Clinical trial NCT01312844: A Study of the Use of IV Scopolamine to Augment the Efficacy of Electroconvulsive Therapy (ECT)
Official title: A Pilot Study of the Use of IV Scopolamine to Augment the Efficacy of Electroconvulsive Therapy (ECT)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Depression
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2011-03-11
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Ham D 17 Scores
timeFrame: At the time of ECT completion (about 2 weeks)
measure: Time to Response for Patients Receiving ECT
timeFrame: Duration of ECT treatment (usually 2 weeks)
measure: Number of ECT Treatments Received to Achieve Response/Remission
timeFrame: Duration of ECTtreatment (usually 2 weeks)
Secondary outcomes:
measure: Number of ECT Treatments Withheld Due to Cognitive Impairment
timeFrame: Duration of ECT treatment (usually 2 weeks)
measure: The Mean Number of Moderate to Severe Side Effects
timeFrame: Duration of ECT treatment (usually 2 weeks)
measure: The Mean Levels of Physiological Measures of ECT (Blood Pressure)
timeFrame: Duration of ECT treatment (usually 2 weeks)
measure: The Mean Levels of Physiological Measures of ECT (Heart Rate)
timeFrame: Duration of ECT treatment (usually 2 weeks)
measure: The Mean Levels of Physiological Measures of ECT (Seizure Duration)
timeFrame: Duration of ECT treatment (usually 2 weeks)
measure: The Mean Levels of Physiological Measures of ECT (Energy Needed)
timeFrame: Duration of ECT treatment (usually 2 weeks)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: John D Matthews, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: David Abramson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: Maurizio Fava, MD
role: PRINCIPAL_INVESTIGATOR
References: