THE EFFECT OF CHRONIC SSRI/SNRI ANTIDEPRESSANT TREATMENT ON PROPOFOL CONSUMPTION IN ELECTIVE SPINE SURGERY

THE EFFECT OF CHRONIC SSRI/SNRI 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:

• 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.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic SSRI/SNRI Use and Intraoperative Propofol Requirements

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 Type: Observational
• Enrollment (Estimated): 216

Contacts and Locations

• Study Contact: Name: AHMET YÜKSEK, MD, ASSOCIATE PROFESSOR; Phone Number: +90 532 658 03 51; Email: mdayuksek@hotmail.com
• Study Contact Backup: Name: İZZET AVCİ, MD, ANESTHESIA ASSISTANT; Phone Number: +90 552 612 36 72; Email: izzetavc.65@gmail.com

Study Locations

• Turkey (Türkiye)
  • Izmit
    • Kocaeli, Izmit, Turkey (Türkiye), 41000
      • Kocaeli City Hospital
      • Contact: AHMET YÜKSEK, ASSOCIATE PROFESSOR; Phone Number: +90 532 658 03 51; Email: mdayuksek@hotmail.com
      • Contact: İZZET AVCİ, ANESTHESIA ASSISTANT; Phone Number: +90 532 612 36 72; Email: izzetavc.65@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

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.

Description

Inclusion Criteria:

• 1. Study period: Between October 2026 and April 2027, 2. Study location: Kocaeli City Hospital Operating Rooms, 3. Type of surgery: Patients scheduled for spinal surgery, 4. 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), 5. Age criterion: Adult individuals aged 18 and over, 6. ASA classification: Patients in ASA 2-3 group,

Exclusion Criteria:

• 1. Patients who cannot give informed consent and individuals under 18 years of age, 2. Patients with an ASA (American Society of Anesthesiologists) physical status classification of ASA IV or higher, 3. Cases requiring emergency surgical intervention, 4. Patients undergoing surgery due to trauma, 5. Patients using antidepressants other than selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), 6. Cases maintained with inhalation anesthesia.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
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 the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From induction of anesthesia until the end of surgery, on the day of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	From induction of anesthesia to the end of surgery

Collaborators and Investigators

• Sponsor: Kocaeli City Hospital

Publications and helpful links

General 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.
• Dean 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/
• Chu 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/
• Fraer 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.
• Loyd 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.
• Zhong 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.
• Liu 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.
• Harbell 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.

Study record dates

Study Major Dates

• Study Start (Estimated): October 30, 2026
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): May 30, 2027

Study Registration Dates

• First Submitted: September 10, 2026
• First Submitted That Met QC Criteria: September 10, 2026
• First Posted (Actual): September 16, 2026

Study Record Updates

• Last Update Posted (Actual): September 16, 2026
• Last Update Submitted That Met QC Criteria: September 10, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Remifentanil; SSRI; SNRI; Selective Serotonin Reuptake Inhibitors; Bispectral Index; Total Intravenous Anesthesia; Propofol Consumption; Serotonin-Norepinephrine Reuptake Inhibitors; Chronic Antidepressant Therapy; Elective Spine Surgery
• Other Study ID Numbers: KAEK-08.bI.03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No