Effectiveness Study of Scopolamine Combined With Escitalopram in Patients With MDD (SCE)

A Double-blind, Controlled, Randomized Study Comparing Escitalopram Combined With Scopolamine or Escitalopram in Patients With Major Depressive Disorder

Despite the availability of a wide range of antidepressant drugs, clinical trials indicate that 30% to 40% of patients with major depression fail to respond to first-line antidepressant treatment, despite adequate dosage, duration, and compliance. Moreover, in those patients who do experience symptomatic relief following conventional anti-depressant treatment, clinical improvement is not evident for 3-4 weeks. Thus, there is a clear need to develop novel and improved therapeutics for unipolar depression.

A previous study showed that the intravenous administration of scopolamine produces antidepressant effects. This study is designed to determine if scopolamine combine with Escitalopram produce antidepressant effects at an early stage.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Scopolamine; Drug: Escitalopram; Drug: Saline

Detailed Description

This study is a randomized, double-blind, placebo-controlled clinical trial. Sixty-six outpatients (ages 18-45) with severe major depressive disorder (MDD) (17-item Hamilton Rating Scale for Depression total score greater than or equal to 20) are enrolled from Beijing Anding Hospital. All participants receive oral escitalopram 10 mg/d throughout the total of 4 weeks treatment. Meanwhile, they are randomized equally to one of three add-on treatment arms during the first three days: (1) intramuscular injection (i.m.) with saline (1 ml) at 9 am and 3 pm per day; (2) scopolamine (0.3 mg in 1ml saline, i.m.) at 9 am and saline (1 ml, i.m.) at 3 pm per day; (3) scopolamine (0.3 mg in 1ml saline, i.m.) at 9 am and 3 pm per day, respectively. Patients were assessed at baseline, day 2, day 3, day 4, day 7, day 14, and day 28 using 17-Item Hamilton Depression Rating Scale(HAMD-17), Montgomery-Asberg Depression Rating Scale(MADRS), Young Mania Rating Scale(YMRS), Generalized Anxiety Disorder-7(GAD-7), Quick Inventory of Depressive Symptomatology Self-report 16(QIDS-SR16) and Clinical Global Impression(CGI) by assessors masked to treatment assignments. The primary outcome measure was the time from randomization (baseline) to early improvement (at least 20% reduction in HAMD-17 score ). The second outcome measures were response rates (at least 50% decrease in the HAMD-17 at any visit from baseline), remission rate (HAMD-17 score≤7) at day 28, change in HAMD-17 score ,MADRS score, QIDS-SR16 score, GAD7 score and YMRS score from baseline to any visit, change in CGI-S from baseline to the end of the trial, and CGI-I score at any visit.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Beijing Anding Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Has given written informed consent.
2. Male or female outpatients aged at least 18 years and not more than 45 years.
3. Has a diagnosis of major depressive disorder by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria.
4. Current HAMD-17 score ≥ 20 and the duration of the index episode is greater than or equal to four weeks.

Exclusion Criteria:

1. Currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug.
2. Current Axis I primary psychiatric diagnosis other than major depressive disorder.
3. Organic mental disease, including mental retardation.
4. History of clinically significant disease, including any cardiovascular, hepatic, renal, respiratory, hematologic, endocrinologic, or neurologic disease, or clinically significant laboratory abnormality that is not stabilized or is anticipated to require treatment during the study.
5. Subjects receiving an investigational agent (including different formulation and generic agents of investigational drug) in the previous 3 months prior to screening.
6. Women in pregnancy or lactation, or female of child bearing potential without appropriate birth control measures.
7. Use of antipsychotics or mood stabilizers within 5 days prior to screening.
8. Has received depot antipsychotic medication within one cycle prior to screening.
9. Known allergy or lack of response to mirtazapine.
10. Has received ECT or MECT within 3 months prior to screening.
11. History of anticholinergic drug allergy or complications (allergic reaction, skin rash, urticaria and other allergic reactions which caused by drugs).
12. Smokers.
13. Significant risk of suicidal and/or self-harm behaviors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: High-dose scopolamine add-on therapy; Scopolamine (0.3 mg/1 ml, i.m.) Bid; escitalopram （10 mg/d p.o.）QD	Drug: Scopolamine; Intramuscular injection with scopolamine (0.3 mg/1ml,QD or Bid) during the first three days; Drug: Escitalopram; Oral escitalopram 10 mg/d throughout the total of 4 weeks treatment
EXPERIMENTAL: Low-dose scopolamine add-on therapy; Scopolamine (0.3 mg/1 ml, i.m.) QD; placebo (1 ml saline, i.m.) QD; escitalopram （10 mg/d p.o.）QD	Drug: Scopolamine; Intramuscular injection with scopolamine (0.3 mg/1ml,QD or Bid) during the first three days; Drug: Escitalopram; Oral escitalopram 10 mg/d throughout the total of 4 weeks treatment; Drug: Saline; Intramuscular injection with saline (1ml, QD or Bid) during the first three days;
PLACEBO_COMPARATOR: Placebo add-on therapy; Placebo (1 ml saline, i.m.) Bid; escitalopram （10 mg/d p.o.）QD	Drug: Escitalopram; Oral escitalopram 10 mg/d throughout the total of 4 weeks treatment; Drug: Saline; Intramuscular injection with saline (1ml, QD or Bid) during the first three days;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The time of early onset	The time from randomization (baseline) to early improvement (at least 20% reduction in HAMD-17 score )	From randomization (base line) to endpoint(Week 4)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate of patients receiving scopolamine	The proportion of subjects with at least 50% decrease in the HAMD-17 at any visit from baseline.Response was defined as ≥50% decrease in the baseline HAMD-17 total scores.	From randomization (base line) to endpoint(Week 4)
The proportion of subjects at endpoint with HAMD-17≤7	Remission was defined as the HAMD total score ≤7	endpoint(Week 4)
Change in 17-item Hamilton Depression Scale (HAMD-17) scores	Change in HAMD-17 scores measured by the difference between baseline HAMD-17 score and HAMD-17 score at endpoint.	From randomization (base line) to endpoint(Week 4)
Change in Montgomery-Asberg Depression Rating Scale(MADRS)	Change in MADRS scores measured by the difference between baseline MADRS score and MADRS score at endpoint.	From randomization (base line) to endpoint(Week 4)
Change in QIDS-SR16 score	Change in QIDS-SR16 score measured by the difference between baseline QIDS-SR16 score and QIDS-SR16 score at endpoint.	From randomization (base line) to endpoint(Week 4)
Change in GAD7 score	Change in GAD7 score measured by the difference between baseline GAD7 score and GAD7 score at endpoint.	From randomization (base line) to endpoint(Week 4)
Change in YMRS score	Change in YMRS score measured by the difference between baseline YMRS score and YMRS score at endpoint.	From randomization (base line) to endpoint(Week 4)
Change in CGI-S score	Change in CGI-S score measured by the difference between baseline CGI-S score and CGI-S score at endpoint.	From randomization (base line) to endpoint(Week 4)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events (safety and tolerability)	The incidence and nature of overall adverse events; the incidence and nature of drug-related adverse events; assessment of cognitive function change by PDQ-D5	From randomization (base line) to endpoint(Week 4)

Collaborators and Investigators

• Sponsor: Capital Medical University
• Investigators: Principal Investigator: Gang Wang, M.D.,Ph.D., Beijing Anding Hospital, Capital Medical University

Publications and helpful links

General Publications

• Furey ML, Drevets WC. Antidepressant efficacy of the antimuscarinic drug scopolamine: a randomized, placebo-controlled clinical trial. Arch Gen Psychiatry. 2006 Oct;63(10):1121-9. doi: 10.1001/archpsyc.63.10.1121.
• Zhou J, Yang J, Zhu X, Zghoul T, Feng L, Chen R, Wang G. The effects of intramuscular administration of scopolamine augmentation in moderate to severe major depressive disorder: a randomized, double-blind, placebo-controlled trial. Ther Adv Psychopharmacol. 2020 Jul 1;10:2045125320938556. doi: 10.1177/2045125320938556. eCollection 2020.
• Zhou J, Wang W, Yang J, Zhu X, Feng L, Xiao L, Wang G. Scopolamine augmentation of a newly initiated escitalopram treatment for major depressive disorder: study protocol for a randomized controlled trial. Trials. 2019 Jan 9;20(1):33. doi: 10.1186/s13063-018-3132-3.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 15, 2017
• Primary Completion (ACTUAL): February 8, 2018
• Study Completion (ACTUAL): March 8, 2018

Study Registration Dates

• First Submitted: April 18, 2017
• First Submitted That Met QC Criteria: April 26, 2017
• First Posted (ACTUAL): April 27, 2017

Study Record Updates

• Last Update Posted (ACTUAL): December 26, 2018
• Last Update Submitted That Met QC Criteria: December 24, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Scopolamine
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Antiemetics; Gastrointestinal Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Adjuvants, Anesthesia; Antidepressive Agents, Second-Generation; Mydriatics; Citalopram; Scopolamine; Butylscopolammonium Bromide
• Other Study ID Numbers: Scopolamine i.m.

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No