Treatment-Resistant Depression in Adolescents: Clinical Features and Measurement of Treatment Resistance

Aaronson, Scott T.; Elmaadawi, Ahmed Z.; Schrodt, G. Randolph; Holbert, Richard; Verdoliva, Sarah; Heart, Karen; Demitrack, Mark A.; Croarkin, Paul E.

doi:10.1089/cap.2020.0008

Cited by 13 publications

(11 citation statements)

References 24 publications

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“…A subsample of adolescents with TRD were treated with active (n = 18, age range 12–19 years) or sham (n = 7, age range 16–19 years) left prefrontal, high-frequency TMS as monotherapy ( Strawn et al, 2020 ; Croarkin et al, 2021 ). Adolescents were evaluated and monitored by child and adolescent psychiatrists for the duration of the study.…”

Section: Methodsmentioning

confidence: 99%

“…Often, the definition diverges from how TRD is characterized in adults, and this presents additional challenges in designing and interpreting studies in adolescents ( Dwyer et al, 2020 ; Strawn and Croarkin, 2020 ). For example, few clinical trials have focused on adolescents with TRD, and the neurobiological characteristics of TRD in adolescents have not been adequately characterized ( Brent et al, 2008 ; Strawn et al, 2020 ). Transcranial magnetic stimulation (TMS) is an emerging treatment for adolescents with TRD ( Croarkin et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Neurostructural Differences in Adolescents With Treatment-Resistant Depression and Treatment Effects of Transcranial Magnetic Stimulation

Seewoo

Rodger

Demitrack

et al. 2022

International Journal of Neuropsychopharmacology

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Background Despite its morbidity and mortality, the neurobiology of treatment resistant depression (TRD) in adolescents and the impact of treatment on this neurobiology is poorly understood. Methods Using automatic segmentation in FreeSurfer, we examined brain magnetic resonance imaging (MRI) baseline volumetric differences among healthy adolescents (n=30), adolescents with major depressive disorder (MDD) (n=19), and adolescents with TRD (n=34) based on objective antidepressant treatment rating criteria. A pooled subsample of adolescents with TRD were treated with six weeks of active (n=18) or sham (n=7) 10 Hz transcranial magnetic stimulation (TMS) applied to the left dorsolateral prefrontal cortex (L-DLPFC). Ten of the adolescents treated with active TMS were part of an open-label trial. The other adolescents treated with active (n=8) or sham (n=7) were participants from a randomized controlled trial. Results Adolescents with TRD and adolescents with MDD had decreased total amygdala (TRD and MDD: -5%, p=0.032), and caudal anterior cingulate cortex volumes (TRD: -3%, p=0.030; MDD: -0.03%, p=0.041) compared to healthy adolescents. Six weeks of active TMS increased total amygdala volumes (+4%, p<0.001) and the volume of the stimulated L-DLPFC (+0.4%, p=0.026) in adolescents with TRD. Conclusions Amygdala volumes were reduced in this sample of adolescents with MDD and TRD. TMS may normalize this volumetric finding raising the possibility that TMS has neurostructural frontolimbic effects in adolescents with TRD. TMS also appears to have positive effects proximal to the site of stimulation.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neurostructural Differences in Adolescents With Treatment-Resistant Depression and Treatment Effects of Transcranial Magnetic Stimulation

Seewoo

Rodger

Demitrack

et al. 2022

International Journal of Neuropsychopharmacology

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“…Adolescence is a critical period for the development of depression, and the worldwide prevalence of any depressive disorder in this age group is 2.6% ( 24 ). However, around 40% of adolescents with depression do not respond to current psychotherapy or pharmacotherapy interventions and more innovative treatments are needed ( 103 ).…”

Section: Potential Tavns Effects On Clinical Symptomsmentioning

confidence: 99%

Therapeutic applications of transcutaneous auricular vagus nerve stimulation with potential for application in neurodevelopmental or other pediatric disorders

Zhu

Zhang²,

Zhou³

et al. 2022

Front. Endocrinol.

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Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) as a newly developed technique involves stimulating the cutaneous receptive field formed by the auricular branch of the vagus nerve in the outer ear, with resulting activation of vagal connections to central and peripheral nervous systems. Increasing evidence indicates that maladaptive neural plasticity may underlie the pathology of several pediatric neurodevelopmental and psychiatric disorders, such as autism spectrum disorder, attention deficit hyperactivity disorder, disruptive behavioral disorder and stress-related disorder. Vagal stimulation may therefore provide a useful intervention for treating maladaptive neural plasticity. In the current review we summarize the current literature primarily on therapeutic use in adults and discuss the prospects of applying taVNS as a therapeutic intervention in specific pediatric neurodevelopmental and other psychiatric disorders. Furthermore, we also briefly discuss factors that would help optimize taVNS protocols in future clinical applications. We conclude from these initial findings that taVNS may be a promising alternative treatment for pediatric disorders which do not respond to other interventions.

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“…Moreover, the initial SSRI dose is often based on the dosages used in clinical trials and the clinician's comfort with titration. The dose a clinician targets for an individual patient is frequently the mean dose used in clinical trials and the adequacy of antidepressant treatment trials for individual patients is based on target doses (Brent et al, 2008;Strawn et al, 2020a), which fail to account for adherence and variation in drug exposure.…”

Section: Introductionmentioning

confidence: 99%

Pediatric Therapeutic Drug Monitoring for Selective Serotonin Reuptake Inhibitors

2021

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Therapeutic drug monitoring (TDM) is uncommon in child and adolescent psychiatry, particularly for selective serotonin reuptake inhibitors (SSRIs)—the first-line pharmacologic treatments for depressive and anxiety disorders. However, TDM in children and adolescents offers the opportunity to leverage individual variability of antidepressant pharmacokinetics to shed light on non-response and partial response, understand drug-drug interactions, evaluate adherence, and characterize the impact of genetic and developmental variation in pharmacokinetic genes. This perspective aims to educate clinicians about TDM principles and examines evolving uses of TDM in SSRI-treated youths and their early applications in clinical practice, as well as barriers to TDM in pediatric patients. First, the impact of pharmacokinetic genes on SSRI pharmacokinetics in youths could be used to predict tolerability and response for some SSRIs (e.g., escitalopram). Second, plasma concentrations are significantly influenced by adherence, which may relate to decreased efficacy. Third, pharmacometric analyses reveal interactions with proton pump inhibitors, oral contraceptives, cannabinoids, and SSRIs in youths. Rapid developments in TDM and associated modeling have enhanced the understanding of variation in SSRI pharmacokinetics, although the treatment of anxiety and depressive disorders with SSRIs in youths often remains a trial-and-error process.

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Treatment-Resistant Depression in Adolescents: Clinical Features and Measurement of Treatment Resistance

Cited by 13 publications

References 24 publications

Neurostructural Differences in Adolescents With Treatment-Resistant Depression and Treatment Effects of Transcranial Magnetic Stimulation

Neurostructural Differences in Adolescents With Treatment-Resistant Depression and Treatment Effects of Transcranial Magnetic Stimulation

Therapeutic applications of transcutaneous auricular vagus nerve stimulation with potential for application in neurodevelopmental or other pediatric disorders

Pediatric Therapeutic Drug Monitoring for Selective Serotonin Reuptake Inhibitors

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