Repeated subcutaneous esketamine for treatment-resistant depression: Impact of the degree of treatment resistance and anxiety comorbidity

2021 ◽  
Vol 35 (2) ◽  
pp. 142-149
Author(s):  
Ana C Lucchese ◽  
Luciana M Sarin ◽  
Eduardo J Muniz Magalhães ◽  
Lorena C Del Sant ◽  
Camila B Puertas ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Anxiety Disorder ◽  
Rating Scale ◽  
Treatment Algorithm ◽  
Treatment Resistance ◽  
Antidepressant Effect ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Clinical Predictors ◽  
Resistant Depression

Background: A large number of studies indicate that subanesthetic doses of ketamine induce a fast antidepressant effect. Limited studies have investigated the subcutaneous (SC) route, and it remains unclear for whom this treatment is most suitable. Aims: The aim of this study was to examine the effect on depressive symptoms of repeated subanesthetic doses of SC esketamine in unipolar and bipolar treatment-resistant depression (TRD) and clinical predictors of response. Methods: A retrospective analysis of 70 patients who received six SC esketamine doses weekly as an adjunctive treatment was carried out. Doses started at 0.5 mg/kg and it could be titrated up to 1 mg/kg, according to response. The primary outcome was reduction in depressive symptoms. Statistical analysis to investigate clinical predictors of effectiveness included logistic regression analysis using a dependent variable of a 50% reduction in rating scale scores at the end of treatment. Comparisons between groups were made through analysis of variance and treatment effects. Results: At baseline, our sample presented with severe treatment resistance in 65.7%, as assessed by the Maudsley Staging Method (MSM), and 47.1% had anxiety disorder comorbidity. The response rate was 50%. A better outcome was predicted by mild and moderate MSM scores (OR = 3.162, p = 0.041) and anxiety disorder comorbidity (OR = 3.149, p = 0.028). Conclusions: Our results suggest that higher levels of treatment resistance may be associated with a poor response to SC esketamine. Unlike traditional pharmacotherapies, it might benefit those with poor prognosis such as patients with depression and comorbid anxiety. Therefore, future research could investigate whether esketamine should receive a more prominent place in the treatment algorithm for TRD.

Efficacy of low-dose ketamine infusion in anxious vs nonanxious depression: revisiting the Adjunctive Ketamine Study of Taiwanese Patients with Treatment-Resistant Depression

CNS Spectrums ◽  
2020 ◽  
pp. 1-6
Author(s):  
Mu-Hong Chen ◽  
Wei-Chen Lin ◽  
Hui-Ju Wu ◽  
Ya-Mei Bai ◽  
Cheng-Ta Li ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Low Dose ◽  
Rating Scale ◽  
Estimating Equation ◽  
Antidepressant Effect ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Ketamine Infusion ◽  
Resistant Depression

Abstract Background. The antidepressant effect of low-dose ketamine infusion on Taiwanese patients with anxious vs nonanxious treatment-resistant depression (ANX-TRD vs NANX-TRD) has remained unknown. Methods. In total, 71 patients with TRD were randomized to three groups. Each group had participants who received saline infusions mixed with 0 (a normal saline infusion), 0.2, and 0.5 mg/kg of ketamine. Participants were followed up for 2 weeks. Anxious depression was defined as major depressive disorder with a total score of 7 or more on the 17-item Hamilton Depression Rating Scale Anxiety-Somatization factor. Generalized estimating equation models were used to investigate the effects of treatment (ketamine vs placebo) and depression type (ANX-TRD vs NANX-TRD) in the reduction of depressive symptoms during the follow-up period. Results. Patients with ANX-TRD were less likely to respond to a single low-dose ketamine infusion than those with NANX-TRD. Among patients with NANX-TRD, low-dose ketamine infusion was significantly superior to placebo for reducing depressive symptoms. However, among patients with ANX-TRD, ketamine was not superior to placebo; nonetheless, approximately 30% of the patients responded to ketamine infusion compared to 13% who responded to the placebo. Conclusions. Low-dose ketamine infusion was effective for Taiwanese patients with NANX-TRD but not so effective for those with ANX-TRD. A higher level of anxiety severity accompanying depression was related to greater depression severity. This may confound and reduce the antidepressant effect of ketamine infusion.

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.

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.

Clinical predictors of antidepressant response to ketamine in unipolar treatment-resistant depression

2017 ◽  
Vol 41 (S1) ◽  
pp. S525-S526 ◽  
Author(s):  
L.C. Del Sant ◽  
E. Magalhães ◽  
A.C. Lucchese ◽  
H.N. Palhares Alves ◽  
L.M. Sarin ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Receptor Antagonist ◽  
Clinical Characteristics ◽  
Treatment Resistant Depression ◽  
Antidepressant Response ◽  
Treatment Resistant ◽  
Clinical Predictors ◽  
Post Infusion ◽  
History Of ◽  
Resistant Depression

IntroductionThe non-competitive N-methyl-d-aspartate glutamate receptor antagonist ketamine has been shown to have rapid antidepressant effects in treatment-resistant depression (TRD). However, only a few studies have investigated which clinical characteristics predict a response to ketamine.ObjectivesTo assess sociodemographic variables and clinical markers that predict response to ketamine in unipolar TRD patients.MethodsSearches of Pubmed, NCBI and Google Scholar were conducted for clinical trials and systematic reviews, through October 2016, using the keywords:ketamine, N-methyl-d-aspartate receptor antagonist, rapid-acting antidepressant, depression, treatment-resistant depression, clinical predictors.ResultsFindings support the following clinical predictors:– sociodemographic variables: positive family history of alcohol abuse disorder in first-degree relative (increased antidepressant response and fewer depressive symptoms for up to 4 weeks post-infusions), higher BMI (improvement in depression severity at 230 minutes and one day post-infusion), negative history of suicide attempt (greater improvement at day 7);– infusion-associated events: greater dissociation during infusion (better antidepressant response at 230 minutes and one week post-infusion); rapid response to first infusion (sustained response to subsequent infusions in one-third responders for up to 83 days);– symptomatology: anxious depression (fewer depression symptoms at day one up to 25 associated with longer time to relapse); neurocognitive performance (lower attention) predicts change in severity of depressive symptoms over six infusions.ConclusionsFindings suggest that specific clinical characteristics are predictors of ketamine response in TRD. Future studies confirming reliable predictors will assist clinicians to implement efficacious and individualized treatment for TRD patients.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Ketamine augmentation for outpatients with treatment-resistant depression: Preliminary evidence for two-step intravenous dose escalation

2016 ◽  
Vol 51 (1) ◽  
pp. 55-64 ◽  
Author(s):  
Cristina Cusin ◽  
Dawn Flosnik Ionescu ◽  
Kara Jean Pavone ◽  
Oluwaseun Akeju ◽  
Paolo Cassano ◽  
...  
Keyword(s):  
Rating Scale ◽  
Treatment Resistance ◽  
Preliminary Evidence ◽  
Primary Outcome Measure ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Open Label ◽  
Antidepressant Efficacy ◽  
Resistant Depression ◽  
Intravenous Ketamine

Objective: Preliminary evidence supports the safety and efficacy of subanesthetic ketamine as an experimental antidepressant, although its effects are often not sustained beyond one week. Studies are lacking that have examined the sustained effects of escalating ketamine doses as augmentation in outpatients with treatment-resistant depression. Therefore, the aims of this study were twofold: (1) to assess the safety and antidepressant efficacy of two-step, repeated-dose ketamine augmentation and (2) to assess the duration of ketamine’s antidepressant efficacy as augmentation to ongoing antidepressant pharmacotherapy for 3 months after the final infusion. Methods: Fourteen patients with treatment-resistant depression were eligible to receive augmentation with six open-label intravenous ketamine infusions over 3 weeks. For the first three infusions, ketamine was administered at a dose of 0.5 mg/kg over 45 minutes; the dose was increased to 0.75 mg/kg over 45 minutes for the subsequent three infusions. The primary outcome measure was response (as measured on Hamilton Depression Rating Scale–28 items). Results: After the completion of three ketamine infusions, 7.1% (1/14) responded; after all six ketamine infusions, 41.7% (5/12) completers responded and 16.7% (2/12) remitted. Intent-to-treat response and remission rates at the end of the final infusion were 35.7% (5/14) and 14.3% (2/14), respectively. However, all but one responder relapsed within 2 weeks after the final infusion. Conclusion: Repeated, escalating doses of intravenous ketamine augmentation were preliminarily found to be feasible, efficacious and well tolerated. Interaction with concomitant medications and elevated level of treatment resistance are possible factors for non-response.

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 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).

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.

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