Rapid effectiveness of intravenous ketamine for ultraresistant depression in a clinical setting and evidence for baseline anhedonia and bipolarity as clinical predictors of effectiveness

2018 ◽  
Vol 32 (10) ◽  
pp. 1110-1117 ◽  
Author(s):  
Rejish K Thomas ◽  
Glen Baker ◽  
John Lind ◽  
Serdar Dursun
Keyword(s):  
Clinical Setting ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Remission Rate ◽  
Treatment Resistance ◽  
Beck Depression Inventory Score ◽  
Treatment Resistant ◽  
Clinical Predictors ◽  
Open Label ◽  
Intravenous Ketamine

Background: Intravenous ketamine has been established as an efficacious and safe treatment, with transient effect, for treatment-resistant depression. However, the effectiveness of intravenous ketamine in non-research settings and with ultraresistant depression patients remains understudied. Aims: This study aims to measure the response and remission rates in ultraresistant depression patients in a clinical setting by means of a retrospective, open label, database study. Secondarily, the study will attempt to support previous findings of clinical predictors of effectiveness with intravenous ketamine treatment. Methods: Fifty patients with ultraresistant depression were treated between May 2015–December 2016, inclusive, in two community hospitals in Edmonton using six ketamine infusions of 0.5 mg/kg over 40 min over 2–3 weeks. Data were collected retrospectively from inpatient and outpatient charts. Statistical analysis to investigate clinical predictors of effectiveness included logistic regression analysis using a dependent variable of a 50% reduction in rating scale score at any point during treatment. Results: At baseline, the average treatment resistance was severe, with a Maudsley Staging Method score of 12.1 out of 15, 90.0% were resistant to electroconvulsive therapy, and the average Beck Depression Inventory score was 34.2. The response rate was 44% and remission rate was 16%. As a single predictor, moderate or severe anhedonia at baseline predicted a 55% increased likelihood of response. As a combined predictor, this level of anhedonia at baseline with a diagnosis of bipolar depression predicted a 73% increase in likelihood of response. Conclusion: In a clinical setting, intravenous ketamine showed effectiveness in a complex, severely treatment-resistant, depressed population on multiple medication profiles concurrently. This study gave support to anhedonia and bipolar depression as clinical predictors of effectiveness.

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 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).

scholarly journals Intravenous Ketamine Infusions in Treatment-Resistant Bipolar Depression: An Open-Label Naturalistic Observational Study

2021 ◽  
Vol Volume 17 ◽  
pp. 2637-2646
Author(s):  
Alina Wilkowska ◽  
Adam Włodarczyk ◽  
Maria Gałuszko-Węgielnik ◽  
Mariusz S Wiglusz ◽  
Wiesław J Cubała
Keyword(s):  
Observational Study ◽  
Bipolar Depression ◽  
Treatment Resistant ◽  
Open Label ◽  
Intravenous Ketamine

scholarly journals A randomized placebo-controlled trial on the antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression

2017 ◽  
Author(s):  
Fernanda Palhano-Fontes ◽  
Dayanna Barreto ◽  
Heloisa Onias ◽  
Katia C Andrade ◽  
Morgana Novaes ◽  
...  
Keyword(s):  
Rating Scale ◽  
Remission Rate ◽  
Controlled Trial ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Open Label ◽  
Double Blind ◽  
Therapeutic Value ◽  
Antidepressant Effects ◽  
Resistant Depression

AbstractRecent open label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression. In order to further 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. Changes in depression severity were assessed with the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale (HAM-D). Assessments were made at baseline, and at one (D1), two (D2) and seven (D7) days after dosing. We observed significant antidepressant effects of ayahuasca when compared to placebo at all timepoints. MADRS scores were significantly lower in the ayahuasca group compared to 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’ s d=0.84; D2: Cohen’ s d=0.84; D7: Cohen’ s d=1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% vs. 27%; p=0.04), while remission rate was marginally significant at D7 (36% vs. 7%, p=0.054). To 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.

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.

scholarly journals Intravenous Ketamine for Adolescents with Treatment-Resistant Depression: An Open-Label Study

2018 ◽  
Vol 28 (7) ◽  
pp. 437-444 ◽  
Author(s):  
Kathryn R. Cullen ◽  
Palistha Amatya ◽  
Mark G. Roback ◽  
Christina Sophia Albott ◽  
Melinda Westlund Schreiner ◽  
...  
Keyword(s):  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Resistant Depression ◽  
Intravenous Ketamine

scholarly journals Rosiglitazone Add-On in Treatment of Depressed Patients with Insulin Resistance: a Pilot Study

2010 ◽  
Vol 10 ◽  
pp. 321-328 ◽  
Author(s):  
Natalie L. Rasgon ◽  
Heather A. Kenna ◽  
Katherine E. Williams ◽  
Bevin Powers ◽  
Tonita Wroolie ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Pilot Study ◽  
Depressive Disorders ◽  
Rating Scale ◽  
Bipolar Depression ◽  
Depression Severity ◽  
Open Label ◽  
Modest Improvement ◽  
Severity Scores ◽  
Matsuda Index

A number of cross-sectional studies have suggested an association between insulin resistance (IR) and affective disorders. However, limited data exist on potential changes in IR in a prospective treatment of depression. The present pilot study tested the hypothesis that improvement of IR with the addition of an insulin-sensitizing agent would improve mood in nondiabetic patients with unipolar or bipolar depression, who had surrogate blood markers suggestive of IR. Surrogate IR-criteria blood markers were fasting plasma glucose >100 mg/dl or triglyceride (TG) to high density lipoprotein (HDL) ratio >3.0. Open-label rosiglitazone, titrated to a dose of 8 mg/day, was administered for 12 weeks to 12 patients with depressive disorder receiving treatment as usual (TAU). Eight patients who completed the 12-week study exhibited significant declines in both depression severity by the Hamilton Depression Rating Scale and the Clinical Global Impression scale, with moderate effect sizes noted. Modest improvement in Matsuda Index scores was also noted at 12 weeks, yet declines in depression severity scores were not associated with improvements in the endocrine markers (Matsuda Index, TG/HDL ratio, and body mass index). These results suggest the potential novel use for an insulin-sensitizing agent in the treatment of depressive disorders. Larger placebo-controlled studies are warranted.

scholarly journals Equivalent beneficial effects of unilateral and bilateral prefrontal cortex transcranial magnetic stimulation in a large randomized trial in treatment-resistant major depression

2013 ◽  
Vol 16 (9) ◽  
pp. 1975-1984 ◽  
Author(s):  
Paul B. Fitzgerald ◽  
Kate E. Hoy ◽  
Ajeet Singh ◽  
Ranil Gunewardene ◽  
Christopher Slack ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Clinical Response ◽  
Magnetic Stimulation ◽  
Rating Scale ◽  
Remission Rate ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Controlled Trial ◽  
Treatment Resistant ◽  
Previous Response ◽  
Beneficial Effects

Abstract Repetitive transcranial magnetic stimulation treatment (rTMS) is an effective treatment for depression but the optimal methods of administration have yet to be determined. Recent studies have produced conflicting results as to whether unilateral rTMS is more or less effective than sequentially applied bilateral rTMS. To address this we conducted a trial comparing sequential bilateral rTMS to right-sided unilateral rTMS using a priming protocol. Patients with treatment-resistant depression (n = 179) were enrolled in a two-arm randomized controlled trial across a 4-wk time period. The primary outcome assessment was the Hamilton Depression Rating Scale. Overall, there was a substantial response rate of >50% (and a 40% remission rate); however, there were no significant differences in clinical response between the two treatment groups. rTMS was well tolerated with a very low discontinuation rate. There was no relationship between response in the current trial and previous response, or non-response, to electroconvulsive therapy. We found no significant differences in clinical response between sequential bilateral rTMS and right-sided unilateral rTMS applied with a priming protocol. The results of this study do not support superior efficacy of bilateral rTMS and instead suggest that other approaches should be explored to increase treatment efficacy.

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