Depressive SymptomsPhase 2/3NCT04425473
Esketamine and Perioperative Depressive Symptoms
A Phase 2/3 study testing Esketamine and Normal saline in people with Depressive Symptoms and Esketamine, run by Beijing Tiantan Hospital at 1 site in China.
Trial summary
Perioperative depressive symptoms (PDS) are common in population undergoing surgery, and this would be sharpened especially for complicated, high-risk major surgery. However, None of treatments could resolve this clinical problem during limited perioperative period. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Depressive Symptoms, Esketamine, Perioperative Complication
- What is being tested?
- Esketamine and Normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 435 participants
- Where
- 1 siteChina
- Study dates
- 19 Feb 2021to 27 Nov 2024
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient undergoing elective major surgery
- Ages between 18 and 65 years old
- Moderate to severe depressive symptoms ( the Patient Health Questionnaire-9 scores equal to or more than 10 and Montgomery-Åsberg Depression Rating Scale scores equal to or more than 22 )
- Signed informed consent
Who cannot join
- had aphasia or any conditions that prevented mental health assessments,
- had a history of psychotic or bipolar disorder,
- had a comorbidity that affected hormone levels,
- required prolonged postoperative mechanical ventilation,
- had received treatment with antidepressants within 2 weeks prior to the screening,
- had a body mass index greater than 30 kg/m2 and a Child-Pugh score greater than 6 points.
Show all 10Show fewer
- had made repeated suicide attempts (as assessed by the 12-item Quick Inventory of Depressive Symptomatology scores less than 3),
- had experienced adverse reactions to ketamine or esketamine,
- had known drug use disorders,
- pregnant or breastfeeding
Trial locations and contacts
1 site in 1 country.
China1 site
Beijing Tiantan Hospital, Capital Medical University
Beijing, 100070
About this study
Official title: Effect of Esketamine on Perioperative Depressive Symptoms in Patients Undergoing Major Surgery
Perioperative depressive symptoms (PDS) are common in population undergoing surgery, and this would be sharpened especially for complicated, high-risk major surgery. However, None of treatments could resolve this clinical problem during limited perioperative period. The remarkable effects of ketamine on treatment resistant depression have been verified by several clinical trials and the enantiomer S-ketamine (esketamine) showed similar antidepressant efficacy with better safety in recent studies. The efficacy and safety of esketamine administrated intra-operatively for PDS will be verified in this study. Other secondary outcomes such as anxiety, postoperative pain and psychiatric symptoms will also be investigated.
- Being tested
- Esketamine, Normal saline
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EsketamineDrug
Esketamine will be administrated intravenously when suturing incision, with total dose of 0.2mg/kg and continuous infusion for 40 minutes.
Normal salineDrug
Equivalent amount of normal saline will be administrated intravenously suturing incision.
| Study group | Role | What they receive |
|---|---|---|
| Esketamine | Experimental | Not described Receives: Drug: Esketamine |
| Placebo | Placebo comparator | Not described Receives: Drug: Normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Depressive symptoms remission
Remission is defined as the Montgomery-Åsberg Depression Rating Scale (MADRS) total score no more than 10, MADRS is a sensitive tool used for tracking improvement or progression in patients with major depressive disorder, consisting of 10 items that jointly assess the degree of depressive symptoms.
Measured: Postoperative 3-day
Secondary outcomes (5)
MADRS scores
The differences in MADRS scores
Measured: Postoperative 3-day
Depressive symptoms response
The rates of patients achieving a response
Measured: Postoperative 3-day
Moderate-to-severe pain
The rate of severe pain after surgery
Measured: postoperative 3-day
Side-effects and Adverse events
All drug-related adverse events during surgery or before discharge
Measured: During surgery or up to 7 days after surgery
Long-term patient outcome
The long-term patient outcomes included depressive symptoms and disability as measured by the 12-item World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) at 1, 3, and 6 months after surgery.
Measured: 1, 3, and 6 months after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study start19 Feb 2021
- Primary completion23 Jun 2024
- Study completion27 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Depressive SymptomsStudies of the same condition, open and under way.
- More trials run by Beijing Tiantan HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 435 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beijing Tiantan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ruquan Han, Beijing Tiantan Hospital
- Investigators
- Ruquan Han, M.D., Ph D., Study chair, Beijing Tiantan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04425473
- Sponsor's protocol ID
- Z191100006619067
- Status last verified
- Jul 2025
- First submitted
- 8 Jun 2020
- Last updated
- 1 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The datasets will be available from the primary investigator (Ruquan Han, Email: ruquan.han@ccmu.edu.cn) upon reasonable request after the publication of the study results.
Publications
Zhou Y, Sun W, Fu Y, Wang A, Zhang H, Tan H, Liu W, Zhang Z, Zhang W, Wang G, Han R. Effect of intraoperative esketamine on moderate-to-severe depressive symptoms in major surgery patients: A randomized clinical trial. Pharmacol Res. 2026 Jul;229:108238. doi: 10.1016/j.phrs.2026.108238. Epub 2026 May 12.
PubMed 42119799Zhou Y, Ma B, Sun W, Wang J, Fu Y, Wang A, Wang G, Han R. Effect of esketamine on perioperative depressive symptoms in major surgery patients (PASSION II): study protocol for a randomised controlled trial. BMJ Open. 2022 Apr 26;12(4):e056713. doi: 10.1136/bmjopen-2021-056713.
PubMed 35473735
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Esketamine on Perioperative Depressive Symptoms in Patients Undergoing Major Surgery
- ClinicalTrials.gov ID
- NCT04425473
- Acronym / sponsor ID
- Z191100006619067
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 435 participants (actual)
- Lead sponsor
- Beijing Tiantan HospitalUniversity, hospital or other
- Study start
- 19 Feb 2021 (actual)
- Primary completion
- 23 Jun 2024 (actual)
- Study completion
- 27 Nov 2024 (actual)
- First posted
- 11 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Perioperative depressive symptoms (PDS) are common in population undergoing surgery, and this would be sharpened especially for complicated, high-risk major surgery. However, None of treatments could resolve this clinical problem during limited perioperative period. The remarkable effects of ketamine on treatment resistant depression have been verified by several clinical trials and the enantiomer S-ketamine (esketamine) showed similar antidepressant efficacy with better safety in recent studies. The efficacy and safety of esketamine administrated intra-operatively for PDS will be verified in this study. Other secondary outcomes such as anxiety, postoperative pain and psychiatric symptoms will also be investigated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Esketamine | Experimental | Drug: Esketamine |
| Placebo | Placebo comparator | Drug: Normal saline |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patient undergoing elective major surgery
- Ages between 18 and 65 years old
- Moderate to severe depressive symptoms ( the Patient Health Questionnaire-9 scores equal to or more than 10 and Montgomery-Åsberg Depression Rating Scale scores equal to or more than 22 )
- Signed informed consent
Key exclusion criteria (10 listed)
- had aphasia or any conditions that prevented mental health assessments,
- had a history of psychotic or bipolar disorder,
- had a comorbidity that affected hormone levels,
- required prolonged postoperative mechanical ventilation,
- had received treatment with antidepressants within 2 weeks prior to the screening,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EsketamineEsketamine will be administrated intravenously when suturing incision, with total dose of 0.2mg/kg and continuous infusion for 40 minutes. | Drug | Esketamine |
| Normal salineEquivalent amount of normal saline will be administrated intravenously suturing incision. | Drug | Placebo |
Primary outcome
Depressive symptoms remission
Time frame: Postoperative 3-day
Remission is defined as the Montgomery-Åsberg Depression Rating Scale (MADRS) total score no more than 10, MADRS is a sensitive tool used for tracking improvement or progression in patients with major depressive disorder, consisting of 10 items that jointly assess the degree of depressive symptoms.
5 secondary outcomes
MADRS scores
Time frame: Postoperative 3-day
Depressive symptoms response
Time frame: Postoperative 3-day
Moderate-to-severe pain
Time frame: postoperative 3-day
Side-effects and Adverse events
Time frame: During surgery or up to 7 days after surgery
Long-term patient outcome
Time frame: 1, 3, and 6 months after surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2025.
- Derived from this study: PubMed 42119799Zhou Y, Sun W, Fu Y, Wang A, Zhang H, Tan H, Liu W, Zhang Z, Zhang W, Wang G, Han R. Effect of intraoperative esketamine on moderate-to-severe depressive symptoms in major surgery patients: A randomized clinical trial. Pharmacol Res. 2026 Jul;229:108238. doi: 10.1016/j.phrs.2026.108238. Epub 2026 May 12.
- Derived from this study: PubMed 35473735Zhou Y, Ma B, Sun W, Wang J, Fu Y, Wang A, Wang G, Han R. Effect of esketamine on perioperative depressive symptoms in major surgery patients (PASSION II): study protocol for a randomised controlled trial. BMJ Open. 2022 Apr 26;12(4):e056713. doi: 10.1136/bmjopen-2021-056713.
- Individual participant dataSharing planned: Yes. The datasets will be available from the primary investigator (Ruquan Han, Email: ruquan.han@ccmu.edu.cn) upon reasonable request after the publication of the study results.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ruquan Han, M.D., Ph D. study chair
Beijing Tiantan Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Esketamine and Normal saline in people with Depressive Symptoms and Esketamine, run by Beijing Tiantan Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Depressive symptoms remission (time frame: Postoperative 3-day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04425473, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2025.