Predictors of remission after repetitive transcranial magnetic stimulation for the treatment of late-life depression.

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment in patients with depression, yet treatment response remains variable. While previous work has identified predictors of remission in younger adults, relatively little data exists in late-life depression (LLD). To address this gap, data from 164 participants with LLD from a randomized non-inferiority treatment trial comparing standard bilateral rTMS to bilateral theta burst stimulation (TBS) (ClinicalTrials.gov identifier: NCT02998580) were analyzed using binary logistic regression and conditional inference tree (CIT) modeling. Lower baseline depression symptom severity, fewer prior antidepressant treatment failures, and higher global cognition predicted remission following rTMS treatment. The CIT predicted a higher likelihood of achieving remission for patients with a total score of 19 or lower on the Montgomery-Åsberg Depression Rating Scale, 1 or fewer prior antidepressant treatment failures, and a total score of 23 or higher on the Montreal Cognitive Assessment. Our results indicate that older adults with lower severity of depression, fewer antidepressant treatment failures, and higher global cognition benefit more from current forms of rTMS. The results suggest that there is potentially higher value in using rTMS earlier in the treatment pathway for depression in older adults.

A randomized sham-controlled trial of high-dosage accelerated intermittent theta burst rTMS in major depression: study protocol.

BACKGROUND: Intermittent theta burst stimulation (iTBS), a novel form of repetitive transcranial magnetic stimulation (rTMS), can be administered in 1/10th of the time of standard rTMS (~ 3 min vs. 37.5 min) yet achieves similar outcomes in depression. The brief nature of the iTBS protocol allows for the administration of multiple iTBS sessions per day, thus reducing the overall course length to days rather than weeks. This study aims to compare the efficacy and tolerability of active versus sham iTBS using an accelerated regimen in patients with treatment-resistant depression (TRD). As a secondary objective, we aim to assess the safety, tolerability, and treatment response to open-label low-frequency right-sided (1 Hz) stimulation using an accelerated regimen in those who do not respond to the initial week of treatment. METHODS: Over three years, approximately 230 outpatients at the Centre for Addiction and Mental Health and University of British Columbia Hospital, meeting diagnostic criteria for unipolar MDD, will be recruited and randomized to a triple blind sham-controlled trial. Patients will receive five consecutive days of active or sham iTBS, administered eight times daily at 1-hour intervals, with each session delivering 600 pulses of iTBS. Those who have not achieved response by the week four follow-up visit will be offered a second course of treatment, regardless of whether they initially received active or sham stimulation. DISCUSSION: Broader implementation of conventional iTBS is limited by the logistical demands of the current standard course consisting of 4-6 weeks of daily treatment. If our proposed accelerated iTBS protocol enables patients to achieve remission more rapidly, this would offer major benefits in terms of cost and capacity as well as the time required to achieve clinical response. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04255784.

Efficacy of insula deep repetitive transcranial magnetic stimulation combined with varenicline for smoking cessation: A randomized, double-blind, sham controlled trial.

BACKGROUND: Current smoking cessation treatments are limited in terms of efficacy, particularly with regards to long term abstinence. There is a large amount of evidence implicating the insula in nicotine addiction. OBJECTIVE: To examine the efficacy of bilateral repetitive transcranial magnetic stimulation (rTMS) directed to the insular cortex with the H11 coil, relative to sham stimulation, on smoking abstinence and smoking outcomes in smokers who are receiving standard varenicline treatment. METHODS: This randomized, double-blind, sham controlled trial recruited 42 participants who were randomized to receive either active (n = 24) or sham (n = 18) high frequency rTMS directed to the insula (4 weeks), while receiving varenicline treatment (12 weeks). The primary outcome was 7-day point prevalence abstinence at the end of 12 weeks. RESULTS: Smokers in the active group had significantly higher abstinence rates than those in the sham group (82.4% vs. 30.7%, p = 0.013) at the end of treatment (Week 12). Secondary outcome measures of abstinence rate at the end of rTMS treatment (Week 4), abstinence rate at 6 months, and smoking outcomes (e.g., craving, withdrawal) showed no significant differences between groups. No differences were found in adverse events reported between the groups. CONCLUSION: This study provides evidence of the potential benefit of having a combined treatment for smoking cessation using insula rTMS with the H11 coil and varenicline. Maintenance rTMS sessions and continuation of varenicline for those in abstinence may induce longer-term effects and should be considered in future studies.

Treatment resistance in schizophrenia: a meta-analysis of prevalence and correlates

Objectives: To determine the prevalence and correlates of treatment-resistant schizophrenia (TRS) through a systematic review and meta-analysis. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, an electronic search was performed in PubMed and Embase through May 17, 2022. All study designs that assessed a minimum of 20 schizophrenia-spectrum patients and provided data on TRS prevalence or allowed its calculation were included. Estimates were produced using a random-effects model meta-analysis. Results: The TRS prevalence across 50 studies (n = 29,390) was 36.7% (95%CI 33.1-40.5, p < 0.0001). The prevalence ranged from 22% (95%CI 18.4-25.8) in first-episode to 39.5% (95%CI 32.2-47.0) in multiple-episode samples (Q = 18.27, p < 0.0001). Primary treatment resistance, defined as no response from the first episode, was 23.6% (95%CI 20.5-26.8) vs. 9.3% (95%CI 6.8-12.2) for later-onset/secondary (≥ 6 months after initial treatment response). Longer illness duration and recruitment from long-term hospitals or clozapine clinics were associated with higher prevalence estimates. In meta-regression analyses, older age and poor functioning predicted greater TRS. When including only studies with lower bias risk, the TRS prevalence was 28.4%. Conclusion: Different study designs and recruitment strategies accounted for most of the observed heterogeneity in TRS prevalence rates. The results point to early-onset and later-onset TRS as two separate disease pathways requiring clinical attention. Registration number: PROSPERO CRD42018092033.

Treatment resistance in schizophrenia: a meta-analysis of prevalence and correlates.

OBJECTIVES: To determine the prevalence and correlates of treatment-resistant schizophrenia (TRS) through a systematic review and meta-analysis. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, an electronic search was performed in PubMed and Embase through May 17, 2022. All study designs that assessed a minimum of 20 schizophrenia-spectrum patients and provided data on TRS prevalence or allowed its calculation were included. Estimates were produced using a random-effects model meta-analysis. RESULTS: The TRS prevalence across 50 studies (n = 29,390) was 36.7% (95%CI 33.1-40.5, p < 0.0001). The prevalence ranged from 22% (95%CI 18.4-25.8) in first-episode to 39.5% (95%CI 32.2-47.0) in multiple-episode samples (Q = 18.27, p < 0.0001). Primary treatment resistance, defined as no response from the first episode, was 23.6% (95%CI 20.5-26.8) vs. 9.3% (95%CI 6.8-12.2) for later-onset/secondary (≥ 6 months after initial treatment response). Longer illness duration and recruitment from long-term hospitals or clozapine clinics were associated with higher prevalence estimates. In meta-regression analyses, older age and poor functioning predicted greater TRS. When including only studies with lower bias risk, the TRS prevalence was 28.4%. CONCLUSION: Different study designs and recruitment strategies accounted for most of the observed heterogeneity in TRS prevalence rates. The results point to early-onset and later-onset TRS as two separate disease pathways requiring clinical attention.

Toward personalized circuit-based closed-loop brain-interventions in psychiatry: using symptom provocation to extract EEG-markers of brain circuit activity.

Symptom provocation is a well-established component of psychiatric research and therapy. It is hypothesized that specific activation of those brain circuits involved in the symptomatic expression of a brain pathology makes the relevant neural substrate accessible as a target for therapeutic interventions. For example, in the treatment of obsessive-compulsive disorder (OCD), symptom provocation is an important part of psychotherapy and is also performed prior to therapeutic brain stimulation with transcranial magnetic stimulation (TMS). Here, we discuss the potential of symptom provocation to isolate neurophysiological biomarkers reflecting the fluctuating activity of relevant brain networks with the goal of subsequently using these markers as targets to guide therapy. We put forward a general experimental framework based on the rapid switching between psychiatric symptom states. This enable neurophysiological measures to be derived from EEG and/or TMS-evoked EEG measures of brain activity during both states. By subtracting the data recorded during the baseline state from that recorded during the provoked state, the resulting contrast would ideally isolate the specific neural circuits differentially activated during the expression of symptoms. A similar approach enables the design of effective classifiers of brain activity from EEG data in Brain-Computer Interfaces (BCI). To obtain reliable contrast data, psychiatric state switching needs to be achieved multiple times during a continuous recording so that slow changes of brain activity affect both conditions equally. This is achieved easily for conditions that can be controlled intentionally, such as motor imagery, attention, or memory retention. With regard to psychiatric symptoms, an increase can often be provoked effectively relatively easily, however, it can be difficult to reliably and rapidly return to a baseline state. Here, we review different approaches to return from a provoked state to a baseline state and how these may be applied to different symptoms occurring in different psychiatric disorders.

Effect of prior pharmacotherapy on remission with sequential bilateral theta-burst versus standard bilateral repetitive transcranial magnetic stimulation in treatment-resistant late-life depression.

Repetitive transcranial magnetic stimulation (rTMS) is used for treatment of late-life depression. In the FOUR-D study, sequential bilateral theta-burst stimulation (TBS) had comparable remission rates to standard bilateral rTMS. Data were analysed from the FOUR-D trial to compare remission rates between two types of rTMS based on the number and class of prior medication trials. The remission rate was higher in participants with ≤1 previous trial (43.9%) than in participants with 2 previous trials (26.5%) or ≥3 previous trials (24.6%; χ² = 6.36, d.f. = 2, P = 0.04). Utilising rTMS earlier in late-life depression may lead to better outcomes.

Neural Correlates of the DEEPP (Anti-suicidal Response to Ketamine in Treatment-Resistant Bipolar Depression) Study: Protocol for a Pilot, Open-Label Clinical Trial.

BACKGROUND: Suicide is among the top 10 leading causes of death worldwide. Of people who died by suicide, the majority are diagnosed with depression. It is estimated that 25%-60% of people with bipolar depression (BD) will attempt suicide at least once, and 10%-15% will die by suicide. Several treatments, such as lithium, clozapine, electroconvulsive therapy, and cognitive behavioral therapy, have been shown to be effective in treating suicidality. However, these treatments can be difficult to tolerate or may take months to take effect. Ketamine, a glutamate N-methyl-D-aspartate antagonist, has been shown to have rapid antisuicidal effect and antidepressant qualities, and is thus a promising intervention to target acute suicidality in patients with BD. However, the biological mechanism underlying its therapeutic action remains poorly understood. Enhancing our understanding of underlying mechanisms of action for ketamine's effectiveness in reducing suicidality is critical to establishing biological markers of treatment response and developing tailored, personalized interventions for patients with BD. OBJECTIVE: This is an open-label clinical trial to test the safety and feasibility of repeated ketamine infusions to treat acute suicidality. The primary objective is to test the safety and feasibility of ketamine intervention. The secondary objective is to examine ketamine's potential neurophysiological mechanisms of action by assessing cortical excitation and inhibition to determine potential biomarkers of clinical response. Other objectives are to evaluate the effect of ketamine on acute suicidality and other clinical outcomes, such as depressive symptoms and quality of life, to inform a future larger trial. METHODS: This open-label clinical trial aims to test the safety and feasibility of repeated ketamine infusions in patients with BD for suicidality and to assess ketamine's neurophysiological effects. A sterile form of racemic ketamine hydrochloride will be administered over a 40-minute intravenous infusion 2 times per week on nonconsecutive days for 4 weeks (8 sessions). We will recruit 30 adults (24-65 year olds) over 2 years from an academic psychiatric hospital in Toronto, Canada. RESULTS: This study is currently ongoing and actively recruiting participants. So far, 5 participants have completed the trial, 1 is currently in active treatment, and 8 participants are on the waitlist to be screened. We anticipate initial results being available in the fall of 2023. This proposal was presented as a poster presentation at the Research to Reality Global Summit on Psychedelic-Assisted Therapies and Medicine, held in May 2022 in Toronto, Canada. CONCLUSIONS: Developing effective interventions for acute suicidality in high-risk populations such as those with BD remains a major therapeutic challenge. Ketamine is a promising treatment due to its rapid antidepressant and antisuicidal effects, but its underlying neurophysiological mechanisms of action remain unknown. TRIAL REGISTRATION: ClinicalTrials.gov NCT05177146; https://clinicaltrials.gov/ct2/show/NCT05177146. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/41013.

The Interactions Between Vulnerabilities for HIV and Syphilis among Cisgender and Transgender People Who Use Drugs.

In Brazil, transgender people are most affected by HIV, and crack cocaine addiction may contribute to social vulnerability and exposure to sexual and violence-related risks. This cross-sectional study comprised 2393 individuals seeking addiction treatment, consisting of 43 trans women, 1995 cisgender men, and 355 cisgender women. Records of rapid test results for HIV and syphilis and screening responses of trans women were compared to both cisgender groups using a logistic regression model to identify associated risk factors. HIV prevalence was higher in the transgender group (39.5%) than in cis women and men (5.9% and 3.6%, respectively). Our study showed an eightfold higher chance of a positive HIV test among transgender individuals who used drugs (OR: 8.79, p < .01, 95% CI: 3.90-19.78) compared to cisgender people who used drugs. A lifetime history of syphilis infection was more common in transgender people (60.0%) and cis women (32.8%) than in cis men (9.5%). Active syphilis was also more common in the transgender population (OR: 5.46, p < .01, 95% CI: 2.63 11.32). In our sample, 44.2% of transgender individuals had a history of at least one suicide attempt in their lifetime. Our results showed that transgender women were at higher risk of crack cocaine use (OR: 5.51, p < .01, 95% CI: 2.16-14.06) than cisgender men and women. The study showed that trans women had a higher prevalence of syphilis and HIV, and a greater chance of being homeless. The synergy of these vulnerabilities may have led to our findings of high psychotic symptoms and a history of suicide attempts in transgender individuals.

Effectiveness of Standard Sequential Bilateral Repetitive Transcranial Magnetic Stimulation vs Bilateral Theta Burst Stimulation in Older Adults With Depression: The FOUR-D Randomized Noninferiority Clinical Trial.

Importance: Treatment-resistant depression (TRD) is common in older adults. Bilateral repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex for 48 minutes has demonstrated efficacy in TRD. Theta burst stimulation (TBS), a newer form of rTMS, can also be delivered bilaterally using left intermittent TBS and right continuous TBS for only 4 minutes. Objective: To establish the effectiveness and tolerability of TBS compared with standard rTMS in older adults with TRD. Design, Setting, and Participants: In this randomized noninferiority trial with open treatment and blinded assessors, recruitment occurred between December 2016 and March 2020. The trial was conducted at the Centre for Addiction and Mental Health in Toronto, Ontario, Canada and included outpatients 60 years and older with a diagnosis of depression, moderate severity, and nonresponse to 1 or more antidepressant trial of adequate dosage and duration or intolerance of 2 or more trials. Interventions: Participants were randomized to receive a course of 4 to 6 weeks of either bilateral standard rTMS or TBS. Main Outcomes and Measures: The primary outcome measure was change in Montgomery-Åsberg Depression Rating Scale; secondary outcome measures included the 17-item Hamilton Rating Scale for Depression, Quick Inventory of Depressive Symptomatology (16-item) (self-report), and dropout rates. A noninferiority margin of 2.75 points was used for the primary outcome. All participants who attained the primary completion point of 4 weeks were analyzed. Results: A total of 87 participants (mean [SD] age, 67.1 [6.7] years; 47 [54.0%] female) were randomized to standard bilateral rTMS and 85 (mean [SD] age, 66.3 [5.3] years; 45 [52.9%] female) to TBS, of whom 85 (98%) and 79 (93%) were assessed for the primary outcome, respectively, whereas tolerability was assessed in all randomized participants. In the rTMS group, 4 (4.6%) were American Indian, reported other, or preferred not to answer; 5 (5.8%) were Asian; and 78 (89.7%) were White. In the TBS group, 6 (7.1%) were Asian, 2 (2.4%) were Black or reported other, and 77 (90.3%) were White. Mean (SD) Montgomery-Åsberg Depression Rating Scale total scores improved from 25.6 (4.0) to 17.3 (8.9) for rTMS and 25.7 (4.7) to 15.8 (9.1) for TBS (adjusted difference, 1.55; lower 95% CI -0.67), establishing noninferiority for TBS. The all-cause dropout rates were relatively similar between groups (rTMS: 2 of 87 [2.3%]; TBS: 6 of 85 [7.1%]; P = .14; χ2 = 2.2). Conclusions and Relevance: In older adults with TRD, bilateral TBS compared with standard bilateral rTMS achieved noninferior reduction in depression symptoms. Both treatments had low and similar dropout rates. Using TBS rather than rTMS could increase access to treatment several-fold for older adults with TRD. Trial Registration: ClinicalTrials.gov Identifier: NCT02998580.

From Cursed to Blessed: the Impact of Spirituality on the Life Course of 10 Brazilian Spiritist Mediums.

This qualitative study analyzed the life course of ten Brazilian spiritist mediums who presented anomalous experiences (AEs). A socio-demographic questionnaire and semi-structured interviews were carried out with a non-clinical group, focusing on spiritual background. The inicial AEs were frightening and anguishing, as mediums have related uncertainty and feeling of being controlled; however, after their contact to Spiritism a new positive context was provided, through acceptance and supportiveness, promoting resilience, altruism and self-knowledge, besides an omnipotence status related to mediumship. It was concluded that harmful spiritual experiences may be positively transformed by reframing processes driven by organized religious doctrines.

The Safety, Clinical, and Neurophysiological Effects of Intranasal Ketamine in Patients Who Do Not Respond to Electroconvulsive Therapy: Protocol for a Pilot, Open-Label Clinical Trial.

BACKGROUND: Major depressive disorder is among the most disabling illnesses worldwide, with a lifetime prevalence of 16.2%. Research suggests that 20% to 40% of patients with depression do not respond to pharmacotherapy, developing treatment-resistant depression. Electroconvulsive therapy is the gold standard for treating individuals with treatment-resistant depression, with remission rates of approximately 75% to 90%. However, 10% to 25% of patients do not respond to electroconvulsive therapy, and many are unable to tolerate it due to the side effects. Both groups are considered to be patients who do not respond to electroconvulsive therapy, because both groups continue to exhibit symptoms of severe depression, have a limited number of treatment options available, and are in need of rapid treatment. Ketamine, an N-methyl-D-aspartate receptor antagonist, has been shown to exert rapid antidepressant effects in patients with treatment-resistant depression when administered in subanesthetic doses through 40-minute intravenous infusions. Recently, a ketamine compound, esketamine (Spravato), that is administered through the intranasal route received regulatory approval by the US Food and Drug Administration and Health Canada to treat depression. However, esketamine is challenging to access due to high costs and limited availability. Racemic ketamine (rketamine) is cheap and easy to access; however, the effects in patients who have not responded to electroconvulsive therapy have yet to be understood or tested. This study will use transcranial magnetic stimulation to study mechanisms of human brain cortical physiology at the systemic level to identify neurobiomarkers of response. OBJECTIVE: The objective of this open-label pilot clinical trial is to test the feasibility and safety of intranasal ketamine in patients who have not responded to electroconvulsive therapy. The primary outcome is to determine the feasibility of a larger randomized controlled trial to test the efficacy of intranasal ketamine for patients who have not responded to electroconvulsive therapy for clinical indicators in unipolar depression. The secondary outcome is to determine the preliminary effects of an intervention on clinical outcomes, such as depressive symptoms, suicidal ideation, and quality of living. The third outcome is to explore neurophysiological changes as measured by transcranial magnetic stimulation electromyography and electroencephalography to measure changes in cortical excitability as potential predictors of clinical response. METHODS: A sterile solution of racemic ketamine hydrochloride will be administered twice per week for 4 weeks (8 sessions) intranasally to patients with treatment-resistant depression who did not respond to or could not tolerate an acute course of electroconvulsive therapy. We will recruit 25 adults (24-65 years old) over the course of 2 years from an academic psychiatric hospital in Toronto, Canada. RESULTS: This study has received ethics approval, and funding has been secured. The study is currently active. CONCLUSIONS: This is the first study to test repeated doses of intranasal rketamine in patients who have not responded to electroconvulsive therapy for depression. Results from this study will (1) inform the development of a larger adequately powered randomized controlled trial to test the efficacy of intranasal ketamine for depression and (2) determine potential neurophysiological markers of clinical response. TRIAL REGISTRATION: Clinical Trials.gov NCT05137938; http://clinicaltrials.gov/ct2/show/NCT05137938. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/30163.

Appraising the effectiveness of electrical and magnetic brain stimulation techniques in acute major depressive episodes: an umbrella review of meta-analyses of randomized controlled trials

Electrical and magnetic brain stimulation techniques present distinct mechanisms and efficacy in the acute treatment of depression. This was an umbrella review of meta-analyses of randomized controlled trials of brain stimulation techniques for managing acute major depressive episodes. A systematic review was performed in the PubMed/MEDLINE databases from inception until March 2020. We included the English language meta-analysis with the most randomized controlled trials on the effects of any brain stimulation technique vs. control in adults with an acute depressive episode. Continuous and dichotomous outcomes were assessed. A Measurement Tool to Assess Systematic Reviews-2 was applied and the credibility of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. Seven meta-analyses were included (5,615 patients), providing evidence for different modalities of brain stimulation techniques. Three meta-analyses were evaluated as having high methodological quality, three as moderate, and one as low. The highest quality of evidence was found for high frequency-repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation, and bilateral rTMS. There is strong clinical research evidence to guide future clinical use of some techniques. Our results confirm the heterogeneity of the effects across these techniques, indicating that different mechanisms of action lead to different efficacy profiles.

Repetitive transcranial magnetic stimulation in patients with borderline personality disorder: A systematic review.

The literature on the application of repetitive transcranial magnetic stimulation (rTMS) in Borderline Personality Disorder (BPD) is unclear, even though its neuromodulatory effects on underlying neural circuitry involved in BPD symptoms suggest that it could be a potential treatment option. We sought to review the evidence on rTMS as a treatment option in BPD. PubMed (for Medline database), Google Scholar, and Scopus were systematically searched following the PRISMA guidelines for studies of any design examining the application of the rTMS treatment in adult patients with precise and primary diagnosis of BPD written in the English language. The systematic review has been registered on PROSPERO (CRD42020215927). Forty one records were screened, and eight fulfilled inclusion criteria (total of 63 patients). The existing studies suggest that rTMS is a well-tolerated treatment in patients with BPD. Double-blind randomized controlled studies are necessary to help elucidate the effects of rTMS in the different symptoms in BPD and establish efficacy and the best cortical targets and stimulation protocols. Longitudinal studies that combine evidenced based psychotherapy with rTMS may be a future line of investigation that could potentially improve outcomes for this population.

Is Obesity A Determinant Of Success With Pharmacological Treatment For Depression? A Systematic Review, Meta-Analysis And Meta-Regression.

BACKGROUND: The bidirectional association between Major Depressive Disorder (MDD) and obesity suggests that body mass index (BMI) at the baseline could influence remission rates (RR) with pharmacological treatment. We evaluated the influence of baseline BMI on the chances of remission among patients with MDD administered antidepressants. METHODS: Based on the guidelines of the PRISMA statement, we conducted a systematic review on PubMed, Cochrane and Embase databases with subsequent meta-analysis and meta-regression. We included only randomized controlled trials evaluating the efficacy of antidepressants of different classes (monotherapy and combined therapies) that evidenced baseline BMI assessment. We created a model to describe the linear relationship between baseline BMI and RR. RESULTS: Our systematic review yielded 70 studies with a total of 9,779 patients in the active group and 7,136 patients in the placebo group. In placebo controlled studies, BMI influenced the RR of patients randomized to active treatment. The RR for antidepressants in monotherapy was higher in normal weight to overweight patients rather than obese patients (33% vs 12%, respectively). Also in monotherapy, the RR is higher when the study is conducted on patients with a lower baseline BMI (p=0.029). For combined therapies, the pooled RR was higher in obese patients rather than in normal weight to overweight patients (75% vs 17%, respectively). LIMITATIONS: BMI provides no information about body composition and obesity can be related to several potential confounders that potentially influence RR. CONCLUSION: The RR with antidepressant therapy seems to be associated with baseline BMI in patients with MDD, although this simple variable was insufficiently explored so far.

Appraising the effectiveness of electrical and magnetic brain stimulation techniques in acute major depressive episodes: an umbrella review of meta-analyses of randomized controlled trials.

Electrical and magnetic brain stimulation techniques present distinct mechanisms and efficacy in the acute treatment of depression. This was an umbrella review of meta-analyses of randomized controlled trials of brain stimulation techniques for managing acute major depressive episodes. A systematic review was performed in the PubMed/MEDLINE databases from inception until March 2020. We included the English language meta-analysis with the most randomized controlled trials on the effects of any brain stimulation technique vs. control in adults with an acute depressive episode. Continuous and dichotomous outcomes were assessed. A Measurement Tool to Assess Systematic Reviews-2 was applied and the credibility of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation framework. Seven meta-analyses were included (5,615 patients), providing evidence for different modalities of brain stimulation techniques. Three meta-analyses were evaluated as having high methodological quality, three as moderate, and one as low. The highest quality of evidence was found for high frequency-repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation, and bilateral rTMS. There is strong clinical research evidence to guide future clinical use of some techniques. Our results confirm the heterogeneity of the effects across these techniques, indicating that different mechanisms of action lead to different efficacy profiles.

Effect of repetitive transcranial magnetic stimulation on anxiety symptoms in patients with major depression: An analysis from the THREE-D trial.

BACKGROUND: Despite the advances in the use of repetitive transcranial magnetic stimulation (rTMS) for the treatment of major depressive disorder (MDD), there is relatively little information about its effect on comorbid anxiety symptoms. METHODS: Data from a large randomized noninferiority trial comparing intermittent theta-burst stimulation (iTBS) and high-frequency (10 Hz) rTMS delivered to the left dorsolateral prefrontal cortex (HFL) were analyzed. The primary aim was assessing changes in anxiety/somatization items from the 17-item Hamilton Depression Rating Scale (HAM-D) and the Brief Symptom Inventory (BSI-A), using baseline-adjusted change with an analysis of covariance (ANCOVA), with the final scores as the outcome and baseline scores as the adjustment covariates. RESULTS: The analytical cohort comprised 388 participants (189 in HFL and 199 in iTBS groups). From baseline to the end of the rTMS course, the combined score from the anxiety items from the HAM-D dropped from 7.43 (SD = 2.15) to 4.24 (SD = 2.33) in the HFL group, and 7.33 (SD = 2.13) to 3.76 (SD = 2.23) in the iTBS group. The ANCOVA resulted in an effect from time (p < .0001), but not from group allocation (p = .793) or time × group interaction (p = .976). We observed mean changes in the BSI-A of -3.5 (SD = 5.4) and -3.2 (SD = 4.8), with significant effect of time (p < .0001) in the ANCOVA, but not group allocation (p = .793) or group × time interaction (.664). CONCLUSIONS: Our findings suggest that both 10 Hz and iTBS may yield potential reductions in anxiety symptoms when used for the treatment of MDD. Our findings warrant future research into the effects of left-sided rTMS on depressed patients struggling with concurrent anxiety symptoms.

Transcranial Direct Current Stimulation for Prader-Willi Syndrome.

BACKGROUND: Given the limited therapeutic options for Prader-Willi syndrome (PWS), we conducted an open-label clinical trial to evaluate the effects of transcranial direct current stimulation (tDCS) for hyperphagia, food craving, and aberrant behaviors on this population. METHODS: Twelve subjects with PWS (11-35 years old) were included. The subjects underwent 10 daily 20-minute sessions of tDCS in 2 weeks. The anode was positioned over the left dorsolateral prefrontal cortex, and the cathode over the contralateral region. RESULTS: We observed amelioration of hyperphagic and food craving symptoms (P < 0.05), as well as amelioration of behavioral symptoms measured with the Aberrant Behavior Checklist (P < 0.05). DISCUSSION: To our knowledge, this is the first proof-of-concept trial to report the positive effects of increasing excitability of the left dorsolateral prefrontal cortex, using tDCS, for the behavioral, hyperphagia, and food craving symptoms in PWS, which is a low-cost, well-studied, safe alternative for brain stimulation.