Oxcarbazepine for Mood

Trileptal is the brand name for oxcarbazepine. It was initially created for seizures in children and adults and is used in children as young as 4 years of age. It is also FDA approved for bipolar disorder in adults and it is used off-label in children and teens who have irritability and anger related to disruptive mood dysregulation disorder. 

What is the mechanism of oxcarbazepine?
It works on brain cells to slow down the voltage gated sodium channels— this leads to a mild slowing of the cells that are implicated in mood dysregulation. It also exerts its effects on the GABA:Glutamate system of the brain which is what regulates the “speed” of the cells in then brain, among other functions. 

What are the important side effects and genetic testing to know about with regards to oxcarbazepine? 

1. Like lamotrigine, oxcarbazepine does have the potential to cause a serious inflammatory reaction (see the question below about Stevens Johnson Syndrome), so we go up on it slowly. In those of Asian descent, genetic testing should be done prior to starting oxcarbazepine to assess their risk for Stevens Johnson Syndrome as they have a higher chance of having HLA-B 1502 (10% of Asians have this....this rare mutation is almost entirely absent in Caucasians, African-Americans, Hispanics, and Native Americans.). Recently the HLA-A*31:01 was added to the list of potentially risky HLA subytypes and this is also more commonly present in Asian populations; but it is also present in 15% of Native American and 5% of African-Americans.
   
2. We should also get labs 2 weeks in and then at 2 months in to follow the sodium level— in some patients, oxcarbazepine can lower sodium. ‍
3. Unlike other mood stabilizers, the chance for weight gain is very low. 

So who should get genetic testing prior to starting oxcarbazepine? 
Patients with Asian, Native American, and African American Ancestry should get genetic testing. We often use genomind or genesight for these purposes.

How is oxcarbazepine dosed? 
— In adults we start at 300mg every 12 hours for 4 days then increase to 300mg in the morning and 600mg at bedtime for 4 days, then 600mg twice per day. The goal dose is usually anywhere from 1200mg to 2400mg total, per day (divided between morning and night). 
— In children, we start lower and often use a liquid preparation at first. The initial dose is 8 to 10mg/kg per day divided into 2 doses. In those < 10 years of age I often start at 1.5ml of liquid oxcarbazepine (equal to 90mg) given twice per day (after breakfast and then again after dinner). In 10 days we can increase to 2.5ml (150mg) twice per day, then in 10 more days we increase to 3.5ml (210mg) twice per day, then 5ml (300mg) 2x per day. This is a slow and cautious approach.

What medications are problematic when taking oxcarbazepine? 

• It may lower the effectiveness of oral contraceptive pills
• Verapamil (for hypertension) can lower the effectiveness of oxcarbazepine. 
• Do not take with MAOI antidepressants. 
• Do not take if you have glaucoma. 
  

What are the medication side effects seen with oxcarbazepine? 
— Dizziness, nausea, somnolence, diplopia, fatigue, and rash were each reported in at least 5% of patients.

Is oxcarbazepine safe in pregnancy? 
-It has not been adequately studied to say for sure but there is a risk of toxicity to the fetus especially if taken during the first trimester. Women of child bearing age should use a backup form of birth control if they plan to take Oxcarbazepine (it may lower the effectiveness of birth control pills).

What are signs that the rash is indicative of Stevens Johnson Syndrome?
‍The first symptoms are usually malaise, or flu-like symptoms including feeling unwell, fever, headache, joint aches, and sometimes a cough. Then, within one to three days the rash develops. This rash usually looks like a red or purple "spotty and target-like lesion" that spread (these are little circles that are darker in the middle and lighter on the outside--scroll down to the bottom of this post to see a picture). Unlike normal drug rashes, these are usually not itchy and they eventually become blisters. The other unique aspect of Stevens Johnson Syndrome rashes is that they involve not only the skin, but mucous membranes. So if there is any rash or blistering on  oral, nasal, eye, vaginal, urethral, GI, and lower respiratory tract mucous membranes, that is concerning for Stevens Johnson Syndrome. Stevens Johnson Syndrome is more dangerous than a normal drug rash and requires that you stop the medicine immediately and go to the ER for monitoring. This rash can lead to skin damage and, when not treated properly, can lead to death in very rare cases.

Do we get serum levels of oxcarbazepine? 
Not usually but in some cases where the higher doses aren’t working, we may. Therapeutic ranges are based on specimens drawn at trough (ie, immediately before the next dose). Most individuals display optimal response to oxcarbazepine therapy when serum levels of the metabolite (measured in this assay) are between 3 and 35 mcg/mL. Some individuals may respond well outside of this range, or may display toxicity within the therapeutic range.