Lamotrigine in Reducing Psychologic Side-Effect of Perioperative Ketamine

Study Overview
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Brief Summary
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Patient will receive lamotrigine vs. placebo with small sips of water. Lamotrigine reaches peak level 1-4 hours after oral administration.

Detailed Description
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1:1 randomization without stratification use web-based software (Redcap) before surgery. Allocation will be concealed from the patient, the nurse, the operating room team. Both patient and the operating room team will be blinded to the treatment allocation (double blind). Standard preoperative care as per anesthesia care team. Patient will receive lamotrigine vs. placebo with small sips of water. Lamotrigine reaches peak level 1-4 hours after oral administration. Single dose lamotrigine is safe and is not associated with rash. Standard intraoperative care as per the anesthesia care team. All patients will receive Ketamine 1 mg/kg at induction. Ketamine 5mcg/kg/min will be started at induction and stopped at the end of surgery. Standard postoperative care as per PACU team. The psychologic side-effects will be measured using Brief Psychiatric Rating Scale (BPRS) using an online tool. Research fellow will receive standardized training in administering BPRS from Dr. Amit Anand using structured material. Dr. Anand has used this training for other current research projects.

Official Title
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The Role of Lamotrigine in Reducing Psychologic Side-Effect of Perioperative Ketamine Use

Conditions
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Reducing Psychological Side Effects of Ketamine

Intervention / Treatment
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* Drug: Lamotrigine 300 MG
* Drug: Placebo
* Drug: Ketamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 -65 Years of age Planned overnight hospital stay Exclusion Criteria: Pregnant and planning to become pregnant No known History of seizure No known History of Schizophrenia No known History of unstable angina Patients taking Antiepileptic medications Known history of Lamotrigine intake in past. Any history of allergic reaction to lamotrigine in the past.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomization without stratification
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: lamotrigine<br>Patient will receive 300 mg of oral lamotrigine with small sips of water to reduce the psychologic side effects (measured by four key items of Brief Psychiatric Rating Scale: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content) of intraoperative ketamine use. | Drug: Lamotrigine 300 MG<br>* 300 mg of oral Lamotrigine. One of the key studies in this area was reported at the Society of Neuroscience meeting in 1997 and later published in the Archives of General Psychiatry. This study reported that, in healthy subjects 300 mg oral lamotrigine significantly decreased ketamine-induced perceptual abnormalities as assessed by the Clinician-Administered Dissociative States Scale (P<.001).31 Furthermore lamotrigine increased the immediate mood-elevating effects of ketamine (P<.05).<br>* Other names: Lamictal 300 mg;Drug: Ketamine<br>* 1mg/kg bolus at induction followed by 5 microgram/kg/min infusion till the end of the surgery<br>|
| Placebo Comparator: Placebo<br>Patient will receive oral Placebo with small sips of water, to reduce the psychologic side effects (measured by four key items of Brief Psychiatric Rating Scale: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content) of intraoperative ketamine use. | Drug: Placebo<br>* 300 mg of oral Placebo<br>Drug: Ketamine<br>* 1mg/kg bolus at induction followed by 5 microgram/kg/min infusion till the end of the surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psychologic Side-effects | The primary outcome of psychologic side-effects was measured in PACU (up to 90 minutes after ketamine infusion). This included four key items of the Brief Psychiatric Rating Scale (BPRS) corresponding to positive symptoms of schizophrenia: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content. Each symptom is rated 1-7 ( 1 = not present, 2 = very mild, 3 = mild, 4 = moderate, 5 = moderately severe, 6 = severe, 7 = extremely severe ), and, therefore, the total score as the primary outcome based on four key items of BPRS will be between 4 (best score) and 28 (worst score). | in PACU (up to 90 minutes after ketamine infusion) | 
| Number of Patients With Psychologic Disturbances- | The psychologic side-effects were measured in PACU (up to 90 minutes after ketamine infusion). This included four key items of the Brief Psychiatric Rating Scale (BPRS) corresponding to positive symptoms of schizophrenia: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content. Each symptom is rated 1-7 ( 1 = not present, 2 = very mild, 3 = mild, 4 = moderate, 5 = moderately severe, 6 = severe, 7 = extremely severe ), and, therefore, the total score as the primary outcome based on four key items of BPRS will be between 4 (best score) and 28 (worst score). Patients who had a total score of 4 (all symptoms not present) were determined as not having psychologic disturbance and patients who had a total score of > 4 (having any symptoms present) were determined as having psychologic disturbance. | Up to 90 minutes of PACU arrival | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Opioid Consumption in PACU (mg) | Total cumulative opioid use (total IV morphine equivalents) in postoperative anesthesia care unit (PACU) | from entry to PACU to leaving PACU, up to 4 hours | 
| Pain Score in PACU | Pain score was scaled from 0-10 where 0 means no pain and 10 means most pain. The time-weighted average of pain scores was used if the pain score was measured multiple times. | from entry to PACU to leaving PACU | 
| Number of Patients Who Had PONV (Postoperative Nausea Vomiting) | PONV was measured through Postoperative Nursing Progress Record, where nausea vomiting severity was recorded as 0 (none), 1 (mild), 2 (moderate), 3 (severe). Patients whose score was 0 were determined as not having PONV and patients whose score was positive were determined as having PONV. | after surgery up to discharge |