Therapy For Treatment-resistant Depression Research Articles

Ketamine can produce oscillatory dynamics by engaging mechanisms dependent on the kinetics of NMDA receptors

Ketamine is an N-methyl-D-aspartate (NMDA)-receptor antagonist that produces sedation, analgesia, and dissociation at low doses and profound unconsciousness with antinociception at high doses. At high and low doses, ketamine can generate gamma oscillations (>25 Hz) in the electroencephalogram (EEG). The gamma oscillations are interrupted by slow-delta oscillations (0.1 to 4 Hz) at high doses. Ketamine's primary molecular targets and its oscillatory dynamics have been characterized. However, how the actions of ketamine at the subcellular level give rise to the oscillatory dynamics observed at the network level remains unknown. By developing a biophysical model of cortical circuits, we demonstrate how NMDA-receptor antagonism by ketamine can produce the oscillatory dynamics observed in human EEG recordings and nonhuman primate local field potential recordings. We have identified how impaired NMDA-receptor kinetics can cause disinhibition in neuronal circuits and how a disinhibited interaction between NMDA-receptor-mediated excitation and GABA-receptor-mediated inhibition can produce gamma oscillations at high and low doses, and slow-delta oscillations at high doses. Our work uncovers general mechanisms for generating oscillatory brain dynamics that differs from ones previously reported and provides important insights into ketamine's mechanisms of action as an anesthetic and as a therapy for treatment-resistant depression.

Trend and geo-availability of somatic therapies for treatment resistant depression in the US

BackgroundHaving failed at least two pharmacotherapies, treatment-resistant depression (TRD) constitutes a major burden to healthcare in the US and globally, affecting close to a third of people diagnosed with depression in the US. Several studies have demonstrated the higher economic burden associated with TRD. This study sought to investigate changes in the availability of TRD somatic treatment options (Electroconvulsive therapy [ECT], Ketamine infusion therapy (KIT), and Transcranial Magnetic Stimulation [TMS]) in the US between 2014 and 2020 and the geographic variations in availability of TRD treatment options in the US as of 2020. MethodThis study is a cross-sectional study of US mental health facilities providing TRD treatment options between 2014 and 2020. We used the 2014 to 2020 National Mental Health Services Survey (N-MHSS) data from the Substance Abuse and Mental Health Service Administration (SAMHSA). We estimated service availability per 100,000 US adults, both nationally and regionally, and computed a random-effect logistic regression to calculate the changes in the availability of the services over the study period. ResultOverall, availability of any one of ECT, KIT, or TMS in US mental health facilities declined between 2014 and 2019 (0.23 vs. 0.18 per 100,000 US adults) but increased to 0.24 in 2020. While availability of ECT consistently declined between 2014 and 2020, ketamine and TMS reportedly became available only in 2020. North Dakota, Wyoming, and Utah had the highest availability per 100,000 US adults (0.86, 0.67, and 0.65) while Nevada, Oregon and Georgia had the lowest availability (0.04, 0.06, and 0.06) regionally. ConclusionThe US had less than one mental health facility offering somatic treatment options for TRD per 100,000 US adults as of 2020. Also, the observed increase in the availability of somatic treatment options for TRD across the US between 2014 and 2020 did not reflect the increasing need for more treatment options for the treatment of TRD.

Vagus nerve stimulation allows to cease maintenance electroconvulsive therapy in treatment-resistant depression: a retrospective monocentric case series.

The use of vagus nerve stimulation (VNS) to reduce or stop electroconvulsive therapy (ECT) in treatment-resistant depression seems promising. The aim of this study was to investigate the efficacy of VNS on the reduction of ECT sessions and mood stabilization. We conducted a monocentric retrospective case series of patients who suffered from treatment-resistant depression, treated with ECT and referred to our center for VNS. We investigated the number and the frequency of ECT sessions before and after VNS implantation. Secondary criteria consisted in the Montgomery Åsberg Depression Rating Scale (MADRS) score, number of medical treatments, dosage of the main treatment and length of hospital stays before and after VNS. Additionally, we sent an anonymous survey to psychiatrists and other physicians in our institution to investigate their knowledge and perception of VNS therapy to treat treatment-resistant depression. Seven patients benefited from VNS: six (86%) were female (mean age of 51.7 +/- 16.0 years at surgery), and five (71%) suffered from bipolar depression (three type I and two type II). All patients were followed up at least 2 years post-implantation (range: 27-68 months). Prior to VNS, six patients were treated by maintenance ECT. After VNS, three (43%) patients did not require maintenance ECT anymore, and three (43%) patients required less frequent ECT session with a mean 14.7 +/- 9.8 weeks between sessions after VNS vs. 2.9 +/- 0.8 weeks before VNS. At last follow-up, 4 (57%) patients had stopped ECT. Five (71%) patients implanted with VNS were good responders (50% decrease relative to baseline MADRS). According to the survey, psychiatrists had a significantly better perception and knowledge of ECT, but a worse perception and knowledge of VNS compared to other physicians. VNS is a good option for treatment-resistant depression requiring maintenance ECT dependence. Larger on-going studies will help broaden the implanted patients while strengthening psychiatrists' knowledge on this therapy.

Ketamine for Adults With Treatment-Resistant Depression or Posttraumatic Stress Disorder: A 2023 Update

What Is the Issue?
 
 Many drug treatments are available for depression, but 22% of people in Canada with the condition have treatment-resistant depression (TRD). For people with TRD, standard drug treatments do not improve their symptoms or do not work for long, and their depression persists.
 Posttraumatic stress disorder (PTSD) is a disabling mental health condition that affects about 9% of people in Canada in their lifetime. Few drugs are available for treating PTSD, none of which are considered effective.
 Ketamine is a hallucinogenic drug used primarily for anesthesia. Ketamine has also been explored for other indications, such as TRD and PTSD, generating questions about whether it could be a treatment option for these conditions.
 
 What Did We Do?
 
 We conducted a review of the clinical effectiveness, cost-effectiveness, and evidence-based guidelines on the use of ketamine in adults with TRD or PTSD, to help guide decisions on the use of ketamine for managing these conditions.
 An information specialist conducted a search of peer-reviewed and grey literature sources published in March 2022 or later. One reviewer screened citations and selected and critically appraised the included studies.
 CADTH engaged a patient with lived experience of TRD who shared their experiences and perspectives on ketamine-assisted psychotherapy. These perspectives helped us to contextualize the literature and appreciate nuances of the experience.
 
 What Did We Find?
 
 Ketamine could lead to an immediate improvement in depressive symptoms and suicidal ideation compared to placebo or midazolam in adults with TRD. The longest follow-up was 90 days, and the longest lasting effect after a dose was 28 days. Serious side effects of ketamine — such as dissociation — were rare and short-lived, lasting hours, in adults with TRD.
 It is uncertain if ketamine is an effective and safe treatment for symptoms of PTSD, due to little to no evidence suggesting its effectiveness or safety against placebo, midazolam, or opioids.
 Most studies evaluated ketamine given intravenously, and we found limited evidence on intramuscular (IM), subcutaneous, and intranasal routes of administration. We found no studies on oral or sublingual administration of ketamine and no studies comparing the different ways that ketamine can be given for TRD or PTSD.
 An economic evaluation found that IV ketamine was likely to be cost-effective compared to intranasal esketamine in adults with TRD from a health care perspective in the US. However, from a patient perspective, IV ketamine was unlikely to be cost-effective compared to esketamine, due to comparable levels of clinical effectiveness and lower costs of esketamine attributable to commercial insurance coverage and manufacturer assistance programs.
 A US guideline on TRD suggests ketamine as augmentation to antidepressants. A US guideline on PTSD does not suggest the use of ketamine as therapy.
 The patient contributor CADTH engaged for this review highlighted the benefits, stigma, and barriers of ketamine therapy, including financial implications.
 
 What Does This Mean?
 
 There is some clinical effectiveness and cost-effectiveness evidence and a guideline recommendation to support the short-term use of ketamine in adults with TRD.
 Clinical effectiveness evidence and a guideline recommendation do not support the use of ketamine in adults with PTSD.
 Future research is necessary to understand the effectiveness and safety of ketamine as therapy for TRD in larger populations over longer periods and for PTSD for any follow-up duration.
 Decision-makers should consider offering ketamine in an equitable manner.

Ketamine Cystitis in a Female Patient Ketamine Therapy for Treatment Resistant Depression

Ketamine Cystitis in a Female Patient Ketamine Therapy for Treatment Resistant Depression

Repurposing of recreational drugs: will these new ‘medicines’ (e.g., psychedelics, psilocybin, cannabinoids, LSD, MDMA, ketamine) deliver short- or longer-term benefits for those with depressive or other mood disorders?

In recent years, there has been considerable enthusiasm among research groups focused on developing novel therapies for treatment-resistant depression, and a wider community that has had experiences using recreational drugs, in more systematic evaluation of the therapeutic value of these compounds (Goodwin et al., 2022; Young, 2023). This has also been associated with advocacy for decriminalization, legalization and possible public licensing for their ‘medicinal’ use (Siegel et al., 2023).

Plasma Brain-Derived Neurotrophic Factor Levels in First-Episode and Recurrent Major Depression and before and after Bright Light Therapy in Treatment-Resistant Depression.

Brain-derived neurotrophic factor (BDNF) is implicated in the etiology and treatment response in major depressive disorder (MDD). However, peripheral BDNF concentrations have not been compared across different MDD stages. Bright light therapy (BLT) offers some potential in treatment-resistant depression (TRD), but its effects on BDNF levels are unknown. This study included a cross-sectional analysis of plasma BDNF concentration in females with TRD, unmedicated MDD patients, and healthy controls (HC), and measurements of longitudinal BLT effects on plasma BDNF levels in TRD patients. The present study included 55 drug-naïve, first-episode patients, 25 drug-free recurrent-episode MDD patients, 71 HC participants, and 54 TRD patients. Patients were rated by Hamilton Depression Rating Scale (HAMD)-17 and the Montgomery-Åsberg Depression Rating Scale (MADRS). Patients with TRD received BLT during 4 weeks. The total HAMD-17 and MADRS scores decreased following BLT. All patient groups had lower plasma BDNF than HC, but BDNF levels did not differ between first- and recurrent-episode BDNF patients and TRD patients before or after BLT. However, responders and remitters to BLT had higher post-treatment plasma BDNF concentrations than patients who did not achieve response or remission. The changes in plasma BDNF levels may be candidates for biomarkers of treatment response to BLT in TRD patients.

Psilocybin therapy for treatment resistant depression: prediction of clinical outcome by natural language processing.

Therapeutic administration of psychedelics has shown significant potential in historical accounts and recent clinical trials in the treatment of depression and other mood disorders. A recent randomized double-blind phase-IIb study demonstrated the safety and efficacy of COMP360, COMPASS Pathways' proprietary synthetic formulation of psilocybin, in participants with treatment-resistant depression. While the phase-IIb results are promising, the treatment works for a portion of the population and early prediction of outcome is a key objective as it would allow early identification of those likely to require alternative treatment. Transcripts were made from audio recordings of the psychological support session between participant and therapist 1 day post COMP360 administration. A zero-shot machine learning classifier based on the BART large language model was used to compute two-dimensional sentiment (valence and arousal) for the participant and therapist from the transcript. These scores, combined with the Emotional Breakthrough Index (EBI) and treatment arm were used to predict treatment outcome as measured by MADRS scores. (Code and data are available at https://github.com/compasspathways/Sentiment2D .) RESULTS: Two multinomial logistic regression models were fit to predict responder status at week 3 and through week 12. Cross-validation of these models resulted in 85% and 88% accuracy and AUC values of 88% and 85%. A machine learning algorithm using NLP and EBI accurately predicts long-term patient response, allowing rapid prognostication of personalized response to psilocybin treatment and insight into therapeutic model optimization. Further research is required to understand if language data from earlier stages in the therapeutic process hold similar predictive power.

Lateral habenula deep brain stimulation alleviates depression-like behaviors and reverses the oscillatory pattern in the nucleus accumbens in an animal model of depression

Depression is a series of symptoms that influence mood, thinking, and behavior and create unpleasant emotions like hopelessness and apathy. Treatment-resistant depression (TRD) affects 30 % of depression patients despite the availability of several non-invasive therapies. Deep brain stimulation (DBS) is a novel therapy for TRD. The aim of the current study was to evaluate the effect of LHb-DBS by recording local field potentials (LFP) and conducting behavioral experiments.Thirty-two mature male Wistar rats were randomly divided into four groups: control, chronic mild stress (CMS), CMS+DBS, and DBS. After surgery and electrode placement in the lateral habenula (LHb), nucleus accumbens (NAc), and prelimbic cortex (PrL), the CMS protocol was applied for 3 weeks to create depression-like models. The open field test (OFT), sucrose preference test (SPT), and forced swim test (FST) were also performed. In the DBS groups, the LHb area was stimulated for four consecutive days. Finally, on the 22nd day, LFP was recorded from the NAc and PrL and analyzed using MATLAB software. Analyzing the findings using ANOVA and P-values ≤ 0.05 was considered.LHb-DBS alleviated depression-like behaviors in chronic moderate stress model rats (P ≤ 0.05). Three weeks of CMS enhanced almost all band powers in the NAc, while LHb-DBS decreased the power of the theta, alpha, beta, and gamma bands in the NAc (P ≤ 0.05), and the low-gamma band in the PrL. CMS also boosted the NAc-PrL coherence in low-frequency bands, while LHb-DBS increased beta and low gamma band coherence (P ≤ 0.05).In sum, the results of the present study showed that depression enhances low-frequency coherence between NAc and PrL cortex. Depression also potentiates many brain oscillations in the NAc, which can be mainly reversed by LHb-DBS.

Long Term Antidepressant Effects of Deep Brain Stimulation for Treatment Resistant Depression – A Research Protocol

Introduction: Individuals with treatment resistant depression (TRD) are those with severe major depressive disorder who fail to respond to conventional pharmacological treatment. As a result, novel technologies in the field of neuromodulation have been investigated to alleviate depressive symptoms in this population. One such neuromodulation therapy is deep brain stimulation (DBS), in which electrodes are neurosurgically implanted into target regions of the brain associated with depression, such as the subgenual anterior cingulate cortex (sgACC). While previous studies have explored the use of DBS as a therapy for TRD, few studies with adequate statistical power have explored the sustained antidepressant effects of DBS when targeting the sgACC of the brain. Methods: This study aims to explore the long-term effects in DBS patients for TRD by measuring changes in cerebral blood flow and cerebral metabolic rate in the sgACC, and its correlation to changes in self-reported depressive symptoms. Forty-five participants will be enlisted into this study. Psychometric evaluation and positron-emission topography imaging will be conducted prior to neurosurgery. Electrodes will be implanted into the sgACC, with extension wires attaching the electrodes to the internal pulse generator. In the six-week blinded phase, progressive increases in stimulation will be administered within the blinded group and sham stimulation in controls. The three-month open label phase will administer the same degree of high-frequency biphasic stimulation to the control and blinded groups and assess depression scores, neuroimaging, and adverse events. After cessation of active stimulation, a one-year, three-year, seven-year, and ten-year follow-up will monitor changes in antidepressant effects of DBS using simple linear contrasts and paired-sample t-tests. Expected Results: This study expects to find a sustained antidepressant response marked by decreases in sgACC metabolism and cerebral blood flow, and a reduction in self-report depression scores. Discussion: The use of DBS shows promise as a successful treatment intervention with sustained long-term effects for individuals with TRD. Additional secondary outcomes to be expected are improved quality of life and health behaviours. Conclusion: Though minor fluctuations are expected due to the presence of comorbidities, this study expects to showcase the long-term efficacy of deep brain stimulation for treatment resistant depression.

Magnetic Waves vs. Electric Shocks: A Non-Inferiority Study of Magnetic Seizure Therapy and Electroconvulsive Therapy in Treatment-Resistant Depression.

Treatment-resistant depression (TRD), characterized by the failure to achieve symptomatic remission despite multiple pharmacotherapeutic treatments, poses a significant challenge for clinicians. Electroconvulsive therapy (ECT) is an effective but limited option due to its cognitive side effects. In this context, magnetic seizure therapy (MST) has emerged as a promising alternative, offering comparable antidepressant efficacy with better cognitive outcomes. However, the clinical outcomes and cognitive effects of MST require further investigation. This double-blinded, randomized, non-inferiority study aims to compare the efficacy, tolerability, cognitive adverse effects, and neurophysiological biomarkers of MST with bilateral ECT (BT ECT) in patients with TRD. This study will employ multimodal nuclear magnetic resonance imaging (MRI) and serum neurotrophic markers to gain insight into the neurobiological basis of seizure therapy. Additionally, neurophysiological biomarkers will be evaluated as secondary outcomes to predict the antidepressant and cognitive effects of both techniques. The study design, recruitment methods, ethical considerations, eligibility criteria, interventions, and blinding procedures are described. The expected outcomes will advance the field by offering a potential alternative to ECT with improved cognitive outcomes and a better understanding of the underlying pathophysiology of depression and antidepressant therapies.

Maintenance repetitive transcranial magnetic stimulation (rTMS) therapy for treatment-resistant depression: a study protocol of a multisite, prospective, non-randomized longitudinal study

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is a widely used treatment for major depressive disorder (MDD), and its effectiveness in preventing relapse/recurrence of MDD has been explored. Although few small sample controlled studies exist, the protocols of maintenance rTMS therapy were heterogeneous and evidence of its effectiveness is not sufficient. Thus, this study aims to evaluate whether maintenance rTMS is effective in maintaining the treatment response in patients with MDD with a large sample size and feasible study design.MethodsIn this multicenter open-labelled parallel-group trial we plan to recruit 300 patients with MDD who have responded or remitted to acute rTMS therapy. Participants would be classified into two groups according to their preference; the maintenance rTMS and pharmacotherapy group, and the pharmacotherapy only group. The protocol of maintenance rTMS therapy is once a week for the first six months and once biweekly for the second six months. The primary outcome is the relapse/recurrence rates during 12 months following enrollment. Other measures of depressive symptoms and recurrence/relapse rates at different time points are the secondary outcomes. The primary analysis is the between-group comparison adjusted for background factors using a logistic regression model. We will perform the group comparison with inverse probability of treatment weighting as the sensitivity analysis to ensure the comparability of the two groups.DiscussionWe hypothesize that maintenance rTMS therapy could be an effective and safe treatment for preventing depressive relapse/recurrence. Considering the limitation of potential bias owing to the study design, we plan to use statistical approaches and external data to avoid overestimation of the efficacy.Trial registrationJapan Registry of Clinical Trials, ID: jRCT1032220048. Registered 1 May 2022.

Esketamine in treatment-resistant depression patients comorbid with substance-use disorder: A viewpoint on its safety and effectiveness in a subsample of patients from the REAL-ESK study

Esketamine, the S-enantiomer of ketamine, has recently emerged as a therapy for treatment-resistant depression (TRD), showing both rapid antidepressant action and good efficacy and high safety. It is also indicated for the acute short-term treatment of psychiatric emergency due to major depressive disorder (MDD) and for depressive symptoms in adults with MDD with acute suicidal thoughts/behavior. We here provide preliminary insights on esketamine nasal spray (ESK-NS) effectiveness and safety among patients with a substance use disorder (SUD) within the sample of patients with TRD collected for the observational, retrospective, multicentre REAL-ESK study. Twenty-six subjects were retrospectively selected according to the presence of a SUD in comorbidity. Subjects enrolled completed the three different follow-up phases (T0/baseline, T1/after one month, and T2/after three months) and there were no dropouts. A decrease in Montgomery-Asberg depression rating scale (MADRS) scores was recorded, thus highlighting the antidepressant efficacy of ESK-NS (MADRS decreased from T0 to T1, t = 6.533, df=23, p<0.001, and from T1 to T2, t = 2.029, df=20, p = 0.056). Considering tolerability and safety issues, one or more side effects were reported by 19/26 subjects (73%) after treatment administration. All reported side effects were time-dependent and did not cause significant sequelae; among them, dissociative symptoms (38%) and sedation (26%) were the most frequently reported. Finally, no cases of abuse or misuse of ESK-NS were reported. Despite study limitations related to the inherent nature of the study, a limited number of patients, and a short follow-up period, ESK-NS showed to be effective and safe in patients diagnosed with TRD comorbid with a SUD.

Response to electroconvulsive therapy in treatment-resistant depression: nationwide observational follow-up study.

Previous studies have not investigated response rates after electroconvulsive therapy (ECT) in patients with non-psychotic treatment-resistant depression (TRD). To assess and compare the response rate of ECT for patients with TRD and non-TRD, in a large and clinically representative patient sample. Patients aged ≥18 years, who were treated for a unipolar, non-psychotic depressive episode with at least one ECT session as part of a first-time, index ECT series between 1 January 2011 and 31 December 2017 were included from the Swedish National Quality Register for ECT. Patients who had initiated a third consecutive trial of antidepressants or add-on medications before start of ECT were classified as having TRD. Patients not meeting criteria for TRD were classified as non-TRD. The main outcome was response to ECT according to the Clinical Global Impressions - Improvement Scale (CGI-I), scored as 1 or 2 ('very much' or 'much improved' after ECT, respectively). Logistic regression was used to compare outcome measures between TRD and non-TRD, adjusting for potential confounders. A total of 4244 patients were included. Of these, 1121 patients had TRD and 3123 patients had non-TRD. The CGI-I response rate was 65.9% in the TRD group compared with 75.9% in the non-TRD group (adjusted odds ratio 0.64, 95% CI 0.54-0.75). Older age and more severe depression were predictors of response in patients with TRD. A clear majority of patients with TRD, as well as patients with non-TRD, responded to ECT, although the response rate was somewhat lower for TRD.

The safety and efficacy of COMP360 psilocybin therapy in treatment-resistant depression: results from a long-term observational follow-up study

The safety and efficacy of COMP360 psilocybin therapy in treatment-resistant depression: results from a long-term observational follow-up study

Electroconvulsive therapy for Depression in Anorexia Nervosa. A review

IntroductionAnorexia nervosa has an important burden on both patients and families, with important comorbidities such as depression and obsessive symptoms. These are more resistant to pharmacological treatment than in non-anorexia patients, due to both biological and psychological mechanisms. Electroconvulsive therapy is the best available therapy for treatment resistant depression making it a treatment to consider in treatment resistant depression in anorexia though only case reports exist.ObjectivesTo review the current evidence for electroconvulsive therapy of depression in patients with anorexia nervosa as well as it’s ethical challengesMethodsNon-systematic review of the literature with selection of scientific articles published in the past 10 years; by searching Pubmed and Medscape databases using the combination of MeSH descriptors. The following MeSH terms were used: “electroconvulsive therapy”, “anorexia nervosa”.ResultsElectroconvulsive therapy in anorexia has no controlled trials with mostly case reports available on scientific databases. It presents important challenges due to patient age, medical status and ethical challenges. Even less evidence exist for electroconvulsive therapy in children and adolescents than for adults, anorexia can complicate medical status presenting an anesthetic and life-support challenge and it’s egosyntonicity can place a legal and ethical challenge when patient refuses treatment.ConclusionsAnorexia has a dramatic burden on patients and families affected, with integrated evidence-based treatment being necessary both for treating the current episode and for remission prevention. Case-reports show that electroconvulsive therapy can play a role on treatment resistant depression in anorexia.DisclosureNo significant relationships.

P336. No Evidence for Changes in Brain Function After Electroconvulsive Therapy in Treatment-Resistant Depression: A Multicenter Study

With electroconvulsive therapy, induced epileptic seizures are known to be an effective treatment for major depressive episodes and to cause (temporary) structural grey matter increases in the brain. Small-sample study findings have been inconsistent in whether these structural increases relate to clinical improvement and/or functional brain changes that in turn may explain clinical outcome.

Case Report: Multiple Courses of Electroconvulsive Therapy for Treatment Resistant Depression in a 68 year old male with a Cardiac Resynchronization Therapy Device with Defibrillator

<h3>Introduction</h3> Background: Electroconvulsive therapy (ECT) has been safely and successfully applied in patients with cardiac pacemakers and implantable cardiac devices, and reviewed in a number of case reports (1, 2). Cardiac Resynchronization Therapy Devices (CRT-D), available with and without defibrillation, benefit patients with Heart Failure with reduced ejection fraction (HfreF) by improving left ventricular function, optimizing ventricular filling, and confers benefits in quality of life and mortality (3). There are currently no case reports on the use of ECT in patients with cardiac resynchronization therapy devices. <h3>Methods</h3> Methods: Patient is a 68-year-old male with a history of major depressive disorder, PTSD, cluster B personality traits who presented in December 2019 for suicidal ideation in the context of a major depressive episode. His medical history is notable for atrial fibrillation on warfarin, DM2 on insulin, non-ischemic cardiomyopathy with HFREF. In 2015, patient's Implantable cardioverter-defribillator (ICD) was replaced with CRT-D. He has a history of 4 previous suicide attempts, most recently four years ago as well as a history of self-injurious behavior. His suicidal ideation on this admission was notable for newly observed command auditory hallucinations telling him to harm himself, suggestive of a mood-congruent psychosis. Patient was started on low-dose risperidone. His other psychotropic medications included bupropion, venlafaxine, and gabapentin with multiple failed medication trials in the past. Patient's initial MADRS was 30 on admission scoring highly for suicidal ideation. After initiation of risperidone, patient's MADRS lowered to 16 prior to first ECT session. Prior to ECT, anesthesia, cardiology, and electrophysiology were consulted. Patient's CRT-D device was interrogated and determined to be functioning and patient was medically optimized for ECT from cardiology standpoint. His ejection fraction was 30% approximately 6 months earlier. Anesthesia expressed concern about management of sympathetic and parasympathetic response to ECT. <h3>Results</h3> Results: Prior to first session, Electrophysiology reprogrammed device and patient had defibrillator pads placed. A brief seizure was achieved. Due to no observed bradycardia after first session, the electrophysiologist recommended patient can undergo further ECT with placement of magnet on CRT-D to disable defibrillator. For the following 3 sessions, an adequate seizure was obtained. Patient reported robust response with MADRS of 6 reported prior to his second session. During ECT therapy, patient underwent echocardiogram which indicated ejection fraction of 20-25%. Cardiology was again consulted and felt patient could continue with ECT if euvolemic and asymptomatic. After 4^th session, a collaborative decision was made with patient to forego further ECT given patient's improvement in mood. Patient returned for another course of 3 sessions of ECT 8 months later and one maintenance session 9 months later. For these sessions, a magnet was used exclusively to disable fibrillator with robust effect on depressive symptoms. <h3>Conclusions</h3> Conclusion: This case indicates ECT can be provided safely to patients with a CRT-D device over an extended period of time; placing device in electrocautery mode with defibrillator pads as well as disabling defibrillator function with a magnet both proved effective methods to provide ECT safely. Further study of ECT in patients with CRT is warranted, in particular, to observe patients who complete a number of sessions more typical in treatment resistant depression. ECT in patients with CRT-P devices have not been reported. <h3>This research was funded by</h3> none

Deep brain stimulation of the "medial forebrain bundle": sustained efficacy of antidepressant effect over years.

Deep brain stimulation (DBS) to the superolateral branch of the medial forebrain bundle (MFB) has emerged as a quite efficacious therapy for treatment resistant depression (TRD), leading to rapid antidepressant effects. In this study, we complete our assessment of our first 10 enrolled patients throughout one year post-implantation, showing sustained antidepressant effect up to 5 years. The primary outcome measure was a 50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) score, which was interpreted as a response. Deterministic fiber tracking was used to individually map the target area. An insertional effect was seen during the 4-week sham stimulation phase (29% mean MADRS reduction, p = 0.02). However, after 2 weeks of initiating stimulation, five patients met response criteria (47% mean MADRS reduction, p < 0.001). One patient withdrew from study participation at 6 weeks. Twelve weeks after initiating stimulation, six of nine remaining patients had a >50% decrease in MADRS scores relative to baseline (52% mean MADRS reduction, p = 0.001); these same six patients continued to meet response criteria at 52 weeks (63% overall mean MADRS reduction, p < 0.001). Four of five patients who achieved the 5-year time point analysis continued to be responders (81% mean MADRS reduction, p < 0.001). Evaluation of modulated fiber tracts reveals significant common prefrontal/orbitofrontal connectivity to the target region in all responders. Key points learned from this study that we can incorporate in future protocols to better elucidate the effect of this therapy are a longer blinded sham stimulation phase and use of scheduled discontinuation concomitant with functional imaging.

The safety and efficacy of COMP360 psilocybin therapy in treatment-resistant depression: results from a phase IIb randomised controlled trial

The safety and efficacy of COMP360 psilocybin therapy in treatment-resistant depression: results from a phase IIb randomised controlled trial