A Study of the Effectiveness and Safety of JS1-1-01 in Patients With Moderate to Severe Depression

Inclusion Criteria:

• All of the following standards must be met:

1. Age range from 18 to 65 years old (including boundary values), both male andfemale;
2. Single or recurrent episodes (296.2/296.3) that meet the diagnostic criteria fordepression in DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5thedition);
3. During the screening and baseline periods, the total score of the MontgomeryAsperger Depression Rating Scale (MADRS) was ≥ 26 points;
4. Screening and baseline periods, with a Clinical Global Impression Scale DiseaseSeverity (CGI-S) score of ≥ 4 points;
5. Voluntary participation in clinical trials, able to sign informed consent forms,and able to understand and comply with research procedures.

Exclusion Criteria:

• Those who meet any of the following criteria cannot be included in this experiment:

1. Individuals with a history of severe drug allergies or allergies to Piper Piper (pepper plant) or Duloxetine;
2. Those who have used at least two antidepressants in sufficient dosage andduration (treated according to the maximum dosage in the instructions for atleast 4 weeks) in a single or current episode in the past but still have noeffect;
3. Those who have been ineffective in using Duloxetine in sufficient amounts duringthe previous treatment course;
4. The patients of depression secondary to other mental or physical illnesses;
5. Patients of depression with accompanying psychiatric symptoms;
6. Significant suicidal attempt or behavior within the past year, with a score of ≥ 3 on the 10th item (suicidal ideation) of the MADRS scale;
7. During the baseline period, those with a reduction rate of ≥ 25% in the MADRSscale score compared to the screening period;
8. Individuals with a history of epileptic seizures (excluding convulsions caused byfebrile seizures in children);
9. Individuals who have received depression related systemic physical therapy within 3 months prior to their first administration: modified electroconvulsive therapy (MECT), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS),deep brain stimulation (DBS), phototherapy, or systemic psychotherapy;
10. Systematically receiving antidepressant treatment within the first 2 weeks ofrandomization, or discontinuing antidepressant medication for less than 5half-lives before randomization;
11. Individuals with severe unstable cardiovascular disease, liver disease, kidneydisease, blood disease, endocrine disease, and other physical diseases or medicalhistory;
12. Accompanied by a history of malignant tumors (excluding cured skin basal cellcarcinoma and cervical carcinoma in situ);
13. Screening or baseline electrocardiogram abnormalities that have clinicalsignificance and are deemed unsuitable for inclusion by investigators, such asmale QTcF ≥ 450 ms, female QTcF ≥ 470 ms, or having a history of long QTsyndrome;
14. A history of symptomatic orthostatic hypotension (i.e. orthostatic syncope) withclinical significance;
15. During the screening or baseline period, TBIL is above 2 times the upper limit ofnormal value, and ALT or AST is above 2 times the upper limit of normal value; Cris higher than 1.2 times the upper limit of normal value;
16. Thyroid dysfunction (TSH above 1.2 times the upper limit of normal value or below 0.8 times the lower limit of normal value) or the presence of hyperthyroidism orhypothyroidism determined by the investigators;
17. Individuals with a history of elevated intraocular pressure or narrow angleglaucoma;
18. Screening period, drug abuse screening positive individuals;
19. A history of alcohol dependence within one year prior to screening;
20. Pregnant and lactating women, male or female subjects who have a family planningor are unable to take effective contraceptive measures within 30 days aftersigning the informed consent form and ending the trial;
21. Screening for individuals who have participated in clinical trials and takeninvestigational drugs within the first 30 days;
22. The investigators believe that the subjects have poor compliance or there areother clinical, social, or family factors that are not suitable for enrollment.