Effectiveness Study of Scopolamine Combined With Escitalopram in Patients With MDD

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Scopolamine
* Drug: Escitalopram
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has given written informed consent. Male or female outpatients aged at least 18 years and not more than 45 years. Has a diagnosis of major depressive disorder by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. Current HAMD-17 score ≥ 20 and the duration of the index episode is greater than or equal to four weeks. Exclusion Criteria: Currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug. Current Axis I primary psychiatric diagnosis other than major depressive disorder. Organic mental disease, including mental retardation. 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. Subjects receiving an investigational agent (including different formulation and generic agents of investigational drug) in the previous 3 months prior to screening. Women in pregnancy or lactation, or female of child bearing potential without appropriate birth control measures. Use of antipsychotics or mood stabilizers within 5 days prior to screening. Has received depot antipsychotic medication within one cycle prior to screening. Known allergy or lack of response to mirtazapine. Has received ECT or MECT within 3 months prior to screening. History of anticholinergic drug allergy or complications (allergic reaction, skin rash, urticaria and other allergic reactions which caused by drugs). Smokers. Significant risk of suicidal and/or self-harm behaviors

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Scopolamine