The value of a multidisciplinary consensus meeting in achieving agreement on eating disorders diagnosis at a specialized referral center.

OBJECTIVE: This study aimed to evaluate the concordance of eating disorders (EDs) diagnoses within a multidisciplinary team in a specialized hospital unit dedicated to the medical care of ED. METHODS: The study analyzed data from 608 female patients who sought consultation at the Eating Disorders Referral Center between 2017 and 2021. The diagnoses were established according to the DSM-5 criteria by endocrinologists, psychiatrists, and finally confirmed or discussed within a monthly multidisciplinary consensus meeting (MCM). Fleiss' Kappa tests were conducted to assess inter-raters' agreement. RESULTS: Overall, substantial agreement was observed between endocrinologists and psychiatrists and the MCM. A more detailed analysis revealed variations in agreement across different disorders. Certain EDs demonstrated substantial agreement (e.g., anorexia nervosa restrictive subtype), while others approached near-perfect agreement (e.g., binge-eating disorder). In contrast, agreement was fair to poor for anorexia nervosa binge-purge subtype (ANBP) and slight for other specified feeding and ED. A period of temporary disagreement was noted for ANBP, partially attributed to practitioner turnover. An improvement in interdisciplinary agreement was observed for all ED diagnoses by the end of the study period. DISCUSSION: Variations or lower levels of inter-rater agreement may stem from atypical cases that fall on the border between two diagnoses or complex cases, as well as fluctuating symptoms. The progress observed throughout the study can be attributed in part to interdisciplinary learning, particularly facilitated by the MCM. The findings underscore the significance of striving for optimal concordance among different medical specialties to enhance patient care in ED treatment. PUBLIC SIGNIFICANCE: This study scrutinizes the agreement levels of ED diagnoses among endocrinologists and psychiatrists within a multidisciplinary team at an Eating Disorders Referral Center. While substantial overall agreement was achieved, disparities or lower agreement levels were evident for certain diagnoses such as anorexia nervosa binge-purge subtype. However, collaborative meetings led to a progressive enhancement in agreement over time. This research underscores the crucial role of a multidisciplinary team working collectively to ensure precise diagnoses and improved care for patients with EDs.

Continuous glucose monitoring assessment in patients suffering from anorexia nervosa reveals chronic prolonged mild hypoglycemia all over the nycthemeron.

OBJECTIVE: Anorexia nervosa (AN) is an eating disorder characterised by voluntary dietary restriction leading to severe undernutrition. Hypoglycaemia is mostly described through severe case reports and is always evaluated by fasting or post-meal blood glucose, showing nothing about hypoglycaemia's length or duration. The interest of continuous interstitial glucose monitoring (CGM), largely used in diabetes mellitus, has never been evaluated in AN patients. METHOD: Glycaemia cycles in AN patients were assessed using CGM over 5 days and then analysed according to food intake. RESULTS: Mean glycaemia was within normal range. 91% of the patients presented with at least one episode with glycaemia under 70 mg/dl. Within the 24 h, the percentage of time spent with a glycaemia under 70 mg/dl was of 20.82 ± 3.90% with a maximum of 52%. We found 2.52 ± 0.33 hypoglycaemia events per 24 h, including 21.11 ± 3.76% at night. CGM parameters correlated with cortisol and IGF1 plasma levels. Comparison with estimated carbohydrate intakes discriminated concordant and non-concordant estimations depending on patient. CONCLUSIONS: AN patients display chronic prolonged mild hypoglycaemia all over the nycthemeron despite normal fasting glycaemia. Associated adaptive increased counter-regulatory hormones might protect AN patients from deeper hypoglycaemia. CGM allowed testing food intake self-estimation reliability of AN patients and could be a very useful biofeedback tool.

Childhood trauma and the severity of past suicide attempts in outpatients with cocaine use disorders.

Introduction: Suicide attempts have been associated with both cocaine use disorder (CocUD) and childhood trauma. We investigated how childhood trauma is an independent risk factor for serious and recurrent suicide attempts in CocUD. Method: 298 outpatients (23% women) with CocUD underwent standardized assessments of substance dependence (Diagnostic and Statistical Manual-mental disorders, fourth edition, text revised), impulsiveness, resilience, and childhood trauma, using validated tools. Suicide attempts history was categorized as single vs. recurrent or non-serious vs. serious depending on the lifetime number of suicide attempts and the potential or actual lethality of the worst attempt reported, respectively. Bivariate and multinomial regression analyses were used to characterize which childhood trauma patterns were associated with the suicide attempts groups. Results: 58% of CocUD patients reported childhood trauma. Recurrent and serious suicide attempts clustered together and were thus combined into "severe SA." Severe suicide attempt risk increased proportionally to the number of childhood traumas (test for trend, p = 9 × 10-7). Non-severe suicide attempt risk increased with impulsiveness and decreased with resilience. In multinomial regression models, a higher number of traumas and emotional abuse were independently and only associated with severe vs. non-severe suicide attempts (effect size = 0.82, AUC = 0.7). The study was limited by its cross-sectional design. Conclusion: These preferential associations between childhood trauma and severe suicide attempts warrant specific monitoring of suicide attempts risk in CocUD, regardless of the severity of addiction profiles.

Improving decision-making and cognitive impulse control in bulimia nervosa by rTMS: An ancillary randomized controlled study.

OBJECTIVE: Impaired decision-making and inhibitory control may be involved in the pathophysiology of psychiatric disorders like bulimia nervosa (BN). Their improvement after neuromodulation may underpin clinical improvement. We assessed the effects of rTMS on these cognitive functions in a sample of women with BN. METHODS: Thirty-nine participants (22 in a sham group and 17 in an rTMS group) were assessed before and after 10 high frequency rTMS sessions over the left dorsolateral prefrontal cortex (DLPFC). RESULTS: The between-group analyses revealed no differences in the final neuropsychological performances. The within-group analyses showed that inhibitory control improved in both the go/no-go task (p = .03) and the BIS cognitive impulsivity subscale (p = .01) in the rTMS group only. Switches toward good choices on the Iowa gambling task significantly improved in the rTMS group only (p = .002), and understanding of the task contingencies increased between the two assessments, also in the rTMS group only (p = .03). DISCUSSION: This preliminary evidence suggests that modulation of left DLPFC might improve two putative cognitive biomarkers of BN.

Effect of telephone follow-up on repeated suicide attempt in patients discharged from an emergency psychiatry department: a controlled study.

BACKGROUND: Attempted suicide is a major public health problem, and the efficacies of current postvention protocols vary. We evaluated the effectiveness of telephone follow-up of patients referred to an emergency psychiatric unit for attempted suicide on any further attempt/s over the following year. METHOD: In a single-center, controlled study with intent to treat, we evaluated the efficacy of a protocol of telephone follow-up of 436 patients at 8, 30, and 60 days after they were treated for attempted suicide. As controls for comparison, we evaluated patients with similar social and demographic characteristics referred to our emergency psychiatric unit in the year prior to the study who did not receive telephone follow-up after their initial hospitalization. Data were analyzed using logistic regression. RESULTS: Very early telephone follow-up of our patients effectively reduced recidivism and seemed to be the only protective factor against repeated suicide attempt. CONCLUSIONS: Implementing a protocol of early telephone follow-up after attempted suicide could help prevent repeated attempt/s. More controlled studies are needed to assess optimal techniques to prevent such repetition.

A Lack of Clinical Effect of High-frequency rTMS to Dorsolateral Prefrontal Cortex on Bulimic Symptoms: A Randomised, Double-blind Trial.

Studies suggest that stimulation of the left dorsolateral prefrontal cortex (DLPFC) reduces food craving in bulimic patients, but evidence supporting repetitive transcranial magnetic stimulation (rTMS) as a therapeutic tool is lacking. We investigated the safety and therapeutic efficacy of an adjunct high-frequency rTMS programme targeting the left DLPFC. Forty-seven women with bulimia nervosa were randomised to a real or sham stimulation group. The real group underwent 10 rTMS sessions, each consisting of 20 trains of 5 seconds with 55-second intervals between trains, at a frequency of 10 Hz. The main outcome was the number of binge episodes in the 15 days following the end of stimulation. Overall, no significant improvement in bingeing and purging symptoms was noted after the programme. rTMS was well tolerated. This suggests that 10 sessions of high-frequency rTMS to the left DLPFC provide no greater benefit than placebo. Future studies should consider methodological issues as well as alternative targets. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

Systematic review of prospective studies assessing risk factors to predict anorexia nervosa onset.

BACKGROUND: According to case‒control studies, a multitude of factors contribute to the emergence of anorexia nervosa (AN). The present systematic review examines prospective studies specifically designed to evaluate the prediction of AN onset. METHODS: According to the ARMSTAR 2 and PRISMA 2020 checklists, the PubMed, PsycINFO and Cochrane databases were searched. The methodological quality of the studies was assessed with the Downs and Black checklist. RESULTS: Three articles concerning prospective studies of the general population were ultimately included in the review. The methodological quality of these studies was not optimal. Bidirectional amplification effects were observed between risk factors, some of which could have a relative predictive force as low bodyweight or body dissatisfaction. Even if not included according to specified criteria for this systematic review 11 longitudinal studies, with retrospective analysis of AN onset' prediction, were also discussed. None of these studies asserted the predictive value of particular risk factors as low body weight, anxiety disorders or childhood aggression. CONCLUSIONS: To date there are insufficient established data to propose predictive markers of AN onset for predictive actions in pre-adolescent or adolescent populations. Future work should further evaluate potential risk factors previously identified in case‒control/retrospective studies within larger prospective investigations in preadolescent populations. It is important to clearly distinguish predisposing factors from precipitating factors in subjects at risk of developing AN.

Currently health care guidelines for eating disorders do not include proposal of markers to predict the onset of anorexia nervosa. The current work provides a systematic review of the scientific literature concerning this subject. To date only three published studies were designed in a prospective longitudinal way to evaluate potential predictors of anorexia nervosa onset. When taking into account these studies only low bodyweight and body dissatisfaction in early puberty were proposed as predicting elements for further anorexia nervosa development. Meanwhile the prediction precision was calculated for none of them. No other psychological elements were retained or studied. The age range of the population entering the follow up in these studies was too large covering the peak age of anorexia nervosa itself (13­16 years of age). Larger prospective studies including prepubescent individual and evaluating more psychological markers (perfectionism, negative affectivity or negative self-evaluation) or environmental ones are needed.

Mechanisms and predictors of menses resumption once normal weight is reached in anorexia nervosa.

BACKGROUND: In cases of Anorexia Nervosa (AN), achieving weight gain recovery beyond the lower limits set by the World Health Organization and normalizing classical nutritional markers appears to be essential for most patients. However, this is not always adequate to restore menstrual cycles. This discrepancy can cause concern for both patients and healthcare providers, and can impact the medical management of these individuals. Thus, the purpose of this study was to assess the ability of anthropometric and hormonal factors to predict the resumption of menstrual cycles in individuals with anorexia nervosa upon reaching a normal body weight. METHOD: Patients with AN who had achieved a normal Body Mass Index but had not yet resumed their menstrual cycles (referred to as ANRec) were evaluated on two occasions: first at visit 1 and then again 6 months later, provided their body weight remained stable over this period (visit 2). Among the 46 ANRec patients who reached visit 2, they were categorized into two groups: 20 with persistent amenorrhea (PA-ANRec) and 26 who had regained their menstrual cycles (RM-ANRec). Anthropometric measurements, several hormone levels, Luteinizing Hormone (LH) pulsatility over a 4-h period, and LH response to gonadotropin-releasing hormone injection (LH/GnRH) were then compared between the two groups at visit 1. RESULTS: Patients in the RM-ANRec group exhibited higher levels of follicular stimulating hormone, estradiol, inhibin B, LH/GnRH, and lower levels of ghrelin compared to those in the PA-ANRec group. Analysis of Receiver Operating Characteristic curves indicated that having ≥ 2 LH pulses over a 4-h period, LH/GnRH levels ≥ 33 IU/l, and inhibin B levels > 63 pg/ml predicted the resumption of menstrual cycles with a high degree of specificity (87%, 100%, and 100%, respectively) and sensitivity (82%, 80%, and 79%, respectively). CONCLUSIONS: These three hormonal tests, of which two are straightforward to perform, demonstrated a high predictive accuracy for the resumption of menstrual cycles. They could offer valuable support for the management of individuals with AN upon achieving normalized weight. Negative results from these tests could assist clinicians and patients in maintaining their efforts to attain individualized metabolic targets. TRIAL REGISTRATION: IORG0004981.

Once a minimally normal weight has been reached during eating disorder recovery for female patients with anorexia nervosa (AN), the persistence of amenorrhea can be a cause for concern both patient and practitioner. In our study, we have discovered that positive results in biological blood tests, which can be conveniently conducted in an ambulatory setting, offer valuable predictive insights. Specifically, parameters such as LH pulse numbers exceeding 2, LH response to GnRH injection surpassing 33 UI/L, or Inhibin B levels in the blood exceeding 63 pg/mL, can accurately predict the resumption of menstrual cycles in the upcoming months, provided that the patient does not experience weight loss or engage in intense exercise. Conversely, negative results from these tests at this critical juncture in the recovery process can serve as valuable tools to encourage and motivate both the healthcare provider and the patient. By maintaining their efforts and continuing to increase their weight, patients can work towards a more comprehensive restoration of their menstrual cycles.

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.

Repetitive Transcranial Magnetic Stimulation (rTMS) as a Promising Treatment for Craving in Stimulant Drugs and Behavioral Addiction: A Meta-Analysis.

Addiction is a mental disorder with limited available treatment options. The therapeutic potential of repetitive transcranial magnetic stimulation (rTMS) on it, by targeting craving in particular, has been explored with heterogenous results. This meta-analysis uses updated evidence to assess overall rTMS efficacy on craving, differential effects between addiction types clustered into three groups (depressant (alcohol, cannabis, opiate), stimulant (nicotine, cocaine, methamphetamine), and behavioral addiction (gambling, eating disorder)), and stimulation settings. Studies on substance use, gambling, and eating disorders are included, with unrestricted stimulation settings, by searching the PubMed, Embase, PsycINFO, and Cochrane databases up to 30 April 2020. A total of 34 eligible studies (42 units of analysis) were identified. Because of highly significant heterogeneity in primary results, a sensitivity analysis was performed on a remaining sample of 26 studies (30 units of analysis). Analyses performed using random effects model revealed a small effect size favoring active rTMS over shamTMS stimulation in the reduction in craving. We found a significant difference between addiction types, with a persistent small effect only for stimulant and behavioral groups. In these groups we found no difference between the different combinations of target and frequency of stimulation, but a significant correlation between number of sessions and craving reduction. In conclusion, efficacy of rTMS on craving in stimulant and behavioral addiction was highlighted, but recommendations on optimal stimulation settings and its clinical application await further research.

Occurrence and severity of cocaine-induced hallucinations: Two distinct phenotypes with shared clinical factors but specific genetic risk factors.

Cocaine-induced transient hallucinations (CIH) are a frequent complication following cocaine intake that is associated with addiction severity. METHODS: Two hundred and forty-two non-psychotic and Caucasian lifetime cocaine users were included in a French multicentric study. Clinical variables and dopamine pathway genotype data were extracted and tested with CIH scores using a zero-inflated binomial model, which allows for the exploration of factors associated with occurrence and severity separately. RESULTS: Cocaine dependence (poccurrence= 6.18 × 10-5, pseverity= 9.25 × 10-8), number of cocaine dependence DSM IV-Tr criteria (poccurrence= 1.22 × 10-7, pseverity= 5.09 × 10-6), and frequency of intake during the worst period of misuse (poccurrence= 8.51 × 10-04, pseverity= 0.04) were associated with greater occurrence and higher severity of CIH. The genetic associations did not yield significant results after correction for multiple tests. However, some nominal associations of SNPs mapped to the VMAT2, DBH, DRD1, and DRD2 genes were significant. In the multivariate model, the significant variables were the number of cocaine dependence criteria, lifetime alcohol dependence, and the nominally associated SNPs. CONCLUSION: Our study shows that CIH occurrence and severity are two distinct phenotypes, with shared clinical risk factors; however, they likely do not share the same genetic background.

[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.

Goal Directed and Self-Control Systems in Bulimia Nervosa: An fMRI Study.

BACKGROUND: Binge eating is apparently the opposite of the strict control over food intake typically set by "maladaptive dieters". Using functional magnetic resonance imaging (fMRI), we investigated the role of goal-directed behaviors, and the related use of self-control, in binge-related food choices in patients with Bulimia Nervosa (BN). METHOD: While undergoing fMRI, women aged 18-35 with BN (N = 35) and healthy control women (N = 26) rated foods for healthiness and tastiness and then made food choices on a 5 points Likert scale between two conflicting options: one food with lower healthiness and higher tastiness (defined as uncontrolled choice) than the other food (defined as controlled choice). RESULTS: BN and healthy participants made more uncontrolled than controlled choices (63% vs 24% and 65% vs 18% respectively). While healthy participants used only food tastiness (chose tastier foods more often) to make food choices (p < .001), BN patients used both food healthiness (chose unhealthy food more often, p < .001) and food tastiness (p < .001) to make binge-related food choices. Activity in the ventromedial prefrontal cortex (vmPFC), which correlated with food choices (pFWE = 0.02), reflected this difference in the integration of food healthiness and food tastiness into a decision value. Functional connectivity analysis showed that the activity in the dorsolateral prefrontal cortex was coupled with vmPFC activity in uncontrolled food choices (pFWE = 0.03). INTERPRETATION: Contrary to what might be expected, not only food tastiness but also unhealthiness (a more abstract cognitive-based attribute than food tastiness) plays a role in uncontrolled choices in BN. These choices are likely goal-directed behaviors and recruit self-control.

Cinemotion, a Program of Cognitive Remediation to Improve the Recognition and Expression of Facial Emotions in Schizophrenia: A Pilot Study.

Objective: Patients with schizophrenia exhibit impaired social cognition, especially in the recognition and expression of facial emotions, aspects of communication profoundly interlinked in an embodied approach of cognition. Nevertheless, many training programs have been developed that focus on either of these deficits but not both. We therefore designed a training program, Cinemotion, intended to remedy the 2 deficits and investigated its feasibility and effects in patients with schizophrenia. Design: Thirty-one patients undergoing treatment for schizophrenia and presenting deficit in emotion recognition were randomized to a group of 16 to undergo Cinemotion training, delivered in weekly group sessions, and to a control treatment group of 15. At the conclusion of training or after 10 weeks in controls, we reassessed and compared original and final results to determine improvement. Methods: Facial emotions recognition (TREF), empathy (Questionnaire of Cognitive and Affective Empathy, QCAE), and attributional style (Ambiguous Intentions Hostility Questionnaire, AIHQ) were assessed before (T0) and after (T1) the program. External evaluators also assessed ability and accuracy of Cinemotion participants to self-generate facial emotion expression in response to verbal instruction. Results: Between T0 and T1, Cinemotion participants significantly improved total TREF, sadness, disgust, and anger scores, compared to findings in control treatment group. They also improved their ability and accuracy to self-generate facial expressions, especially sadness and fear, with no significant improvement in other components of social recognition. Conclusions: Our findings show the apparent efficacy of training using the Cinemotion program to improve the recognition and expression of facial emotions in schizophrenia.

Childhood trauma and emotional processing circuits in schizophrenia: A functional connectivity study.

Childhood trauma strongly impacts emotional responses in schizophrenia. We have explored an association between early trauma and the amygdala functional connectivity using generalized psychophysiological interaction during an emotional task. Twenty-one schizophrenia patients and twenty-five controls were included. In schizophrenia patients, higher levels of sexual abuse and physical neglect during childhood were associated with decreased connectivity between the amygdala and the posterior cingulate/precuneus region. Additionally, patients showed decreased coupling between the amygdala and the posterior cingulate/precuneus region compared to controls. These findings suggest that early trauma could impact later connectivity in specific stress-related circuits affecting self-consciousness and social cognition in schizophrenia.

Childhood trauma are not associated with the intensity of transient cocaine induced psychotic symptoms.

A personal history of childhood trauma has been associated with the severity of psychotic symptoms in several disorders. We evaluated retrospectively cocaine-induced psychotic symptoms with the SAPS-CIP and childhood trauma with the CTQ in a clinical sample of 144 cocaine users. The SAPS-CIP score was not statistically associated with the presence or number or intensity of trauma, but was associated with rapid routes of administration (intravenous and smoked) and with frequent cocaine use.

The efficacy and safety of low frequency repetitive transcranial magnetic stimulation for treatment-resistant depression: the results from a large multicenter French RCT.

CONTEXT: The aim of this study was to assess whether the combination of low frequency repetitive transcranial magnetic stimulation (rTMS) and venlafaxine (150-225 mg/day) is effective and safe for treatment-resistant unipolar depression (TRD). METHOD: In a multicenter (18 centers) randomized double blind controlled trial with three arms, 170 patients were allocated to receive active rTMS combined with active venlafaxine (n = 55), active rTMS combined with placebo venlafaxine (n = 60) or sham rTMS combined with active venlafaxine (n = 55). The patients received once daily sessions of active or sham 1 Hz rTMS applied over the right dorsolateral prefrontal cortex (360 pulses/day delivered at 120% of the resting motor threshold) for two to six weeks; rTMS was combined with active or sham venlafaxine (mean dose: 179.0 ± 36.6 mg/day). The primary outcome was the number of patients who achieved remission, which was defined as an HDRS17 score <8. RESULTS: We reported a similar significant antidepressant effect in the 3 groups (P < 10(-6)), with a comparable delay of action and a comparable number of remitters at the endpoint (28% in the combination group, 41% in the rTMS group and 43% in the venlafaxine group; P = 0.59). CONCLUSION: Low frequency rTMS appears to be as effective as venlafaxine and as effective as the combination of both treatments for TRD. Because of its short session duration (the duration of one session was 8.5 min) and its safety, slow rTMS might be a useful alternative treatment for patients with TRD.