Lamotrigine in Reducing Psychologic Side-Effect of Perioperative Ketamine

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

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

Study Overview

• Status: Completed
• Conditions: Reducing Psychological Side Effects of Ketamine
• Intervention / Treatment: Drug: Lamotrigine 300 MG; Drug: Ketamine; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: lamotrigine; 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; 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).; Other Names: Lamictal 300 mg; Drug: Ketamine; 1mg/kg bolus at induction followed by 5 microgram/kg/min infusion till the end of the surgery
Placebo Comparator: Placebo; 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: Ketamine; 1mg/kg bolus at induction followed by 5 microgram/kg/min infusion till the end of the surgery; Drug: Placebo; 300 mg of oral Placebo

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Daily Average Opioid Use During Hospital Stay	The average daily opioid use (mg) during the hospital stay.	from admission up to discharge
Opioid Related Side-effects (ORSDS)-POD1	ORSDS is a 4 point-scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness for 12 opioid-related side effects, with a score of each item ranging from 0 to 4 where higher scores mean more side effects). The final ORSDS score is the average of all 12 scores from those 12 items, ranging from 0 to 4 where a higher score means worse outcome. This one measure ORSDS at postoperative day 1	postoperative day 1
Opioid Related Side-effects (ORSDS)-POD2	ORSDS is a 4 point-scale that evaluates 3 symptom distress dimensions (frequency, severity, bothersomeness for 12 opioid-related side effects, with a score of each item ranging from 0 to 4 where higher scores mean more side effects). The final ORSDS score is the average of all 12 scores from those 12 items, ranging from 0 to 4 where a higher score means a worse outcome. This one measure ORSDS at postoperative day 2.	postoperative day 2
PACU Length of Stay, Hours	Hours spent in PACU (Postanesthesia Care Unit).	in PACU

Collaborators and Investigators

• Sponsor: The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2019
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: December 3, 2018
• First Submitted That Met QC Criteria: February 4, 2019
• First Posted (Actual): February 6, 2019

Study Record Updates

• Last Update Posted (Actual): June 9, 2021
• Last Update Submitted That Met QC Criteria: May 12, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anticonvulsants; Sodium Channel Blockers; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Ketamine; Lamotrigine
• Other Study ID Numbers: 18-952

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There is no plan to make subjects data available to outside researchers

Drug and device information, study documents

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