Ketamine in Adolescents With Treatment-Resistant Depression
Open-Label Intravenous Subanesthetic Ketamine for Adolescents With Treatment-Resistant Depression
調査の概要
詳細な説明
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.
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
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Minnesota
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Minneapolis、Minnesota、アメリカ、55454
- University of Minnesota
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：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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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Number of Responders Measured by Clinical Global Impression (CGI)
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Children's Depression Rating Scale-Revised
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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
時間枠：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
時間枠：baseline, 45 minutes post infusion
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baseline, 45 minutes post infusion
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Maximum Change in Heart Rate
時間枠：4 hours
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4 hours
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|
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Maximum Decrease in Pulse Oximetry
時間枠：4 hours
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4 hours
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協力者と研究者
スポンサー
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- 22225
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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