Chronic SSRI/SNRI Use and Intraoperative Propofol RequirementsNCT07822295
The Effect of Chronic ssrı/snrı Antidepressant Treatment on Propofol Consumption in Elective Spine Surgery
An observational study of Chronic SSRI/SNRI Use and Intraoperative Propofol Requirements, run by Kocaeli City Hospital at 1 site in Turkey (Türkiye).
Trial summary
The goal of this observational study is to learn whether long-term use of selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressants is related to the amount of propofol needed during planned spine surgery. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Chronic SSRI/SNRI Use and Intraoperative Propofol Requirements
- Type of treatment
- Injection or infusion
- How many people
- 216 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 30 Oct 2026to 30 May 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: The study population will be drawn from patients scheduled for elective spine surgery at Kocaeli City Hospital in Kocaeli, Türkiye. Potential participants will be identified during routine preoperative evaluations in the anesthesia clinic or relevant inpatient surgical wards before surgery.
Who may be able to join
- Study period: Between October 2026 and April 2027,
- Study location: Kocaeli City Hospital Operating Rooms,
- Type of surgery: Patients scheduled for spinal surgery,
- Medication use: Patients using chronic SSRI or SNRI group antidepressants in the preoperative period, but not using antipsychotics or other group antidepressants (e.g., TCA, MAOI, atypical antidepressants),
- Age criterion: Adult individuals aged 18 and over,
- ASA classification: Patients in ASA 2-3 group,
Who cannot join
- Patients who cannot give informed consent and individuals under 18 years of age,
- Patients with an ASA (American Society of Anesthesiologists) physical status classification of ASA IV or higher,
- Cases requiring emergency surgical intervention,
- Patients undergoing surgery due to trauma,
- Patients using antidepressants other than selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs),
- Cases maintained with inhalation anesthesia.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Turkey (Türkiye)1 site
Kocaeli City Hospital
Kocaeli, Izmit, 41000
AHMET YÜKSEK, ASSOCIATE PROFESSOR, +90 532 658 03 51, mdayuksek@hotmail.com
İZZET AVCİ, ANESTHESIA ASSISTANT, +90 532 612 36 72, izzetavc.65@gmail.com
About this study
Official title: The Effect of Chronic ssrı/snrı Antidepressant Treatment on Propofol Consumption in Elective Spine Surgery: a Prospective Cohort Study
The goal of this observational study is to learn whether long-term use of selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressants is related to the amount of propofol needed during planned spine surgery. Propofol is a medicine given through a vein to produce and maintain anesthesia.
The main questions this study aims to answer are:
Read more
- Do patients who regularly take an SSRI or SNRI need a different total amount of propofol during surgery than patients who do not take these medicines?
- Are there differences in propofol and remifentanil use, depth of anesthesia, vital signs, or recovery time between the study groups?
The study will include 216 adults undergoing planned spine surgery. Researchers will compare 108 participants who regularly take an SSRI or SNRI with 108 participants who do not take these medicines.
All participants will receive routine anesthesia care. The study will not start, stop, or change any antidepressant treatment, and participants will not be randomly assigned to a group. Researchers will record the amount of propofol and remifentanil used during surgery, blood pressure, heart rate, oxygen level, depth of anesthesia, and recovery time.
Read the detailed description
Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are considered first-line pharmacological agents in the treatment of depression and anxiety disorders (1). These drugs selectively increase serotonin concentrations in the synaptic cleft by inhibiting the serotonin transporter (SERT); they suppress norepinephrine and dopamine reuptake only minimally (1). However, SSRI and SNRI agents have the potential to cause hypertensive effects (2). The hypertensive mechanism is associated with SSRIs raising synaptic serotonin levels through SERT inhibition, resulting in overstimulation of 5-HT1A and 5-HT2A receptors (3). Serotonin excess activates the sympathetic nervous system, triggering vasoconstriction, tachycardia, and catecholamine release, leading to an increase in blood pressure; this indirectly increases the need for intraoperative anesthetic (4). Additionally, SSRIs-especially potent CYP2D6 inhibitors such as paroxetine and fluoxetine-can reduce the analgesic effects of prodrug-type opioids (e.g., codeine, hydrocodone, and tramadol) by inhibiting their metabolism (5). This interaction blocks the conversion of prodrugs to active metabolites (codeine → morphine; hydrocodone → hydromorphone) via the CYP2D6 enzyme in the liver, reducing plasma active opioid concentrations and disrupting μ-opioid receptor activation; ultimately leading to a higher opioid dose requirement for patients (5). As a parallel mechanism, serotonin excess (at high doses or in interaction with other agents) can induce serotonin-induced hyperalgesia; this process occurs through stimulation of the cAMP secondary messenger system via 5-HT1A receptors in peripheral nerve endings and potentiates the tendency towards hyperalgesia (6). Considering these described mechanisms, maintaining a constant remifentanil dose during the intraoperative period may increase propofol consumption (7). However, despite this theoretical information, the effect of SSRI-SNRI use on propofol consumption during the perioperative period has not been sufficiently investigated. Therefore, this study will investigate the relationship between these two factors.
- Keywords
- Selective Serotonin Reuptake Inhibitors, Serotonin-Norepinephrine Reuptake Inhibitors, SSRI, SNRI, Propofol Consumption, Chronic Antidepressant Therapy, Elective Spine Surgery, Remifentanil, Bispectral Index, Total Intravenous Anesthesia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Chronic SSRI/SNRI Treatment Group | Participants receiving chronic selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) therapy before elective spine surgery. These medications will not be initiated, discontinued, or modified for study purposes. Intraoperative propofol consumption and prespecified perioperative outcomes will be recorded. | |
| Control Group | Adults undergoing elective spine surgery who are not receiving chronic SSRI or SNRI therapy and are not using antipsychotic or other antidepressant medications. Participants will receive routine BIS-guided total intravenous anesthesia with propofol and remifentanil. No study-specific intervention will be administered. Perioperative variables and total anesthetic drug consumption will be recorded. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Intraoperative Propofol Consumption
The total cumulative dose of propofol administered during anesthetic induction and BIS-guided total intravenous anesthesia maintenance will be recorded in milligrams (mg) for each participant. Total propofol consumption will be compared between participants receiving chronic SSRI/SNRI therapy and control participants.
Measured: From induction of anesthesia until the end of surgery, on the day of surgery
Secondary outcomes (2)
Total Intraoperative Remifentanil Consumption
The total cumulative dose of remifentanil administered during total intravenous anesthesia will be recorded in micrograms (µg) for each participant and compared between the study groups.
Measured: From induction of anesthesia until the end of surgery, on the day of surgery
Difference in Total Intraoperative Propofol Consumption Between the SSRI and SNRI Groups
Total intraoperative propofol consumption, measured in milligrams (mg), will be compared between participants receiving chronic selective serotonin reuptake inhibitor (SSRI) therapy and those receiving chronic serotonin-norepinephrine reuptake inhibitor (SNRI) therapy.
Measured: From induction of anesthesia to the end of surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2026
- Study start30 Oct 2026 (estimated)
- Primary completion30 Apr 2027 (estimated)
- Study completion30 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Chronic SSRI/SNRI Use and Intraoperative Propofol RequirementsStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 216 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kocaeli City Hospital
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07822295
- Sponsor's protocol ID
- KAEK-08.bI.03
- Status last verified
- Sep 2026
- First submitted
- 10 Sep 2026
- Last updated
- 30 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data are not planned to be shared with external researchers because the approved protocol and informed consent process do not include external sharing of individual-level data. Study findings will be reported only in aggregate form in scientific presentations and publications to protect participant confidentiality.
Publications
Pan WT, Ji MH, Ma D, Yang JJ. Effect of perioperative autonomic nervous system imbalance on surgical outcomes: a systematic review. Br J Anaesth. 2025 Sep;135(3):608-622. doi: 10.1016/j.bja.2025.06.004. Epub 2025 Jul 4.
PubMed 40615330Dean L, Kane M. Codeine Therapy and CYP2D6 Genotype. 2012 Sep 20 [updated 2026 Jul 6]. In: Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK100662/
PubMed 28520350Chu A, Wadhwa R. Selective Serotonin Reuptake Inhibitors. 2023 May 1. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK554406/
PubMed 32119293Fraer M, Kilic F. Serotonin: a different player in hypertension-associated thrombosis. Hypertension. 2015 May;65(5):942-8. doi: 10.1161/HYPERTENSIONAHA.114.05061. Epub 2015 Mar 9. No abstract available.
PubMed 25753975Loyd DR, Henry MA, Hargreaves KM. Serotonergic neuromodulation of peripheral nociceptors. Semin Cell Dev Biol. 2013 Jan;24(1):51-7. doi: 10.1016/j.semcdb.2012.09.002. Epub 2012 Sep 19.
PubMed 23000387Zhong Z, Wang L, Wen X, Liu Y, Fan Y, Liu Z. A meta-analysis of effects of selective serotonin reuptake inhibitors on blood pressure in depression treatment: outcomes from placebo and serotonin and noradrenaline reuptake inhibitor controlled trials. Neuropsychiatr Dis Treat. 2017 Nov 7;13:2781-2796. doi: 10.2147/NDT.S141832. eCollection 2017.
PubMed 29158677Liu T, Zhang X, Li A, Liu T, Yang X, Zhang H, Lei Y, Yang Q, Dong H. Effects of intra-operative administration of subanesthetic s-ketamine on emergence from sevoflurane anesthesia: a randomized double-blind placebo-controlled study. BMC Anesthesiol. 2023 Jun 23;23(1):221. doi: 10.1186/s12871-023-02170-5.
PubMed 37353750Harbell MW, Dumitrascu C, Bettini L, Yu S, Thiele CM, Koyyalamudi V. Anesthetic Considerations for Patients on Psychotropic Drug Therapies. Neurol Int. 2021 Nov 29;13(4):640-658. doi: 10.3390/neurolint13040062.
PubMed 34940748
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Chronic ssrı/snrı Antidepressant Treatment on Propofol Consumption in Elective Spine Surgery: a Prospective Cohort Study
- ClinicalTrials.gov ID
- NCT07822295
- Acronym / sponsor ID
- KAEK-08.bI.03
- Keywords
- Selective Serotonin Reuptake Inhibitors, Serotonin-Norepinephrine Reuptake Inhibitors, SSRI, SNRI, Propofol Consumption, Chronic Antidepressant Therapy, Elective Spine Surgery, Remifentanil
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 216 participants (estimated)
- Lead sponsor
- Kocaeli City HospitalOther government
- Study start
- 30 Oct 2026 (estimated)
- Primary completion
- 30 Apr 2027 (estimated)
- Study completion
- 30 May 2027 (estimated)
- First posted
- 16 Sep 2026 (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.
The goal of this observational study is to learn whether long-term use of selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressants is related to the amount of propofol needed during planned spine surgery. Propofol is a medicine given through a vein to produce and maintain anesthesia.
The main questions this study aims to answer are:
- Do patients who regularly take an SSRI or SNRI need a different total amount of propofol during surgery than patients who do not take these medicines?
- Are there differences in propofol and remifentanil use, depth of anesthesia, vital signs, or recovery time between the study groups?
The study will include 216 adults undergoing planned spine surgery. Researchers will compare 108 participants who regularly take an SSRI or SNRI with 108 participants who do not take these medicines.
All participants will receive routine anesthesia care. The study will not start, stop, or change any antidepressant treatment, and participants will not be randomly assigned to a group. Researchers will record the amount of propofol and remifentanil used during surgery, blood pressure, heart rate, oxygen level, depth of anesthesia, and recovery time.
Detailed description
Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are considered first-line pharmacological agents in the treatment of depression and anxiety disorders (1). These drugs selectively increase serotonin concentrations in the synaptic cleft by inhibiting the serotonin transporter (SERT); they suppress norepinephrine and dopamine reuptake only minimally (1). However, SSRI and SNRI agents have the potential to cause hypertensive effects (2). The hypertensive mechanism is associated with SSRIs raising synaptic serotonin levels through SERT inhibition, resulting in overstimulation of 5-HT1A and 5-HT2A receptors (3). Serotonin excess activates the sympathetic nervous system, triggering vasoconstriction, tachycardia, and catecholamine release, leading to an increase in blood pressure; this indirectly increases the need for intraoperative anesthetic (4). Additionally, SSRIs-especially potent CYP2D6 inhibitors such as paroxetine and fluoxetine-can reduce the analgesic effects of prodrug-type opioids (e.g., codeine, hydrocodone, and tramadol) by inhibiting their metabolism (5). This interaction blocks the conversion of prodrugs to active metabolites (codeine → morphine; hydrocodone → hydromorphone) via the CYP2D6 enzyme in the liver, reducing plasma active opioid concentrations and disrupting μ-opioid receptor activation; ultimately leading to a higher opioid dose requirement for patients (5). As a parallel mechanism, serotonin excess (at high doses or in interaction with other agents) can induce serotonin-induced hyperalgesia; this process occurs through stimulation of the cAMP secondary messenger system via 5-HT1A receptors in peripheral nerve endings and potentiates the tendency towards hyperalgesia (6). Considering these described mechanisms, maintaining a constant remifentanil dose during the intraoperative period may increase propofol consumption (7). However, despite this theoretical information, the effect of SSRI-SNRI use on propofol consumption during the perioperative period has not been sufficiently investigated. Therefore, this study will investigate the relationship between these two factors.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Chronic SSRI/SNRI Treatment Group | – | –Participants receiving chronic selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) therapy before elective spine surgery. These medications will not be initiated, discontinued, or modified for study purposes. Intraoperative propofol consumption and prespecified perioperative outcomes will be recorded. |
| Control Group | – | –Adults undergoing elective spine surgery who are not receiving chronic SSRI or SNRI therapy and are not using antipsychotic or other antidepressant medications. Participants will receive routine BIS-guided total intravenous anesthesia with propofol and remifentanil. No study-specific intervention will be administered. Perioperative variables and total anesthetic drug consumption will be recorded. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The study population will be drawn from patients scheduled for elective spine surgery at Kocaeli City Hospital in Kocaeli, Türkiye. Potential participants will be identified during routine preoperative evaluations in the anesthesia clinic or relevant inpatient surgical wards before surgery.
Key inclusion criteria (6 listed)
- Study period: Between October 2026 and April 2027,
- Study location: Kocaeli City Hospital Operating Rooms,
- Type of surgery: Patients scheduled for spinal surgery,
- Medication use: Patients using chronic SSRI or SNRI group antidepressants in the preoperative period, but not using antipsychotics or other group antidepressants (e.g., TCA, MAOI, atypical antidepressants),
- Age criterion: Adult individuals aged 18 and over,
Key exclusion criteria (6 listed)
- Patients who cannot give informed consent and individuals under 18 years of age,
- Patients with an ASA (American Society of Anesthesiologists) physical status classification of ASA IV or higher,
- Cases requiring emergency surgical intervention,
- Patients undergoing surgery due to trauma,
- Patients using antidepressants other than selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs),
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Total Intraoperative Propofol Consumption
Time frame: From induction of anesthesia until the end of surgery, on the day of surgery
The total cumulative dose of propofol administered during anesthetic induction and BIS-guided total intravenous anesthesia maintenance will be recorded in milligrams (mg) for each participant. Total propofol consumption will be compared between participants receiving chronic SSRI/SNRI therapy and control participants.
2 secondary outcomes
Total Intraoperative Remifentanil Consumption
Time frame: From induction of anesthesia until the end of surgery, on the day of surgery
Difference in Total Intraoperative Propofol Consumption Between the SSRI and SNRI Groups
Time frame: From induction of anesthesia to the end of surgery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2026.
- Background: PubMed 40615330Pan WT, Ji MH, Ma D, Yang JJ. Effect of perioperative autonomic nervous system imbalance on surgical outcomes: a systematic review. Br J Anaesth. 2025 Sep;135(3):608-622. doi: 10.1016/j.bja.2025.06.004. Epub 2025 Jul 4.
- Results publication: PubMed 28520350Dean L, Kane M. Codeine Therapy and CYP2D6 Genotype. 2012 Sep 20 [updated 2026 Jul 6]. In: Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK100662/
- Results publication: PubMed 32119293Chu A, Wadhwa R. Selective Serotonin Reuptake Inhibitors. 2023 May 1. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK554406/
- Results publication: PubMed 25753975Fraer M, Kilic F. Serotonin: a different player in hypertension-associated thrombosis. Hypertension. 2015 May;65(5):942-8. doi: 10.1161/HYPERTENSIONAHA.114.05061. Epub 2015 Mar 9. No abstract available.
- Results publication: PubMed 23000387Loyd DR, Henry MA, Hargreaves KM. Serotonergic neuromodulation of peripheral nociceptors. Semin Cell Dev Biol. 2013 Jan;24(1):51-7. doi: 10.1016/j.semcdb.2012.09.002. Epub 2012 Sep 19.
- Results publication: PubMed 29158677Zhong Z, Wang L, Wen X, Liu Y, Fan Y, Liu Z. A meta-analysis of effects of selective serotonin reuptake inhibitors on blood pressure in depression treatment: outcomes from placebo and serotonin and noradrenaline reuptake inhibitor controlled trials. Neuropsychiatr Dis Treat. 2017 Nov 7;13:2781-2796. doi: 10.2147/NDT.S141832. eCollection 2017.
- Results publication: PubMed 37353750Liu T, Zhang X, Li A, Liu T, Yang X, Zhang H, Lei Y, Yang Q, Dong H. Effects of intra-operative administration of subanesthetic s-ketamine on emergence from sevoflurane anesthesia: a randomized double-blind placebo-controlled study. BMC Anesthesiol. 2023 Jun 23;23(1):221. doi: 10.1186/s12871-023-02170-5.
- Results publication: PubMed 34940748Harbell MW, Dumitrascu C, Bettini L, Yu S, Thiele CM, Koyyalamudi V. Anesthetic Considerations for Patients on Psychotropic Drug Therapies. Neurol Int. 2021 Nov 29;13(4):640-658. doi: 10.3390/neurolint13040062.
- Individual participant dataSharing planned: No. Individual participant data are not planned to be shared with external researchers because the approved protocol and informed consent process do not include external sharing of individual-level data. Study findings will be reported only in aggregate form in scientific presentations and publications to protect participant confidentiality.
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic SSRI/SNRI Use and Intraoperative Propofol Requirements, run by Kocaeli City Hospital at 1 site in Turkey (Türkiye).
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 6 inclusion and 6 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: opening soon, as of the sponsor's last update on 30 Sep 2026. 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 Turkey (Türkiye). 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact AHMET YÜKSEK, MD, ASSOCIATE PROFESSOR (+90 532 658 03 51, mdayuksek@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total Intraoperative Propofol Consumption (time frame: From induction of anesthesia until the end of surgery, on the day of surgery). 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 NCT07822295, which also lists 8 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 30 Sep 2026.