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

Depression Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01312844
• Other study ID #: 2009P002288
• Status: Recruiting
• Phase: N/A
• First received: May 4, 2010
• Last updated: July 24, 2014
• Start date: April 2010
• Est. completion date: December 2014

Study information

• Verified date: July 2014
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression

Intervention

Drug:
• Scopolamine
Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ham D 17 scores		Duration of ECT treatment (on average, 2 weeks)	No
Secondary	Time to response/remission		Duration of ECT treatment (usually 2 weeks)	No
Secondary	Number of ECT treatments to response/remission		Duration of ECT treatment (usually 2 weeks)	No