Depressive symptom trajectories with prolonged rTMS treatment.

BACKGROUND: A prolonged repetitive transcranial magnetic stimulation (rTMS) treatment course could be beneficial for some patients experiencing major depressive episodes (MDE). We identified trajectories of rTMS response in depressive patients who received an extended rTMS treatment course and sought to determine which trajectories achieved the greatest benefit with a prolonged treatment course. METHOD: We applied group-based trajectory modeling to a naturalistic dataset of depressive patients receiving a prolonged course of sequential bilateral rTMS (up to 51 treatment sessions) to the dorsolateral prefrontal cortex. Trajectories of the PHQ-9 with extended treatment courses were characterized, and we explored the association between baseline clinical characteristics and group membership using multinomial logistic regression. RESULTS: Among the 324 study participants, four trajectories were identified: "linear response, extended course" (N = 73; 22.5 %); "nonresponse" (N = 23; 7.1 %); "slowed response" (N = 159; 49.1 %); "rapid response, standard treatment length" (N = 69; 21.3 %). Only the "linear response, extended course" group showed considerable clinical improvement after receiving additional rTMS treatments. Greater baseline depressive symptoms were associated with linear response and non-response. CONCLUSION: Our results confirmed the distinctive response trajectories in depressive patients receiving rTMS and further highlighted that prolonged rTMS treatment courses may be beneficial for a subset of patients with higher initial symptom levels and linear early treatment response.

Neuropsychological Assessments of Cognitive Impairment in Major Depressive Disorder: A Systematic Review and Meta-Analysis with Meta-Regression.

INTRODUCTION: Cognitive dysfunction or deficits are common in patients with major depressive disorder (MDD). The current study systematically reviews and meta-analyzes multiple domains of cognitive impairment in patients with MDD. METHODS: PubMed/MEDLINE, PsycINFO, Cochrane Library, Embase, Web of Science, and Google Scholar were searched from inception through May 17, 2023, with no language limits. Studies with the following inclusion criteria were included: (1) patients with a diagnosis of MDD using standardized diagnostic criteria; (2) healthy controls (i.e., those without MDD); (3) neuropsychological assessments of cognitive impairment using Cambridge Neuropsychological Test Automated Battery (CANTAB); and (4) reports of sufficient data to quantify standardized effect sizes. Hedges' g standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) were used to quantify effect sizes of cognitive impairments in MDD. SMDs were estimated using a fixed- or random-effects models. RESULTS: Overall, 33 studies consisting of 2,596 subjects (n = 1,337 for patients with MDD and n = 1,259 for healthy controls) were included. Patients with MDD, when compared to healthy controls, had moderate cognitive deficits (SMD, -0.39 [95% CI, -0.47 to -0.31]). In our subgroup analyses, patients with treatment-resistant depression (SMD, -0.56 [95% CI, -0.78 to -0.34]) and older adults with MDD (SMD, -0.51 [95% CI, -0.66 to -0.36]) had greater cognitive deficits than healthy controls. The effect size was small among unmedicated patients with MDD (SMD, -0.19 [95% CI, -0.37 to -0.00]), and we did not find any statistical difference among children. Cognitive deficits were consistently found in all domains, except the reaction time. No publication bias was reported. CONCLUSION: Because cognitive impairment in MDD can persist in remission or increase the risk of major neurodegenerative disorders, remediation of cognitive impairment in addition to alleviation of depressive symptoms should be an important goal when treating patients with MDD.

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.

Twin pregnancy and severe maternal mental illness: a Canadian population-based cohort study.

Twin pregnancy is a risk factor for postpartum depression and anxiety. Whether this translates into a higher risk of severe maternal mental illness in the short-term or long-term is unknown. This study was a population-based retrospective cohort study, using linked health administrative databases for the entire province of Ontario, Canada. Included were primiparas aged 15-50 years with a twin vs. singleton hospital livebirth, between January 1, 2003, and March 31, 2019. Propensity-score inverse probability of treatment weights accounted for potential confounding. The primary outcome of severe mental illness comprised a composite of an emergency department visit or hospitalization for mental illness or self-injury, or death by suicide, assessed in the first year after birth, and in long-term follow-up, up to 17 years thereafter. Fifteen thousand twenty-four twin and 796,804 (15,022 weighted) singleton births were included, with a mean (IQR) duration of follow-up of 9 (5-13) years. After weighting, the mean (SD) maternal age was 31.3 (5.5) years. In the first 365 days postpartum, severe mental illness occurred at rates of 10.5 and 8.7 per 1000 person-years in twin and singleton mothers, respectively, corresponding to a hazard ratio (HR) of 1.21 (95% CI 1.07-1.47). From 366 days onward, the corresponding figures were 5.9 and 6.1 per 1000 person-years (HR 0.96, 95% CI 0.89-1.04). Individuals with a twin birth appear to experience an increased risk for severe mental illness in the first year postpartum, but not thereafter. This suggests a potential need for targeted counselling and mental health services for mothers within the first year after birth.

Differential symptom cluster responses to repetitive transcranial magnetic stimulation treatment in depression.

Background: Repetitive transcranial magnetic stimulation (rTMS) can target specific neural circuits, which may allow for personalized treatment of depression. Treatment outcome is typically determined using sum scores from validated measurement scales; however, this may obscure differential improvements within distinct symptom domains. The objectives for this work were to determine: (1) whether a standard depression measure can be represented using a four symptom cluster model and (2) whether these symptom clusters had a differential response to rTMS treatment. Methods: Data were obtained from two multi-centre randomized controlled trials of rTMS delivered to the left dorsolateral prefrontal cortex (DLPFC) for participants with treatment-resistant depression (TRD) conducted in Canada (THREE-D [Conducted between Sept 2013, and Oct 2016] and CARTBIND [Conducted between Apr 2016 and Feb 2018]). The first objective used confirmatory factor analytic techniques, and the second objective used a linear mixed effects model. Trial Registration: NCT01887782, NCT02729792. Findings: In the total sample of 596 participants with TRD, we found a model consisting of four symptom clusters adequately fit the data. The primary analysis using the THREE-D treatment trial found that symptom clusters demonstrated a differential response to rTMS treatment (F(3,5984) = 31.92, p < 0.001). The anxiety symptom cluster was significantly less responsive to treatment than other symptom clusters (t(6001) = -8.02, p < 0.001). These findings were replicated using data from the CARTBIND trial. Interpretation: There are distinct symptom clusters experienced by individuals with TRD that have a differential response to rTMS. Future work will determine whether differing rTMS treatment targets have distinct patterns of symptom cluster responses with the eventual goal of personalizing rTMS protocols based on an individual's clinical presentation. Funding: Canadian Institutes of Health Research, Brain Canada.

Risk of suicide death following electroconvulsive therapy treatment for depression: a propensity score-weighted, retrospective cohort study in Canada.

BACKGROUND: Previous studies examining the risk of suicide death after treatment with electroconvulsive therapy have been confounded and the resulting uncertainty around the risk-benefit profile of electroconvulsive therapy might contribute to its underuse. We aimed to compare the risk of death by suicide after psychiatric hospitalisation among individuals with depression who had been exposed to electroconvulsive therapy with those who had not. METHODS: This was a propensity score-weighted, retrospective cohort study using linked population-level administrative health data for adults with depression who had been admitted to a designated psychiatric bed in Ontario, Canada for more than 3 days between April 1, 2007 and Dec 31, 2017. Electroconvulsive therapy exposure was defined as one or more physician billing procedure codes during hospitalisation. The primary outcome was death by suicide identified using administrative health records within 365 days following discharge. We used cause-specific Cox proportional hazards model to estimate the cause-specific hazard ratio (csHR) for electroconvulsive therapy-exposed and electroconvulsive therapy-unexposed individuals. Secondary outcomes were non-suicide death and all-cause mortality. FINDINGS: In the analytic cohort, there were 67 327 psychiatric hospitalisation records (27 231 men and 40 096 women; mean age 45·1 years [SD 16·8; range 18-103]), of whom 4982 were exposed to electroconvulsive therapy and 62 345 were not exposed to electroconvulsive therapy. No ethnicity data were available. In propensity-score weighted analyses, electroconvulsive therapy was associated with a significantly reduced risk of suicide death (csHR 0·53 [95% CI 0·31-0·92]). Accounting for non-suicide death as a competing risk had no effect on the findings. Electroconvulsive therapy was also associated with a significantly reduced risk of all-cause mortality (0·75 [0·58-0·97]), but not non-suicide death (0·83 [0·61-1·12]). INTERPRETATION: Among individuals admitted to hospital with depression, electroconvulsive therapy is associated with a significantly reduced risk of death by suicide in the year after discharge. This study reinforces the importance of electroconvulsive therapy, particularly for people with severe depression. FUNDING: Norris Scholars Award, Department of Psychiatry, University of Toronto, and the Canadian Institutes for Health Research.

Repetitive transcranial magnetic stimulation (rTMS) in bipolar disorder: A systematic review.

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.

Risk of serious medical events in patients with depression treated with electroconvulsive therapy: a propensity score-matched, retrospective cohort study.

BACKGROUND: Previous studies examining the risk of medical complications from electroconvulsive therapy have been confounded and this might contribute to its underuse. This study aimed to compare the risk of serious medical events, defined as those resulting in hospitalisation or death, among patients with depression who received electroconvulsive therapy versus patients who did not receive electroconvulsive therapy. METHODS: This was a propensity score-matched, retrospective cohort study using linked population-based administrative health data for adults admitted to designated psychiatric facilities in Ontario, Canada, for more than 3 days with depression between April 1, 2007, to Feb 28, 2017. Electroconvulsive therapy exposure was defined as one or more physician billing procedure codes during hospitalisation. The unit of analysis was individual admissions and propensity score matching was used to match each exposed admission to an unexposed admission to estimate the average treatment effect of electroconvulsive therapy among those treated. The primary outcome was serious medical events, a composite of hospitalisation for medical (ie, non-psychiatric) reasons or non-suicide death within 30 days from electroconvulsive therapy exposure or matched date in the unexposed group. Effect modification was examined using tests of interaction for three clinically relevant prespecified subgroups (sex, presence of psychotic symptoms, and illness polarity). Secondary outcomes were medical hospitalisation and non-suicide death separately, suicide death, and specific serious medical events. FINDINGS: In propensity score matched analyses, there were 10 016 psychiatric hospitalisation records (6628 women, 3388 men) with mean age 56·6 years (SD 16·3) and no ethnicity data available. 65 818 admissions were eligible for matching and 5008 were matched (1:1) in each exposure group. In the propensity score matched cohort, the incidence of serious medical events was 0·25 per person-year in the exposed group and 0·33 per person-year in the unexposed group (cause-specific hazard ratio 0·78 [95% CI 0·61-1·00]). Suicide death as a competing risk did not alter this finding. The risk of suicide death was significantly lower in the exposed (≤5 of 5008 admissions) versus the unexposed group (11 [0·2%] of 5008 admissions; p<0·03). Bipolar depression, compared with unipolar depression, was associated with a greater reduction in the risk of serious medical events with electroconvulsive therapy. Electroconvulsive therapy was not associated with medical hospitalisation or non-suicide death separately, nor with any specific serious medical event. INTERPRETATION: Among individuals hospitalised with depression, we found no evidence for a clinically significant increased risk for serious medical events with exposure to electroconvulsive therapy, and the risk of suicide was found to be significantly reduced, suggesting the benefits of electroconvulsive therapy for depression outcomes might outweigh its risks in this population. FUNDING: Norris Scholars Award, Department of Psychiatry, University of Toronto; the Canadian Institutes for Health Research.

A practical overview and decision tool for analyzing recurrent events in mental illness: A review.

Mental illnesses are chronic conditions in which an individual will often experience recurrent outcomes such as hospitalization, symptomatic relapse or self-harm behaviours. Most clinical research in psychiatry considers only the first event, and does not analyze subsequent recurrent events. Methods exist to analyze recurrent events; however, these methods are underused in the psychiatric research literature. This review identifies that recurrent events can be analyzed using a time homogenous or time-to-recurrent-event (TTRE) framework. The TTRE framework is underutilized in psychiatric research; however, this framework allows for longitudinal observations that are more congruent with the chronic nature of psychiatric illness than typical first event analyses. There are several readily available statistical models using the TTRE framework extending the standard Cox proportional hazards model. Our decision tool outlines four aspects of a research question to consider when selecting a TTRE model: (1) importance of event timing, (2) explanatory vs predictive, (3) common vs event-specific hazard, and (4) correlation of events within an individual. Analyzing recurrent events in psychiatric research provides an opportunity to address research questions aimed at understanding the longitudinal course of a chronic condition. These approaches may provide novel insights into risk factors or interventions for psychiatric illness, and ultimately improved outcomes for these chronic conditions.

Distinct trajectories of response to prefrontal tDCS in major depression: results from a 3-arm randomized controlled trial.

Transcranial direct current stimulation (tDCS) is a safe, effective treatment for major depressive disorder (MDD). While antidepressant effects are heterogeneous, no studies have investigated trajectories of tDCS response. We characterized distinct improvement trajectories and associated baseline characteristics for patients treated with prefrontal tDCS, an active pharmacotherapy (escitalopram), and placebo. This is a secondary analysis of a randomized, non-inferiority, double-blinded trial (ELECT-TDCS, N = 245). Participants were diagnosed with an acute unipolar, nonpsychotic, depressive episode, and presented Hamilton Depression Rating Scale (17-items, HAM-D) scores ≥17. Latent trajectory modeling was used to identify HAM-D response trajectories over a 10-week treatment. Top-down (hypothesis-driven) and bottom-up (data-driven) methods were employed to explore potential predictive features using, respectively, conservatively corrected regression models and a cross-validated stability ranking procedure combined with elastic net regularization. Three trajectory classes that were distinct in response speed and intensity (rapid, slow, and no/minimal improvement) were identified for escitalopram, tDCS, and placebo. Differences in response and remission rates were significant early for all groups. Depression severity, use of benzodiazepines, and age were associated with no/minimal improvement. No significant differences in trajectory assignment were found in tDCS vs. placebo comparisons (38.3, 34, and 27.6%; vs. 23.3, 43.3, and 33.3% for rapid, slow, and no/minimal trajectories, respectively). Additional features are suggested in bottom-up analyses. Summarily, groups treated with tDCS, escitalopram, and placebo differed in trajectory class distributions and baseline predictors of response. Our results might be relevant for designing further studies.

Patient-level Characteristics and Inequitable Access to Inpatient Electroconvulsive Therapy for Depression: A Population-based Cross-sectional Study: Caractéristiques au niveau du patient et accès inéquitable à la thérapie électroconvulsive pour patients hospitalisés.

OBJECTIVE: A variety of patient characteristics drive the use of electroconvulsive therapy (ECT) in depression. However, the extent to which each characteristic influences the receipt of ECT, and whether they are appropriate, is unknown. The aim of this study is to identify patient-level characteristics associated with receiving inpatient ECT for depression. METHOD: We identified all psychiatric inpatients with a major depressive episode admitted to hospital ≥3 days in Ontario, Canada (2009 to 2017). The association between patient-level characteristics at admission and receipt of inpatient ECT was determined using logistic regression, where a generalized estimating equations approach accounted for repeat admissions. RESULTS: The cohort included 53,174 inpatients experiencing 75,429 admissions, with 6,899 admissions involving ECT (9.2%). Among demographic factors, age was most associated with ECT-younger adults had reduced (OR = 0.30, 95%CI, 0.24 to 0.37; 18 to 25 years) while older adults had increased (OR = 3.08, 95%CI, 2.41 to 3.93; 85+ years) odds compared to middle-aged adults (46 to 55 years). The likelihood of ECT was greater for individuals who were married/partnered, had postsecondary education, and resided in the highest neighborhood income quintile. Among clinical factors, illness polarity was most associated with receiving ECT-bipolar depression had reduced odds of receiving ECT (OR = 0.62, 95%CI, 0.57 to 0.69) The likelihood of receiving ECT was greater in psychotic depression, more depressive symptoms, and incapable to consent to treatment and was reduced with comorbid substance use disorders and several medical comorbidities. CONCLUSIONS: Nearly 1 in 10 admissions for depression in Ontario, Canada, involve ECT. Many clinical factors associated with receiving inpatient ECT were concordant with clinical guidelines; however, nonclinical factors associated with its use warrant investigation of their impact on equitable access to ECT.

Treatment Capacity and Clinical Outcomes for Patients With Schizophrenia Who Were Treated With Electroconvulsive Therapy: A Retrospective Cohort Study.

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.

Early symptomatic improvements as a predictor of response to repeated-dose intravenous ketamine: Results from the Canadian Rapid Treatment Center of Excellence.

BACKGROUND: Early symptomatic improvement with monoamine-based antidepressants is predictive of treatment response. The objective of this study was to determine if early symptomatic improvements with intravenous (IV) ketamine predicted treatment response to an acute course of four infusions. METHOD: 134 adults with treatment resistant depression (TRD) received four ketamine infusions over one to two weeks. Depressive symptoms were measured using the Quick Inventory for Depressive Symptomatology Self-Report16 (QIDS-SR16) at baseline and post-infusions 1, 2, 3, and 4. Early improvement was defined as ≥20% reduction in QIDS-SR16 scores after the first or second infusion. Linear models were used to determine whether early improvement was associated with post-infusion 4 QIDS-SR16 scores after controlling for baseline characteristics. RESULTS: Early improvement post-infusion 1 (ß = -3.52, 95% BCa CI [-5.40, -1.78]) and 2 (ß = -3.16, 95% BCa CI [-5.75, -1.59]) both significantly predicted QIDS-SR16 scores post-infusion 4. Early improvers had significantly lower QIDS-SR16 scores at post-infusion 4 (post-infusion 1 improvers: M = 9.8, SD = 4.5; post-infusion 2 improvers: M = 10.6, SD = 5.7) compared to non-early improvers (post-infusion 1 non-improvers: M = 13.7, SD = 5.8; post-infusion 2 non-improvers: M = 14.1, SD = 5.3) when controlling for baseline characteristics. The majority (58%) of individuals who did not improve post-infusions 1 or 2 still experienced an antidepressant response or partial response (≥20% reduction in QIDS-SR16) post-infusion 4. LIMITATIONS: This is a post-hoc analysis of an open-label study. CONCLUSION: Early improvement was associated with greater antidepressant effects following a course of four ketamine infusions. However, individuals who did not show early improvements still had a high likelihood of experiencing clinically significant symptom reduction after the fourth infusion, suggesting that completing four infusions, regardless of early symptom changes, is appropriate and merited.

Depressive symptom trajectories associated with standard and accelerated rTMS.

BACKGROUND: To determine if an accelerated rTMS protocol results in distinct depressive symptom response trajectories, compared to a standard rTMS protocol. We also sought to validate previous analyses that identified distinct depressive symptom response trajectories with rTMS treatment using an external dataset. METHOD: Data from two recent clinical trials comparing accelerated rTMS protocol delivered to the left dorsolateral prefrontal cortex (DLPFC) with standard once-daily rTMS protocol were used to identify depressive symptom response trajectories. The accelerated protocol in Trial 1 was conventional 10-Hz rTMS, while Trial 2 employed intermittent theta burst stimulation (iTBS). Participants were adult outpatients (18-70 years old) with bipolar or unipolar depression and moderate-severe depression (Montgomery Asberg Depression Rating Scale score >19) who had failed to respond to adequate courses of two different antidepressants. We used group-based trajectory modeling to identify MADRS response trajectories, and regression techniques adjusting for baseline depressive symptom severity to determine the association between treatment protocol and depressive symptom response trajectory. RESULTS: Treatment outcomes of 189 participants were analysed. We identified four distinct response trajectories: "nonresponse" (N = 59; 30.7%), "minimal response" (N = 65; 34.1%), "higher symptoms, response" (N = 26; 14.6%), "lower symptoms, response" (N = 39; 20.6%). We failed to find an association between rTMS protocol (accelerated vs standard) with depressive symptom response trajectory even after adjusting for baseline depressive symptom severity. CONCLUSION: The accelerated rTMS protocol in this study did not impact depressive symptom response trajectories. This work provides further confirmatory evidence that there are distinct depressive symptom response trajectories with rTMS delivered to the left DLPFC. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY: ACTRN12616000443493 and ACTRN12613000044729.

Clinical Effectiveness of Maintenance Electroconvulsive Therapy in Patients with Schizophrenia: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to assess the clinical effectiveness and cognitive effects of maintenance electroconvulsive therapy (mECT) in patients with schizophrenia or schizoaffective disorder and explore factors associated with both outcomes. METHODS: In this retrospective cohort study, we examined clinical records of 47 patients with a Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnosis of schizophrenia or schizoaffective disorder treated with mECT at an academic mental health hospital between April 2010 and July 2016. Sixty-two mECT courses were reviewed. We assessed clinical effectiveness and cognitive effects as well as factors associated with response to treatment, including psychiatric diagnosis, concomitant pharmacological treatment, and previous treatment response. RESULTS: Maintenance electroconvulsive therapy was able to maintain clinical response in 48 (77%) treatment courses. Significant cognitive adverse effects were reported in 7 (11%) of the courses. Use of antipsychotic, antidepressant or benzodiazepine medications, psychiatric disorder, and sex were not associated with response. CONCLUSION: This study shows meaningful clinical effectiveness and good tolerability of mECT in patients with resistant schizophrenia over extended periods.

Post-traumatic stress and cancer: Findings from a cross-sectional nationally representative sample.

OBJECTIVE: Trauma and post-traumatic stress disorder (PTSD) have been associated with a variety of physical conditions; however, their relationship with cancer is unclear. METHODS: Using the cross-sectional 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III; N = 36,309), we examined the association between trauma, PTSD and cancer (breast, gastrointestinal, 'other', and 'any'). Respondents were categorized into three groups: no-trauma, trauma-exposed, and PTSD using DSM-5 criteria. We conducted cancer- and sex-stratified regression analyses to examine the relationship between PTSD and cancer using the non-trauma exposed group as the reference. RESULTS: Cancer prevalence was significantly greater in PTSD than trauma-exposed and no-trauma exposed respondents, and greater in trauma-exposed than no-trauma exposed respondents. After adjusting for covariates, odds of cancer were significantly greater in PTSD compared to non trauma-exposed respondents for 'any' cancer (adjusted odds ratio [AOR]: 2.99; 95% CI=[2.31, 3.88], gastrointestinal (GI) cancer (AOR: 17.48; 95% CI=[8.09, 37.77]), and 'other' cancer (AOR: 3.21; 95% CI=[2.41, 4.27]). Breast cancer was non-significant. Although both males and females with PTSD had significantly increased odds of 'any', GI, and 'other' cancer, differential findings emerged across sexes for those who were trauma exposed, compared to non-trauma exposed. CONCLUSION: Traumatic exposure and PTSD appear to be associated with cancer. The comorbid relationship between traumatic exposure, PTSD and cancer differs by cancer type and sex.

Trajectories of Response to Dorsolateral Prefrontal rTMS in Major Depression: A THREE-D Study.

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