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Objectives: Repetitive transcranial magnetic stimulation (rTMS) is commonly used in unipolar depression; yet, its evidence in bipolar disorder (BD) is limited. We sought to review the evidence on the use of rTMS across the different stages of BD. Methods: MEDLINE database was systematically searched using the PubMed interface following the PRISMA guidelines. Inclusion criteria were as follows: (i) randomized clinical trials (RCTs), open‐label studies, and case series; (ii) specific evaluation of the treatment outcomes using psychometric scales; (iii) clinical studies in adults; and (iv) articles in the English language. The systematic review has been registered on PROSPERO (CRD42020192788). Results: Thirty‐one papers were included in the review. Most studies included participants diagnosed with a bipolar depressive episode (N = 24), have yielded mixed findings, and have yet to reach a consensus on the most effective rTMS protocol. Few studies examined the effect of rTMS during manic (N = 5) or mixed episode (N = 1), or as maintenance treatment (N = 1). The limited data thus far suggest rTMS to be relatively safe and well tolerated. Small sample sizes, heterogeneity among study designs, patients and control groups recruited, rTMS parameters, and outcome measures are among the most significant limitations to these studies. Conclusion: The current data regarding the application of rTMS in BD patients remain limited. More adequately powered sham‐controlled studies are required to verify its efficacy. Large‐scale clinical trials are needed to also determine whether its effects extend to manic and mixed episodes, as well as its role in mood stabilization and amelioration of suicidal behavior. [ABSTRACT FROM AUTHOR]

Background: Many patients with major depressive disorder (MDD) experience substantial impairment despite the availability of efficacious treatments. We performed a systematic review and meta-analysis to compare antidepressant outcomes in MDD with or without physical or psychiatric comorbidities.Methods: Pubmed, EMBASE, and PsycInfo were searched up to May 14th, 2020 using keywords including MDD, antidepressant, medication, and comorbid. 1915 studies were reviewed. Studies that performed a direct and quantitative comparison of antidepressant effect in patients with MDD with or without comorbidities were included. Study characteristics and primary outcomes were extracted. Continuous and dichotomous variables were considered using standardized mean difference (SMD). Heterogeneity was measured using χ2 and I2 tests. Risk of bias was assessed using Cochrane Risk of Bias tool and NIH Quality Assessment Tool.Results: 26 studies met selection criteria. Studies of physical (6 studies; I2 = 57.69%, p = 0.04) and psychiatric comorbidities (20 studies; I2 = 75.75%, p < 0.001) were heterogeneous. When compared to patients with MDD without comorbidities, those with physical (SMD = -0.19, 95% CI: -0.30 to -0.08, p = 0.001; 1910 and 2905 patients with or without comorbidities) or psychiatric comorbidities (SMD = -0.20, 95% CI: -0.31 to -0.095, p < 0.001; 4308 and 6867 patients with or without comorbidities) had worse antidepressant outcomes.Limitations: Our limitations included aggregating the comorbidities into physical and psychiatric comorbidities and the high heterogeneity of the studies.Conclusions: Our review provides updated evidence demonstrating that patients with MDD and physical or psychiatric comorbidities experience worse antidepressant outcomes. [ABSTRACT FROM AUTHOR]

Background Patients with schizophrenia are often found incapable to consent to psychiatric treatment. We evaluated clinical outcomes for incapable and capable patients with schizophrenia treated with electroconvulsive therapy (ECT). Methods We conducted a chart review of all inpatients treated with an acute course of ECT between 2010 and 2018 at the Centre for Addiction and Mental Health, Toronto, Canada. Short-term outcomes included treatment response and cognitive impairment. We assessed whether incapable patients regained the capacity to consent to treatment. Long-term outcomes included readmissions and subsequent courses of acute or maintenance ECT. Results A total of 159 (67%) incapable and 79 (33%) capable patients were included. Patients experienced treatment response (incapable, n = 108, 67.9%; capable, n = 52, 65.8%; P =.771) and few experienced cognitive impairment (incapable, n = 21, 13.2%; capable, n = 19, 24.1%; P =.043). A minority of patients were treated with a subsequent course of acute ECT (incapable, n = 46, 28.9%; capable, n = 16, 20.3%; P =.162). Incapable patients were more likely to be treated with maintenance ECT for at least 6 months (incapable, n = 46, 28.9%; capable, n = 13, 16.5%; P =.039). Both groups had similar readmission rates (incapable, n = 70, 44.0%; capable, n = 35, 44.3%; P = 1.000). Eight (5.0%) incapable patients regained capacity and 7 consented to further treatment. Conclusions Irrespective of treatment capacity, the majority of patients demonstrated clinical improvement. Incapable patients experienced less cognitive side effects when compared with capable patients, though they had fewer treatments overall. This study informs clinicians, patients, and substitute decision-makers about the outcomes and challenges of ECT in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Background: There is growing interest in the potential of neuromodulation options in treatment‐resistant obsessive–compulsive disorder (OCD). Magnetic seizure therapy (MST), is a new treatment intervention in which generalized seizures are induced with transcranial magnetic stimulation. We conducted a pilot study to assess the efficacy and cognitive effects of MST in patients with treatment‐resistant OCD. Methods: In an open‐label pilot study, participants with treatment‐resistant OCD and a baseline Yale‐Brown Obsessive–Compulsive Scale (Y‐BOCS) scores of ≥16 were treated with up to 24 acute treatments. The primary clinical outcomes were clinical response (Y‐BOCS score reduction ≥30%) and remission (final Y‐BOCS score ≤8). A neurocognitive battery, the Quick Inventory for Depressive Symptoms–Self Report (QIDS‐SR), the Beck Scale for Suicidal Ideation (SSI), and the Quality of Life Enjoyment and Satisfaction Questionnaire‐Short Form (Q‐LES‐Q‐SF) were also completed as secondary measures. Results: Ten participants with OCD who had not responded to medications or psychotherapy enrolled in the study and seven completed an adequate trial (defined as ≥8 treatments). MST was associated with minimal cognitive effects except for some decrease in autobiographical memory and no serious adverse effects. Only one participant met the predefined criteria for response, and none for remission. The baseline and endpoint Y‐BOCS scores were not statistically different. Conclusion: Overall, MST was not beneficial in a small group of patients with treatment‐resistant OCD. At this time, other studies of MST for OCD are not warranted until different coil placements targeting other brain circuits can be proposed. [ABSTRACT FROM AUTHOR]

Biological strategies to improve treatment efficacy in clozapine-treated patients are urgently needed. Repetitive transcranial magnetic stimulation (rTMS) merits consideration as intervention for patients with persistent auditory hallucinations (AH) or negative symptoms (NS) not responding sufficiently to clozapine treatment. Data from 10 international RCTs of rTMS for patients being treated with clozapine were pooled. Two levels of symptomatic response were defined: improvement of ≥20% and ≥50% on study-specific primary endpoint scales. Changes in the positive and negative syndrome scale (PANSS) from baseline to endpoint assessment were also analysed. Analyses of 131 patients did not reveal a significant difference for ≥20% and ≥50% response thresholds for improvement of AH, negative or total symptoms between active and sham rTMS groups. The number needed to treat (NNT) for an improvement in persistent AH was nine following active rTMS. PANSS scores did not improve significantly from baseline to endpoint between active and sham groups in studies investigating NS and AH. rTMS as a treatment for persistent symptoms in clozapine-treated patients did not show a beneficial effect of active compared to sham treatment. For AH, the size of the NNTs indicates a possible beneficial effect of rTMS. [ABSTRACT FROM AUTHOR]

Background: Treatment-resistant bipolar depression can be treated effectively using electroconvulsive therapy, but its use is limited because of stigma and cognitive adverse effects. Magnetic seizure therapy is a new convulsive therapy with promising early evidence of antidepressant effects and minimal cognitive adverse effects. However, there are no clinical trials of the efficacy and safety of magnetic seizure therapy for treatment-resistant bipolar depression. Methods: Participants with treatment-resistant bipolar depression were treated with magnetic seizure therapy for up to 24 sessions or until remission. Magnetic seizure therapy was applied over the prefrontal cortex at high (100 Hz; n = 8), medium (50 or 60 Hz; n = 9) or low (25 Hz; n = 3) frequency, or over the vertex at high frequency (n = 6). The primary outcome measure was the 24-item Hamilton Rating Scale for Depression. Participants completed a comprehensive battery of neurocognitive tests. Results: Twenty-six participants completed a minimally adequate trial of magnetic seizure therapy (i.e., ≥ 8 sessions), and 20 completed full treatment per protocol. Participants showed a significant reduction in scores on the Hamilton Rating Scale for Depression. Adequate trial completers had a remission rate of 23.1% and a response rate of 38.5%. Per-protocol completers had a remission rate of 30% and a response rate of 50%. Almost all cognitive measures remained stable, except for significantly worsened recall consistency on the autobiographical memory inventory. Limitations: The open-label study design and modest sample size did not allow for comparisons between stimulation parameters. Conclusion: In treatment-resistant bipolar depression, magnetic seizure therapy produced significant improvements in depression symptoms with minimal effects on cognitive performance. These promising results warrant further investigation with larger randomized clinical trials comparing magnetic seizure therapy to electroconvulsive therapy. Clinical trial registration: NCT01596608; clinicaltrials.gov [ABSTRACT FROM AUTHOR]

Objective: Obsessive-compulsive disorder (OCD) is a chronic and disabling condition that often responds unsatisfactorily to pharmacological and psychological treatments. Converging evidence suggests a dysfunction of the cortical-striatal-thalamic-cortical circuit in OCD, and a previous feasibility study indicated beneficial effects of deep transcranial magnetic stimulation (dTMS) targeting the medial prefrontal cortex and the anterior cingulate cortex. The authors examined the therapeutic effect of dTMS in a multicenter double-blind sham-controlled study.Methods: At 11 centers, 99 OCD patients were randomly allocated to treatment with either high-frequency (20 Hz) or sham dTMS and received daily treatments following individualized symptom provocation, for 6 weeks. Clinical response to treatment was determined using the Yale-Brown Obsessive Compulsive Scale (YBOCS), and the primary efficacy endpoint was the change in score from baseline to posttreatment assessment. Additional measures were response rates (defined as a reduction of ≥30% in YBOCS score) at the posttreatment assessment and after another month of follow-up.Results: Eighty-nine percent of the active treatment group and 96% of the sham treatment group completed the study. The reduction in YBOCS score among patients who received active dTMS treatment was significantly greater than among patients who received sham treatment (reductions of 6.0 points and 3.3 points, respectively), with response rates of 38.1% and 11.1%, respectively. At the 1-month follow-up, the response rates were 45.2% in the active treatment group and 17.8% in the sham treatment group. Significant differences between the groups were maintained at follow-up.Conclusions: High-frequency dTMS over the medial prefrontal cortex and anterior cingulate cortex significantly improved OCD symptoms and may be considered as a potential intervention for patients who do not respond adequately to pharmacological and psychological interventions. [ABSTRACT FROM AUTHOR]

An editorial is presented on the personalizing transcranial magnetic stimulation (TMS) targets to improve treatment outcomes in depression. Topics include how the network-based substrates of depression have synergistically advanced circuit-based treatment techniques; and how Repetitive transcranial magnetic stimulation (rTMS) has been used to treat depression noninvasively by putatively stimulating large-scale, functionally interconnected brain regions.

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]

Background/Objectives Metabolic syndrome (MetS) is the co-occurrence of obesity and metabolic derangements. Prior research implicates MetS in prolongation of the course of depression in older adults, but its effect on antidepressant response is unknown in this population. The objective was to determine whether MetS and related metabolic dyscrasias are associated with decreased rate of remission from depression in older adults treated pharmacologically for depression. Design Secondary analysis of a randomized controlled trial. Setting Three academic medical centers in North America. Participants Adults aged 60 and older (mean age 69.1) with major depressive disorder ( MDD) (N = 435). Intervention Open-label, protocolized treatment with extended-release venlafaxine for 12 or more weeks. Measurements Time to remission from depression, with remission defined as a Montgomery-Åsberg Depression Rating Scale ( MADRS) score of 10 or less at last two visits. Results Two hundred twenty-two participants (51%) met criteria for MetS at baseline; MetS was associated with greater severity ( MADRS score) and chronicity of depression at baseline. Remission was achieved in 182 participants (42%). In the unadjusted analysis, MetS was associated with prolonged time to remission (hazard ratio for remission = 0.71, 95% confidence interval = 0.52-0.95), but this relationship was not significant in the adjusted model; greater number of MetS components and lower high-density lipoprotein cholesterol had similar effects. Only diastolic blood pressure ( DBP) was a significant predictor of time to remission before and after adjustment, with higher DBP predicting longer time to remission. Insulin sensitivity did not predict time to remission. Conclusion The presence of MetS in older adults with depression was associated with greater symptom severity and chronicity of depression, which appears to have accounted for the poorer antidepressant response observed in those with MetS. Additionally, our preliminary finding of an association between higher DBP and poorer antidepressant response bears further examination and replication. [ABSTRACT FROM AUTHOR]

Background: Treatment resistant depression (TRD) remains a clinical challenge, and finding biomarkers that predict treatment response are a long sought goal to precisely indicate treatments. This pilot study aims to characterize brain dysfunction in TRD patients who underwent rTMS to define neuroimaging biomarkers that discriminate non-responders (NR) from responders (R).Methods: 20 TRD patients who underwent a course of rTMS to the left DLPFC were categorized into R and NR groups based on a >50% reduction in HRSD scores. Utilizing resting-state fMRI and ICA techniques, this study compared baseline RSNs of R vs. NR as well as TRD vs. healthy volunteer group. Regression analysis was conducted to link regions with clinical improvements. ROC analysis was further conducted to confirm the utility of the identified regions in classifying the patients.Results: Prior to treatment, non-responders displayed hyper-connectivity in ACC/VMPFC, PCC/pC, dACC and insula within RSNs that have been associated with MDD pathology. Regression results showed that regions associated with clinical improvements overlapped largely with regions that showed aberrant connectivity. ACC/VMPFC, dACC and left insula, which are hub regions of DMN and SN, exhibited excellent performance (highest sensitivity=100% and highest specificity=82%) in discriminating the response status of the patients.Limitations: Relatively small sample size.Conclusions: Our findings provide insight into fMRI predictive measures of treatment response to rTMS treatment, and demonstrate the potential of RSNs-based biomarkers in predicting response to rTMS treatment. Future studies are needed to validate the application of these measures to inform individual treatment indications. [ABSTRACT FROM AUTHOR]

Objective: The primary objective of this study was to investigate five putatively functional variants of the norepinephrine transporter (SLC6A2, NET) and serotonin transporter (SLC6A4, SERT) genes and remission in depressed older adults treated with venlafaxine. A secondary objective was to analyze 17 other variants in serotonergic system genes (HTR1A, HTR2A, HTR1B, HTR2C, TPH1, TPH2) potentially involved in the mechanism of action of venlafaxine.Method: The sample included 350 adults age 60 or older with DSM-IV-defined major depressive disorder and a score of at least 15 on the Montgomery-Åsberg Depression Rating Scale (MADRS). Participants received protocolized treatment with open-label venlafaxine, up to 300 mg/day for approximately 12 weeks, as part of a three-site clinical trial. Each individual was genotyped for 22 polymorphisms in eight genes, which were tested for association with venlafaxine remission (a MADRS score ≤10) and changes in MADRS score during treatment.Results: After adjusting for multiple comparisons, NET variant rs2242446 (T-182C) was significantly associated with remission (odds ratio=1.66, 95% CI=1.13, 2.42). Individuals with the rs2242446 C/C genotype were more likely to remit (73.1%) than those with either the C/T (51.8%) or the T/T genotype (47.3%). Individuals with the C/C genotype also had a shorter time to remission than those with the C/T or T/T genotypes and had a greater percentage change in MADRS score from baseline to end of treatment (up to week 12).Conclusions: NET rs2242446/T-182C may serve as a biomarker to predict the likelihood of remission with venlafaxine in older adults with major depression. These findings may help to optimize antidepressant outcomes in older adults. [ABSTRACT FROM AUTHOR]

Over 350 million people worldwide suffer from depression, a third of whom are medication-resistant. Seizure therapy remains the most effective treatment in depression, even when many treatments fail. The utility of seizure therapy is limited due to its cognitive side effects and stigma. The biological targets of seizure therapy remain unknown, hindering design of new treatments with comparable efficacy. Seizures impact the brains temporal dynamicity observed through electroencephalography. This dynamicity reflects richness of information processing across distributed brain networks subserving affective and cognitive processes. We investigated the hypothesis that seizure therapy impacts mood (depressive symptoms) and cognition by modulating brain temporal dynamicity. We obtained resting-state electroencephalography from 34 patients (age = 46.0 ± 14.0, 21 females) receiving two types of seizure treatments-electroconvulsive therapy or magnetic seizure therapy. We used multi-scale entropy to quantify the complexity of the brain's temporal dynamics before and after seizure therapy. We discovered that reduction of complexity in fine timescales underlined successful therapeutic response to both seizure treatments. Greater reduction in complexity of fine timescales in parieto-occipital and central brain regions was significantly linked with greater improvement in depressive symptoms. Greater increase in complexity of coarse timescales was associated with greater decline in cognition including the autobiographical memory. These findings were region and timescale specific. That is, change in complexity in occipital regions (e.g. O2 electrode or right occipital pole) at fine timescales was only associated with change in depressive symptoms, and not change in cognition, and change in complexity in parieto-central regions (e.g. Pz electrode or intra and transparietal sulcus) at coarser timescale was only associated with change in cognition, and not depressive symptoms. Finally, region and timescale specific changes in complexity classified both antidepressant and cognitive response to seizure therapy with good (80%) and excellent (95%) accuracy, respectively. In this study, we discovered a novel biological target of seizure therapy: complexity of the brain resting state dynamics. Region and timescale dependent changes in complexity of the brain resting state dynamics is a novel mechanistic marker of response to seizure therapy that explains both the antidepressant response and cognitive changes associated with this treatment. This marker has tremendous potential to guide design of the new generation of antidepressant treatments. [ABSTRACT FROM AUTHOR]

Background: Dementia frequently presents with aggression, agitation, and disorganized behavior for which current treatment is partially effective and is associated with significant adverse effects.Objective: The aim of this study was to retrospectively assess the clinical effectiveness and tolerability of electroconvulsive therapy (ECT) in a sample of patients with neuropsychiatric symptoms of dementia (NPS) and to explore factors associated with response and with cognitive adverse effects.Methods: We examined the clinical records of 25 patients with dementia and a pre-existing psychiatric disorder treated with ECT at an academic mental health hospital between April 1, 2010 and January 28, 2016. Twenty-nine acute ECT courses and fifteen maintenance courses were reviewed. We assessed treatment effectiveness and cognitive adverse effects as well as factors associated with response to treatment, including pre-existing psychiatric disorders, concomitant pharmacological treatment and types of dementia.Results: ECT resulted in a clinically meaningful response in 72% of acute treatment courses. Cognitive adverse effects affecting functioning were reported in 7% of the acute treatment courses. Maintenance treatment was effective in sustaining the response in 87% of treatment courses with two reports of significant cognitive adverse effects. One patient fell and experienced a hip fracture a day after treatment. Use of antipsychotic or antidepressant medications, pre-existing psychiatric disorder, or gender were not associated with response.Conclusion: This study shows meaningful clinical effectiveness and good tolerability of ECT in patients with severe NPS of dementia. Furthermore, maintenance ECT was effective in sustaining treatment response. [ABSTRACT FROM AUTHOR]

Theta-burst stimulation is an emerging protocol for repetitive transcranial magnetic stimulation that takes 1-3 min to administer, yet offers equal/superior potency to conventional protocols lasting 30-60 min. However, preclinical evidence suggests that D2 receptor blockade may abolish the acute effects of theta-burst stimulation on synaptic facilitation or inhibition. As many patients presenting for repetitive transcranial magnetic stimulation are taking antipsychotic medications as augmentation for treatment-resistant depression, this finding is potentially concerning for the implementation of theta-burst stimulation in clinical settings. Here, we examined whether treatment-resistant depression patients taking antipsychotics have worse outcomes after a course of intermittent theta-burst stimulation. A chart review identified 105 treatment-resistant depression patients who underwent dorsomedial prefrontal-intermittent theta-burst stimulation; clinical outcomes on Hamilton Depression Rating Scale and Beck Depression Inventory were compared for those taking and not taking antipsychotics. The 29 of 105 patients who were taking antipsychotics showed non-significantly better response and remission rates, and non-significantly larger percentage improvements on both scales, with a positive but non-significant correlation between higher antipsychotic dose and larger percentage improvement. Contrary to expectations, outcomes were not significantly worse, and in some analyses trended towards being better, in patients taking antipsychotics. Future randomized controlled studies of repetitive transcranial magnetic stimulation combined with standardized dopaminergic manipulations may be justified and warranted. [ABSTRACT FROM AUTHOR]

Background: Several factors may mitigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) over sham rTMS in patients with treatment-resistant depression (TRD). These factors include unilateral stimulation (i.e., treatment of only the left dorsolateral prefrontal cortex [DLPFC]), suboptimal methods of targeting the DLPFC and insufficient stimulation intensity (based on coil-to-cortex distance). Methods: We recruited patients with TRD between the ages of 18 and 85 years from a university hospital, and participants were randomized to receive sequential bilateral rTMS (600 pulses at 1 Hz followed by 1500 pulses at 10 Hz), unilateral high-frequency left (HFL)-rTMS (2100 pulses at 10 Hz) or sham rTMS for 3 or 6 weeks depending on treatment response. Stimulation was targeted with MRI localization over the junction of the middle and anterior thirds of the middle frontal gyrus, using 120% of the coil-to-cortex adjusted motor threshold. Our primary outcome of interest was the remission rate. Results: A total of 121 patients participated in this study. The remission rate was significantly higher in the bilateral group than the sham group. The remission rate in the HFL-rTMS group was intermediate and did not differ statistically from the rate in the 2 other groups. There were no significant differences in reduction of depression scores among the 3 groups. Limitations: The number of pulses used per session in the unilateral group was somewhat lower in our trial than in more recent trials, and the sham condition did not involve active stimulation. Conclusion: Our findings suggest that sequential bilateral rTMS is superior to sham rTMS; however, adjusting for coil-to-cortex distance did not yield enhanced efficacy rates. [ABSTRACT FROM AUTHOR]

Importance: Magnetic seizure therapy (MST) is a novel therapeutic option for treatment-resistant depression (TRD). Suicidal ideation is often associated with TRD and contributes to the increased mortality and morbidity of the disorder.Objective: To identify a biomarker that may serve as an indicator of remission of suicidal ideation following a course of MST by using cortical inhibition measures from interleaved transcranial magnetic stimulation and electroencephalography (TMS-EEG).Design, Setting, and Participants: Thirty-three patients with TRD were part of an open-label clinical trial of MST treatment. Data from 27 patients (82%) were available for analysis in this study. Baseline TMS-EEG measures were assessed within 1 week before the initiation of MST treatment using the TMS-EEG measures of cortical inhibition (ie, N100 and long-interval cortical inhibition [LICI]) from the left dorsolateral prefrontal cortex and the left motor cortex, with the latter acting as a control site.Interventions: The MST treatments were administered under general anesthesia, and a stimulator coil consisting of 2 individual cone-shaped coils was used.Main Outcomes and Measures: Suicidal ideation was evaluated before initiation and after completion of MST using the Scale for Suicide Ideation (SSI). Measures of cortical inhibition (ie, N100 and LICI) from the left dorsolateral prefrontal cortex were selected. N100 was quantified as the amplitude of the negative peak around 100 milliseconds in the TMS-evoked potential (TEP) after a single TMS pulse. LICI was quantified as the amount of suppression in the double-pulse TEP relative to the single-pulse TEP.Results: Of the 27 patients included in the analyses, 15 (56%) were women; mean (SD) age of the sample was 46.0 (15.3) years. At baseline, patients had a mean SSI score of 9.0 (6.8), with 8 of 27 patients (30%) having a score of 0. After completion of MST, patients had a mean SSI score of 4.2 (6.3) (pre-post treatment mean difference, 4.8 [6.7]; paired t26 = 3.72; P = .001), and 18 of 27 individuals (67%) had a score of 0 for a remission rate of 53%. The N100 and LICI in the frontal cortex-but not in the motor cortex-were indicators of remission of suicidal ideation with 89% accuracy, 90% sensitivity, and 89% specificity (area under the curve, 0.90; P = .003).Conclusions and Relevance: These results suggest that cortical inhibition may be used to identify patients with TRD who are most likely to experience remission of suicidal ideation following a course of MST. Stronger inhibitory neurotransmission at baseline may reflect the integrity of transsynaptic networks that are targeted by MST for optimal therapeutic response. [ABSTRACT FROM AUTHOR]

Background: A significant proportion of patients with depression fail to respond to psychotherapy and standard pharmacotherapy, leading to treatment-resistant depression (TRD). Due to the significant prevalence of TRD, alternative therapies for depression have emerged as viable treatments in the armamentarium for this disorder. Repetitive transcranial magnetic stimulation (rTMS) is now being offered in clinical practice in broader numbers. Many studies have investigated various different neurobiological predictors of response of rTMS. However, a synthesis of this literature and an understanding of what biological targets predict response is lacking. This review aims to systematically synthesize the literature on the neurobiological predictors of rTMS in patients with depression.Methods: Medline (1996-2014), Embase (1980-2014), and PsycINFO (1806-2014) were searched under set terms. Two authors reviewed each article and came to consensus on the inclusion and exclusion criteria. All eligible studies were reviewed, duplicates were removed, and data were extracted individually.Results: The search identified 1,673 articles, 41 of which met both inclusion and exclusion criteria. Various biological factors at baseline appear to predict response to rTMS, including levels of certain molecular factors, blood flow in brain regions implicated in depression, electrophysiological findings, and specific genetic polymorphisms.Conclusions: Significant methodological variability in rTMS treatment protocols limits the ability to generalize conclusions. However, response to treatment may be predicted by baseline frontal lobe blood flow, and presence of polymorphisms of the 5-hydroxytryptamine (5-HT) -1a gene, the LL genotype of the serotonin transporter linked polymorphic region (5-HTTLPR) gene, and Val/Val homozygotes of the brain-derived neurotrophic factor (BDNF) gene. [ABSTRACT FROM AUTHOR]

Objective: This study explored whether older black and white adults with major depressive disorder differed in rates of remission or attrition during open-label treatment with venlafaxine and supportive care.Methods: A total of 47 black (10%) and 412 white (90%) adults age ≥60 were treated with open-label venlafaxine extended-release (≤300 mg per day) for 12-14 weeks during the initial phase of an multisite, randomized, placebo-controlled augmentation trial. Participants were help-seeking older adults with nonpsychotic major depressive disorder (single or recurrent episode) referred from specialty clinics, primary care practices, advertisements, and research programs. Remission was defined as a Montgomery-Asberg Depression Rating Scale score of ≤10 for two consecutive assessments at the end of 12 weeks. Kaplan-Meier curves displayed time to dropout and time to initial remission. Cox proportional hazards models assessed differences in attrition and remission rates.Results: Black participants had greater baseline general medical comorbidity, worse physical health-related quality of life, and poorer cognitive function than white participants. White participants were more likely to have received an adequate trial of antidepressant and psychotherapy before study entry. Baseline depression severity, depression duration, age at onset, and recurrence history did not differ between groups. The groups had similar final doses of venlafaxine and similar rates of attrition and remission. Side-effect profiles were comparable between the groups.Conclusions: Despite greater medical comorbidity, lower cognitive function, and less adequate prior exposure to antidepressant treatment and psychotherapy, black participants were no more likely to discontinue antidepressant pharmacotherapy and experienced a rate of remission comparable to white participants. [ABSTRACT FROM AUTHOR]

The article discusses the use of repetitive transcranial magnetic stimulation (rTMS) in the treatment of neuropsychiatric symptoms in several diseases. Diseases discussed include Alzheimer disease with mild cognitive impairment, fibromyalgia, and multiple sclerosis. Other diseases discussed include Parkinson disease, and cerebrovascular disease.

The article describes the history of transcranial direct current stimulation (tDCS) for treating major depression and its potential antidepressant mechanism of action and reviews findings from recent clinical trials and discuses the potential role of tDCS in treating depressive disorders. Topics discussed include an investigation on the utility of tDCS as a treatment for depression in the 1960s and randomized controlled trials conducted to examine the efficacy of tDCS in treating depression.

Abstract: Having failed to respond to an adequate antidepressant treatment course predicts poorer treatment outcomes in patients with major depression. However, little is known about the impact of prior treatment on the outcome of major depression with psychotic features (MDpsy). We examined the effect of prior treatment history on the outcome of pharmacotherapy of MDpsy in patients who participated in the STOPD-PD study, a randomized, double-blind, clinical trial comparing a combination of olanzapine plus sertraline vs. olanzapine plus placebo. The strength of treatment courses received prior to randomization was classified using a validated method. A hierarchy of outcomes was hypothesized based on treatments received prior to randomization and randomized treatment. A high remission rate was observed in subjects with a history of no prior treatment or inadequate treatment who were treated with a combination of olanzapine and sertraline. A low remission rate was observed in subjects who had previously failed to respond to an antidepressant alone and who were treated with olanzapine monotherapy. A low remission rate was also observed in subjects who had previously failed to respond to a combination of an antipsychotic and an antidepressant. Similar to patients with major depression, these results emphasize the impact of prior pharmacotherapy on treatment outcomes in patients with MDpsy. [Copyright &y& Elsevier]

The article discusses repetitive transcranial magnetic stimulation (rTMS) as an emerging medication for treatment-resistant depression. Information is provided on the use of rTMS, patients who are eligible for the treatment like those with treatment-resistant depression, and its common adverse effects like scalp pain during stimulation and transient headache after the treatment.

Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for major depressive disorder (MDD); however, this treatment currently lacks reliable biomarkers of treatment response. TMS-evoked potentials (TEPs), measured using TMS-electroencephalography (TMS-EEG), have been suggested as potential biomarker candidates, with the N100 peak being one of the most promising. This study investigated the association between baseline N100 amplitude and 1 Hz right dorsolateral prefrontal cortex (R-DLPFC) accelerated rTMS (arTMS) treatment in MDD. Baseline TMS-EEG sessions were performed for 23 MDD patients. All patients then underwent 40 sessions of 1 Hz R-DLPFC (F4) arTMS over 5 days and a follow-up TMS-EEG session one week after the end of theses arTMS sessions. Baseline N100 amplitude at F4 showed a strong positive association (p <.001) with treatment outcome. The association between the change in N100 amplitude (baseline to follow-up) and treatment outcome did not remain significant after Bonferroni correction (p =.06, corrected; p =.03, uncorrected). Furthermore, treatment responders had a significantly larger mean baseline F4 TEP amplitude during the N100 time frame compared to non-responders (p <.001). Topographically, after Bonferroni correction, F4 is the only electrode at which its baseline N100 amplitude showed a significant positive association (p <.001) with treatment outcome. Lack of control group and auditory masking. Baseline N100 amplitude showed a strong association with treatment outcome and thus demonstrated great potential to be utilized as a cost-effective and widely adoptable biomarker of rTMS treatment in MDD. • Baseline F4 N100 amplitude showed a strong association (p<.001) with 1Hz R-DLPFC rTMS treatment outcome. • Treatment responders had a larger mean F4 TEP amplitude during the N100 time frame compared to non-responders (p <.001). • N100 amplitude at F3 and F4 had the strongest association with outcome (F3: p = 0.015, uncorr.; F4 p <.001, corrected). • Our results suggest that N100 amplitude has great potential to be a cost-effective and widely-adoptable biomarker. [ABSTRACT FROM AUTHOR]

In recent years, there has been debate about the effectiveness of treatments from different fields, such as neurostimulation, neurofeedback, brain training, and pharmacotherapy. This debate has been fuelled by contradictory and nuanced experimental findings. Notably, the effectiveness of a given treatment is commonly evaluated by comparing the effect of the active treatment versus the placebo on human health and/or behaviour. However, this approach neglects the individual's subjective experience of the type of treatment she or he received in establishing treatment efficacy. Here, we show that individual differences in subjective treatment - the thought of receiving the active or placebo condition during an experiment - can explain variability in outcomes better than the actual treatment. We analysed four independent datasets (N = 387 participants), including clinical patients and healthy adults from different age groups who were exposed to different neurostimulation treatments (transcranial magnetic stimulation: Studies 1 and 2; transcranial direct current stimulation: Studies 3 and 4). Our findings show that the inclusion of subjective treatment can provide a better model fit either alone or in interaction with objective treatment (defined as the condition to which participants are assigned in the experiment). These results demonstrate the significant contribution of subjective experience in explaining the variability of clinical, cognitive, and behavioural outcomes. We advocate for existing and future studies in clinical and non- clinical research to start accounting for participants' subjective beliefs and their interplay with objective treatment when assessing the efficacy of treatments. This approach will be crucial in providing a more accurate estimation of the treatment effect and its source, allowing the development of effective and reproducible interventions. [ABSTRACT FROM AUTHOR]

Guidance on Major Depressive Disorder (MDD) treatment in those with comorbid Alcohol Use Disorder (AUD) is limited. We performed a secondary analysis on the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, examining the association between comorbid AUD and depression outcomes. STAR*D was a real-world effectiveness trial starting with citalopram in level 1. Non-responding participants progressed through 3 other sequential treatment levels with different switch or augmentation options. Antidepressant outcomes were compared between MDD (n = 2826) and comorbid MDD and AUD (n = 864). Logistic regressions were performed to evaluate remission and response predictors in the total STAR*D sample and the AUD-comorbidity interaction. Chi-squared tests showed no significant difference in response or remission rates from depression between groups across treatment levels. Higher Hamilton Rating Scale for Depression (HRSD) score was associated with overall lower odds of remission in treatment level 1 (OR = 0.93, p < 0.001) and 2 (OR = 0.95, p < 0.001), with no significant interaction with comorbid AUD. Higher baseline suicidality had overall lower odds of remission in level 1 (OR = 0.82, p < 0.001) and 2 (OR = 0.1, p < 0.001), but with comorbid AUD compared to no AUD, suicidality increased odds of level 1 remission (OR = 1.30, p = 0.012). In comorbid AUD in level 2, venlafaxine was associated with lower odds of remission (OR = 0.13, p = 0.013) and response (OR = 0.12, p = 0.006); bupropion with lower odds of response (OR = 0.22, p = 0.024). Open label study design and lack of alcohol use data. Comorbid AUD may interact with predictors of antidepressant response in MDD and using venlafaxine or bupropion may be less effective. Addressing this comorbidity requires unique assessment and treatment approaches. • In STAR*D, comorbid MDD + AUD did not differ from MDD alone in remission. • In MDD + AUD, baseline suicidality may be associated with better outcomes. • In MDD + AUD, treatment with either venlafaxine or bupropion may be less effective. • No apparent difference of AUD on the effect of depression severity with remission. • When treating MDD + AUD, prognostic factors and treatment may be different. [ABSTRACT FROM AUTHOR]

Intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex is effective for treatment-resistant depression, but the effects of iTBS on neurophysiological markers remain unclear. Here, we indexed transcranial magnetic stimulation–electroencephalography (TMS-EEG) markers, specifically, the N45 and N100 amplitudes, at baseline and post-iTBS, comparing separated and contiguous iTBS schedules. TMS-EEG markers were also compared between iTBS responders and nonresponders. TMS-EEG was analyzed from a triple-blind 1:1 randomized trial for treatment-resistant depression, comparing a separated (54-minute interval) and contiguous (0-minute interval) schedule of 2 × 600-pulse iTBS for 30 treatments. Participants underwent TMS-EEG over the left dorsolateral prefrontal cortex at baseline and posttreatment. One hundred fourteen participants had usable TMS-EEG at baseline, and 98 at posttreatment. TMS-evoked potential components (N45, N100) were examined via global mean field analysis. The N100 amplitude decreased from baseline to posttreatment, regardless of the treatment group (F 1,106 = 5.20, p =.02). There were no changes in N45 amplitude in either treatment group. In responders, the N100 amplitude decreased after iTBS (F 1,102 = 11.30, p =.001, p corrected =.0004). Responders showed higher posttreatment N45 amplitude than nonresponders (F 1,94 = 4.11, p =.045, p corrected =.016). Higher baseline N100 amplitude predicted lower post-iTBS depression scores (F 4,106 = 6.28, p =.00014). These results provide further evidence for an association between the neurophysiological effects of iTBS and treatment efficacy in treatment-resistant depression. Future studies are needed to test the predictive potential for clinical applications of TMS-EEG markers. [ABSTRACT FROM AUTHOR]

Objective: Executive function (EF) deficits in patients with autism spectrum disorder (ASD) are ubiquitous and understudied. Further, there are no effective, neuroscience-based treatments to address this impairing feature of ASD. Repetitive transcranial magnetic stimulation (rTMS) has demonstrated promise in addressing EF deficits in adult neuropsychiatric disorders. This article will outline the design of a novel randomized-controlled trial of bilateral, 20 Hz, rTMS applied to the dorsolateral prefrontal cortex (DLPFC) for treatment of EF deficits in ASD that is currently ongoing. We describe prior therapeutic rTMS research for ASD and prior rTMS trials targeting EFs in adult neuropsychiatric disorders. A neurophysiological rationale for rTMS treatment of EF deficits in ASD is presented.Methods: An ongoing protocol will enroll participants aged 16-35 with ASD and no intellectual disability. Psychotropic medications will be continued during the 4-week trial of active 20 Hz versus sham rTMS applied to the DLPFC. Twenty, active treatment sessions consisting of 25 stimulation trains at a 90% motor threshold will be administered. The primary outcome measure is the Cambridge Neuropsychological Test Automated Battery (CANTAB) spatial working memory task. At present, recruitment, enrollment, and treatment within the described clinical trial are ongoing.Conclusions: EF deficits are common and impairing symptoms of ASD. There are no evidence-based treatments for EF deficits in ASD. The protocol described here will provide important preliminary data on the feasibility and efficacy of 20 Hz rTMS to DLPFC for EF deficits in ASD. [ABSTRACT FROM AUTHOR]

Background and Objective: Repetitive transcranial magnetic stimulation (rTMS) is an effective and safe treatment for major depressive disorder (MDD). rTMS is in need of a reliable biomarker of treatment response. High frequency (HF) dorsolateral prefrontal cortex (DLPFC) rTMS has been reported to induce significant changes in the cardiac activity of MDD patients. Low frequency DLPFC rTMS has many advantages over HF-DLPFC rTMS and thus this study aims to further investigate the effect of low frequency 1 Hz right hemisphere (R)-DLPFC rTMS on the cardiac activity of MDD patients, as well as the potential of using electrocardiogram (ECG) parameters as biomarkers of treatment outcome.Methods: Baseline ECG sessions were performed for 19 MDD patients. All patients then underwent 40 sessions of accelerated 1 Hz R-DLPFC rTMS one week after the baseline session.Results: Heart rate (HR) significantly decreased from the resting period to the first and third minute of the 1 Hz R-DLPFC rTMS period. Resting HR was found to have a significant negative association with treatment outcome. Prior to Bonferroni correction, HR during stimulation and the degree of rTMS-induced HR reduction were significantly negatively associated with treatment outcome. No significant changes were observed for the heart rate variability (HRV) parameters.Limitations: Sample size (n = 19); the use of electroencephalography equipment for ECG; lack of respiration monitoring; relatively short recording duration for HRV parameters.Conclusion: This novel study provides further preliminary evidence that ECG may be utilized as a biomarker of rTMS treatment response in MDD.Trial Registration: ClinicalTrials.gov Identifier: NCT04376697. [ABSTRACT FROM AUTHOR]

• Repetitive transcranial magnetic stimulation (rTMS) is an evidence-based treatment for late-life depression (LLD), but treatment response varies. • Demographic, clinical, and cognitive predictors of remission after rTMS in LLD were evaluated. • Lower baseline depression symptom severity, fewer prior antidepressant treatment failures, and higher global cognition predicted remission following rTMS treatment. • A decision tree analyses established hierarchical order as well as cutoff values for the identified predictors. • No evidence that executive dysfunction worsened treatment outcomes was found, an important finding as executive dysfunction is consistently associated with worse outcomes with pharmacotherapy. 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. [ABSTRACT FROM AUTHOR]

• rTMS treatment outcome is quadratically related to the individual alpha peak frequency (IAF) in depression. • Absolute distance of IAF to 10 Hz is linearly related to clinical outcome. • These results strengthen the theory that 10 Hz rTMS entrains brain oscillations. The aim of the current study was to attempt to replicate the finding that the individual alpha frequency (IAF) as well as the absolute difference between IAF and 10 Hz stimulation frequency (IAF-prox) is related to treatment outcome. Correlations were performed to investigate the relationship between IAF-prox and percentage symptom improvement in a sample of 153 patients with major depressive disorder treated with 10 Hz (N = 59) to the left dorsolateral prefrontal cortex (DLPFC) or 1 Hz (N = 94) to the right DLPFC repetitive Transcranial Magnetic Stimulation (rTMS). There was a significant negative correlation between IAF-prox and the percentage of symptom improvement only for the 10 Hz group. Curve fitting models revealed that there was a quadratic association between IAF and treatment response in the 10 Hz group, with a peak at 10 Hz IAF. The main result of Corlier and colleagues was replicated, and the findings suggest that the distance between 10 Hz stimulation frequency and the IAF may influence clinical outcome in a non-linear manner. rTMS is often administered at a frequency of 10 Hz, which is the center of the EEG alpha frequency band. The results can make a significant contribution to optimizing the clinical application of rTMS. [ABSTRACT FROM AUTHOR]

Introduction: Although the antidepressant efficacy of rTMS is well documented, patient reported outcomes (PROs) with rTMS are poorly characterized. The aim of the current study is to assess short and long-term changes in self-reported quality of life and disability following a 6-week course of rTMS.Methods: We performed a secondary analysis of data from the multi-centre THREE-D trial of 10 Hz high-frequency (HF) rTMS (n = 192) vs. intermittent theta-burst stimulation (iTBS) (n = 193) of the left dorsolateral prefrontal cortex (DLPFC). We assessed changes in the Quality of Life Enjoyment and Satisfaction Questionnaire and Sheehan Disability Scale pre-treatment, at 1-week post-rTMS treatment (Acute Follow-up), and at 12-weeks post-treatment (Long-Term Follow-Up).Results: PROs significantly improved with rTMS. There were no differences in PROs between iTBS and HF left DLPFC rTMS at either the Acute or Long-Term Follow-Up. The magnitude of the change in effect sizes seen for the PROs were significantly greater in those who achieved greater resolution their depressive symptoms, with remitters demonstrating very large effect size improvements in PROs compared to small-to-medium effect sizes in non-remitters.Conclusions: This study is the largest in the literature exploring at the effect of rTMS on PROs. rTMS yielded acute and sustained improvements in PROs. The improvements in PROs were strongly associated with the degree of resolution of depressive symptoms. The magnitude of the change in remitters was comparable to those reported with ECT. The goal of a course of rTMS should be for full remission of depressive symptoms in order to achieve optimal functional outcomes. [ABSTRACT FROM AUTHOR]

Background: Conventional treatments for youth depression, such as antidepressants, have modest efficacy, side effects, and ongoing controversies regarding safety. Repetitive transcranial magnetic stimulation (rTMS), specifically theta burst stimulation (TBS), applied to the dorsolateral prefrontal cortex (DLPFC) has demonstrated efficacy for the treatment of depression in adults. However, the feasibility and clinical response to TBS for youth depression has yet to be explored.Methods: Twenty participants between the ages of 16 to 24 years old with MDD were recruited. The intervention consisted of 10 treatment sessions over the course of two weeks, in which participants received intermittent TBS and continuous TBS stimulation to the left and right DLPFC, respectively. Change in the Hamilton Rating Scale for Depression (HRSD-17) score was the primary outcome. Clinical assessments occurred at baseline, after the fifth treatment session, and within a week after treatment completion.Results: Of the twenty participants, eighteen received all TBS sessions, and seventeen completed all clinical assessments. There was a significant reduction in depressive symptoms following treatment completion (p < 0.001). Four of the twenty patients had more than 50% reduction in their depressive symptoms, two of whom achieved remission. All participants received and tolerated at least six daily TBS treatments with no major adverse events.Limitations: Study was an uncontrolled, open-label design.Conclusion: Ten sessions of TBS was feasible, well tolerated, and appeared to have clinical effects for the treatment of depressed youth. Future sham-controlled randomized trials are warranted to validate these findings in a larger cohort of youth depression. [ABSTRACT FROM AUTHOR]

Background: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation modality that has been increasingly used for major depressive disorder (MDD) treatment. Although studies in healthy volunteers showed that the technique is well-tolerated, tDCS safety and acceptability have not been sufficiently explored in patients with MDD.Methods: We collected individual patient data from 6 randomized clinical trials that had been previously identified in a systematic review and meta-analysis. Primary outcomes were safety (rate of adverse events) and acceptability (rate of dropouts). Secondary outcomes were clinical, demographic and treatment predictors of the primary outcomes.Results: Dropout rates between active (8.8%) and sham (12%) groups were not significantly different (OR= 0.7, p=0.38). Adverse event rates between active (73.5%) and sham (68.3%) groups were not significantly different (OR= 1.4, p= 0.23). Higher current densities were associated with lower adverse event rates.Limitations: Dropout reasons were not systematically reported and adverse events were not collected using questionnaires standardized across studies.Conclusions: Active tDCS is as acceptable and safe as sham tDCS, as found in randomized clinical trials of MDD. [ABSTRACT FROM AUTHOR]

Personalizing treatment for late-life depression requires identifying and integrating information from multiple factors that influence treatment efficacy (moderators). We performed exploratory moderator analyses using data from a multi-site, randomized, placebo-controlled, double-blind trial of aripiprazole augmentation. Patients (n = 159) aged ≥60 years had major depressive disorder that failed to remit with venlafaxine monotherapy. We examined effect sizes of 39 potential moderators of aripiprazole (vs. placebo) augmentation efficacy using the outcome of percentage reduction in depressive symptom after 12 weeks. We then incorporated information from the individually relevant variables in combined moderators. A larger aripiprazole treatment effect was related to: white race, better physical function, better performance on Trail-Making, attention, immediate, and delayed memory tests, greater psychomotor agitation and suicidality symptoms, and a history of adequate antidepressant pharmacotherapy. A smaller aripiprazole treatment effect was observed in patients with: more pain and more work/activity impairment and libido symptoms. Combining information from race and Trail-Making test performance (base combined moderator ( M b *)) produced a larger effect size (Spearman effect size = 0.29 (95% confidence interval (CI): 0.15, 0.42)) than any individual moderator. Adding other individually relevant moderators in the full combined moderator ( M f *) further improved effect size (Spearman effect size = 0.39 (95% CI: 0.25, 0.52)) and identified a sub-group benefiting more from placebo plus continuation venlafaxine monotherapy than adjunctive aripiprazole. Combining moderators can help clinicians personalize depression treatment. We found the majority of our patients benefited from adjunctive aripiprazole, but a smaller subgroup that is identifiable using clinical measures appeared to benefit more from continuation venlafaxine plus placebo. [ABSTRACT FROM AUTHOR]