scholarly journals Use of Ketamine to Treat Depressive Symptoms in Schizoaffective Disorder

2019 ◽  
pp. 271-274
Author(s):  
Isaac Freedman ◽  
Daniel Rabin ◽  
Prabhneet Pannu ◽  
Tariq Bandoo ◽  
Bal Nandra ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Growth Factor ◽  
Schizoaffective Disorder ◽  
Bipolar Depression ◽  
Synaptic Connections ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Complex Disorders ◽  
Resistant Depression ◽  
Psychotic Features

The use of subanesthetic ketamine infusions in treatment resistant depression and bipolar depression is becoming more common. Subanesthetic doses of ketamine cause the patient to dissociate, which was initially considered a side effect of this treatment; it is believed to play a role in a patient’s clinical improvement. Researchers attribute this result to an increase in brain-derived neurotrophic factor, a growth factor that stimulates the formation of new synaptic connections. Due to its psychogenic affect, ketamine treatment is less suitable for patients who experience mood disorders with psychotic features. Although symptomatic hallucinations seemingly conflict with the dissociative effects of ketamine, treatment of a patient with depressive type schizoaffective disorder revealed significant improvements in his depressive symptoms, demonstrating ketamine’s potential to be safely administered to patients with a variety of complex disorders.

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.

Baseline Working Memory Predicted Response to Low-Dose Ketamine Infusion in Patients with Treatment-Resistant Depression

2021 ◽  
Author(s):  
Mu-Hong Chen ◽  
Wei-Chen Lin ◽  
Cheng-Ta Li ◽  
Shih-Jen Tsai ◽  
Hui-Ju Wu ◽  
...  
Keyword(s):  
Working Memory ◽  
Depressive Symptoms ◽  
Treatment Response ◽  
Low Dose ◽  
Memory Function ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Ketamine Infusion ◽  
Treatment Groups ◽  
Resistant Depression

Abstract Introduction Pretreatment neurocognitive function may predict the treatment response to low-dose ketamine infusion in patients with treatment-resistant depression (TRD). However, the association between working memory function at baseline and the antidepressant efficacy of ketamine infusion remains unclear. Methods A total of 71 patients with TRD were randomized to one of three treatment groups: 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, or normal saline. Depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale (HDRS) at baseline and after treatment. Cognitive function was evaluated using working memory and go-no-go tasks at baseline. Results A generalized linear model with adjustments for demographic characteristics, treatment groups, and total HDRS scores at baseline revealed only a significant effect of working memory function (correct responses and omissions) on the changes in depressive symptoms measured by HDRS at baseline (F=12.862, p<0.05). Correlation analysis further showed a negative relationship (r=0.519, p=0.027) between pretreatment working memory function and changes in HDRS scores in the 0.5 mg/kg ketamine group. Discussion An inverse relationship between pretreatment working memory function and treatment response to ketamine infusion may confirm that low-dose ketamine infusion is beneficial and should be reserved for patients with TRD.

scholarly journals 118 Use of Patient Health Questionnaire to Predict Relapses in Patients with Treatment-resistant Depression Treated With Esketamine + Oral Antidepressant

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 276-277
Author(s):  
Carol Jamieson ◽  
Nan Li ◽  
Ella Daly ◽  
Adam Janik ◽  
Rosanne Lane ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Patient Health Questionnaire ◽  
Controlled Study ◽  
Health Questionnaire ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Relapse Risk ◽  
Total Score Range ◽  
Patient Health ◽  
Resistant Depression

Abstract:Objective:To assess the Patient Health Questionnaire (PHQ-9) as a predictor of relapse of depressive symptoms in treatment-resistant depression (TRD).Method:Analysis included maintenance phase data from SUSTAIN-1 (NCT02493868), a randomized, double-blind, active-controlled study in TRD patients that evaluated efficacy of intranasal esketamine (ESK) + oral antidepressant (AD) vs AD + intranasal placebo in delaying relapse of depressive symptoms. A ≥50% reduction in initial symptom score and total score of ≤12 were considered as response and remission, respectively, using the Montgomery-Asberg Depression Rating Scale. PHQ-9 total score (range, 0–27), PHQ-2 total score (0–6), and individual items of the PHQ-9 (0–3) were examined as predictors of relapse. Data were collected every 2 weeks. Association between time-varying PHQ-9 and event of depression relapse was evaluated in Andersen-Gill Cox model.Results:Of 176 stable remitters, 63 had a relapse event (ESK+AD [n=24]; AD+placebo [n=39]). Of 121 stable responders, 50 had a relapse event (ESK+AD [n=16]; AD+placebo [n=34]). Among stable remitters, PHQ-9 total score (HR; 95% CI [1.12; 1.04–1.21]) and PHQ-2 total score (1.58; 1.25–1.99) were associated with relapse risk. PHQ-9 items #1 (loss of pleasure, 2.07; 1.38–3.09), #2 (feeling down, 2.18; 1.51–3.15), #4 (feeling tired, 1.54; 1.13–2.11), and #6 (negative self-view, 2.27; 1.41–3.66) were associated with relapse risk. PHQ-2 total scale yielded the smallest Akaike’s Information Criterion among stable remitters and responders.Conclusion:PHQ-9, PHQ-2 total scores or individual items may be useful for predicting relapse of depressive symptoms among stable TRD patients.Funding Acknowledgements:This study was sponsored by Janssen Research and Development, LLC.

scholarly journals Additional intranasal oxytocin to escitalopram improves depressive symptoms in resistant depression: An open trial

2015 ◽  
Vol 30 (1) ◽  
pp. 65-68 ◽  
Author(s):  
G. Scantamburlo ◽  
M. Hansenne ◽  
V. Geenen ◽  
J.J. Legros ◽  
M. Ansseau
Keyword(s):  
Depressive Symptoms ◽  
Rating Scale ◽  
Open Trial ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Hamilton Depression Rating Scale ◽  
Resistant Depression ◽  
Synthetic Oxytocin

AbstractThe aim of this open trial was to assess the antidepressant/anxiolytic effects of oxytocin used as an adjunct to antidepressant in treatment-resistant depression. Fourteen patients, who have not responded to 40 mg of escitalopram, received intranasal synthetic oxytocin during 4 weeks, in association with antidepressant. This is the first open trial study suggesting OT in association with escitalopram significantly reduced scores on Hamilton Depression Rating Scale.

Magnetic seizure therapy in treatment-resistant depression: clinical, neuropsychological and metabolic effects

2014 ◽  
Vol 45 (5) ◽  
pp. 1073-1092 ◽  
Author(s):  
S. Kayser ◽  
B. H. Bewernick ◽  
A. Matusch ◽  
R. Hurlemann ◽  
M. Soehle ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Depressive Symptoms ◽  
Fdg Pet ◽  
Metabolic Effects ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Magnetic Seizure Therapy ◽  
Resistant Depression ◽  
Pet Scans

Background.Magnetic seizure therapy (MST), despite being in an early phase of clinical research, has been demonstrated to be associated with antidepressant efficacy. However, safety, tolerability and efficacy data in connection with functional brain activity from larger samples are lacking. The aim of this study was to determine clinical and cognitive effects of MST and the influence of MST on regional brain glucose metabolism.Method.Twenty-six patients suffering from treatment-resistant depression (TRD) underwent MST. Ten patients underwent a randomized trial and 16 patients an open-label study design. The primary outcome criterion was the severity of depressive symptoms assessed with the Hamilton Depression Rating Scale (HAMD). Depressive symptoms, tolerability and cognitive safety, along with social functioning and quality of life parameters, were assessed using various rating scales. A clinical follow-up visit 6 months following the completion of a course of MST and [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) scans of 12 patients were analysed.Results.A significant response to MST was demonstrated by 69% of the patient sample, with 46% meeting remission criteria. Anxiety ratings were significantly reduced in responders and their quality of life was improved. Half of the responders relapsed within 6 months. No cognitive side-effects were observed. FDG-PET scans showed a metabolic increase in the frontal cortex bilaterally and a decrease in the left striatum.Conclusions.Robust antidepressant and anti-anxiety efficacy of MST was demonstrated, and found to be associated with localized metabolic changes in brain areas that are strongly implicated in depression. Thus, MST presents an effective, well-tolerated and safe treatment option for patients unable to respond to other forms of therapy for depression.

Clinical and neurocognitive characteristics associated with treatment-resistant depression

2017 ◽  
Vol 41 (S1) ◽  
pp. S542-S542 ◽  
Author(s):  
G. Serafini ◽  
G. Adavastro ◽  
G. Canepa ◽  
C. Conigliaro ◽  
M. Pompili ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Early Onset ◽  
Rating Scale ◽  
Color Word ◽  
Late Onset ◽  
Anxiety Symptoms ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Interference Test ◽  
Resistant Depression

IntroductionTreatment resistant depression (TRD) is a disabling condition associated with a relevant psychosocial impairment worldwide.ObjectivesThis exploratory study is aimed to evaluate the main clinical and neurocognitive characteristics in a sample of 21 subjects admitted to the Psychiatric Clinic of University of Genoa as inpatients between 2015 and 2016 and diagnosed with TRD according to Thase and Rush staging method.MethodsPatients have been assessed using the Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale, and Clinical Global Impression (CGI). The Continuous Performance Test (CPT), Trial Making Test (TMT-A/B), Stroop Color Word Interference Test, Verbal Fluency Test, and Rey auditory-verbal learning test (RAVLT) have been administered as well.ResultsSubjects with early-onset (< 50 years) depression had a longer illness duration, higher depressive episodes and more impaired performance at RAVLT while individuals with late-onset (> 50 years) depression showed a higher severity of depressive symptoms and more anxiety symptoms. Depressive symptoms were positively associated with anxiety (r = 0.82; P = 0.00) and negatively with TMT-A/B (r = −0.56, P = 0.01), Stroop Color Word Interference Test (r = −0.72, P = 0.005 and r = −0.616, P = 0.008), and RAVLT (r = −0.60; P = 0.02) performances. According to regression analyses, anxiety symptoms were the only significant predictor of depression severity (P = 0.02).ConclusionsEarly-onset depression is associated with more disability and worse neurocognitive performance whereas late-onset depression is linked to more anxiety symptoms and more depressive symptoms severity. Clinicians should closely monitor patients with TRD for the presence of anxiety symptoms that may represent a significant risk factor of poorer long-term outcome.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals PAX-D: study protocol for a randomised placebo-controlled trial evaluating the efficacy and mechanism of pramipexole as add-on treatment for people with treatment resistant depression

2021 ◽  
pp. ebmental-2021-300282
Author(s):  
Sheena Kristine Au-Yeung ◽  
James Griffiths ◽  
Sophie Roberts ◽  
Chloe Edwards ◽  
Ly-Mee Yu ◽  
...  
Keyword(s):  
Decision Making ◽  
Depressive Symptomatology ◽  
Bipolar Depression ◽  
Antidepressant Medication ◽  
Well Being ◽  
Reward Processing ◽  
Self Report ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression

IntroductionClinical depression is usually treated in primary care with psychological therapies and antidepressant medication. However, when patients do not respond to at least two or more antidepressants within a depressive episode, they are considered to have treatment resistant depression (TRD). Previous small randomised controlled trials suggested that pramipexole, a dopamine D2/3 receptor agonist, may be effective for treating patients with unipolar and bipolar depression as it is known to influence motivational drive and reward processing. PAX-D will compare the effects of pramipexole vs placebo when added to current antidepressant medication for people with TRD. Additionally, PAX-D will investigate the mechanistic effect of pramipexole on reward sensitivity using a probabilistic decision-making task.Methods and analysisPAX-D will assess effectiveness in the short- term (during the first 12 weeks) and in the longer-term (48 weeks) in patients with TRD from the UK. The primary outcome will be change in self-reported depressive symptoms from baseline to week 12 post-randomisation measured using the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). Performance on the decision-making task will be measured at week 0, week 2 and week 12. Secondary outcomes include anhedonia, anxiety and health economic measures including quality of life, capability, well-being and costs. PAX-D will also assess the adverse effects of pramipexole including impulse control difficulties.DiscussionPramipexole is a promising augmentation agent for TRD and may be a useful addition to existing treatment regimes. PAX-D will assess its effectiveness and test for a potential mechanism of action in patients with TRD.Trial registration numberISRCTN84666271

scholarly journals Use of 30-Hz Accelerated iTBS in Drug-Resistant Unipolar and Bipolar Depression in a Public Healthcare Setting: A Case Series

2022 ◽  
Vol 12 ◽  
Author(s):  
Filippo Cantù ◽  
Giandomenico Schiena ◽  
Domenico Sciortino ◽  
Lorena Di Consoli ◽  
Giuseppe Delvecchio ◽  
...  
Keyword(s):  
Rating Scale ◽  
Bipolar Depression ◽  
Case Series ◽  
Healthcare Setting ◽  
Public Healthcare ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression ◽  
Depressive Episodes ◽  
Hamilton Rating Scale

Background: Depressive episodes, especially when resistant to pharmacotherapy, are a hard challenge to face for clinicians and a leading cause of disability worldwide. Neuromodulation has emerged as a potential therapeutic option for treatment-resistant depression (TRD), in particular transcranial magnetic stimulation (TMS). In this article, we present a case series of six patients who received TMS with an accelerated intermittent theta-burst stimulation (iTBS) protocol in a public healthcare setting.Methods: We enrolled a total number of six participants, affected by a treatment-resistant depressive episode, in either Major Depressive Disorder (MDD) or Bipolar Disorder (BD). Patients underwent an accelerated iTBS protocol, targeted to the left dorsolateral prefrontal cortex (DLPFC), 3-week-long, with a total of 6 days of overall stimulation. On each stimulation day, the participants received 3 iTBS sessions, with a 15-min pause between them. Patients were assessed by the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Rating Scale for Anxiety (HAM-A), and the Mania Rating Scale (MRS). At baseline (T0), at the end of the second week (T1), and at the end of the cycle of stimulation (T2).Results: The rANOVA (repeated Analysis of Variance) statistics showed no significant effect of time on the rating scale scores, with a slight decrease in MADRS scores and a very slight increase in HAM-A and HAM-D scores. No manic symptoms emerged during the entire protocol.Conclusions: Although accelerated iTBS might be considered a less time-consuming strategy for TMS administration, useful in a public healthcare setting, our results in a real-word six-patient population with TRD did not show a significant effect. Further studies on wider samples are needed to fully elucidate the potential of accelerated iTBS protocols in treatment-resistant depression.

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