A Study of the Use of IV Scopolamine to Augment the Efficacy of Electroconvulsive Therapy (ECT)

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01312844
• Collaborator: (none)
• Enrollment: 7
• Location: 1
• Arms: 2
• Duration (Months): 27
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The primary purpose of this study is to assess the ability of scopolamine to improve the antidepressant effects of ECT and to determine whether scopolamine will shorten the time to response and remission for patients receiving ECT.

The hypothesis are:

1. Patients receiving ECT plus scopolamine will have greater improvement in depression symptoms than those receiving ECT plus placebo.

2. Patients receiving scopolamine in addition to ECT will require fewer ECT treatments to obtain response/remission compared to the group receiving ECT plus placebo.

3. Time to response and to remission in the scopolamine group will be significantly shorter compared to ECT alone.

Condition or Disease	Intervention/Treatment	Phase
Depression	Drug: Scopolamine	Phase 2

Detailed Description

Electroconvulsive therapy (ECT) is a highly effective treatment for severe major depression. It has been estimated that approximately 10 percent of all patients admitted to the hospital for treatment of major depressive disorder receive ECT.

However, not all patients who receive ECT respond, and of those who do, not all achieve remission. Furthermore, while there is a wide range in the number of ECT treatments done among all people with depression, the average is approximately eight treatments. Because treatments are usually done three times per week (Monday, Wednesday, and Friday), the minimal length of stay for the average person receiving inpatient ECT is typically greater than two weeks.

Finally, ECT is not without risk, and every round of ECT incurs additional risk of not just the treatment itself, but also the risks of general anesthesia. Thus, although ECT is a robust mode of treatment for Major Depressive Disorder (MDD), there remains a need for improved treatment efficacy and speed of onset. Improving the efficacy of ECT would not only benefit individuals with MDD, but also have far-reaching effects for the health care system as it could impact the cost and resources utilized.

Ideally, an agent could be added to augment the effect of ECT, both in terms of efficacy as well as speed of onset. In 2006, Furrey et al, reported the rapid antidepressant effect of the antimuscarinic drug, scopolamine, delivered parenterally. Significant antidepressant effect was found after the first scopolamine administration. The improvement was reported immediately following the first IV administration, increased across all treatments, and was sustained into the placebo crossover period.

Scopolamine is an anticholinergic muscarinic agent, with activity in the CNS and pilot data to suggest a significant impact on rapidly improving depressive symptoms in patient with MDD, when administered IV. Thus, it serves as a reasonable choice to augment the effects of ECT in the treatment of patients with MDD.

Primary Aim 1) Assess the ability of scopolamine to augment the antidepressant effects of ECT.

Hypothesis 1a: Patients receiving ECT plus scopolamine will have significantly greater mean improvement on total HAM-D score between baseline and endpoint than those receiving ECT plus placebo.

Hypothesis 1b: Patients receiving scopolamine in addition to ECT will require fewer mean ECT treatments to obtain response/remission compared to the group receiving ECT plus placebo.

Primary Aim 2) Evaluate the hypothesis that scopolamine will shorten the time to response and remission for patients receiving ECT.

Hypothesis 2: Time to response and to remission in the Scopolamine group will be significantly shorter compared to ECT alone.

Secondary Aim: Provide evidence for the tolerability of intravenous scopolamine administered during ECT.

Hypothesis 3a: There will be no between group difference (between ECT plus scopolamine vs ECT plus placebo) in mean number of ECT sessions withheld due to cognitive impairment (as determined by attending psychiatrist).

Hypothesis 3b: There will be no between group differences (between ECT plus scopolamine vs ECT plus placebo) with regards to the mean number of moderate to severe side effects.

Hypothesis 3c: There will be no significant difference between the scopolamine plus ECT group and the placebo plus ECT group on mean levels of physiological measures of ECT including: heart rate, blood pressure, seizure length, duration of muscle paralysis, duration of asystole, and energy need to induce seizure.

Exploratory Analyses: we will assess whether the scopolamine plus ECT group will have a shorter average length of stay on the inpatient psychiatric unit compared to those receiving ECT plus placebo.

We will also assess whether the scopolamine plus ECT group will have significant differences in the cognitive measures at endpoint compared to those receiving ECT plus placebo.

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Pilot Study of the Use of IV Scopolamine to Augment the Efficacy of Electroconvulsive Therapy (ECT)
• Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Jul 1, 2012
• Actual Study Completion Date: Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Scopolamine Patients receiving IV scopolamine at ECT treatment	Drug: Scopolamine; Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT
Placebo Comparator: Placebo Patients receiving IV placebo at ECT treatment	Drug: Scopolamine; Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT

Outcome Measures

Primary Outcome Measures

1. Change in Ham D 17 Scores [At the time of ECT completion (about 2 weeks)]

   Change in Ham D 17 scores measured by the difference between baseline HAM D score and HAM D score at last ECT administration. The HAM D 17 measures severity of depression with 52 being most severe and 0 being no depression. A negative change score refers to a decrease in HAM D score, while a positive change score would refer to an increase in HAM D score.

2. Time to Response for Patients Receiving ECT [Duration of ECT treatment (usually 2 weeks)]

   The number of days between baseline HAM D score and HAM D score showing response (defined as a HAM D score less than half of baseline). If patients HAM D score rose above this marker at any point in the study, they were not considered as responding.The HAM D 17 measures severity of depression with 52 being most severe and 0 being no depression. .

3. Number of ECT Treatments Received to Achieve Response/Remission [Duration of ECTtreatment (usually 2 weeks)]

   The number of ECT treatments needed to achieve response (defined as a HAM D score less than half of baseline) and remission (defined as a HAM D score of less than 8). If patients HAM D score rose above these markers at any point in the study, they were not considered as responding or remitting.The HAM D 17 measures severity of depression with 52 being most severe and 0 being no depression.

Secondary Outcome Measures

1. Number of ECT Treatments Withheld Due to Cognitive Impairment [Duration of ECT treatment (usually 2 weeks)]

   The number of ECT treatments withheld during the course of the study due to cognitive impairment. In these cases, the participant would still be enrolled in the study but have a reduced # of ECTs. This outcome measure does not include patients who withdrew from the study.

2. The Mean Number of Moderate to Severe Side Effects [Duration of ECT treatment (usually 2 weeks)]

   The mean number of adverse events classified as moderate to severe.

3. The Mean Levels of Physiological Measures of ECT (Blood Pressure) [Duration of ECT treatment (usually 2 weeks)]

   Blood pressure was taken immediately post ECT administration at each ECT visit. We averaged Blood pressure for each participant at each ECT administration. The reported mean refers to the average among all participants in each group.

4. The Mean Levels of Physiological Measures of ECT (Heart Rate) [Duration of ECT treatment (usually 2 weeks)]

   Heart rate was taken immediately post ECT administration at each ECT visit. We averaged heart rate for each participant at each ECT administration. The reported mean refers to the average among all participants in each group.

5. The Mean Levels of Physiological Measures of ECT (Seizure Duration) [Duration of ECT treatment (usually 2 weeks)]

   Mean duration in seconds of the seizure induced by ECT for each participant at each ECT administration they received.The reported mean refers to the average among all participants in each group.

6. The Mean Levels of Physiological Measures of ECT (Energy Needed) [Duration of ECT treatment (usually 2 weeks)]

   Mean energy needed to induce the seizure for each participant at each ECT administration they received. The reported mean refers to the average among all participants in each group.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males and females between the ages of 18-50 (inclusive)

• DSM-IV diagnosis of Major Depressive Disorder (MDD), without psychotic features, and a HAM-D-17 score of 18 or higher

• Female subjects must be postmenopausal, surgically sterile, or, if of child-bearing age, using double-barrier contraceptive method or prescription oral contraceptives (e.g. estrogen-progestin combinations), contraceptive implants (e.g. NorplantTM, DepoProveraTM, or transdermally delivered contraceptives (Ortho EvraTM) before entry and throughout the study; and have a negative urine b-HCG pregnancy test at screening.

Exclusion Criteria:

1. Substance use disorder active use within the last 6 months (per assessment using SCID)

2. Organic mental disorders

3. Seizure disorders

4. Unstable physical disorder or physical disorder judged to significantly affect the central nervous system function

5. Heart block

6. Pre-existing sick-sinus

7. Chronic treatment with beta blockers

8. Any cardiac arrhythmia

9. Hypotension

10. Coronary artery disease

11. Liver and renal function impairment

12. Urge incontinence or prostatic hypertrophy

13. Colitis

14. Crohn's disease

15. GI motility disorders

16. Asthma

17. COPD

18. Treatment with anti-cholinergic and cholinomimetic medications

19. Contraindications to scopolamine including hypersensitivity to scopolamine, other belladonna alkaloids, and/or any component of the formulation

20. Wide and narrow angle glaucoma

21. Acute hemorrhage

22. Paralytic ileus

23. Myasthenia gravis

24. Patients on belladonna, belladonna alkaloids, cisapride, or potassium chloride

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02144

Sponsors and Collaborators

• Massachusetts General Hospital

Investigators

• Principal Investigator: John D Matthews, MD, Massachusetts General Hospital
• Principal Investigator: David Abramson, MD, Massachusetts General Hospital
• Principal Investigator: Maurizio Fava, MD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: John D. Matthews, Principal Investigator, Assistant Professor of Psychiatry, Harvard Medical School, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01312844
• Other Study ID Numbers: 2009P002288
• First Posted: Mar 11, 2011
• Last Update Posted: May 30, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Depression; Scopolamine; Butylscopolammonium Bromide

Study Results

Participant Flow

Arm/Group Title	Scopolamine	Placebo
Arm/Group Description	Patients receiving IV scopolamine at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT	Patients receiving IV placebo at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT
Period Title: Overall Study
STARTED	4	3
COMPLETED	4	3
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Scopolamine	Placebo	Total
Arm/Group Description	Patients receiving IV scopolamine at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT	Patients receiving IV placebo at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT	Total of all reporting groups
Overall Participants	4	3	7
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	4 100%	2 66.7%	6 85.7%
>=65 years	0 0%	1 33.3%	1 14.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.25 (8.62)	56.67 (21.78)	51.86 (14.68)
Sex: Female, Male (Count of Participants)
Female	3 75%	1 33.3%	4 57.1%
Male	1 25%	2 66.7%	3 42.9%
Region of Enrollment (participants) [Number]
United States	4 100%	3 100%	7 100%

Outcome Measures

1. Primary Outcome

Title	Change in Ham D 17 Scores
Description	Change in Ham D 17 scores measured by the difference between baseline HAM D score and HAM D score at last ECT administration. The HAM D 17 measures severity of depression with 52 being most severe and 0 being no depression. A negative change score refers to a decrease in HAM D score, while a positive change score would refer to an increase in HAM D score.
Time Frame	At the time of ECT completion (about 2 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Scopolamine	Placebo
Arm/Group Description	Patients receiving IV scopolamine at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT	Patients receiving IV placebo at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT
Measure Participants	4	3
Mean (Standard Deviation) [units on a scale]	-17.50 (10.47)	-14.00 (11.00)

2. Primary Outcome

Title	Time to Response for Patients Receiving ECT
Description	The number of days between baseline HAM D score and HAM D score showing response (defined as a HAM D score less than half of baseline). If patients HAM D score rose above this marker at any point in the study, they were not considered as responding.The HAM D 17 measures severity of depression with 52 being most severe and 0 being no depression. .
Time Frame	Duration of ECT treatment (usually 2 weeks)

Outcome Measure Data

Analysis Population Description

Only 3 (out of 4) Scopolamine patients and 2 (out of 3) placebo patients reached response

Arm/Group Title	Scopolamine	Placebo
Arm/Group Description	Patients receiving IV scopolamine at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT	Patients receiving IV placebo at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT
Measure Participants	3	2
Mean (Standard Deviation) [days]	8.33 (3.21)	5.00 (1.41)

3. Primary Outcome

Title	Number of ECT Treatments Received to Achieve Response/Remission
Description	The number of ECT treatments needed to achieve response (defined as a HAM D score less than half of baseline) and remission (defined as a HAM D score of less than 8). If patients HAM D score rose above these markers at any point in the study, they were not considered as responding or remitting.The HAM D 17 measures severity of depression with 52 being most severe and 0 being no depression.
Time Frame	Duration of ECTtreatment (usually 2 weeks)

Outcome Measure Data

Analysis Population Description

Only 3 (out of 4) Scopolamine patients and 2 (out of 3) placebo patients reached response and remission.

Arm/Group Title	Scopolamine	Placebo
Arm/Group Description	Patients receiving IV scopolamine at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT	Patients receiving IV placebo at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT
Measure Participants	3	2
# of ECT administrations to response	2.33 (2.21)	2.50 (0.71)
# of ECT administrations to remission	10.00 (3.46)	6.50 (0.71)

4. Secondary Outcome

Title	Number of ECT Treatments Withheld Due to Cognitive Impairment
Description	The number of ECT treatments withheld during the course of the study due to cognitive impairment. In these cases, the participant would still be enrolled in the study but have a reduced # of ECTs. This outcome measure does not include patients who withdrew from the study.
Time Frame	Duration of ECT treatment (usually 2 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Scopolamine	Placebo
Arm/Group Description	Patients receiving IV scopolamine at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT	Patients receiving IV placebo at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT
Measure Participants	3	3
Mean (Standard Deviation) [ECT Treatments withheld]	0 (0)	0 (0)

5. Secondary Outcome

Title	The Mean Number of Moderate to Severe Side Effects
Description	The mean number of adverse events classified as moderate to severe.
Time Frame	Duration of ECT treatment (usually 2 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Scopolamine	Placebo
Arm/Group Description	Patients receiving IV scopolamine at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT	Patients receiving IV placebo at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT
Measure Participants	4	3
Mean (Standard Deviation) [number of side effects]	.75 (1.5)	0 (0)

6. Secondary Outcome

Title	The Mean Levels of Physiological Measures of ECT (Blood Pressure)
Description	Blood pressure was taken immediately post ECT administration at each ECT visit. We averaged Blood pressure for each participant at each ECT administration. The reported mean refers to the average among all participants in each group.
Time Frame	Duration of ECT treatment (usually 2 weeks)

Outcome Measure Data

Analysis Population Description

Missing vitals forms for one participant in Scopolamine group (n=4), only reported data for 3 participants in Scopolamine group

Arm/Group Title	Scopolamine	Placebo
Arm/Group Description	Patients receiving IV scopolamine at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT	Patients receiving IV placebo at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT
Measure Participants	3	3
Systolic blood pressure immediately post ECT	170.35 (37.88)	131.05 (27.57)
Diastolic Blood Pressure Immediately Post ECT	87.41 (16.92)	78.80 (16.61)

7. Secondary Outcome

Title	The Mean Levels of Physiological Measures of ECT (Heart Rate)
Description	Heart rate was taken immediately post ECT administration at each ECT visit. We averaged heart rate for each participant at each ECT administration. The reported mean refers to the average among all participants in each group.
Time Frame	Duration of ECT treatment (usually 2 weeks)

Outcome Measure Data

Analysis Population Description

Missing vitals forms for one participant in Scopolamine group (n=4), only reported data for 3 participants in Scopolamine group

Arm/Group Title	Scopolamine	Placebo
Arm/Group Description	Patients receiving IV scopolamine at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT	Patients receiving IV placebo at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT
Measure Participants	3	3
Mean (Standard Deviation) [Beats per minute]	69.24 (11.45)	86.20 (15.62)

8. Secondary Outcome

Title	The Mean Levels of Physiological Measures of ECT (Seizure Duration)
Description	Mean duration in seconds of the seizure induced by ECT for each participant at each ECT administration they received.The reported mean refers to the average among all participants in each group.
Time Frame	Duration of ECT treatment (usually 2 weeks)

Outcome Measure Data

Analysis Population Description

Missing ECT forms for one participant in Scopolamine group (n=4), only reported data for 3 participants in Scopolamine group

Arm/Group Title	Scopolamine	Placebo
Arm/Group Description	Patients receiving IV scopolamine at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT	Patients receiving IV placebo at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT
Measure Participants	3	3
Mean (Standard Deviation) [seconds]	30.25 (7.77)	31.89 (10.56)

9. Secondary Outcome

Title	The Mean Levels of Physiological Measures of ECT (Energy Needed)
Description	Mean energy needed to induce the seizure for each participant at each ECT administration they received. The reported mean refers to the average among all participants in each group.
Time Frame	Duration of ECT treatment (usually 2 weeks)

Outcome Measure Data

Analysis Population Description

Missing ECT forms for one participant in Scopolamine group (n=4), only reported data for 3 participants in Scopolamine group

Arm/Group Title	Scopolamine	Placebo
Arm/Group Description	Patients receiving IV scopolamine at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT	Patients receiving IV placebo at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT
Measure Participants	3	3
Mean (Standard Deviation) [joules]	73.83 (31.12)	67.06 (30.02)

Adverse Events

Arm/Group Title	Scopolamine		Placebo
Arm/Group Description	Patients receiving IV scopolamine at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT		Patients receiving IV placebo at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT
All Cause Mortality
	Scopolamine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Scopolamine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25%)		0/3 (0%)
Nervous system disorders
Recent memory loss	1/4 (25%)	1	0/3 (0%)	0
Psychiatric disorders
Agitation requiring restraint	1/4 (25%)	1	0/3 (0%)	0
Other (Not Including Serious) Adverse Events
	Scopolamine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25%)		1/3 (33.3%)
Psychiatric disorders
Deja vu / confusion	1/4 (25%)	1	0/3 (0%)	0
Respiratory, thoracic and mediastinal disorders
Hypoxia event	0/4 (0%)	0	1/3 (33.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.