Search

Background: Recently, a small literature has emerged suggesting that repetitive transcranial magnetic stimulation (rTMS) may offer benefit for MDD even in BPD patients, perhaps by enhancing cognitive control, and/or disrupting excessive 'non-reward' activity in right orbitofrontal regions. This study aimed primarily to assess the therapeutic effects of dorsomedial prefrontal cortex (DMPFC)-rTMS against MDD symptoms in BPD patients, and secondarily to assess whether the therapeutic effects ensued via mechanisms of reduced impulsivity and core BPD pathology on clinical scales (BIS-11, ZAN-BPD) or of reduced alpha- and theta-band activity on EEG recordings of right orbitofrontal cortex..Methods: In a crossover-design trial, 20 BPD patients with MDD underwent 2 × 30 session/15 day blocks of either active-then-sham or sham-then-active bilateral 20 Hz DMPFC-rTMS.Results: Sixteen out of 20 patients completed treatment. A significant (p = 0.00764) crossover effect was detected, with overall reductions in HamD17 score from 23.1±SD3.1 to 10.75±SD5.8. Nine out of 16 (56.3%) treatment completers achieved response (>50% improvement) and 6/16 (37.5%) achieved remission (HamD≤7), maintained at 1 month followup. BIS-11 scores remained unchanged, and ZAN-BPD scores improved similarly in both groups with no significant crossover effect. Change in low-band power over right orbitofrontal regions correlated with clinical improvement.Limitations: This was a crossover study with a small sample size. A randomized controlled trial with larger sample size will be needed to establish the efficacy more definitively.Conclusions: The results suggest efficacy for DMPFC-rTMS in treating MDD in BPD, and provide a foundation for a larger future trial. [ABSTRACT FROM AUTHOR]

Background: Healthy individuals show subtle orienting bias, a phenomenon known as pseudoneglect, reflected in a tendency to direct greater attention toward one hemispace. Accumulating evidence indicates that this bias is an individual trait, and attention is preferentially directed contralaterally to the hemisphere with higher dopamine signaling. Administration of methylphenidate (MPH), a dopamine transporter inhibitor, was shown to normalize aberrant spatial attention bias in psychiatric and neurological patients, suggesting that the reduced orienting bias following administration of MPH reflects an asymmetric effect of the drug, increasing extracellular dopamine in the hemisphere with lower dopamine signaling. Aim: We predicted that, similarly to its effect on patients with brain pathology, MPH will reduce the orienting bias in healthy subjects. Methods: To test this hypothesis, we examined the behavioral effects of a single dose (20 mg) of MPH on orienting bias in 36 healthy subjects (18 females) in a randomized, double-blind placebo-controlled, within-subject design, using the greyscales task, which has been shown to detect subtle attentional biases in both patients and healthy individuals. Results/outcomes: Results demonstrate that healthy individuals vary in both direction and magnitude of spatial orienting bias and show reduced magnitude of orienting bias following MPH administration, regardless of the initial direction of asymmetry. Conclusions/interpretations: Our findings reveal, for the first time in healthy subjects, that MPH decreases spatial orienting bias in an asymmetric manner. Given the well-documented association between orienting bias and asymmetric dopamine signaling, these findings also suggest that MPH might exert a possible asymmetric neural effect in the healthy brain. [ABSTRACT FROM AUTHOR]

Dorsomedial prefrontal cortex (DMPFC) repetitive transcranial magnetic stimulation (rTMS) is a novel intervention for treatment-refractory depression (TRD). To date, many open-label case series and one randomized controlled trial of modest sample size have provided preliminary evidence that DMPFC-rTMS is an effective treatment for TRD. Here, we report the results of a large, double-blinded, sham-controlled trial of DMPFC-rTMS for TRD. The primary aim of this study was to determine the efficacy of DMPFC-rTMS for TRD under sham-controlled conditions. 120 TRD patients were randomized to receive 30 twice-daily sessions of either active high-frequency, active low-frequency, or sham DMPFC-rTMS using a novel bent active/sham double-cone coil. Placebo stimulation also involved the use of surface electrodes placed above the eyebrows. The 17-item Hamilton Rating Scale for Depression served as the primary outcome measure. Although there was a significant main effect of treatment across all arms, active DMPFC-rTMS was not superior to sham. Both participants and assessors were unable to accuracy determine whether patients received active or placebo stimulation. However, technicians' treatment arm guesses were significantly above chance. DMPFC rTMS did not result in improvement of depressive symptoms greater than sham stimulation. We cannot rule out that the sham apparatus may also have elicited an antidepressant effect via electrical trigeminal stimulation; future DMPFC-rTMS trials are therefore warranted. • Although there was a significant main treatment effect, active dorsomedial prefrontal rTMS was not superior to sham. • The sham apparatus may have elicited an antidepressant effect via electrical trigeminal stimulation; future trials are therefore warranted. • The novel active/placebo TMS coil successfully blinded clinical assessors and participants who received treatment; but not technicians. [ABSTRACT FROM AUTHOR]

Objective: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for refractory major depressive disorder, yet no studies have characterized trajectories of rTMS response. The aim of this study was to characterize response trajectories for patients with major depression undergoing left dorsolateral prefrontal cortex rTMS and to determine associated baseline clinical characteristics.Methods: This was a secondary analysis of a randomized noninferiority trial (N=388) comparing conventional 10-Hz rTMS and intermittent theta burst stimulation (iTBS) rTMS. Participants were adult outpatients who had a primary diagnosis of major depressive disorder, had a score ≥18 on the 17-item Hamilton Depression Rating Scale (HAM-D), and did not respond to one to three adequate antidepressant trials. Treatment was either conventional 10-Hz rTMS or iTBS rTMS applied to the dorsolateral prefrontal cortex, 5 days/week over 4-6 weeks (20-30 sessions). Group-based trajectory modeling was applied to identify HAM-D response trajectories, and regression techniques were used to identify associated characteristics.Results: Four trajectories were identified: nonresponse (N=43, 11%); rapid response (N=73, 19%); higher baseline symptoms, linear response (N=118, 30%); and lower baseline symptoms, linear response (N=154, 40%). Significant differences in response and remission rates between trajectories were detectable by week 1. There was no association between treatment protocol and response trajectory. Higher baseline scores on the HAM-D and the Quick Inventory of Depression Symptomatology-Self-Report (QIDS-SR) were associated with the nonresponse trajectory, and older age, lower QIDS-SR score, and lack of benzodiazepine use were associated with the rapid response trajectory.Conclusions: Major depression shows distinct response trajectories to rTMS, which are associated with baseline clinical characteristics but not treatment protocol. These response trajectories with differential response to rTMS raise the possibility of developing individualized treatment protocols. [ABSTRACT FROM AUTHOR]

In recent years the use of psychostimulants for cognitive enhancement in healthy individuals with no psychiatric disorders has been on the rise. However, it is still unclear whether psychostimulants improve certain cognitive functions at the cost of others, and how these psychostimulants interact with individual personality differences. In the current study, we investigated whether the effect of one common stimulant, methylphenidate (MPH), on creativity is associated with novelty seeking. Thirty-six healthy adults, without attention-deficit hyperactivity disorder (ADHD) symptomology, were assigned randomly in a double-blind fashion to receive MPH or placebo. We found that the effect of MPH on creativity was dependent on novelty-seeking (NS) personality characteristics of the participants. MPH increased creativity in individuals with lower NS, while it reduced creativity levels in individuals with high NS. These findings highlight the role of the dopaminergic system in creativity, and indicate that among healthy individuals NS can be seen as a predictor of the effect of MPH on creativity. [ABSTRACT FROM AUTHOR]

Objective High rates of placebo responses are consistently reported in patients with major depressive disorder. Nonetheless, treating depression with placebo is still ethically controversial and generally prohibited in the clinical setting. In the present study, we assess the acceptability of placebo usage among depressed patients. Method Ninety-six outpatients with major depressive disorder were matched to 114 healthy controls. After a thorough explanation of the placebo effect, its efficacy and limitations in the treatment of depression, the study participants completed a 32-item self-report questionnaire. The five core questions addressed the attitude and willingness of subjects to be treated with a placebo in the clinical setting. Results Among study group patients, the majority (56.7%) conveyed consent for placebo treatment if they were to suffer another depressive episode. Both study group and control group expressed high rates of willingness to waive their right to informed consent (55.6% and 50%, respectively), and they did not consider placebo treatment to be a deceit (56%) or to diminish their sense of autonomy (56.7%). Conclusions Most patients with depression are willing to waive their right to informed consent in order to receive placebo treatment. These findings should encourage further studies of placebo usage and its legitimacy in clinical practice. [ABSTRACT FROM AUTHOR]

Several letters to the editor are presented in response to articles in previous issues including one related to promotion of independent research among junior psychiatrists, second on the treatment of schizophrenia and third on the role of methylphenidate drug in hyperactivity disorder research.

The aim of this study was to investigate the opinions of healthy students regarding the acceptability of placebo treatment if they were to experience depression. A survey was conducted among 344 students in five academic centers in Israel. After a thorough explanation of the placebo effect, its efficacy and limitations in the treatment of depression, the study participants completed a 32-item self-report questionnaire. Seventy percent (n = 243) of the participants answered that they would agree to treatment with a placebo as a first-line treatment if they were to experience depression in the future. Eighty-eight percent (n = 297) of the subjects did not think that a physician who administered placebos was deceitful. Once aware of the possible benefits and limitations of placebo treatment, most of our study population was willing to accept placebo as a legitimate treatment of depression. Additional studies on the possible use of placebo as an effective, safe, and acceptable form of therapy are warranted. [ABSTRACT FROM AUTHOR]

Background: Treatment-resistant major depressive disorder is common; repetitive transcranial magnetic stimulation (rTMS) by use of high-frequency (10 Hz) left-side dorsolateral prefrontal cortex stimulation is an evidence-based treatment for this disorder. Intermittent theta burst stimulation (iTBS) is a newer form of rTMS that can be delivered in 3 min, versus 37·5 min for a standard 10 Hz treatment session. We aimed to establish the clinical effectiveness, safety, and tolerability of iTBS compared with standard 10 Hz rTMS in adults with treatment-resistant depression.Methods: In this randomised, multicentre, non-inferiority clinical trial, we recruited patients who were referred to specialty neurostimulation centres based at three Canadian university hospitals (Centre for Addiction and Mental Health and Toronto Western Hospital, Toronto, ON, and University of British Columbia Hospital, Vancouver, BC). Participants were aged 18-65 years, were diagnosed with a current treatment-resistant major depressive episode or could not tolerate at least two antidepressants in the current episode, were receiving stable antidepressant medication doses for at least 4 weeks before baseline, and had an HRSD-17 score of at least 18. Participants were randomly allocated (1:1) to treatment groups (10 Hz rTMS or iTBS) by use of a random permuted block method, with stratification by site and number of adequate trials in which the antidepressants were unsuccessful. Treatment was delivered open-label but investigators and outcome assessors were masked to treatment groups. Participants were treated with 10 Hz rTMS or iTBS to the left dorsolateral prefrontal cortex, administered on 5 days a week for 4-6 weeks. The primary outcome measure was change in 17-item Hamilton Rating Scale for Depression (HRSD-17) score, with a non-inferiority margin of 2·25 points. For the primary outcome measure, we did a per-protocol analysis of all participants who were randomly allocated to groups and who attained the primary completion point of 4 weeks. This trial is registered with ClinicalTrials.gov, number NCT01887782.Findings: Between Sept 3, 2013, and Oct 3, 2016, we randomly allocated 205 participants to receive 10 Hz rTMS and 209 participants to receive iTBS. 192 (94%) participants in the 10 Hz rTMS group and 193 (92%) in the iTBS group were assessed for the primary outcome after 4-6 weeks of treatment. HRSD-17 scores improved from 23·5 (SD 4·4) to 13·4 (7·8) in the 10 Hz rTMS group and from 23·6 (4·3) to 13·4 (7·9) in the iTBS group (adjusted difference 0·103 [corrected], lower 95% CI -1·16; p=0·0011), which indicated non-inferiority of iTBS. Self-rated intensity of pain associated with treatment was greater in the iTBS group than in the 10 Hz rTMS group (mean score on verbal analogue scale 3·8 [SD 2·0] vs 3·4 [2·0] out of 10; p=0·011). Dropout rates did not differ between groups (10 Hz rTMS: 13 [6%] of 205 participants; iTBS: 16 [8%] of 209 participants); p=0·6004). The most common treatment-related adverse event was headache in both groups (10 Hz rTMS: 131 [64%] of 204; iTBS: 136 [65%] of 208).Interpretation: In patients with treatment-resistant depression, iTBS was non-inferior to 10 Hz rTMS for the treatment of depression. Both treatments had low numbers of dropouts and similar side-effects, safety, and tolerability profiles. By use of iTBS, the number of patients treated per day with current rTMS devices can be increased several times without compromising clinical effectiveness.Funding: Canadian Institutes of Health Research. [ABSTRACT FROM AUTHOR]

Introduction: Combining a successful career with family planning has become increasingly important in recent years. However, maintaining a relationship, deciding upon the optimal time for pregnancy and other family planning decisions can still be quite challenging, especially for junior doctors whose training is long and demanding. Currently, women form an important part of the medical workforce, and there is noticeable feminization in migration. However, little is known about the personal characteristics of junior doctors in Europe and how these play a role in their decision to migrate. Methods: Survey of psychiatric trainees in 33 European countries, exploring how personal characteristics, such as gender, relationship status and parenthood, impact their attitudes toward migration. Results: 2,281 psychiatric trainees in Europe took part in the study. In this sample, the majority of psychiatric trainees were in a relationship, but only one quarter had children, although there were variations across Europe. Both men and women indicated personal reasons as their top reason to stay. However, women ranked personal reasons as the top reason to leave, and men financial reasons. Single woman were the most likely of all subgroups to choose academic reasons as their top reason to leave. Interestingly, when women were in a relationship or had children, their attitudes toward migration changed. Conclusions: In this study, a low number of psychiatric trainees in Europe had children, with differences across Europe. These findings raise awareness as to the role of parental conditions, which may be favoring or discouraging parenthood in junior doctors in different countries.