 0.04). No differences were observed regarding tBDNF levels at baseline. The multiple logistic regression model controlled for age and sex revealed that having a higher baseline mBDNF level was significantly associated with future remission after ECT sessions (odd ratio = 1.38; 95% confidence interval = 1.07-2.02, p = 0.04). Despite the limitations of the study, current findings provide additional elements regarding the major role of BDNF and especially the mBDNF isoform in the clinical response to ECT in major depression.

Examining transcranial random noise stimulation as an add-on treatment for persistent symptoms in schizophrenia (STIM'Zo): a study protocol for a multicentre, double-blind, randomized sham-controlled clinical trial.

BACKGROUND: One out of three patients with schizophrenia failed to respond adequately to antipsychotics and continue to experience debilitating symptoms such as auditory hallucinations and negative symptoms. The development of additional therapeutic approaches for these persistent symptoms constitutes a major goal for patients. Here, we develop a randomized-controlled trial testing the efficacy of high-frequency transcranial random noise stimulation (hf-tRNS) for the treatment of resistant/persistent symptoms of schizophrenia in patients with various profiles of symptoms, cognitive deficits and illness duration. We also aim to investigate the biological and cognitive effects of hf-tRNS and to identify the predictors of clinical response. METHODS: In a randomized, double-blind, 2-arm parallel-group, controlled, multicentre study, 144 patients with schizophrenia and persistent symptoms despite the prescription of at least one antipsychotic treatment will be randomly allocated to receive either active (n = 72) or sham (n = 72) hf-tRNS. hf-tRNS (100-500 Hz) will be delivered for 20 min with a current intensity of 2 mA and a 1-mA offset twice a day on 5 consecutive weekdays. The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left temporoparietal junction. Patients' symptoms will be assessed prior to hf-tRNS (baseline), after the 10 sessions, and at 1-, 3- and 6-month follow-up. The primary outcome will be the number of responders defined as a reduction of at least 25% from the baseline scores on the Positive and Negative Syndrome Scale (PANSS) after the 10 sessions. Secondary outcomes will include brain activity and connectivity, source monitoring performances, social cognition, other clinical (including auditory hallucinations) and biological variables, and attitude toward treatment. DISCUSSION: The results of this trial will constitute a first step toward establishing the usefulness of hf-tRNS in schizophrenia whatever the stage of the illness and the level of treatment resistance. We hypothesize a long-lasting effect of active hf-tRNS on the severity of schizophrenia symptoms as compared to sham. This trial will also have implications for the use of hf-tRNS as a preventive intervention of relapse in patients with schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov NCT02744989. Prospectively registered on 20 April 2016.

Using EEG to Predict Clinical Response to Electroconvulsive Therapy in Patients With Major Depression: A Comprehensive Review.

Introduction: An important approach to improve the therapeutic effect of electroconvulsive therapy (ECT) may be to early characterize patients who are more likely to respond. Our objective was to explore whether baseline electroencephalography (EEG) settings before the beginning of ECT treatment can predict future clinical response to ECT in patients with depressive disorder. Methods: We conducted a systematic search in the MEDLINE, EMBASE, PsycINFO, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases to identify studies using EEG in adults with depressive disorder treated by ECT. To investigate the predictive value of baseline EEG on clinical outcomes of ECT, we extracted from the retrieved studies and qualitatively described the association between the baseline EEG markers characteristics and the rates of future responders and/or remitters to ECT. Results: The primary search yielded 2,531 potentially relevant citations, and 12 articles were selected according to inclusion criteria. Most of the studies were prospective studies with small sample size. Sociodemographic and clinical characteristics of patients, ECT settings, EEG settings, and outcomes were heterogeneous. Event-related potential (ERP) paradigms were used in three studies, polysomnography was used in three studies, and the six other studies used EEG to measure cerebral connectivity and activity. Conclusions: P300 amplitude, coherence, and connectivity measures were correlated with remission in patients with depression treated by ECT. Sleep EEG recordings seemed not to be correlated with remission after ECT. Further prospective studies with large sample size are needed to determine optimal EEG parameters associated with clinical response to ECT in depressive disorder. Systematic Review Registration: PROSPERO CRD42020181978.

Predicting Exact Valence and Arousal Values from EEG.

Recognition of emotions from physiological signals, and in particular from electroencephalography (EEG), is a field within affective computing gaining increasing relevance. Although researchers have used these signals to recognize emotions, most of them only identify a limited set of emotional states (e.g., happiness, sadness, anger, etc.) and have not attempted to predict exact values for valence and arousal, which would provide a wider range of emotional states. This paper describes our proposed model for predicting the exact values of valence and arousal in a subject-independent scenario. To create it, we studied the best features, brain waves, and machine learning models that are currently in use for emotion classification. This systematic analysis revealed that the best prediction model uses a KNN regressor (K = 1) with Manhattan distance, features from the alpha, beta and gamma bands, and the differential asymmetry from the alpha band. Results, using the DEAP, AMIGOS and DREAMER datasets, show that our model can predict valence and arousal values with a low error (MAE < 0.06, RMSE < 0.16) and a strong correlation between predicted and expected values (PCC > 0.80), and can identify four emotional classes with an accuracy of 84.4%. The findings of this work show that the features, brain waves and machine learning models, typically used in emotion classification tasks, can be used in more challenging situations, such as the prediction of exact values for valence and arousal.

Improvement of Insight with Non-Invasive Brain Stimulation in Patients with Schizophrenia: A Systematic Review.

Patients with schizophrenia are often unaware of their condition and the consequences of their illness. This lack of insight results in impaired functioning, treatment non-adherence and poor prognosis. Here, we aimed to investigate the effects of non-invasive brain stimulation (NIBS) on two forms of insight, clinical and cognitive, in patients with schizophrenia. We conducted a systematic review of the literature registered in the PROSPERO database (CRD42020220323) according to PRISMA guidelines. The literature search was conducted in Medline and Web of Science databases based on studies published up until October 2020 that included pre-NIBS and post-NIBS measurements of clinical and/or cognitive insight in adults with schizophrenia. A total of 14 studies were finally included, and their methodological quality was assessed by using the QualSyst tool. Despite the lack of well-conducted large randomized-controlled studies using insight as the primary outcome, the available findings provide preliminary evidence that NIBS can improve clinical insight in patients with schizophrenia, with a majority of studies using transcranial direct current stimulation with a left frontotemporal montage. Further studies should investigate the effect of NIBS on insight as a primary outcome and how these effects on insight could translate into clinical and functional benefits in patients with schizophrenia.

Impact of vascular risk factors on clinical outcome in elderly patients with depression receiving electroconvulsive therapy.

BACKGROUND: Although electroconvulsive therapy (ECT) is a highly effective, safe, and well-tolerated antidepressant treatment for late-life depression (LLD), there is large variability in response rates across individuals. We hypothesized that these variations would be in part explained by the level of vascular risk in this population. We therefore compared response rates to ECT in patients with LLD presenting with or without vascular risk factors (VRF). METHODS: 52 patients with LLD (age > 55) who received a course of ECT were separated into 2 groups according to the presence of VRF (n = 20) or not (n = 32). Framingham score (10-year risk for developing a coronary heart disease) was calculated for each patient. Our primary outcome was the number of responders to ECT in each group (defined as at least 50% decrease of the Montgomery-Åsberg Depression Rating Scale score following ECT course). Scores at the self-rated Beck Depression Inventory are also reported. RESULTS: Patients with VRF presented significant lower response rates to ECT (12 out of 20; 60%) than patients without VRF (30 out of 32; 94%; p = 0.004). A negative correlation was found between Framingham score and changes in depression scores pre/post ECT (r = -0.42; p = 0.0039). LIMITATIONS: Our study was limited by sample size and retrospective design. CONCLUSION: Patients with LLD and VRF showed lower response rates to ECT than those without VRF. The more the VRF increased, the less the antidepressant effect of ECT was observed. Results are discussed in light of the role of apathy in clinical response to ECT.

The Combination of Propofol and Ketamine Does Not Enhance Clinical Responses to Electroconvulsive Therapy in Major Depression-The Results From the KEOpS Study.

OBJECTIVE: We investigated the clinical effects of the combination of ketamine and propofol as anesthetic agents during electroconvulsive therapy (ECT) in patients with uni- or bipolar major depressive episodes. We hypothesized that ketamine may confer short- and long- term advantages in improving depressive symptoms at the early stages of ECT. METHODS: In a randomized placebo-controlled trial, remission rates after 4 and 8 weeks of ECT were compared between patients who were randomly allocated to receive either the combination of ketamine (0.5 mg/kg) + propofol (n= 11) or placebo + propofol (n = 16). Depressive symptoms were assessed weekly using the Montgomery-Åsberg Depression Rating Scale (MADRS); ECT sessions were administered twice per week for a maximum of 8 weeks (16 sessions). RESULTS: After 4 weeks, we observed significantly fewer remitters (MADRS score < 10) in the ketamine + propofol group (0/11; 0%) than in the placebo + propofol group (5/16; 31%; χ2 = 4.22; p = 0.040). No significant difference was observed between the two groups regarding the number of patients who achieved remission weekly throughout the study period (Chi² = 3.588; p = 0.058). The mean duration of seizures was significantly shorter in the ketamine + propofol group than in the placebo + propofol group. CONCLUSIONS: The results from the current study corroborated results from previously published studies and did not support the use of the combination of ketamine + propofol as an anesthetic agent for ECT in patients with major depressive episodes in clinical settings.

[Mood disorders: When should we use repetitive transcranial magnetic stimulation?] / Troubles de l'humeur : quand recourir à la stimulation magnétique transcrânienne ?

Repeated transcranial magnetic stimulation (rTMS) is still a recent treatment in psychiatry. This article aims at updating the clinicians'knowledge about rTMS in the treatment of mood disorders (uni and bipolar depressive disorders, manic/mixed states, suicidal risk, catatonia). It is intended for clinicians who are required to indicate and/or use rTMS in their current practice. rTMShas the highest level of evidence for the treatment of unipolar depression, provided that effective parameters are used, that is to say, for classical high frequency protocols: 20 to 30 sessions, 1000 pulses/session, 5 to 20Hz, and 110 % of the motor threshold. Low frequency protocol are also efficient and well tolerated. The duration of the efficacy varies with relapses rates around 50 % at one year. Pharmacological treatment generally remains associated. With regard to manic states, and mixed states the results are preliminary and limited to a possible reduction in symptoms. In the suicidal risk associated with mood disorders, the interest of rTMS is still to demonstrate, as well as in catatonia. The current place of the rTMS is no longer disputed in the curative treatment of major depressive disorder, preferentially used after one or two lines of antidepressants upstream. Further studies are needed to confirm preliminary positive findings in other aspects of mood disorders.

How Much Do Benzodiazepines Matter for Electroconvulsive Therapy in Patients With Major Depression?

BACKGROUND: Electroconvulsive therapy (ECT) is one of the most effective treatments for major depressive disorder (MDD), especially in cases of treatment-resistant MDD. Because of their pharmacological profiles, benzodiazepines (BZDs) are suspected to decrease the efficacy of ECT. This study investigated the effect of BZDs on ECT-induced clinical outcomes and ECT course parameters in patients with MDD. METHOD: The impact of BZDs on severity of depression (Montgomery-Asberg Depression Rating Scale scores) and on ECT course parameters (seizure threshold, clinical and electroencephalographic seizure duration) was investigated in 70 patients with MDD who received an ECT course using dose-titration method (22 received concomitant BZDs). RESULTS: Lower remission rates (52.0%) and smaller decreases in Montgomery-Asberg Depression Rating Scale scores were observed in the non-BZD group than in the BZD group (81.2%, P = 0.02). There were no significant differences between the 2 groups regarding seizure duration and seizure threshold. LIMITATIONS: This was a retrospective study. Impact of BZDs on anxiety and cognition was not assessed. CONCLUSIONS: Benzodiazepines increased the clinical efficacy of ECT when delivered using dose-titration method and bitemporal stimulation. Further studied are needed to understand the interaction between BZDs and ECT on clinical outcomes.

Pertinence of Titration and Age-Based Dosing Methods for Electroconvulsive Therapy: An International Retrospective Multicenter Study.

BACKGROUND: Although the dosage of electroconvulsive therapy (ECT) stimulus has a major impact on the efficacy and safety of this treatment, the method used to determine an optimal dosage remains a matter of debate. OBJECTIVE: We investigated factors influencing the seizure threshold (ST) in a large-sample study and compared age-based and titration dosing methods in terms of charge. METHODS: A retrospective study examined data from 503 patients across France and Canada. The patients underwent right unilateral (RUL) or bitemporal (BT) ECT during a titration session before undergoing ECT. Seizure threshold and charge differences between age-based and titration-predicted methods were derived for each RUL and BT patient and compared according to sex, age, and anesthetic agents. RESULTS: Based on our results, ST is a function of electrode placement, sex, age, and anesthetic agents. Titration and age-based methods led to completely different patterns of charges for the same electrode placement, especially in elderly and in women in the RUL group. Regression models showed that differences between the age-based and titration methods varied with respect to age, sex, and anesthetic agent. Specifically, significant effects of sex and age were observed for RUL ECT and of sex and anesthetics for BT ECT. CONCLUSIONS: This study revealed that several factors significantly influence the prediction of ECT dose, depending on individuals and treatment modalities. Caution should be exercised when using nonindividualized methods to calculate ST.