Cognitive Effects Following Offline High-Frequency Repetitive Transcranial Magnetic Stimulation (HF-rTMS) in Healthy Populations: A Systematic Review and Meta-Analysis.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) is a commonly used form of rTMS to treat neuropsychiatric disorders. Emerging evidence suggests that 'offline' HF-rTMS may have cognitive enhancing effects, although the magnitude and moderators of these effects remain unclear. We conducted a systematic review and meta-analysis to clarify the cognitive effects of offline HF-rTMS in healthy individuals. A literature search for randomised controlled trials with cognitive outcomes for pre and post offline HF-rTMS was performed across five databases up until March 2022. This study was registered on the PROSPERO international prospective protocol for systematic reviews (PROSPERO 2020 CRD 42,020,191,269). The Risk of Bias 2 tool was used to assess the risk of bias in randomised trials. Separate analyses examined the cognitive effects of excitatory and inhibitory forms of offline HF-rTMS on accuracy and reaction times across six cognitive domains. Fifty-three studies (N = 1507) met inclusion criteria. Excitatory offline HF-rTMS showed significant small sized effects for improving accuracy (k = 46, g = 0.12) and reaction time (k = 44, g = -0.13) across all cognitive domains collapsed. Excitatory offline HF-rTMS demonstrated a relatively greater effect for executive functioning in accuracy (k = 24, g = 0.14). Reaction times were also improved for the executive function (k = 21, g = -0.11) and motor (k = 3, g = -0.22) domains following excitatory offline HF-rTMS. The current review was restricted to healthy individuals and future research is required to examine cognitive enhancement from offline HF-rTMS in clinical cohorts.

Drug dependence and prescribing ketamine for treatment-resistant depression in Australia and New Zealand.

Ketamine is a restricted and regulated medication in Australia and New Zealand, which has implications when considering treatment for patients with treatment-resistant depression and a history of illicit drug use, abuse or dependence. Regulations governing prescription of ketamine for treatment-resistant depression vary between jurisdictions in Australia and New Zealand, though most restrict use in those with drug dependence. There is substantial variation in definitions of drug dependence used in each jurisdiction, and between the legal and clinical definitions, with the latter specified in the current International Classification of Diseases, Eleventh Revision and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. This paper reviews the literature assessing the risk of ketamine misuse and dependence in patients with a history of illicit drug use, abuse or dependence and presents recommendations for psychiatrists who prescribe ketamine in such patients with treatment-resistant depression.

Electroconvulsive Therapy Credentialing for Psychiatrists-Review of Required Standards Across States and Territories in Australia.

ABSTRACT: Electroconvulsive therapy (ECT) is a complex medical procedure, the delivery of which requires specialist knowledge and skills. We reviewed the standards required for ECT credentialing in different jurisdictions in Australia. We reviewed the Chief Psychiatrist guidelines and statewide policy standards on ECT and focused on standards required for initial credentialing and ongoing privileging in ECT. We compared the credentialing requirements within these documents with the standards specified in the Royal Australian and New Zealand College of Psychiatrists professional practice guideline for ECT. Most of the jurisdictions had specific standards for initial credentialing and maintenance of this credentialing; however, there was significant variance in the credentialing process and standards required. It would be useful to have a minimum standard for credentialing for ECT psychiatrists and prescribers. This standard would be relevant for practice of ECT internationally. States and territories would have the responsibility for implementation of these standards. Appropriate training and establishing good clinical governance processes are essential to the provision of high quality ECT.

Transcranial Direct Current Stimulation Modulates Working Memory Maintenance Processes in Healthy Individuals.

The effects of transcranial direct current stimulation (tDCS) at the pFC are often investigated using cognitive paradigms, particularly working memory tasks. However, the neural basis for the neuromodulatory cognitive effects of tDCS, including which subprocesses are affected by stimulation, is not completely understood. We investigated the effects of tDCS on working memory task-related spectral activity during and after tDCS to gain better insights into the neurophysiological changes associated with stimulation. We reanalyzed data from 100 healthy participants grouped by allocation to receive either sham (0 mA, 0.016 mA, and 0.034 mA) or active (1 mA or 2 mA) stimulation during a 3-back task. EEG data were used to analyze event-related spectral power in frequency bands associated with working memory performance. Frontal theta event-related synchronization (ERS) was significantly reduced post-tDCS in the active group. Participants receiving active tDCS had slower RTs following tDCS compared with sham, suggesting interference with practice effects associated with task repetition. Theta ERS was not significantly correlated with RTs or accuracy. tDCS reduced frontal theta ERS poststimulation, suggesting a selective disruption to working memory cognitive control and maintenance processes. These findings suggest that tDCS selectively affects specific subprocesses during working memory, which may explain heterogenous behavioral effects.

Prescribing electroconvulsive therapy for depression: Not as simple as it used to be.

In the last century, prescribing electroconvulsive therapy usually involved considering the relative merits of unilateral versus bilateral electroconvulsive therapy, with most other parameters fixed. However, research over the last 30 years has discovered that several parameters of the electroconvulsive therapy stimulus can have a significant impact on efficacy and cognitive side effects. The stimulus dose relative to seizure threshold was shown to significantly affect efficacy, especially for right unilateral electroconvulsive therapy, where suprathreshold doses in the vicinity of 5-6 times seizure threshold were far more efficacious than doses closer to threshold. However, this did not hold for bitemporal electroconvulsive therapy, where near-threshold stimuli were equally effective as suprathreshold stimuli. Then, changes in stimulus pulse width were found to also have a significant impact on both efficacy and side effects, with ultrabrief pulse widths of 0.3 ms having significantly fewer cognitive side effects in unilateral electroconvulsive therapy than standard brief pulse widths of 1.0 ms, with only slightly reduced efficacy. Therefore, choosing the optimum electroconvulsive therapy prescription for an individual patient now requires consideration of placement, pulse width and stimulus dose relative to seizure threshold, and how these three interact with each other. This viewpoint aims to raise awareness of these issues for psychiatrists involved in electroconvulsive therapy practice.

A novel approach for targeting the left dorsolateral prefrontal cortex for transcranial magnetic stimulation using a cognitive task.

Repetitive transcranial magnetic stimulation (rTMS) has the potential to be developed as a novel treatment for cognitive dysfunction. However, current methods of targeting rTMS for cognition fail to consider inter-individual functional variability. This study explored the use of a cognitive task to individualise the target site for rTMS administered to the left dorsolateral prefrontal cortex (L-DLPFC). Twenty-five healthy participants were enrolled in a sham-controlled, crossover study. Participants performed a random letter generation task under the following conditions: no stimulation, sham and active 'online' rTMS applied to F3 (International 10-20 System) and four standardised surrounding sites. Across all sites combined, active 'online' rTMS was associated with significantly reduced performance compared to sham rTMS for unique trigrams (p = 0.012), but not for unique digrams (p > 0.05). Using a novel localisation methodology based on performance outcomes from both measures, a single optimal individualised site was identified for 92% [n = 23] of participants. At the individualised site, performance was significantly poorer compared to a common standard site (F3) and both control conditions (ps < 0.01). The current results suggest that this localisation methodology using a cognitive task could be used to individualise the rTMS target site at the L-DLPFC for modulating and potentially enhancing cognitive functioning.

The Impact of COVID-19 on Electroconvulsive Therapy: A Multisite, Retrospective Study From the Clinical Alliance and Research in Electroconvulsive Therapy and Related Treatments Network.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has led to reported change in electroconvulsive therapy (ECT) services worldwide. However, minimal data have been published demonstrating tangible changes across multiple ECT centers. This article aimed to examine changes in ECT patients and ECT service delivery during the pandemic. METHODS: We retrospectively assessed data collected on ECT patients within the Clinical Alliance and Research in Electroconvulsive Therapy and Related Treatments (CARE) Network during a 3-month period starting at the first COVID-19 restrictions in 2020 and compared data with predicted values based on the corresponding 3-month period in 2019. Mixed-effects repeated-measures analyses examined differences in the predicted and actual number of acute ECT courses started and the total number of acute ECT treatments given in 2020. Sociodemographic, clinical, treatment factors, and ECT service delivery factors were compared for 2020 and 2019. RESULTS: Four Australian and 1 Singaporean site participated in the study. There were no significant differences between the predicted and actual number of acute ECT courses and total number of acute ECT treatments administered in 2020. During 2020, there were statistically significant increases in the proportion of patients requiring ECT under substitute consent and receiving ECT for urgent reasons compared with 2019. CONCLUSIONS: This multisite empirical study is among the first that supports anecdotal reports of changes in the triaging and delivery of ECT during COVID-19. Results suggest that ECT was prioritized for the most severely ill patients. Further data assessing the impacts of COVID-19 on ECT are needed.

Assessing neurophysiological changes associated with combined transcranial direct current stimulation and cognitive-emotional training for treatment-resistant depression.

Transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation, is a promising treatment for depression. Recent research suggests that tDCS efficacy can be augmented using concurrent cognitive-emotional training (CET). However, the neurophysiological changes associated with this combined intervention remain to be elucidated. We therefore examined the effects of tDCS combined with CET using electroencephalography (EEG). A total of 20 participants with treatment-resistant depression took part in this open-label study and received 18 sessions over 6 weeks of tDCS and concurrent CET. Resting-state and task-related EEG during a 3-back working memory task were acquired at baseline and immediately following the treatment course. Results showed an improvement in mood and working memory accuracy, but not response time, following the intervention. We did not find significant effects of the intervention on resting-state power spectral density (frontal theta and alpha asymmetry), time-frequency power (alpha event-related desynchronisation and theta event-related synchronisation) or event-related potentials (P2 and P3 components). We therefore identified little evidence of neurophysiological changes associated with treatment using tDCS and concurrent CET, despite significant improvements in mood and near-transfer effects of cognitive training to working memory accuracy. Further research incorporating a sham-controlled group may be necessary to identify the neurophysiological effects of the intervention.

Transcranial Random Noise Stimulation for the Acute Treatment of Depression: A Randomized Controlled Trial.

BACKGROUND: Transcranial electrical stimulation has broad potential as a treatment for depression. Transcranial random noise stimulation, which delivers randomly fluctuating current intensities, may have greater cortical excitatory effects compared with other forms of transcranial electrical stimulation. We therefore aimed to investigate the antidepressant efficacy of transcranial random noise stimulation. METHODS: Depressed participants were randomly assigned by computer number generator to receive 20 sessions of either active or sham transcranial random noise stimulation over 4 weeks in a double-blinded, parallel group randomized-controlled trial. Transcranial random noise stimulation was delivered for 30 minutes with a direct current offset of 2 mA and a random noise range of 2 mA. Primary analyses assessed changes in depression severity using the Montgomery-Asperg Depression Rating Scale. Neuroplasticity, neuropsychological, and safety outcomes were analyzed as secondary measures. RESULTS: Sixty-nine participants were randomized, of which 3 discontinued treatment early, leaving 66 (sham n = 34, active n = 32) for per-protocol analysis. Depression severity scores reduced in both groups (Montgomery-Asperg Depression Rating Scale reduction in sham = 7.0 [95% CI = 5.0-8.9]; and active = 5.2 [95% CI = 3.2-7.3]). However, there were no differences between active and sham groups in the reduction of depressive symptoms or the number of participants meeting response (sham = 14.7%; active = 3.1%) and remission criteria (sham = 5.9%; active = 0%). Erythema, paresthesia, fatigue, and dizziness/light-headedness occurred more frequently in the active transcranial random noise stimulation group. Neuroplasticity, neuropsychological, and acute cognitive effects were comparable between groups. CONCLUSION: Our results do not support the use of transcranial random noise stimulation with the current stimulation parameters as a therapeutic intervention for the treatment of depression. CLINICAL TRIAL REGISTRATION AT CLINICALTRIALS: gov/NCT01792414.

A systematic review and meta-analysis on the effects of transcranial direct current stimulation in depressive episodes.

BACKGROUND: Transcranial direct current stimulation (tDCS) has shown mixed results for depression treatment. OBJECTIVE: To perform a systematic review and meta-analysis of trials using tDCS to improve depressive symptoms. METHODS: A systematic review was performed from the first date available to January 06, 2020 in PubMed, EMBASE, Cochrane Library, and additional sources. We included randomized, sham-controlled clinical trials (RCTs) enrolling participants with an acute depressive episode and compared the efficacy of active versus sham tDCS, including association with other interventions. The primary outcome was the Hedges' g for continuous depression scores; secondary outcomes included odds ratios (ORs) and number needed to treat (NNT) for response, remission, and acceptability. Random effects models were employed. Sources of heterogeneity were explored via metaregression, sensitivity analyses, subgroup analyses, and bias assessment. RESULTS: We included 23 RCTs (25 datasets, 1,092 participants), most (57%) presenting a low risk of bias. Active tDCS was superior to sham regarding endpoint depression scores (k = 25, g = 0.46, 95% confidence interval [CI]: 0.22-0.70), and also achieved superior response (k = 18, 33.3% vs. 16.56%, OR = 2.28 [1.52-3.42], NNT = 6) and remission (k = 18, 19.12% vs. 9.78%, OR = 2.12 [1.42-3.16], NNT = 10.7) rates. Moreover, active tDCS was as acceptable as sham. No risk of publication bias was identified. Cumulative meta-analysis showed that effect sizes are basically unchanged since total sample reached 439 participants. CONCLUSIONS: TDCS is modestly effective in treating depressive episodes. Further well-designed, large-scale RCTs are warranted.

Neurocognitive effects of transcranial direct current stimulation (tDCS) in unipolar and bipolar depression: Findings from an international randomized controlled trial.

OBJECTIVE: Transcranial direct current stimulation (tDCS) has been found to have antidepressant effects and may have beneficial neurocognitive effects. However, prior research has produced an unclear understanding of the neurocognitive effects of repeated exposure to tDCS. The study's aim was to determine the neurocognitive effects following tDCS treatment in participants with unipolar or bipolar depression. METHOD: The study was a triple-masked, randomized, controlled clinical trial across six international academic medical centers. Participants were randomized to high dose (2.5 mA for 30 min) or low dose (0.034 mA, for 30 min) tDCS for 20 sessions over 4 weeks, followed by an optional 4 weeks of open-label high dose treatment. The tDCS anode was centered over the left dorsolateral prefrontal cortex at F3 (10/20 EEG system) and the cathode over F8. Participants completed clinical and neurocognitive assessments before and after tDCS. Genotype (BDNF Val66Met and catechol-o-methyltransferase [COMT] Val158Met polymorphisms) were explored as potential moderators of neurocognitive effects. RESULTS: The study randomized 130 participants. Across the participants, tDCS treatment (high and low dose) resulted in improvements in verbal learning and recall, selective attention, information processing speed, and working memory, which were independent of mood effects. Similar improvements were observed in the subsample of participants with bipolar disorder. There was no observed significant effect of tDCS dose. However, BDNF Val66Met and COMT Val158Met polymorphisms interacted with tDCS dose and affected verbal memory and verbal fluency outcomes, respectively. CONCLUSIONS: These findings suggest that tDCS could have positive neurocognitive effects in unipolar and bipolar depression. Thus, tDCS stimulation parameters may interact with interindividual differences in BDNF and COMT polymorphisms to affect neurocognitive outcomes, which warrants further investigation.

Brief cognitive screening instruments for electroconvulsive therapy: Which one should I use?

OBJECTIVES: To review brief cognitive screening instruments for routine clinical monitoring in electroconvulsive therapy. METHODS: Brief cognitive screening instruments specifically developed for electroconvulsive therapy and commonly used brief generalised cognitive screening instruments were reviewed with relative advantages and disadvantages highlighted. RESULTS: Several brief cognitive screening tests designed for use in electroconvulsive therapy have been found sensitive for monitoring electroconvulsive therapy-related cognitive side effects. The choice of a brief generalised cognitive screening instrument for use in an electroconvulsive therapy clinical context comes with several pertinent considerations. CONCLUSION: Electroconvulsive therapy is a highly effective treatment for pharmacoresistant and severe neuropsychiatric illness although cognitive side effects can be a barrier for treatment. Routine monitoring using brief cognitive screening instruments has advantages in busy clinical settings and can assist with optimising patient outcomes. More detailed neuropsychological assessment is recommended if the results from brief cognitive screening raise concerns.

A Comparison of Computerized Versus Pen-and-Paper Cognitive Tests for Monitoring Electroconvulsive Therapy-Related Cognitive Side Effects.

OBJECTIVE: Cognitive side effects are a common unintended outcome of electroconvulsive therapy (ECT). Routine cognitive assessment is important for monitoring patient outcomes, although it can pose challenges in busy clinical settings. Computerized cognitive testing has advantages that can facilitate routine monitoring. This study explored the construct and criterion validity of computerized cognitive testing compared with standard pen-and-paper tests for monitoring cognition in ECT patients. METHODS: The study included 24 participants with major depression who received an acute course of ECT. Cognition was assessed at pretreatment and at posttreatment with 3 computerized tests from the CogState battery (International Shopping List task, One-Card Learning, and One-Back Task) and 3 conceptually matched pen-and-paper-administered neuropsychological tests. RESULTS: At pretreatment, only performance on the computer-administered test of verbal anterograde memory (International Shopping List task) was significantly correlated with the analogous pen-and-paper measure, whereas the other computerized tests were not. Of the computerized measures, only the International Shopping List task showed significant changes from pretreatment to posttreatment (P < 0.01, Cohen d > 1.0). In contrast, all the pen-and-paper-administered tests showed significant changes from pretreatment to posttreatment (P < 0.01, Cohen d range, 0.8-1.2). Pretreatment to posttreatment cognitive changes on the computerized measures were not correlated with changes on the pen-and-paper-administered tests. CONCLUSION: Construct and criterion validity and tolerability varied between the computerized measures. The results highlighted potentially important issues related to the interpretation and utility of computerized tests in this patient population.

Effects of High-Definition Transcranial Direct Current Stimulation and Theta Burst Stimulation for Modulating the Posterior Parietal Cortex.

OBJECTIVES: Noninvasive brain stimulation methods, including high-definition transcranial direct current stimulation (HD-tDCS) and theta burst stimulation (TBS) have emerged as novel tools to modulate and explore brain function. However, the relative efficacy of these newer stimulation approaches for modulating cognitive functioning remains unclear. This study investigated the cognitive effects of HD-tDCS, intermittent TBS (iTBS) and prolonged continuous TBS (ProcTBS) and explored the potential of these approaches for modulating hypothesized functions of the left posterior parietal cortex (PPC). METHODS: Twenty-two healthy volunteers attended four experimental sessions in a cross-over experimental design. In each session, participants either received HD-tDCS, iTBS, ProcTBS or sham, and completed cognitive tasks, including a divided attention task, a working memory maintenance task and an attention task (emotional Stroop test). RESULTS: The results showed that compared to sham, HD-tDCS, iTBS and ProcTBS caused significantly faster response times on the emotional Stroop task. The effect size (Cohen's d) was d = .32 for iTBS (p < .001), .21 for ProcTBS (p = .01) and .15 for HD-tDCS (p = .044). However, for the performance on the divided attention and working memory maintenance tasks, no significant effect of stimulation was found. CONCLUSIONS: The results suggest that repetitive transcranial magnetic stimulation techniques, including TBS, may have greater efficacy for modulating cognition compared with HD-tDCS, and extend existing knowledge about specific functions of the left PPC.

Validation of the 10-Item Orientation Questionnaire: A New Tool for Monitoring Post-Electroconvulsive Therapy Disorientation.

OBJECTIVES: Assessment of post-electroconvulsive therapy (ECT) disorientation at a single time point after ECT treatment may prove an effective and clinically useful method for monitoring the severity of disorientation and predicting ECT-induced retrograde amnesia. In this study, we aimed to validate a novel instrument (10-Item Orientation Questionnaire) developed to assess the level of disorientation after ECT. METHODS: Twenty-four depressed inpatients who were prescribed an acute course of ECT were administered the 10-Item Orientation Questionnaire at 30 minutes after ECT and had time to reorientation assessed at 3 time points after ECT (10, 30, and 60 minutes) at ECT treatments 1 to 3. The association between average performance of the 10-Item Orientation Questionnaire across the acute ECT course and retrograde amnesia at post-ECT was examined using the Autobiographical Memory Interview-Short Form. RESULTS: Mean performance on the 10-Item Orientation Questionnaire across treatments 1 to 3 was moderately correlated with average time to reorientation (r = -0.52, P = 0.02, n = 20). Across the acute ECT course, poorer performance on the 10-Item Orientation Questionnaire was associated with greater retrograde amnesia at post-ECT (r = 0.53, P = 0.03, n = 16). CONCLUSIONS: The 10-Item Orientation Questionnaire when administered at 30 minutes after ECT is sensitive for detecting patients with slow recovery of orientation after ECT. Use of this instrument therefore has potential for improving routine patient monitoring in clinical practice and identifying patients at increased risk of retrograde memory adverse effects following treatment.

Transcranial Direct Current Stimulation in the Acute Depressive Episode: A Systematic Review of Current Knowledge.

Major depressive disorder is a severe, refractory mental disorder. Only one third of patients treated with antidepressants achieve remission after 3 trials, while subject to adverse effects. Therefore, the investigation of alternative treatments is paramount. The aim of this systematic review was to summarize the most recent evidence of transcranial direct current stimulation (tDCS) intervention for the acute phase of major depressive disorder. A PubMed search was performed including the terms "transcranial direct current stimulation" OR "transcranial direct stimulation" OR "tDCS" AND "major depressive disorder" OR "major depression" OR "depression" AND "trial." The search was conducted from inception until February 2018. Our search yielded initially 165 results, and 14 randomized clinical trials were included according to eligibility criteria. Most studies were pilot studies, with mixed findings. Two large randomized clinical trials recently published also presented primary negative findings. Study protocols usually used anodal left/cathodal right dorsolateral prefrontal cortex stimulation, 1 to 2.5 mA, and 5 to 20 tDCS sessions. We discuss the limitations of the included trials, such as sample and tDCS parameters heterogeneity between studies. To conclude, tDCS seems to be safe and devoid of serious adverse effects, although robust efficacy has not been consistently demonstrated in clinical trials assessing an acute treatment course of up to 4 weeks. Further directions are discussed, such as parameter individualization, investigation of biological markers, and home-use tDCS.

The Clinical Alliance and Research in Electroconvulsive Therapy Network: An Australian Initiative for Improving Service Delivery of Electroconvulsive Therapy.

OBJECTIVE: There is currently substantial heterogeneity in electroconvulsive therapy (ECT) treatment methods between clinical settings. Understanding how this variation in clinical practice is related to treatment outcomes is essential for optimizing service delivery. The Clinical Alliance and Research in ECT Network is a clinical and research framework with the aims of improving clinical practice, enabling auditing and benchmarking, and facilitating the collection of naturalistic clinical data. METHODS: The network framework and clinical and treatment variables collected and rationale for the use of particular outcome measures are described. Survey results detailing the use of ECT across initial participating clinical centers were examined. RESULTS: The data are reported from 18 of 22 participating centers, the majority based in Australia. Melancholic unipolar depression was the most common clinical indication (78%). Right unilateral (44%) and bifrontal (39%) were the most commonly used electrode placements. Eighty one percent of the centers used individual seizure titration for initial dosing. CONCLUSIONS: There was substantial heterogeneity in the use of ECT between participating centers, indicating that the Network is representative of modern ECT practice. The Clinical Alliance and Research in ECT Network may therefore offer the opportunity to improve service delivery and facilitate the investigation of unresolved research questions pertaining to modern ECT practice.

Pilot Randomized Controlled Trial of Titrated Subcutaneous Ketamine in Older Patients with Treatment-Resistant Depression.

OBJECTIVE: To assess the efficacy and safety of subcutaneous ketamine for geriatric treatment-resistant depression. Secondary aims were to examine if repeated treatments were safe and more effective in inducing or prolonging remission than a single treatment. METHODS: In this double-blind, controlled, multiple-crossover study with a 6-month follow-up (randomized controlled trial [RCT] phase), 16 participants (≥60 years) with treatment-resistant depression who relapsed after remission or did not remit in the RCT were administered an open-label phase. Up to five subcutaneous doses of ketamine (0.1, 0.2, 0.3, 0.4, and 0.5 mg/kg) were administered in separate sessions (≥1 week apart), with one active control (midazolam) randomly inserted (RCT phase). Twelve ketamine treatments were given in the open-label phase. Mood, hemodynamic, and psychotomimetic outcomes were assessed by blinded raters. Remitters in each phase were followed for 6 months. RESULTS: Seven of 14 RCT-phase completers remitted with ketamine treatment. Five remitted at doses below 0.5 mg/kg. Doses ≥ 0.2 mg/kg were significantly more effective than midazolam. Ketamine was well tolerated. Repeated treatments resulted in higher likelihood of remission or longer time to relapse. CONCLUSION: Results provide preliminary evidence for the efficacy and safety of ketamine in treating elderly depressed. Dose titration is recommended for optimizing antidepressant and safety outcomes on an individual basis. Subcutaneous injection is a practical method for giving ketamine. Repeated treatments may improve remission rates (clinicaltrials.gov; NCT01441505).

Cognitive enhancing effects of rTMS administered to the prefrontal cortex in patients with depression: A systematic review and meta-analysis of individual task effects.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an approved therapeutic treatment of major depressive disorder and has increasing clinical use throughout the world. However, it remains unclear whether an rTMS course for depression may also produce cognitive enhancement. In a recent meta-analysis of sham-controlled randomized controlled studies (RCTs) conducted in patients with neuropsychiatric conditions, no evidence was found for generalized cognitive enhancing effects across cognitive domains with active compared to sham rTMS. Notwithstanding, there remains the possibility of cognitive effects following an rTMS course that are more highly specific, for example, in specific clinical conditions, or at the individual task level. This study aimed to determine whether a therapeutic rTMS course in patients with depression is associated with cognitive enhancing effects at the task level. METHODS: A systematic review and meta-analysis of outcomes on individual neuropsychological tasks from sham-controlled RCTs where an rTMS course was administered to the dorsolateral prefrontal cortex (DLPFC) in patients with depression. RESULTS: Eighteen studies met the inclusion criteria. Active rTMS treatment showed no specific enhancing effects on the majority of cognitive tasks. Modest effect size improvements with active compared to sham rTMS treatment were found for performance on the Trail Making Test Parts A (g = 0.28, 95% CI = 0.06-0.50) and B (g = 0.26, 95% CI = 0.06-0.47). CONCLUSION: A therapeutic rTMS course administered to the prefrontal cortex for depression may produce modest cognitive enhancing effects specific to psychomotor speed, visual scanning, and set-shifting ability.

Seizure threshold increases can be predicted by EEG quality in right unilateral ultrabrief ECT.

Increases in seizure threshold (ST) over a course of brief pulse ECT can be predicted by decreases in EEG quality, informing ECT dose adjustment to maintain adequate supra-threshold dosing. ST increases also occur over a course of right unilateral ultrabrief (RUL UB) ECT, but no data exist on the relationship between ST increases and EEG indices. This study (n = 35) investigated if increases in ST over RUL UB ECT treatments could be predicted by a decline in seizure quality. ST titration was performed at ECT session one and seven, with treatment dosing maintained stable (at 6-8 times ST) in intervening sessions. Seizure quality indices (slow-wave onset, mid-ictal amplitude, regularity, stereotypy, and post-ictal suppression) were manually rated at the first supra-threshold treatment, and last supra-threshold treatment before re-titration, using a structured rating scale, by a single trained rater blinded to the ECT session being rated. Twenty-one subjects (60%) had a ST increase. The association between ST changes and EEG quality indices was analysed by logistic regression, yielding a significant model (p < 0.001). Initial ST (p < 0.05) and percentage change in mid-ictal amplitude (p < 0.05) were significant predictors of change in ST. Percentage change in post-ictal suppression reached trend level significance (p = 0.065). Increases in ST over a RUL UB ECT course may be predicted by decreases in seizure quality, specifically decline in mid-ictal amplitude and potentially in post-ictal suppression. Such EEG indices may be able to inform when dose adjustments are necessary to maintain adequate supra-threshold dosing in RUL UB ECT.