scholarly journals Antianhedonic Effect of Repeated Ketamine Infusions in Patients With Treatment Resistant Depression

2021 ◽  
Vol 12 ◽  
Author(s):  
Alina Wilkowska ◽  
Mariusz Stanisław Wiglusz ◽  
Maria Gałuszko-Wegielnik ◽  
Adam Włodarczyk ◽  
Wiesław Jerzy Cubała
Keyword(s):  
Depressive Symptoms ◽  
Depressive Episode ◽  
Controlled Trial ◽  
Self Report ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Antidepressive Effect ◽  
Resistant Depression ◽  
Depression Symptomatology

Anhedonia constitutes one of the main symptoms of depressive episode. It correlates with suicidality and significantly effects the quality of patient's lives. Available treatments are not sufficient against this group of symptoms. Ketamine is a novel, rapid acting strategy for treatment resistant depression. Here we report the change in symptoms of anhedonia measured by Snaith-Hamilton Pleasure Scale as an effect of eight ketamine infusions as an add-on treatment in 42 patients with treatment resistant depression. We also determined the effect of this change on the severity of depressive symptoms measured by Inventory for Depression Symptomatology-Self Report 30-Item (IDS-SR 30). We have observed statistically significant decrease in the level of anhedonia during ketamine treatment. After adjusting for potential confounders we have found that significant reduction in Snaith-Hamilton Pleasure Scale (SHAPS) after each infusion and 1 week post treatment was observed only among patients who did not use benzodiazepines. The reduction in symptoms of anhedonia mediates the antidepressive effect of ketamine. The results need replication in a larger randomized placebo controlled trial.

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.

Factors associated with response after deep transcranial magnetic stimulation in a real-world clinical setting: Results from the first 40 cases of treatment-resistant depression

2017 ◽  
Vol 44 ◽  
pp. 61-67 ◽  
Author(s):  
K. Feffer ◽  
K.A.B. Lapidus ◽  
Y. Braw ◽  
Y. Bloch ◽  
S. Kron ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Transcranial Magnetic Stimulation ◽  
Clinical Global Impression ◽  
Real World ◽  
Depressive Episode ◽  
Magnetic Stimulation ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression ◽  
T1 And T2

AbstractBackground:Deep transcranial magnetic stimulation (dTMS) has been sanctioned by the United States Food and Drug Administration for treatment-resistant depression. In a retrospective cohort study, we evaluated response and effectiveness of dTMS in real-world practice, as an add-on treatment for resistant depression.Methods:Forty adult outpatients suffering from depression, all taking psychiatric medications, underwent 20 dTMS treatments over a 4–6 week period. At baseline (T0), visit 10 (T1), and visit 20 (T2), the Clinical Global Impression-Severity (CGI-S) scale was administered, and the Clinical Global Impression Improvement (CGI-I) scale was completed at T1 and T2; the Hamilton Depression Rating Scale (HDRS-21) was administrated at T0 and T2 only. The patients also completed the Quick Inventory of Depressive Symptoms–Self-Report (QIDS-SR) at T0, T1, and T2.Results:Depressive symptoms (HDRS-21 total score) decreased significantly following treatment. The HDRS total score decreased from an average of 21.22 (± 6.09) at T0, to 13.95 (± 7.24) at T2. Correspondingly, at T2, 32.5% were responders to the treatment and 20% were in remission, based on the HDRS-21. Treatment was well tolerated, with a discontinuation rate of 7.5%. While depressive symptoms at baseline did not predict remission/response at T2, higher HDRS scores at T0 were associated with a larger decrease in depressive symptoms during the study.Conclusions:Significant antidepressant effects were seen following 20 dTMS treatments, given as augmentation to ongoing medications in treatment-resistant depression. The findings suggest that among patients with TRD, the severity of the depressive episode (and not necessarily the number of failed antidepressant medication trials) is associated with a positive therapeutic effect of dTMS. Hence, the initial severity of the depressive episode may guide clinicians in referring patients for dTMS.

scholarly journals Clinical Features and Outcomes of 124 Italian Patients With Treatment Resistant Depression: A Real-World, Prospective Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Giulio Perugi ◽  
Paola Calò ◽  
Sergio De Filippis ◽  
Gianluca Rosso ◽  
Antonio Vita ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Real World ◽  
Depressive Episode ◽  
Major Depressive Episode ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Major Depressive ◽  
The Mean ◽  
Resistant Depression

Introduction: Treatment-resistant depression (TRD) is a debilitating condition affecting 20–30% of patients with major depressive disorders (MDD). Currently, there is no established standard of care for TRD, and wide variation in the clinical approach for disease management has been documented. Real-world data could help describe TRD clinical features, disease burden, and treatment outcome and identify a potential unmet medical need.Methods: We analyzed the Italian data from a European, prospective, multicentric, observational cohort study of patients fulfilling TRD criteria by the European Medicine Agency, with moderate to severe major depressive episode, and starting a new antidepressant treatment according to routinary clinical practice. They were followed up for minimum 6 months. Treatments received throughout the study period, disease severity, health-related quality of life and functioning were prospectively recorded and analyzed.Results: The Italian subcohort included 124 TRD patients (30.2% of patients of the European cohort; mean age 53.2 [sd = 9.8], women: 82, 66.1%). At enrollement, the mean (SD) duration of MDD was 16 years (sd = 11.1) and the mean duration of the ongoing major depressive episode (MDE) was 97.5 weeks (sd = 143.5); low scores of quality of life and functioning were reported. The most frequently antidepressant classes started at baseline (data available for 98 subjects) were selective serotonin reuptake inhibitors (SSRI, 42 patients [42.9%]) and serotonin-norepinephrine reuptake inhibitors (SNRI, 32 patients [32.7%]). In terms of treatment strategies, 50 patients (51%) started augmentation therapies, 18 (18.4%) combination therapies and 24 (24.5%) monoterapies (6 patients [6%] started a non-antidepressant drug only). Fourteen patients (11.3%) were treated with a psychosocial approach, including psychotherapy. After 6 months of treatment, clinical assessments were collected for 89 patients: 64 (71.9%) showed no response, 9 (10.1%) response without remission and 16 (18.0%) were in remission; non-responder patients showed lower quality of life and higher disability scores than responder patients.Conclusions: In our sample of TRD patients, we documented substantial illness burden, low perceived quality of life and poor outcome, suggesting an unmet treatment need in TRD care in Italy.Registration Number:ClinicalTrials.gov, number: NCT03373253.

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 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).

Efficacy of Intravenous Ketamine in Adolescent Treatment-Resistant Depression: A Randomized Midazolam-Controlled Trial

2021 ◽  
pp. appi.ajp.2020.2
Author(s):  
Jennifer B. Dwyer ◽  
Angeli Landeros-Weisenberger ◽  
Jessica A. Johnson ◽  
Amalia Londono Tobon ◽  
José M. Flores ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Adolescent Treatment ◽  
Resistant Depression ◽  
Intravenous Ketamine

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 Pharmacological Augmentation in Unipolar Depression: A Guide to the Guidelines

2020 ◽  
Vol 23 (9) ◽  
pp. 587-625 ◽  
Author(s):  
Rachael W Taylor ◽  
Lindsey Marwood ◽  
Emanuella Oprea ◽  
Valeria DeAngel ◽  
Sarah Mather ◽  
...  
Keyword(s):  
Treatment Guidelines ◽  
Evidence Based ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Comprehensive Overview ◽  
Objective Evidence ◽  
Resistant Depression ◽  
Evidence Based Care ◽  
Guidelines For Depression

Abstract Background Pharmacological augmentation is a recommended strategy for patients with treatment-resistant depression. A range of guidelines provide advice on treatment selection, prescription, monitoring and discontinuation, but variation in the content and quality of guidelines may limit the provision of objective, evidence-based care. This is of importance given the side effect burden and poorer long-term outcomes associated with polypharmacy and treatment-resistant depression. This review provides a definitive overview of pharmacological augmentation recommendations by assessing the quality of guidelines for depression and comparing the recommendations made. Methods A systematic literature search identified current treatment guidelines for depression published in English. Guidelines were quality assessed using the Appraisal of Guidelines for Research and Evaluation II tool. Data relating to the prescription of pharmacological augmenters were extracted from those developed with sufficient rigor, and the included recommendations compared. Results Total of 1696 records were identified, 19 guidelines were assessed for quality, and 10 were included. Guidelines differed in their quality, the stage at which augmentation was recommended, the agents included, and the evidence base cited. Lithium and atypical antipsychotics were recommended by all 10, though the specific advice was not consistent. Of the 15 augmenters identified, no others were universally recommended. Conclusions This review provides a comprehensive overview of current pharmacological augmentation recommendations for major depression and will support clinicians in selecting appropriate treatment guidance. Although some variation can be accounted for by date of guideline publication, and limited evidence from clinical trials, there is a clear need for greater consistency across guidelines to ensure patients receive consistent evidence-based care.

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