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

Cullen, Kathryn R.; Amatya, Palistha; Roback, Mark G.; Albott, C. Sophia; Schreiner, Melinda Westlund; Ren, Yanan; Eberly, Lynn E.; Carstedt, Patricia; Samikoglu, Ali; Gunlicks-Stoessel, Meredith; Reigstad, Kristina; Horek, Nathan; Tye, Susannah J.; Lim, Kelvin O.; Klimes‐Dougan, Bonnie

doi:10.1089/cap.2018.0030

Cited by 67 publications

(44 citation statements)

References 49 publications

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“…Thirteen adolescents with treatment-resistant depression (TRD) completed a clinical trial investigating intravenous ketamine as a treatment for adolescent depression [see ( 7 ) for clinical results and details about treatment procedures and tolerance]. This study was approved by the University of Minnesota Institutional Review Board.…”

Section: Methodsmentioning

confidence: 99%

“…Participants also completed a magnetic resonance imaging (MRI) scan at baseline. Following baseline visits, participants who met inclusion criteria received six ketamine infusions across 2 weeks (see ( 7 ) for more details about ketamine infusions and assessment schedule). Post-treatment assessments, including a post-treatment MRI scan, were completed 1 day following the last ketamine infusion.…”

Section: Methodsmentioning

confidence: 99%

“…Post-treatment assessments, including a post-treatment MRI scan, were completed 1 day following the last ketamine infusion. In contrast to our other work ( 7 ), this study is not intended to assess the impact of ketamine treatment, but rather to identify neural correlates of clinical improvement of ketamine treatment in this sample of youth with TRD.…”

Section: Methodsmentioning

confidence: 99%

“…Ketamine has utility for such research because of its known rapid and strong antidepressant effects with adults who are suffering from depression ( 3 – 6 ). In our recent pilot study testing open-label ketamine in adolescents with depression, there was significant variability in response at 2 weeks, ranging from full remission, partial response, non-response, or clinical worsening ( 7 ). Although we had expected more consistently positive outcomes, this variability provides an advantage for identifying neurobehavioral correlates of symptom improvement.…”

Section: Introductionmentioning

confidence: 99%

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Neural and Behavioral Correlates of Clinical Improvement to Ketamine in Adolescents With Treatment Resistant Depression

et al. 2020

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Treatment-resistant depression (TRD) is a serious problem in adolescents. Development and optimization of novel interventions for these youth will require a deeper knowledge of the neurobiology of depression. A well-established phenomenon of depression is an attention bias toward negativity and away from positivity that is evidenced behaviorally and neurally, but it is unclear how symptom reduction is related to changes to this bias. Neurobiological research using a treatment probe has promise to help discover the neural changes that accompany symptom improvement. Ketamine has utility for such research because of its known rapid and strong antidepressant effects in the context of TRD. Our previous study of six open-label ketamine infusions in 11 adolescents with TRD showed variable response, ranging from full remission, partial response, non-response, or clinical worsening. In this study, we examined the performance of these participants on Word Face Stroop (WFS) fMRI task where they indicated the valence of affective words superimposed onto either congruent or incongruent emotional faces before and after the ketamine infusions. Participants also completed a clinical assessment (including measurement of depression symptomology and anhedonia/pleasure) before and after the ketamine infusions. Following ketamine treatment, better WFS performance correlated with self-reported decreased depressive symptoms and increased pleasure. Analyses of corticolimbic, corticostriatal and default mode (DMN) networks showed that across networks, decreased activation during all conditions (congruent negative, congruent positive, incongruent negative, and incongruent positive) correlated with decreases in depressive symptoms and with increases in pleasure. These findings suggest that in adolescents with TRD, clinical improvement may require an attenuation of the negativity bias and re-tuning of these three critical neural networks to attenuate DMN and limbic regions activation and allow more efficient recruitment of the reward network. Lower activation across conditions may facilitate shifting across different salient emotional stimuli rather than getting trapped in downward negative spirals.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neural and Behavioral Correlates of Clinical Improvement to Ketamine in Adolescents With Treatment Resistant Depression

et al. 2020

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“…Meta-analysis of ketamine crossover trials also demonstrates significant antisuicidal properties (Wilkinson et al, 2018). Initial case reports (Dwyer et al, 2017) and a small open-label trial (Cullen et al, 2018) have suggested possible efficacy in pediatric populations, although there are currently no published randomized, controlled trials evaluating efficacy in pediatric populations. Recently, the FDA has approved esketamine (an intranasally delivered formulation of the l-enantiomer of ketamine) for the treatment of treatmentrefractory depression in adults (Singh et al, 2016) and initial studies have suggested that esketamine may also be effective acutely in reducing suicidal ideation (Canuso et al, 2018).…”

Section: Interventional Treatmentsmentioning

confidence: 99%

Annual Research Review: Defining and treating pediatric treatment‐resistant depression

Dwyer

Stringaris

Brent

et al. 2020

Child Psychology Psychiatry

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Background Adolescent major depressive disorder (MDD) is a significant health problem, associated with substantial morbidity, cost, and mortality. Depression is a significant risk factor for suicide, which is now the second leading cause of death in young people. Up to twenty per cent of adolescents will experience MDD before adulthood, and while a substantial proportion will improve with standard‐of‐care treatments (psychotherapy and medication), roughly one third will not. Methods Here, we have reviewed the literature in order to discuss the concept of treatment‐resistant depression (TRD) in adolescence, examine risk factors, diagnostic difficulties, and challenges in evaluating symptom improvement, and providing guidance on how to define adequate medication and psychotherapy treatment trials. Results We propose a staging model for adolescent TRD and review the treatment literature. The evidence base for first‐ and second‐line treatments primarily derives from four large pediatric clinical trials (TADS, TORDIA, ADAPT, and IMPACT). After two medications and a trial of evidence‐based psychotherapy have failed to alleviate depressive symptoms, the evidence becomes quite thin for subsequent treatments. Here, we review the evidence for the effectiveness of medication switches, medication augmentation, psychotherapy augmentation, and interventional treatments (i.e., transcranial magnetic stimulation, electroconvulsive therapy, and ketamine) for adolescent TRD. Comparisons are drawn to the adult TRD literature, and areas for future pediatric depression research are highlighted. Conclusions As evidence is limited for treatments in this population, a careful consideration of the known risks and side effects of escalated treatments (e.g., mood stabilizers and atypical antipsychotics) is warranted and weighed against potential, but often untested, benefits.

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Treatment Approaches with Suicidal Adolescents

Spirito¹,

Webb²,

Wolff³

et al. 2021

Suicide Risk Assessment and Prevention

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

Cited by 67 publications

References 49 publications

Neural and Behavioral Correlates of Clinical Improvement to Ketamine in Adolescents With Treatment Resistant Depression

Neural and Behavioral Correlates of Clinical Improvement to Ketamine in Adolescents With Treatment Resistant Depression

Annual Research Review: Defining and treating pediatric treatment‐resistant depression

Treatment Approaches with Suicidal Adolescents

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