Lamotrigine with Sertraline Interaction Details

Brand Names Associated with Lamotrigine

Brand Names Associated with Sertraline

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 08, 2023

Interaction Effect

An increased risk of lamotrigine toxicity (fatigue, sedation, confusion, decreased cognition)

Interaction Summary

Two case reports describe patients with epilepsy who experienced lamotrigine toxicity when sertraline therapy was initiated. Lamotrigine is metabolized primarily via glucuronidation, while sertraline relies on N-demethylation, hydroxylation, oxidative deamination, and glucuronidation. It is hypothesized that sertraline decreases lamotrigine metabolism through competitive inhibition of glucuronidation.

Severity

Moderate

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Caution should be exercised when combining sertraline and lamotrigine therapy. Lamotrigine blood levels should be closely monitored and dosages adjusted accordingly.

Mechanism Of Interaction

Inhibition of lamotrigine glucuronidation

Literature Reports

A) A 39-year-old female patient with epilepsy was maintained on lamotrigine 200 mg daily with a baseline lamotrigine blood level of 2.5 mcg/mL (9.8 mcmol/L). Because of an intermittent explosive disorder, sertraline 25 mg daily was initiated. Six weeks later, the lamotrigine level was 5.1 mcg/mL (20 mcmol/L) and the patient complained of confusion and cognitive impairment. Sertraline was increased to 50 mg daily while lamotrigine was decreased to 100 mg daily. This lower lamotrigine dose eliminated the patient's confusion and impaired cognition, and the blood level of lamotrigine stabilized at 3.1 mcg/mL (12.1 mcmol/L) .

B) Lamotrigine 450 mg daily was not controlling seizures in a 17-year-old female patient with mixed epileptic disorder and explosivity. Sertraline therapy was initiated and titrated to 75 mg daily without any side effects. Lamotrigine was also increased to 600 mg daily, and six weeks later, the patient complained of sedation, fatigue, and decreased cognition. The lamotrigine blood level was 19.3 mcg/mL (75.4 mcmol/L) at this time. The sertraline dose was decreased to 50 mg daily while the lamotrigine level was increased to 800 mg daily, resulting in a new steady-state lamotrigine level of 9.8 mcg/mL (38.3 mcmol/L). In this case report, the lamotrigine blood level decreased to approximately 50% with a 33% decrease in the sertraline daily dose, even though the lamotrigine dose had been increased by 33% .

Lamotrigine Overview

• Lamotrigine extended-release (long-acting) tablets are used with other medications to treat certain types of seizures in patients who have epilepsy. All types of lamotrigine tablets (tablets, orally disintegrating tablets, and chewable tablets) other than the extended-release tablets are used alone or with other medications to treat seizures in people who have epilepsy or Lennox-Gastaut syndrome (a disorder that causes seizures and often causes developmental delays). All types of lamotrigine tablets other than the extended-release tablets are also used to increase the time between episodes of depression, mania (frenzied or abnormally excited mood), and other abnormal moods in patients with bipolar I disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Lamotrigine has not been shown to be effective when people experience the actual episodes of depression or mania, so other medications must be used to help people recover from these episodes. Lamotrigine is in a class of medications called anticonvulsants. It works by decreasing abnormal electrical activity in the brain.

Sertraline Overview

• Sertraline is used to treat depression, obsessive-compulsive disorder (bothersome thoughts that won't go away and the need to perform certain actions over and over), panic attacks (sudden, unexpected attacks of extreme fear and worry about these attacks), posttraumatic stress disorder (disturbing psychological symptoms that develop after a frightening experience), and social anxiety disorder (extreme fear of interacting with others or performing in front of others that interferes with normal life). It is also used to relieve the symptoms of premenstrual dysphoric disorder, including mood swings, irritability, bloating, and breast tenderness. Sertraline is in a class of antidepressants called selective serotonin reuptake inhibitors (SSRIs). It works by increasing the amounts of serotonin, a natural substance in the brain that helps maintain mental balance.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.