N-methyl-D-aspartate Antagonist (Ketamine) Augmentation of Electroconvulsive Treatment for Severe Major Depression
Electroconvulsive therapy (ECT), is considered the most effective treatment for severe treatment resistant major depressive disorder (MDD), but it requires about 3 weeks of treatments and can cause considerable acute deficits in memory. It would be a major advance in treatment if ECT could work faster with fewer treatments and result in decrease incidence of memory problems. Ketamine is an excellent candidate for augmentation of ECT because of its acute effects on depression, its short half-life, and its safety profile when given at low doses. Ketamine is given as an infusion and could easily be incorporated into the routine management of patients undergoing ECT, but has never been evaluated prospectively in this context.
The investigators propose to assess the efficacy, feasibility, tolerability and safety of N-methyl-D-aspartate antagonist augmentation of ECT using ketamine.
Přehled studie
Postavení
Podmínky
Intervence / Léčba
Detailní popis
Aim #1: To assess the efficacy of ketamine augmentation in reducing time to remission of a major depressive episode (MDE).
Aim #2: To assess the efficacy of ketamine augmentation on ECT-related cognitive side effects.
Aim #3: To assess the feasibility, safety, and tolerability of ketamine augmentation of ECT.
Exploratory aim #4: We propose to assess the patterns of functional connectivity before, during and after ECT using standard clinical EEG to better characterize the effect of ECT and to correlate clinical effects with changes in EEG measurements.
Thirty (30) participants will be recruited over 24 months. Participants will be males and females, ages 18-60, with severe MDD (baseline score HAM_D-28 >= 20) deemed appropriate for ECT treatment by their treating physician, agreeing to receive ECT treatment as part of their clinical care, and able to provide informed consent.
Exclusion criteria are any other DSM-IV primary diagnoses including major depressive disorder with psychotic features, bipolar disorder, schizoaffective disorder, schizophrenia, dementia, any history of psychosis, substance use disorder (abuse or dependence with active use within the last 6 months), and any lifetime history of ketamine abuse or dependence, organic mental disorders, seizure disorder or chronic antiepileptic medications, severe or unstable medical illness, pregnancy.
Study procedures: eligible patients will be randomized to a double-blind administration of ketamine (0.5 mg/kg) or saline before the first three ECT treatments. Right Unilateral ECT (RUL-ECT) will be administered at 6 times the seizure threshold, using the d'Elia placement of the electrodes. Electroconvulsive therapy will be given 3 times per week, as per standard of care at MGH. Depression severity will be assessed weekly with the HAM-D 28 (the main outcome measure), administered by a clinician blinded to randomization.
The neuropsychological assessment battery is designed to include instruments sensitive to the cognitive impairment associated with depression in general and ECT treatment in particular will be repeated at baseline, at the end of acute treatment series and at 3 months follow-up.
Also patients will undergo repeated EEG monitoring, at baseline after one week of treatment and at follow up with the aim of possibly identifying EEG features associated with response.
Typ studie
Zápis (Aktuální)
Fáze
- Fáze 4
Kontakty a umístění
Studijní místa
-
-
Massachusetts
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Boston, Massachusetts, Spojené státy, 02114
- Massachusetts General Hospital
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-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- males and females between the ages of 18-65,
- DSM-IV diagnosis of Major Depressive Disorder (MDD), without psychotic features
- HAM-D-28 score of 20 or higher
- requiring ECT treatment as part of their psychiatric care Comorbid anxiety disorders (OCD, Generalized anxiety, panic disorder) will be allowed as long as the clinician administering the SCID believes that they are not the primary diagnosis.
Exclusion Criteria:
- MDD with a score of <20 on the HAM-D 28,
- Other DSM-IV primary diagnoses including major depressive disorder with psychotic features, bipolar disorder, schizoaffective disorder, schizophrenia, dementia
- any history of psychosis
- substance use disorder (abuse or dependence with active use within the last 6 months), and any lifetime history of ketamine abuse or dependence;
- organic mental disorders;
- seizure disorder or chronic antiepileptic medications;
- severe or unstable medical illness, including history of closed head injury resulting in loss of consciousness, medical contraindication to anesthesia or to ECT (i.e. recent myocardial infarction, increased intracranial pressure)
- current treatment with memantine
- pregnancy, or females of reproductive age who are not using an accepted method of contraception (birth control pill, IUD, combination of barrier methods).
- known hypersensitivity to ketamine
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Dvojnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: ketamine
ketamine (0.5 mg/kg) followed by anesthetic agent titrated to sedation and succinylcholine titrated to muscle relaxation Right unilateral ECT at 5-6x seizure threshold three times a week
|
eligible patients will be randomly assigned to a double-blind administration of ketamine (0.5 mg/kg) or IV Saline, followed by the routine anesthetic agent and muscle relaxant.
ECT will be administered as per standard of care
ECT will be administered as per standard of care
All participant will receive routine course of muscle relaxant with ECT as per standard of care
All participant will receive routine course of anesthetic agents with ECT as per standard of care
|
|
Komparátor placeba: placebo
IV saline, followed by anesthestic agent titrated to sedation and succinylcholine titrated to muscle relaxation. Right unilateral ECT at 5-6x seizure threshold three times a week |
ECT will be administered as per standard of care
All participant will receive routine course of muscle relaxant with ECT as per standard of care
All participant will receive routine course of anesthetic agents with ECT as per standard of care
eligible patients will be randomly assigned to a double-blind administration of ketamine (0.5 mg/kg) or IV Saline, followed by the routine anesthetic agent and muscle relaxant.
ECT will be administered as per standard of care
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Change in Hamilton Depression Rating Scale - 28
Časové okno: baseline, one month
|
HAMD will be administered at every ECT treatment.The HAM D 28 is a 28 item scale with scores ranging from 0 to 83, with 0 being no depression and 83 being high levels of depression symptoms. The change in HAM S score was determined by the difference of the HAM D score at the last ECT administration and the baseline HAM D score. A negative change score reflects a decreased HAM D score between the first and last ECT administration and therefore a reduction in depressive symptoms. |
baseline, one month
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Number of Participants With Cognitive Side Effects
Časové okno: 3 months
|
will compare the incidence of participants with memory deficits between groups, as determined by incidents of clinician reported cognitive adverse events
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3 months
|
Spolupracovníci a vyšetřovatelé
Sponzor
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
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
- Symptomy chování
- Duševní poruchy
- Poruchy nálady
- Deprese
- Deprese
- Depresivní porucha, major
- 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
- Antagonisté excitačních aminokyselin
- Excitační aminokyselinové látky
- Ketamin
- Anestetika
Další identifikační čísla studie
- 2010P001672
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