Clinical trial NCT02924090: Hyperventilation Combined With Etomidate or Ketamine Anesthesia in ECT Treatment of Major Depression
Official title: Hyperventilation and ECT Seizure Duration: Effects on Cerebral Oxygen Saturation, and Therapeutic Outcome With Comparisons Between Etomidate and Ketamine in Patients With Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Depression
Keywords: Major depressive disorder
Etomidate
Ketamine
Hyperventilation
Electroconvulsive therapy
Depression
Anesthesia
Nervous System Diseases
Mental Disorders
Electroencephalography
Cerebral Metabolism
Lead sponsor: University of Manitoba
Sponsor class: OTHER
First posted: 2016-10-05
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized controlled study assessing the effect of pre-emptive hyperventilation on ECT seizure duration, cerebral desaturation and remission of depressive symptoms in patients with Major Depressive Disorder. Comparison of etomidate and ketamine on remission of depressive symptoms with and without pre-emptive hyperventilation will also be studied.

Detailed description: Electroconvulsive therapy (ECT) is an effective treatment for medication-resistant forms of depression, including major depressive disorder and mania. Therapeutic success of ECT is related to the duration and quality of Electroencephalogram (EEG) and motor seizures. Previous studies have demonstrated that deliberate hyperventilation augments seizure duration in anesthetized subjects. It has also been shown that seizure activity significantly increases cerebral metabolic rate, predisposing the patient to potentially severe cerebral desaturation events. These desaturation events are predicted to be exacerbated by pre-emptive hyperventilation which has a potent cerebral vasoconstrictive effect. Despite the widespread use of ECT, little is known about the effect of hyperventilation on cerebral metabolism in this setting. Ketamine has recently been demonstrated to have anti-depressant properties in patients with major depressive disorder, suggesting that patients treated with ketamine anesthesia and then ECT, may benefit clinically from the additive effects of both treatment modalities, compared to ECT alone.

The investigators hypothesize that hyperventilation will facilitate prolonged seizure duration and faster remission of depressive symptoms. As well there may be significant cerebral desaturation and cardiovascular side effects of ECT therapy following hyperventilation. Lastly, the effect of hyperventilation on the efficacy of ECT therapy may be improved when ketamine anesthesia is used simultaneously. To test this hypothesis this study will compare ketamine anesthesia to etomidate anesthesia. Etomidate is a short acting anesthetic that is commonly used in these procedures.

The study objectives (primary and secondary) are as follows:

1. To quantify the effect of hyperventilation and type of anesthetic agent on ECT-induced seizure duration
2. To assess the effect of hyperventilation immediately prior to ECT on cerebral metabolism as measured by cerebral oximetry
3. To determine the effect of hyperventilation and anesthetic agent on the remission of symptoms in Major Depressive Disorder
4. To assess the side effect profile of hyperventilation during ECT on hemodynamics

Eligibility criteria: Inclusion Criteria:

* Adults patients aged 18 to 85 years
* Diagnosed with Major Depressive Disorder, unipolar or bipolar depression
* Undergoing ECT for treatment of their symptoms
* Currently residing in Manitoba

Exclusion Criteria:

* Relative contraindications to ECT therapy (recent MI or CVA, increased intracranial pressure, intracranial mass lesion, intracranial aneurysm, epilepsy, known cardiac arrhythmia, pheochromocytoma, pregnancy)
* Contraindications to etomidate (sepsis, primary or secondary adrenal insufficiency, porphyria)
* DSM-V diagnosis of a lifetime history of psychotic spectrum disorder
* Drug or alcohol dependence, or abuse within the past 3 months, soy-bean oil allergy

Primary outcomes:
measure: EEG seizure duration (seconds)
timeFrame: Up to 3 minutes post ECT
measure: ECT-induced seizure duration (seconds)
timeFrame: Up to 3 minutes post ECT
Secondary outcomes:
measure: Changes in cerebral metabolism assessed by cerebral saturation (%)
timeFrame: Up to 5 minutes post ECT
measure: Remission of depressive symptoms assessed by HAM-D
timeFrame: Approximately one week prior to, and at 2, 4 and 8 weeks post ECT
measure: Remission of depressive symptoms assessed by MADRS
timeFrame: Approximately one week prior to, and at 2, 4 and 8 weeks post ECT
measure: Effect on blood pressure
timeFrame: Up to 7 minutes post ECT
measure: Effect on heart rate
timeFrame: Up to 7 minutes post ECT
measure: Duration of stay in post-anesthesia care unit (hours)
timeFrame: Up to 2 hours post arrival in post-anesthesia care unit (PACU).
measure: Incidence of nausea in post-anesthesia care unit (%)
timeFrame: Up to 2 hours post arrival in PACU.
measure: Incidence of vomiting in post-anesthesia care unit (%)
timeFrame: Up to 2 hours post arrival in PACU.
Other outcomes:
Locations:
city: Winnipeg
country: Canada
facility: Health Sciences Centre
state: Manitoba
Study officials:
affiliation: University of Manitoba
name: Ian McIntyre, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Manitoba
name: Michael Harrington, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Loo C, Simpson B, MacPherson R. Augmentation strategies in electroconvulsive therapy. J ECT. 2010 Sep;26(3):202-7. doi: 10.1097/YCT.0b013e3181e48143.
citation: Aksay SS, Bumb JM, Janke C, Hoyer C, Kranaster L, Sartorius A. New evidence for seizure quality improvement by hyperoxia and mild hypocapnia. J ECT. 2014 Dec;30(4):287-91. doi: 10.1097/YCT.0000000000000109.
citation: Fabbri F, Henry ME, Renshaw PF, Nadgir S, Ehrenberg BL, Franceschini MA, Fantini S. Bilateral near-infrared monitoring of the cerebral concentration and oxygen-saturation of hemoglobin during right unilateral electro-convulsive therapy. Brain Res. 2003 Dec 5;992(2):193-204. doi: 10.1016/j.brainres.2003.08.034.
citation: Ghasemi M, Kazemi MH, Yoosefi A, Ghasemi A, Paragomi P, Amini H, Afzali MH. Rapid antidepressant effects of repeated doses of ketamine compared with electroconvulsive therapy in hospitalized patients with major depressive disorder. Psychiatry Res. 2014 Feb 28;215(2):355-61. doi: 10.1016/j.psychres.2013.12.008. Epub 2013 Dec 13.