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Background: Following a traumatic event, 40–80% of the patients with acute stress disorder (ASD) will develop post-traumatic stress disorder (PTSD), 67% at 6 months. Alpha1-blockers are effective in treating some symptoms of PTSD but their usefulness in acute stress situations remains unclear. We hypothesized that reducing noradrenergic hyperactivity with an alpha1-blocker during the acute phase after a traumatic event could prevent the transition to PTSD in patients with ASD. Objective: To investigate the efficacy and safety of a 1-month course of alpha1-blocker (prazosin) to prevent the transition to PTSD in patients with ASD at 6 months. Method: In a monocentric open-label prospective pilot study, 15 patients with ASD were included within 3–7 days of exposure to a traumatic event. After enrolment, they received prazosin LP at home at bedtime at 2.5 mg/day for 7 days and then 5 mg/day for 21 days. Incidence of PTSD was assessed at 6 months using the Clinician Administrated PTSD Scale (CAPS). Results: At 6 months, 22% of patients who completed the study (2/9) met the diagnostic criteria for PTSD. This rate was significantly lower than that observed in previous studies (67%; p = .047). The treatment was well tolerated and there were no serious adverse events. Conclusions: These preliminary findings indicating the safety of prazosin and suggesting its potential to prevent the development of PTSD in ASD require to be replicated in large-scale randomized placebo-controlled studies. Trial registration: The study was pre-registered on a public database (www.clinicalTrials.gov identifier: NCT03045016).

Abstract Optimal noninvasive brain stimulation parameters for the treatment of negative symptoms of schizophrenia remain unclear. Here, we aimed to investigate the clinical and biological effects of intermittent theta burst transcranial magnetic stimulation (iTBS) in patients with treatment-resistant negative symptoms of schizophrenia (NCT00875498). In a randomized sham-controlled 2-arm study, 22 patients with schizophrenia and treatment-resistant negative symptoms received 20 sessions of either active (n = 12) or sham (n = 10) iTBS. Sessions were delivered twice a day on 10 consecutive working days. Negative symptom severity was assessed 5 times using the Scale for the Assessment of Negative Symptoms (SANS): before iTBS, after iTBS, and 1, 3, and 6 months after iTBS. As a secondary objective, we explored the acute effects of iTBS on functional connectivity of the left dorsolateral prefrontal cortex (DLPFC) using seed-based resting-state functional connectivity MRI (rsFC fMRI) images acquired before and after iTBS. Active iTBS over the left DLPFC significantly decreased negative symptoms severity compared to sham iTBS (F (3,60) = 3.321, p = 0.026). Post hoc analyses revealed that the difference between groups was significant 6 months after the end of stimulation sessions. Neuroimaging revealed an increase in rsFC between the left DLPFC and a brain region encompassing the right lateral occipital cortex and right angular gyrus and a right midbrain region that may encompass dopamine neuron cell bodies. Thus, iTBS over the left DLPFC can alleviate negative symptoms of schizophrenia. The effect might be driven by significant modulation of dopamine transmission.

IntroductionSuicide is the fourth leading cause of death in youth. Previous suicide attempts are among the strongest predictors of future suicide re-attempt. However, the lack of data and understanding of suicidal re-attempt behaviors in this population makes suicide risk assessment complex and challenging in clinical practice. The primary objective of this study is to determine the rate of suicide re-attempts in youth admitted to the emergency department after a first suicide attempt. The secondary objectives are to explore the clinical, socio-demographic, and biological risk factors that may be associated with re-attempted suicide in adolescents and young adults.MethodsWe have developed a single-center prospective and naturalistic study that will follow a cohort of 200 young people aged 16 to 25 years admitted for a first suicide attempt to the emergency department of Lyon, France. The primary outcome measure will be the incidence rate of new suicide attempts during 3 months of follow-up. Secondary outcomes to investigate predictors of suicide attempts will include several socio-demographic, clinical and biological assessments: blood and hair cortisol levels, plasma pro- and mature Brain-Derived Neurotrophic Factor (BDNF) isoforms proportion, previous infection with toxoplasma gondii, and C-Reactive Protein (CRP), orosomucoid, fibrinogen, interleukin (IL)-6 inflammatory markers.DiscussionTo our knowledge, the present study is the first prospective study specifically designed to assess the risk of re-attempting suicide and to investigate the multidimensional predictive factors associated with re-attempting suicide in youth after a first suicide attempt. The results of this study will provide a unique opportunity to better understand whether youth are an at-risk group for suicide re-attempts, and will help us identify predictive factors of suicide re-attempt risk that could be translated into clinical settings to improve psychiatric care in this population.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT03538197, first registered on 05/29/2018. The first patient was enrolled 05/22/2018.

Abstract Background Suicide is a major public health issue and the majority of those who attempt suicide suffer from mental disorders. Beyond psychopharmacotherapy, seizure therapies and noninvasive brain stimulation interventions have been used to treat such patients. However, the effect of these nonpharmacological treatments on the suicidal ideation and incidence of suicidality remains unclear. Here, we aimed to provide an update on the effects of seizure therapies and noninvasive brain stimulation on suicidality. Methods We conducted a systematic review of the literature in the PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Elsevier ScienceDirect, and Wiley Online Library databases using the MeSH terms “Electroconvulsive Therapy”, “Magnetic Seizure Stimulation”, “repetitive Transcranial Magnetic Stimulation”, “transcranial Direct Current Stimulation”, “Cranial Electrostimulation” and “suicide”. We included studies using seizure therapies and noninvasive brain stimulation as a main intervention that evaluated suicidality, regardless of diagnosis. Results Among 1,019 records screened, 26 studies met the inclusion criteria using either electroconvulsive therapy (n = 14), magnetic seizure therapy (n = 2), repetitive transcranial magnetic stimulation (n = 9), or transcranial direct current stimulation (n = 1). We observed that studies reported significant results, suggesting these techniques can be effective on the suicidal dimension of mental health pathologies, but a general statement regarding their efficacy is premature due to limitations. Conclusions Future enquiry is necessary to address methodological limitations and evaluate the long‐term efficacy of these methods both alone and in combination with pharmacotherapy and/or psychotherapy.

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