scholarly journals Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression (SAINT-TRD)

2019 ◽  
Author(s):  
Eleanor J. Cole ◽  
Katy H. Stimpson ◽  
Brandon S. Bentzley ◽  
Merve Gulser ◽  
Kirsten Cherian ◽  
...  
Keyword(s):  
Side Effects ◽  
Rating Scale ◽  
Neuropsychological Testing ◽  
Anterior Cingulate ◽  
High Dose ◽  
Delayed Response ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resting Motor Threshold ◽  
Resistant Depression

AbstractBackgroundCurrent treatments for depression are limited by suboptimal efficacy, delayed response, and frequent side effects. Intermittent theta-burst stimulation (iTBS) is a non-invasive brain stimulation treatment that is FDA-approved for treatment-resistant depression (TRD). Recent methodological advancements suggest iTBS could be improved through 1) treating with multiple sessions per day at optimally-spaced intervals, 2) applying a higher overall pulse-dose of stimulation and 3) precision targeting of the left dorsolateral prefrontal cortex (L-DLPFC) to subgenual anterior cingulate cortex (sgACC) circuit. We examined the feasibility, tolerability, and preliminary efficacy of an accelerated, high-dose, resting-state functional connectivity MRI (fcMRI)-guided iTBS protocol for TRD termed ‘Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT)’.MethodsTwenty-one participants with TRD received open-label SAINT. FcMRI was used to individually target the region of L-DLPFC most anticorrelated with sgACC. Fifty iTBS sessions (1800 pulses per session, 50-minute inter-session interval) were delivered as 10 daily sessions over 5 consecutive days at 90% resting motor threshold (adjusted for cortical depth). Neuropsychological testing was conducted before and after SAINT.ResultsNineteen of 21 participants (90.48%) met criteria for remission (≤10 on the Montgomery-Åsberg Depression Rating Scale) immediately after SAINT. Neuropsychological testing demonstrated no negative cognitive side-effects. There were no seizures or other severe adverse events.DiscussionOur accelerated, high-dose, iTBS protocol with fcMRI-guided targeting (SAINT) was well tolerated and safe. Efficacy was strikingly high, especially for this treatment-resistant population. Double-blinded sham-controlled trials are required to confirm the high remission rate found in this initial study.Trial registrationClinicalTrials.gov NCT03240692

scholarly journals The Neurostimulation of the Brain in Depression Trial: Protocol for a Randomized Controlled Trial of Transcranial Direct Current Stimulation in Treatment-Resistant Depression (Preprint)

2020 ◽  
Author(s):  
Raheem Suleman ◽  
Benjamin V Tucker ◽  
Serdar M Dursun ◽  
Michael L Demas
Keyword(s):  
Side Effects ◽  
Adverse Events ◽  
Rating Scale ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
University Of Alberta ◽  
Randomized Controlled ◽  
Resistant Depression ◽  
Double Blinded ◽  
The Brain

BACKGROUND Major depressive disorder (MDD) is the second highest cause of disability worldwide. Standard treatments for MDD include medicine and talk therapy; however, approximately 1 in 5 Canadians fail to respond to these approaches and must consider alternatives. Transcranial direct current stimulation (tDCS) is a safe, noninvasive method that uses electrical stimulation to change the activation pattern of different brain regions. By targeting those regions known to be affected in MDD, tDCS may be useful in ameliorating treatment-resistant depression. OBJECTIVE The objective of the Neurostimulation of the Brain in Depression trial is to compare the effectiveness of active versus sham tDCS in treating patients with ultraresistant MDD. The primary outcome will be the improvement in depressive symptoms, as measured by the change on the Mongtomery-Asberg Depression Rating Scale. Secondary outcomes will include changes in the Quick Inventory of Depressive Symptomatology Scale (subjective assessment), the World Health Organization Disability Assessment Schedule 2.0 (functional assessment), and the Screen for Cognitive Impairment in Psychiatry (cognitive assessment). Adverse events will be captured using the Young Mania Rating Scale; tDCS Adverse Events Questionnaire; Frequency, Intensity, and Burden of Side Effects Rating Scale; and Patient-Rated Inventory of Side Effects Scale. A parallel component of the study will involve assaying for baseline language function and the effect of treatment on language using an exploratory acoustic and semantic corpus analysis on recorded interviews. Participant accuracy and response latency on an auditory lexical decision task will also be evaluated. METHODS We will recruit inpatients and outpatients in the city of Edmonton, Alberta, and will deliver the study interventions at the Grey Nuns and University of Alberta Hospitals. Written informed consent will be obtained from all participants before enrollment. Eligible participants will be randomly assigned, in a double-blinded fashion, to receive active or sham tDCS, and they will continue receiving their usual pharmacotherapy and psychotherapy throughout the trial. In both groups, participants will receive 30 weekday stimulation sessions, each session being 30 minutes in length, with the anode over the left dorsolateral prefrontal cortex and the cathode over the right. Participants in the active group will be stimulated at 2 mA throughout, whereas the sham group will receive only a brief period of stimulation to mimic skin sensations felt in the active group. Measurements will be conducted at regular points throughout the trial and 30 days after trial completion. RESULTS The trial has been approved by the University of Alberta Research Ethics Board and is scheduled to commence in June 2021. The target sample size is 60 participants. CONCLUSIONS This is a protocol for a multicenter, double-blinded, randomized controlled superiority trial comparing active versus sham tDCS in patients with treatment-resistant MDD. CLINICALTRIAL ClinicalTrials.gov NCT04159012; http://clinicaltrials.gov/ct2/show/NCT04159012. INTERNATIONAL REGISTERED REPORT PRR1-10.2196/22805

scholarly journals Prolonged ketamine infusion modulates limbic connectivity and induces sustained remission of treatment-resistant depression

2021 ◽  
Author(s):  
Joshua S. Siegel ◽  
Ben J. A. Palanca ◽  
Beau M. Ances ◽  
Evan D. Kharasch ◽  
Julie A. Schweiger ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Limbic System ◽  
Anterior Cingulate ◽  
Sustained Remission ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Open Label ◽  
Subgenual Anterior Cingulate Cortex ◽  
Post Infusion ◽  
Resistant Depression

AbstractKetamine produces a rapid antidepressant response in over 50% of adults with treatment-resistant depression. A long infusion of ketamine may provide durable remission of depressive symptoms, but the safety, efficacy, and neurobiological correlates are unknown. In this open-label, proof-of-principle study, adults with treatment-resistant depression (N = 23) underwent a 96-h infusion of intravenous ketamine (0.15 mg/kg/h titrated toward 0.6 mg/kg/h). Clonidine was co-administered to reduce psychotomimetic effects. We measured clinical response for 8 weeks post-infusion. Resting-state functional magnetic resonance imaging was used to assess functional connectivity in patients pre- and 2 weeks post-infusion and in matched non-depressed controls (N = 27). We hypothesized that responders to therapy would demonstrate response-dependent connectivity changes while all subjects would show treatment-dependent connectivity changes. Most participants completed infusion (21/23; mean final dose 0.54 mg/kg/h, SD 0.13). The infusion was well tolerated with minimal cognitive and psychotomimetic side effects. Depressive symptoms were markedly reduced (MADRS 29 ± 4 at baseline to 9 ± 8 one day post-infusion), which was sustained at 2 weeks (13 ± 8) and 8 weeks (15 ± 8). Imaging demonstrated a response-dependent decrease in hyperconnectivity of the subgenual anterior cingulate cortex to the default mode network, and a treatment-dependent decrease in hyperconnectivity within the limbic system (hippocampus, amygdala, medial thalamus, nucleus accumbens). In exploratory analyses, connectivity was increased between the limbic system and frontal areas, and smaller right hippocampus volume at baseline predicted larger MADRS change. A single prolonged infusion of ketamine provides a tolerated, rapid, and sustained response in treatment-resistant depression and normalizes depression-related hyperconnectivity in the limbic system and frontal lobe.ClinicalTrials.gov: Treatment Resistant Depression (Pilot), NCT01179009.

scholarly journals Comprehensive assessment of side effects associated with a single dose of ketamine in treatment-resistant depression

2020 ◽  
Vol 263 ◽  
pp. 568-575 ◽  
Author(s):  
Elia E. Acevedo-Diaz ◽  
Grace W. Cavanaugh ◽  
Dede Greenstein ◽  
Christoph Kraus ◽  
Bashkim Kadriu ◽  
...  
Keyword(s):  
Single Dose ◽  
Side Effects ◽  
Comprehensive Assessment ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression

scholarly journals Using Oral and Intranasal Dosage Forms of Ketamine for Managing Treatment-Resistant Depression: A Review of the Literature

2016 ◽  
Vol 4 (2) ◽  
pp. 64-71 ◽  
Author(s):  
Patrick Arthur Twohig ◽  
Vaughn Huckfeldt
Keyword(s):  
Health Care ◽  
Side Effects ◽  
Care Setting ◽  
Dosage Forms ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Similar Reduction ◽  
Aspartate Receptor ◽  
Pubmed Database ◽  
Resistant Depression

A lack of effective treatment for patients with treatment-resistant depression (TRD) has led to the evaluation of ketamine, an N-methyl- D-aspartate receptor antagonist. Despite the demonstrated short-term benefits of using intravenous (IV) ketamine, side effects and the difficulty in administering ketamine outside the health-care setting has raised interest in alternative dosage forms. Research articles evaluating oral or intranasal (IN) ketamine were retrieved from the PubMed database. Patients who received oral or IN ketamine experienced a similar reduction in depressive symptoms within 24 hours of treatment and fewer side effects compared to patients who received IV ketamine. Novel administration forms of ketamine provide an opportunity for patients with TRD to achieve remission with fewer adverse side effects. Future studies should continue to evaluate these administration strategies in the hope of promoting ketamine’s use outside health-care settings and for longer time periods.

scholarly journals Prevalence and Impact of Treatment-Resistant Depression in Latin America: a Prospective, Observational Study

2021 ◽  
Author(s):  
Bernardo Soares ◽  
Gabriela Kanevsky ◽  
Chei Tung Teng ◽  
Rodrigo Pérez-Esparza ◽  
Gerardo Garcia Bonetto ◽  
...  
Keyword(s):  
Latin America ◽  
Observational Study ◽  
Latin American ◽  
Prospective Observational Study ◽  
Rating Scale ◽  
Fisher Exact Test ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Work Impairment ◽  
Resistant Depression

AbstractApproximately one-third of patients with major depressive disorder (MDD) have treatment-resistant depression (TRD). The TRAL study will evaluate the prevalence and impact of TRD among patients with MDD in four Latin American countries. In this multicenter, prospective, observational study, patients with MDD were recruited from 33 reference sites in Mexico, Colombia, Brazil, and Argentina. Patients were assessed for TRD, defined as failure to respond to ≥ 2 antidepressant medications of adequate dose and duration. Demographics, previous/current treatments, depressive symptoms, functioning, healthcare resource utilization, and work impairment were also collected and evaluated using descriptive statistics, chi-square test, Fisher exact test, t-test for independent samples, or the Mann–Whitney nonparametric test, as appropriate. 1475 patients with MDD were included in the analysis (mean age, 45.6 years; 78% women); 89% were receiving relevant psychiatric treatment. 429 patients met criteria for TRD, and a numerically higher proportion of patients with TRD was present in public versus private sites of care (31% vs 27%). The mean Montgomery-Asberg Depression Rating Scale score was 25.0 among all MDD patients and was significantly higher for patients with TRD versus non-TRD (29.4 vs 23.3; P < 0.0001). Patients with TRD, versus those with non-TRD, were significantly more likely to be older, have a longer disease duration, have more comorbidities, be symptomatic, have a higher median number of psychiatric consultations, and report greater work impairment. Patients with TRD have a disproportionate burden of disease compared to those with non-TRD. Appropriate treatment for TRD is a substantial unmet need in Latin America. https://www.ClinicalTrials.gov identifier NCT03207282, 07/02/2017.

scholarly journals Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial

2018 ◽  
Vol 49 (4) ◽  
pp. 655-663 ◽  
Author(s):  
Fernanda Palhano-Fontes ◽  
Dayanna Barreto ◽  
Heloisa Onias ◽  
Katia C. Andrade ◽  
Morgana M. Novaes ◽  
...  
Keyword(s):  
Rating Scale ◽  
Remission Rate ◽  
Controlled Trial ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Open Label ◽  
Double Blind ◽  
Therapeutic Value ◽  
Antidepressant Effects ◽  
Resistant Depression

AbstractBackgroundRecent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression.MethodsTo test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing.ResultsWe observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p= 0.04), and at D7 (p< 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen'sd= 0.84; D2: Cohen'sd= 0.84; D7: Cohen'sd= 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64%v.27%;p= 0.04). Remission rate showed a trend toward significance at D7 (36%v.7%,p= 0.054).ConclusionsTo our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered athttp://clinicaltrials.gov(NCT02914769).

Esketamine: A Novel Option for Treatment-Resistant Depression

2019 ◽  
Vol 54 (6) ◽  
pp. 567-576 ◽  
Author(s):  
Kevin M. Bozymski ◽  
Ericka L. Crouse ◽  
Erika N. Titus-Lay ◽  
Carol A. Ott ◽  
Jill L. Nofziger ◽  
...  
Keyword(s):  
English Language ◽  
Rating Scale ◽  
Data Extraction ◽  
Fixed Dose ◽  
Depression Symptoms ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Pubmed Search ◽  
Resistant Depression ◽  
Suicidal Thoughts And Behaviors

Objective:To review the pharmacology, pharmacokinetics, efficacy, safety, use requirements, and place in therapy of esketamine for treatment-resistant depression (TRD). Data Sources: A comprehensive PubMed search (1966 to October 2019) was conducted using the search terms depression, treatment-resistant, suicide, intranasal, esketamine, and JNJ-54135419. Additional data were obtained from references of identified articles, governmental sources, manufacturer product labeling, and Clinicaltrials.gov . Study Selection and Data Extraction: All English-language trials evaluating intranasal esketamine for TRD were included and discussed. Data Synthesis: Intranasal esketamine was approved by the US Food and Drug Administration, in conjunction with an oral antidepressant, for treating TRD in adults. Two short-term trials (TRANSFORM-1 and -2) found statistically significant reduction in the Montgomery-Asberg Depression Rating Scale score at day 28 for the fixed 56-mg dose (−4.1; 95% CI = −7.69 to −0.49; P = 0.027 [exploratory]) and flexible-dosed arms (−4.0; 95% CI = −7.31 to −0.64; P = 0.02), though the fixed-dose 84-mg arm (−3.2; 95% CI = −6.88 to 0.45; P = 0.088) of TRANSFORM-1 and TRANSFORM-3 did not (−3.6; 95% CI = −7.2 to 0.07; P = 0.059). Two long-term trials (SUSTAIN-1 and -2) suggested maintenance of response with continued use. Esketamine’s adverse effects include dizziness, dysgeusia, somnolence, dissociation, suicidal thoughts and behaviors, and increased heart rate and blood pressure. Relevance to Patient Care and Clinical Practice: Although providing a novel antidepressant mechanism and formulation for TRD, esketamine’s role in treatment will likely be limited by cost, administration, and diversion concerns. Conclusion: Intranasal esketamine significantly reduced depression symptoms in TRD, though with tolerability issues.

scholarly journals Long-term deep brain stimulation of the ventral anterior limb of the internal capsule for treatment-resistant depression

2019 ◽  
Vol 91 (2) ◽  
pp. 189-195 ◽  
Author(s):  
Junus M. van der Wal ◽  
Isidoor O. Bergfeld ◽  
Anja Lok ◽  
Mariska Mantione ◽  
Martijn Figee ◽  
...  
Keyword(s):  
Rating Scale ◽  
Response Rate ◽  
Internal Capsule ◽  
Maintenance Phase ◽  
Efficacy And Safety ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression ◽  
Deep Brain

ObjectiveDeep brain stimulation (DBS) reduces depressive symptoms in approximately 40%–60% of patients with treatment-resistant depression (TRD), but data on long-term efficacy and safety are scarce. Our objective was to assess the efficacy and safety of DBS targeted at the ventral anterior limb of the internal capsule (vALIC) in 25 patients with TRD during a 1-year, open-label, maintenance period, which followed a 1-year optimisation period.MethodsDepression severity was measured using the 17-item Hamilton Depression Rating Scale (HAM-D-17), Montgomery-Asberg Depression Rating Scale (MADRS) and self-reported Inventory of Depressive Symptomatology (IDS-SR). Primary outcomes were response rate (≥50% HAM-D-17 score reduction) after the maintenance phase, approximately 2 years after DBS surgery, and changes in depression scores and occurrence of adverse events during the maintenance phase.ResultsOf 25 operated patients, 21 entered and 18 completed the maintenance phase. After the maintenance phase, eight patients were classified as responder (observed response rate: 44.4%; intention-to-treat: 32.0%). During the maintenance phase, HAM-D-17 and MADRS scores did not change, but the mean IDS-SR score decreased from 38.8 (95% CI 31.2 to 46.5) to 35.0 (95% CI 26.1 to 43.8) (p=0.008). Non-responders after optimisation did not improve during the maintenance phase. Four non-DBS-related serious adverse events occurred, including one suicide attempt.ConclusionsvALIC DBS for TRD showed continued efficacy 2 years after surgery, with symptoms remaining stable after optimisation as rated by clinicians and with patient ratings improving. This supports DBS as a viable treatment option for patients with TRD.Trial registration numberNTR2118.

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