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

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.

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Faculty Opinions recommendation of Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.2203956.1814054 ◽

2010 ◽

Author(s):

Randal Dull ◽

Scott Tadler

Keyword(s):

Repeated Dose ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Safety And Efficacy ◽

Resistant Depression ◽

Intravenous Ketamine

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Faculty Opinions recommendation of Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726375864.793520560 ◽

2016 ◽

Author(s):

Rainer Spanagel

Keyword(s):

Feasibility Study ◽

Psychological Support ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Open Label ◽

Resistant Depression

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

Psychopharmacology ◽

10.1007/s00213-021-05762-6 ◽

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.

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