Lamotrigine
What is lamotrigine (aka Lamictal) used for in psychiatry?
-Bipolar 2 mood stability or depression treatment
-irritability and/or anger across all ages and conditions
-Unipolar depression that hasn’t responded to various traditional agents
-It’s also used to treat certain kinds of pain and headaches including migraines
What is lamotrigine FDA approved to treat?
-Bipolar maintenance
-Seizure disorders
How is lamotrigine dosed?
It is purposefully dosed very slowly. Goal doses are usually 150mg to 300mg per day (sometimes it goes as high as 400mg and may be divided at doses above 200mg/day).
The normal dosing schedule to get to a therapeutic dose is as follows:
-25 mg once a day for 2 weeks, then
-50 mg per day for 2 weeks, then
-Increase to 100 mg per day x2 weeks. We may maintain here (which is more often the case in adolescents) but most adults will continue to increase by 50mg every 2 weeks until they reach the goal dose of 150mg to 200mg/day.
Why is the dosing so cautious?
Because of the risk of a serious inflammatory reaction called Stevens Johnson Syndrome. This reaction is minimized by titrating up on the dose slowly. If more than 3 doses are missed even after someone has been on lamotrigine for years, the dosing schedule is started over at 25mg as if the patient was never on lamotrigine.
What do we know about rashes associated with lamotrigine?
-The risk of rashes while taking lamotrigine is higher than it is with other medications (about 1 in 10!). The most common type of rash is a normal drug rash, which is often itchy and usually small dots spread over various parts of the body.
-The other type of rash is associated with a rare inflammatory reaction called Steven Johnson Syndrome, which requires that you go to the emergency room. This risk is less than 1/2500 people (0.04%) who start lamotrigine and this risk is actually lower in those who go up on the dose slowly. More on that below.
What are the signs that the rash is indicative of Stevens Johnson Syndrome?
-The first symptoms are usually (not always!) malaise, or flu-like symptoms including feeling unwell, fever, headache, joint aches, low appetite, and sometimes a runny nose and/or a cough. Lymph glands are often swollen too.
-Then, within one to three days the rash develops. This rash usually looks like a red or purple "spotty and target-like lesions" 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, blistering, or pain on oral, nasal, eye, vaginal, urethral, GI, and lower respiratory tract mucous membranes, that is concerning for Stevens Johnson Syndrome. Sometimes the whole face is swollen.
-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.
Can lamotrigine be used in those who are planning to get pregnant?
In most cases it is stopped during pregnancy as it can lead to birth defects. In some cases it is continued if it is thought that the benefits to the mother's mental health outweigh the potential risk to the developing baby. Please consult with your practitioner, preferably one who specializes in women's & perinatal psychiatry.
What should women on birth control know about lamotrigine?
-There is some concern that lamotrigine MIGHT make oral contraceptive birth control less effective. And it is possible some birth control can make the lamotrigine get broken down faster by the body, and therefore be less effective unless doses are adjusted. Read here for more because this is not a sure thing; many practitioners do use both together, but the theoretical risk is there. Female patients can consider using a non-hormonal contraceptive such as the copper IUD or the Paragard IUD.
-Do not take the supplement folate (or folic acid) with lamotrigine as it inhibits the effectiveness of lamotrigine. There is evidence that using a bioactive form of folic acid called l-methylfolate, which is available over the counter, is safe to use with lamotrigine.
Who should get an ECG when starting lamotrigine?
There is a very small chance of ECG changes (cardiac rhythm changes) so those with a personal or first person relative history of heart arrhythmias should get an ECG and clearance from their cardiologist prior to starting lamotrigine.
What are some precautions I should take when starting lamotrigine?
-When starting lamotrigine, do not start any new skin or hair product (soap, shampoo, etc) that you may have an allergic reaction to because we don’t want to be confused by the origin if a rash does develop.
-Avoid excess exposure to sun for the first few months as your skin may be more sensitive.
-Check your entire body, front and back, for any skin rash. This includes looking in a mirror. Do this daily for the first few months when the risk of a serious allergic reaction is the highest.
- If any skin rash occurs, hold the medicine and contact the office AND also go to your nearest walk-in center or ER just to be certain it is not Stevens Johnson Syndrome.
-If for any reason this medicine is missed for 3 days, do NOT restart it. Call your doctor to ask about starting again on a very low dose and titrating the dose up
-Please read additional important information about lamotrigine here.
Besides folate and oral contraceptives what other medications should be used with caution or avoided when using lamotrigine?
-Ketamine infusions or intranasal esketamine (Spravato): there is some evidence that lamotrigine may interfere with achieving the maximum benefit of ketamine in treatment resistant depression.
-Anticonvulsants such as phenytoin (Dilantin), carbamazepine (Tegretol), phenobarbital, and primidone (Mysoline).
-Rifampin (Rifadin), a rarely used antibiotic.
-Ritonavir (Norvir), an antiviral medication used to treat HIV/AIDS.
What is the proposed mechanism of lamotrigine?
It enhances the release of GABA in the brain which tends to act as an inhibitory molecule in certain parts of the brain implicated in mood, anger, and seizures.
