Clinical trial NCT03131050: Effectiveness Study of Scopolamine Combined With Escitalopram in Patients With MDD
Official title: A Double-blind, Controlled, Randomized Study Comparing Escitalopram Combined With Scopolamine or Escitalopram in Patients With Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Major Depressive Disorder
Keywords: Scopolamine
Lead sponsor: Capital Medical University
Sponsor class: OTHER
First posted: 2017-04-27
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: GROUP 1: The patients received intramuscular injection treatment of scopolamine (0.3 mg/ml) at 9 am and 0.9% saline treatment at 3pm. GROUP 2: The patients received intramuscular injection treatment of scopolamine (0.3 mg/ml) at 9 am and 3 PM. GROUP 3: The patients received intramuscular injection treatment of 0.9% saline (1 ml) at 9 am and 3 PM.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: The time of early onset
timeFrame: From randomization (base line) to endpoint(Week 4)
Secondary outcomes:
measure: Response rate of patients receiving scopolamine
timeFrame: From randomization (base line) to endpoint(Week 4)
measure: The proportion of subjects at endpoint with HAMD-17≤7
timeFrame: endpoint(Week 4)
measure: Change in 17-item Hamilton Depression Scale (HAMD-17) scores
timeFrame: From randomization (base line) to endpoint(Week 4)
measure: Change in Montgomery-Asberg Depression Rating Scale(MADRS)
timeFrame: From randomization (base line) to endpoint(Week 4)
measure: Change in QIDS-SR16 score
timeFrame: From randomization (base line) to endpoint(Week 4)
measure: Change in GAD7 score
timeFrame: From randomization (base line) to endpoint(Week 4)
measure: Change in YMRS score
timeFrame: From randomization (base line) to endpoint(Week 4)
measure: Change in CGI-S score
timeFrame: From randomization (base line) to endpoint(Week 4)
Other outcomes:
measure: Incidence of treatment-emergent adverse events (safety and tolerability)
timeFrame: From randomization (base line) to endpoint(Week 4)
Locations:
city: Beijing
country: China
facility: Beijing Anding Hospital
Study officials:
affiliation: Beijing Anding Hospital, Capital Medical University
name: Gang Wang, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.