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.

Recurrence After Stopping Maintenance Electroconvulsive Therapy: A Retrospective Case Series.

OBJECTIVES: Relapses and recurrence remain the greatest risks posed by patients with severe mood disorders after discontinuation of electroconvulsive therapy (ECT). To date, despite a wide range of literature on ECT, little is known about the rate of recurrence of depression after maintenance ECT (mECT) discontinuation specifically. This study sought to address this lacuna, confronting literature data to the results of a retrospective case study. METHODS: A comprehensive review was conducted, followed by a retrospective analysis of 18 cases of mECT discontinuation between January 2011 and June 2016 involving patients with affective disorders. RESULTS: The comprehensive review revealed that only 3 studies have assessed recurrence rate after c/mECT discontinuation. In our retrospective analysis, mean (SD) mECT duration was 12.69 (12.16) months. A new mood event (usually a depressive state) was observed in 50% of the cases, and 44% of those recurrences occurred during the first 6 months after discontinuation. DISCUSSION: Given that high recurrence rates are observed after mECT discontinuation, the authors discuss the advantages of long-term mECT and the choice of concomitant pharmacotherapy for severe and complex affective disorders.

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.

Cost-utility analysis of transcranial direct current stimulation (tDCS) in non-treatment-resistant depression: the DISCO randomised controlled study protocol.

INTRODUCTION: Depression is among the most widespread psychiatric disorders in France. Psychiatric disorders are associated with considerable social costs, amounting to €22.6 billion for treatment and psychotropic medication in 2011. Treatment as usual (TAU), mainly consisting of pharmacotherapy and psychotherapy, is effective for only a third of patients and in most cases fails to prevent treatment resistance and chronicity. Transcranial direct current stimulation (tDCS) consists in a non-invasive and painless application of low-intensity electric current to the cerebral cortex through the scalp. Having proved effective in depressed patients, it could be used in combination with TAU to great advantage. The objective is to compare, for the first time ever, the cost-utility of tDCS-TAU and of TAU alone for the treatment of a depressive episode that has been refractory to one or two drug treatments. METHODS AND ANALYSIS: This paper, based on the DISCO study protocol, focuses on the design of a prospective, randomised, controlled, open-label multicentre economic study to be conducted in France. It will include 214 patients with unipolar or bipolar depression, assigning them to two parallel arms: group A (tDCS-TAU) and group B (TAU alone). The primary outcome is the incremental cost-effectiveness ratio, that is, the ratio of the difference in cost between each strategy to the difference in their effects. Their effects will be expressed as numbers of quality-adjusted life-years, determined through administration of the EuroQol Five-Dimension questionnaire over a 12-month period to patients (EQ-5D-5L). Expected benefits are the reduction of treatment resistance and suicidal ideation as well as social and professional costs of depression. Should depression-related costs fall significantly, tDCS might be considered an efficient treatment for depression. ETHICS AND DISSEMINATION: This protocol has been approved by a French ethics committee, the CPP--Est IV (Comité de Protection des Personnes-Strasbourg). Data are to be published in peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: RCB 2018-A00474-51; NCT03758105.

Twice-daily neuronavigated intermittent theta burst stimulation for bipolar depression: A Randomized Sham-Controlled Pilot Study.

The safety and efficacy of neuronavigated intermittent theta burst stimulation (iTBS) in patients with bipolar depression has not yet been investigated. We hypothesized the superiority of active iTBS over sham. Twenty-six patients were randomly allocated to receive either active (n=12) or sham (n=14) iTBS. Response and remission rates according to changes in depression MADRS score were high following active iTBS (72% and 42% for response and remission rates, respectively), but no significant difference was found after sham stimulation (42%and 25%). No adverse events were observed. This study revealed the safety and tolerability of twice daily iTBS in patients with bipolar depression. Larger controlled studies are warranted to prove iTBS superiority in treatment-resistant bipolar depression.

[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.

Bipolar disorder and adherence: implications of manic subjective experience on treatment disruption.

OBJECTIVE: Therapeutic observance is one of the cornerstones of bipolar disease prognosis. Nostalgia of previous manic phase has been described as a cause of treatment retrieval in bipolar disorder. But to date no systematic study has examined manic episode remembering stories. Our aim was to describe manic experience from the patient's point of view and its consequences on subjective relation to care and treatment adherence. PATIENTS AND METHODS: Twelve euthymic patients with bipolar I disorder were interviewed about their former manic episodes and data was analyzed, thanks to a grounded theory method. RESULTS: Nostalgia was an anecdotal reason for treatment retrieval in bipolar I disease. Although the manic experience was described as pleasant in a certain way, its consequences hugely tarnish the memory of it afterward. Treatment interruption appears to be mostly involuntary and state-dependent, when a euphoric subject loses insight and does not see any more benefit in having treatment. CONCLUSION: Consciousness destructuring associated with mood elation should explain treatment disruption in bipolar I patients more than nostalgia. Taking a manic episode story into account may help patients, family, and practitioners to achieve better compliance by improving their comprehension and integration of this unusual experience.

Both active and sham low-frequency rTMS single sessions over the right DLPFC decrease cue-induced cravings among pathological gamblers seeking treatment: A randomized, double-blind, sham-controlled crossover trial.

Background Craving is a core symptom of addictive disorders, such as pathological gambling for example. Over the last decade, several studies have assessed the efficacy of repetitive transcranial magnetic stimulation (rTMS) in the addiction field, which triggers the dorsolateral prefrontal cortex (DLPFC) to decrease craving. The STIMJEU study investigated whether a single session of low-frequency (LF, i.e., 1 Hz) rTMS applied to the right DLPFC reduced cue-induced gambling craving in a sample of treatment-seeking pathological gamblers. Methods Thirty patients received both active and sham rTMS in random order and were blinded to the condition in a within-subject crossover design. Outcome measures included self-reported gambling craving (Visual Analog Scale and Gambling Craving Scale) and physiological measures (heart rate and blood pressure). Results The rTMS sessions were associated with a significant decrease in the gambling urge, regardless of whether the session was active or sham. When controlling cue-induced craving levels, no effects were observed on craving for active rTMS. Overall, rTMS was well-tolerated, and the credibility of the sham procedure was assessed and appeared to be appropriate. Conclusions We failed to demonstrate the specific efficacy of one session of LF rTMS to decrease cue-induced craving in pathological gamblers. A strong placebo-effect and rTMS parameters may partly explain these results. Yet, we are convinced that rTMS remains a promising therapeutic method. Further studies are required to examine its potential effect.

Management of Emergency Electroconvulsive Therapy in the Intensive Care Unit for Life-Threatening Psychiatric Conditions: A Case Series.

Catatonia can lead to severe complications and may be lethal but is often underdiagnosed. The clinical presentation can be similar to coma. In these situations, electroconvulsive therapy (ECT) can be used as first-line treatment to enable extubation, recovery of autonomy, and rapid discharge from intensive care. We report 4 cases of patients hospitalized in the intensive care unit with comatose clinical presentation and life-threatening condition caused by catatonia. All patients received ECT sessions, after which the catatonic symptoms partially or fully remitted. We discuss the clinical identification, general considerations, ECT feasibility, and parameters in the intensive care unit, as well as the differential diagnosis, drug precautions, and prevention concerns.

Efficacy of intermittent Theta Burst Stimulation (iTBS) and 10-Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant unipolar depression: study protocol for a randomised controlled trial.

BACKGROUND: The treatment of depression remains a challenge since at least 40% of patients do not respond to initial antidepressant therapy and 20% present chronic symptoms (more than 2 years despite standard treatment administered correctly). Repetitive transcranial magnetic stimulation (rTMS) is an effective adjuvant therapy but still not ideal. Intermittent Theta Burst Stimulation (iTBS), which has only been used recently in clinical practice, could have a faster and more intense effect compared to conventional protocols, including 10-Hz high-frequency rTMS (HF-rTMS). However, no controlled study has so far highlighted the superiority of iTBS in resistant unipolar depression. METHODS/DESIGN: This paper focuses on the design of a randomised, controlled, double-blind, single-centre study with two parallel arms, carried out in France, in an attempt to assess the efficacy of an iTBS protocol versus a standard HF- rTMS protocol. Sixty patients aged between 18 and 75 years of age will be enrolled. They must be diagnosed with major depressive disorder persisting despite treatment with two antidepressants at an effective dose over a period of 6 weeks during the current episode. The study will consist of two phases: a treatment phase comprising 20 sessions of rTMS to the left dorsolateral prefrontal cortex, localised via a neuronavigation system and a 6-month longitudinal follow-up. The primary endpoint will be the number of responders per group, defined by a decrease of at least 50% in the initial score on the Montgomery and Asberg Rating Scale (MADRS) at the end of rTMS sessions. The secondary endpoints will be: response rate 1 month after rTMS sessions; number of remissions defined by a MADRS score of <8 at the endpoint and 1 month after; the number of responses and remissions maintained over the next 6 months; quality of life; and the presence of predictive markers of the therapeutic response: clinical (dimensional scales), neuropsychological (evaluation of cognitive functions), motor (objective motor testing) and neurophysiological (cortical excitability measurements). DISCUSSION: The purpose of our study is to check the assumption of iTBS superiority in the management of unipolar depression and we will discuss its effect over time. In case of a significant increase in the number of therapeutic responses with a prolonged effect, the iTBS protocol could be considered a first-line protocol in resistant unipolar depression. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier NCT02376491 . Registered on 17 February 2015 at http://clinicaltrials.gov .

[Concordance between hospital prescriptions and recommendations in the treatment of mania]. / Concordance entre prescriptions hospitalières et recommandations dans le traitement de la manie.

PURPOSE: There are differences between recommendations and practice in the pharmacological treatment of acute mania. OBJECTIVE: The objective was to assess conformity of the anti-manic prescription between national recommendations (Haute Autorité de santé [French health authority, HAS] and "résumé des caractéristiques du produit" [product characteristics, RCP]) and clinical practice. METHODS: We observed the drug prescriptions of in-patients for a manic episode. The main outcome measure was the concordance rate with the recommendations of the drugs prescriptions at the 48th hour. The secondary outcome repeated the same process with the hospital discharge statement of switches, associations, the presence of symptomatic and antidepressant treatments. RESULTS: Sixty-six episodes were included, 40 patients (60%) had a prescription complies with RCP recommendations H48 and 46 patients (70%) to HAS. These rates fall at hospital discharge. CONCLUSIONS: Off-label prescriptions, drug combinations and choices of not listed molecules are the most common reasons for non-conformity.

Transcranial direct current stimulation (tDCS) in behavioral and food addiction: a systematic review of efficacy, technical, and methodological issues.

OBJECTIVES: Behavioral addictions (BA) are complex disorders for which pharmacological and psychotherapeutic treatments have shown their limits. Non-invasive brain stimulation, among which transcranial direct current stimulation (tDCS), has opened up new perspectives in addiction treatment. The purpose of this work is to conduct a critical and systematic review of tDCS efficacy, and of technical and methodological considerations in the field of BA. METHODS: A bibliographic search has been conducted on the Medline and ScienceDirect databases until December 2014, based on the following selection criteria: clinical studies on tDCS and BA (namely eating disorders, compulsive buying, Internet addiction, pathological gambling, sexual addiction, sports addiction, video games addiction). Study selection, data analysis, and reporting were conducted according to the PRISMA guidelines. RESULTS: Out of 402 potential articles, seven studies were selected. So far focusing essentially on abnormal eating, these studies suggest that tDCS (right prefrontal anode/left prefrontal cathode) reduces food craving induced by visual stimuli. CONCLUSIONS: Despite methodological and technical differences between studies, the results are promising. So far, only few studies of tDCS in BA have been conducted. New research is recommended on the use of tDCS in BA, other than eating disorders.

[Role of the psychiatric liaison nurse in suicide risk prevention]. / Rôle de l'infirmière de psychiatrie de liaison dans la prévention du risque suicidaire.

From suicide risk prevention to treatment, the suicidal crisis process must be known to all carers to ensure appropriate and effective care. The psychiatry liaison team at the Nantes University Hospital advocates it with somatic teams through its liaison and consultation work. At the heart of this care network, the clinical expertise of the psychiatric liaison nurse educates nursing colleagues in identifying suicide risk. The nurse's clinical assessment and knowledge of the care system optimises the overall management and the path of patient care.

Using the Brief Assessment of Cognition in Schizophrenia (BACS) to assess cognitive impairment in older patients with schizophrenia and bipolar disorder.

OBJECTIVES: A growing body of evidence suggests that impairment in cognitive functioning is an important clinical feature of both schizophrenia and bipolar disorder, and that these cognitive alterations worsen with age. Although cognitive assessments are increasingly becoming a part of research and clinical practice in schizophrenia, a standardized and easily administered test battery for elderly patients with bipolar disorder is still lacking. The Brief Assessment of Cognition in Schizophrenia (BACS) captures those domains of cognition that are the most severely affected in patients with schizophrenia and the most strongly correlated with functional outcome. The primary aim of our study was to investigate the clinical usefulness of the BACS in assessing cognitive functioning in elderly euthymic patients with bipolar disorder, and to compare their cognitive profile to that of elderly patients with schizophrenia. METHODS: Elderly euthymic patients with bipolar disorder or schizophrenia were assessed using the BACS and a standard cognitive test battery. RESULTS: Fifty-seven elderly patients (aged 60 years and older) with bipolar disorder (n = 42) or schizophrenia (n = 15) were invited to participate. All of the patients were assessed by the BACS as being cognitively impaired. The patients with bipolar disorder scored significantly higher on the global scale and the verbal memory and attention sub-scores of the BACS than the patients with schizophrenia. DISCUSSION: The BACS appears to be a feasible and informative cognitive assessment tool for elderly patients with bipolar disorder. We believe that these preliminary results merit further investigation.

[The psychiatric liaison nurse in somatic care departments]. / L'infirmière de psychiatrie de liaison dans les services de soins somatiques.

The role of the psychiatric liaison nurse is continuing to develop within somatic wards. Its foundations are based on the recognition of the value accorded to interactions between physical and psychical dimension. This account of a psychiatric liaison nurse's practice at the university hospital of Nantes shows the positive impact a successful collaboration on inpatients.

Attention and visual orienting in siblings, schizophrenic patients, and controls: impairment in attentional disengagement.

Visual orienting tasks reveal an impaired disengagement of attention in schizophrenia. We explored visual orientation in 20 schizophrenia patients (SZ), 20 full siblings (FS), and 20 controls (C) using a cued target detection (gap vs. no gap) and a choice reaction time task. SZ but not FS had longer reaction time with comparable reactions to warning. In contrast to C, SZ and FS did not display a significant gap effect. The disengagement deficit in schizophrenia patients and their siblings provides arguments for altered early attention mechanisms (in schizophrenic patients and their nonpsychotic relatives).