Ketamine in Adolescents With Treatment-Resistant Depression
Open-Label Intravenous Subanesthetic Ketamine for Adolescents With Treatment-Resistant Depression
Přehled studie
Detailní popis
Depression frequently emerges during adolescence and is associated with severe outcomes. Current interventions do not lead to remission for many adolescents. Treatment-resistant depression (TRD) in adolescence is an ominous prognostic indicator for a lifetime of suffering and increased risk for suicide. Efforts should be directed toward novel interventions that could alter this perilous course. Theoretically, restoration of healthy development during this critical window would substantially improve outcomes over the lifespan.
Ketamine is a noncompetitive, high-affinity antagonist of the N-methyl-D-aspartate type glutamate receptor that has long been used for induction and maintenance of anesthesia in children and adults, and recently has been investigated for its rapid antidepressant effects. Randomized, double-blind, saline-controlled trials in adults with TRD have demonstrated that a single, subanesthetic infusion of intravenous (IV) ketamine at 0.5 mg/kg over 40 minutes can produce a rapid (within 2 hours) antidepressant response (Ibrahim et al., 2011; Zarate et al., 2006). Recent evidence suggests that serial doses of ketamine may be even more effective and may lead to more prolonged remission (aan het Rot et al., 2010; Murrough et al., 2012). Our current research at using serial dosing of IV ketamine among adult veterans with TRD over a 2-week period has shown promising results, with a response rate of 92% among the 12 participants to date.
No results from any studies examining effectiveness of either single-dose or serial-dose ketamine have yet been published in adolescents with TRD. Because of the ongoing neurodevelopment in adolescence, which is thought to confer enhanced neuroplasticity, it is possible that adolescents with TRD could show greater responses and more sustained remission than adults with TRD. The biological mechanisms of depression impacted by ketamine are only now being uncovered in adults (Zarate et al., 2013). Characterization of the neural mechanisms underlying ketamine response or non-response in adolescents with TRD will represent a significant advance. The specific aims of this preliminary study are as follows:
Aim #1: To determine the efficacy of repeated-dose subanesthetic IV ketamine among adolescent patients with TRD.
Hypothesis: Based on previous results in adults with TRD, we predict that response rates will improve over the course of six treatments of ketamine.
Aim #2: To explore durability of antidepressant response to repeated dose of IV ketamine in a 4-week observational period.
Hypothesis: Based on the inherent neuroplasticity in adolescence due to ongoing neurodevelopment, adolescents may show a more durable clinical response than has been seen in adults.
Aim #3: To study the neurobiological mechanisms of response to ketamine. We will examine relevant biological systems using several different brain imaging indices and measures of intracellular functioning from peripheral blood.
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 2
Kontakty a umístění
Studijní místa
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Minnesota
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Minneapolis, Minnesota, Spojené státy, 55454
- University of Minnesota
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- Male and female adolescents aged 12 to 18 years.
- Presence of recurrent major depression without psychotic features confirmed by the Kiddie-Schedule for Affective Disorders and Schizophrenia - Parent and Lifetime Version (Kaufman et al., 1997).
- Current depression severity measured by the Children's Depression Rating Scale (CDRS) (Poznanski, 1985) raw score greater than or equal to 36 at screening and the day ketamine is due to be received for the first time.
- Current depressive episode resistant to treatment, defined as failure to achieve remission (elimination of symptoms and restoration of pre-morbid psychosocial functioning) from at least 2 antidepressant trials of different pharmacological classes. Systematic evaluation of previous antidepressant trials will be assessed by using the Antidepressant Treatment History Form (Sackeim, 2001).
- If present, current antidepressant medication treatment must be dose stable for at least 2 months prior to beginning the study. (Patients will continue with current antidepressant treatment throughout the study. Based on our experience in current research at the VA Medical Center using serial ketamine for adult TRD, patients have shown positive results while continuing their current antidepressant treatment.)
Exclusion Criteria:
- Inability to speak English
- Inability or unwillingness to provide written informed consent
- A history of Mental Retardation or any Pervasive Developmental Disorder
- Current or lifetime diagnosis of schizophrenia, schizoaffective disorder, or psychosis Not Otherwise Specified.
- Family history with a first degree relative with schizophrenia, schizoaffective disorder, or psychosis Not Otherwise Specified.
- Diagnosis of seizures or other neurological disorders.
- Comorbid diagnosis of substance abuse or dependence, current or past.
- Clinically unstable medical illness.
- Current use of the following medications: any barbiturates, any narcotics, any non-benzodiazepine hypnotics at doses higher than zolpidem 10 mg qhs or equivalent for insomnia.
- For women: pregnancy (confirmed by baseline lab test).
- The presence of any MRI contra-indications such as MRI-incompatible metals in the body or claustrophobia.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: ketamine
Intravenous ketamine 0.5 mg/kg over 40 minutes will be given 6 times over 2 weeks.
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IV infusions of 0.5mg/kg of Ketamine hydrochloride over a 40-minute infusion period.
Participants will receive a total of 6 doses over a 2-week period.
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Number of Responders Measured by Clinical Global Impression (CGI)
Časové okno: 2 weeks
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Responders will be defined as those with CGI ratings (given by the study clinician) of 1 or 2 (much or very much improved).
Patients that are given a scores of 3-7 (minimally improved to very much worse) will be considered non-responders.
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2 weeks
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Children's Depression Rating Scale-Revised
Časové okno: 2 weeks
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The CDRS-R measure is given in interview form to child and parent separately.
A consensus is then created with best-estimate for 17 items (each with a range of 1-5 or 1-7) using both sources of information.
The total score is the sum of 17 item scores, ranging from 17-113 with higher scores indicating greater depression symptoms.
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2 weeks
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Montgomery-Åsberg Depression Rating Scale (MADRS)
Časové okno: 2 weeks
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MADRS is a 10-item clinician-administered inventory measuring depression symptoms.
Items are scored on a scare from 0 (none) to 6 (constant).
Total scores are a sum of the 10 item scores, ranging from 0 to 60, with higher scores indicating greater symptom severity.
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2 weeks
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Beck Depression Inventory-II (BDI-II)
Časové okno: 2 weeks
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BDI-II is a 21-item self-report multiple-choice inventory that assesses the severity of depressive symptoms over the prior week.
Items are rated on a 4-point scale ranging from 0 to 3. Total scores are a sum of the 21 item scores ranging from 0 to 63.
Higher scores indicate more severe depression symptoms.
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2 weeks
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Change in Clinician Administered Dissociative States Scale (CADSS)
Časové okno: baseline, 2 weeks
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CADSS is a 27-item instrument measuring symptoms of dissociative stress, with 19 items completed by the patient and 8 items completed by the clinician.
Items are rated on a scale of 0 (not at all) to 4 (extreme).
Total scores are a sum of the 27 item scores and range from 0 to 108, with higher scores indicating greater symptom severity.
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baseline, 2 weeks
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Maximum Change in Systolic Blood Pressure
Časové okno: 2 hours and 40 minutes
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Vital signs were measured every 15 minutes, starting from the beginning of the infusion and ending 2 hours after the infusion ended (2 hours, 40 minutes total).
Maximum increase of blood pressure compared to baseline was calculated.
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2 hours and 40 minutes
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Maximum Change in Diastolic Blood Pressure
Časové okno: baseline, 45 minutes post infusion
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baseline, 45 minutes post infusion
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Maximum Change in Heart Rate
Časové okno: 4 hours
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4 hours
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Maximum Decrease in Pulse Oximetry
Časové okno: 4 hours
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4 hours
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Spolupracovníci a vyšetřovatelé
Sponzor
Publikace a užitečné odkazy
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia
Primární dokončení (Aktuální)
Dokončení studie (Aktuální)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Odhad)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Duševní poruchy
- Poruchy nálady
- Deprese
- Depresivní porucha, major
- Depresivní porucha, odolnost vůči léčbě
- Fyziologické účinky léků
- Neurotransmiterové látky
- Molekulární mechanismy farmakologického působení
- Depresiva centrálního nervového systému
- Agenti periferního nervového systému
- Analgetika
- Agenti smyslového systému
- Anestetika, disociační
- Anestetika, nitrožilní
- Anestetika, generále
- Anestetika
- Antagonisté excitačních aminokyselin
- Excitační aminokyselinové látky
- Ketamin
Další identifikační čísla studie
- 22225
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