Lamotrigine

If you are taking any drug, over the counter, prescribed, recreationally, you need to understand:

1. The reason why you take the drug
2. Risks and (side) effects of taking this drugx
3. Alternatives to taking a medication

Making sure you understand this is part of my jobs as a psychiatrist (either as a patient of mine here in Brooklyn or a reader of my blog). I suggest you start seeing yourself as the CEO of YourBody&Mind Inc and a drug you take is on your payroll. You pay for it - one way or another. Therefore, the drug has to do its job to deserve that spot on your payroll. If I were you, I would fir it, if it doesn't. More about payroll and how this applies to other areas of your life in a future post. 

This post is about lamotrigine, a medication I often use for treating bipolar illness II. Lamotrigine, also known by the brand name Lamictal, has been around for more than 25 years. I think it is fair to say that it is well established, and that we know what to expect from using it. Lamotrigine came to psychiatry as a re-purposed drug. Just like valproic acid, it was originally used as an anti-seizure medication by our colleagues in neurology. I treat quite a few people on the bipolar spectrum here in Brooklyn. Lamotrigine has become one of my patients' favorites for treating bipolar II. 

Here are the basics I want my patients and their families to know know about it:

Lamotrigine - what is it good for?

• Stabilizing your mood - i.e. preventing abnormal highs and lows
• Treating depressive episodes in bipolar illness - lamotrigine has a reliable antidepressant effect. Compared to other psychotropic medications, lamotrigine has remarkably few and rare side effects. Weight gain is not a problem.

What does it not treat well?

• A manic episode

Because of that, it might not work well for bipolar I alone. Bipolar I means distinct manic and depressive phases, not just mood swings. Lamotrigine treats the lows well, not so much the highs. 

For bipolar II on the other hand, it can be a very good fit. In bipolar II patients struggle most with the lows. The highs are much less pronounced and problematic for my patients. Here lamotrigine treats the symptoms well without much (if any) side effects. Compared to antidepressants such as the SSRI fluoxetine, it has very little potential to push patients into manic symptoms. It does happen, for some patients lamotrigine works too much like an antidepressants if I had to give you an estimate based on personal experience, conversations with colleagues and online research, probably 1 out of 25 patients treated with lamotrigine will get worse, i.e. experience manic symptoms. 

What about side effects?

The one concern with lamotrigine is that it can cause a serious skin rash know as Stevens–Johnson syndrome (SJS). That's an allergic reaction, the probability for SJS is around 1 out of 1000 patients treated. The incidence (how often this happens) is higher with children and adolescents. Nearly all cases of SJS associated with lamotrigine have occurred within 2 to 8 weeks of beginning treatment. To minimize the risk, lamotrigine should be started very slowly and I do so with all of my patients. What complicates matters is that there is also a harmless rash that occurs much more often - about 1 in 10 patients will experience this. Increasing the medication. Now, being told about both, finding yourself with the much more common harmless rash will nevertheless send you in a tizzy. To minimize the possibility for even the harmless rash, I will start low and go slow with lamotrigine. 

Lamotrigine is notorious for the rare potential to cause SJS. Please know that there are other medications, that have the same potential: Carbamazepine (Tegretol), valproate (Depakote) and phenytoin (Dilantin) can also cause SJS, albeit at a lower rate compared to lamotrigine with the exception of phenytoin. I will stay away from prescribing lamotrigine together with these drugs, specifically with valproate. 

About that rash...

Because you will worry about it despite the low likelihood anyways, here are warning signs:

• Any rash on the face
• Any rash above the neck
• Any rash around or in the mouth
• Rash on the mucous membranes of mouth, nose, eyes (the conjunctiva), anus. 

If in doubt, at that means if you develop a rash while on lamotrigine, go see your doctor. 

Should one of my patients develop a rash, I would have them see a dermatologist within 1-2 days and hold the doses until then. If this is not feasible, I would stop the medication for any rash above the neck. If there is a rash anywhere else, I would reduce the dose to the previous level and hold it there, observing the rash to see if it is going away. If it does, I would increase the dose again, this time more slowly and by smaller steps. For itchiness, Benadryl works well. I would want you to see a dermatologist to stop the medication right away is necessary. In addition, the medication needs to be started from scratch and that is at the lowest level when it is stopped for more than 3 days. 

After the rash?

Studies show that re-challenging with lamotrigine after you experienced a rash can be done safely. A lot of participants did not experience a recurrence of the rash.

Re-challenging should be done at an even lower starting dose and dose increase, e.g. 2.5mg steps per week. 

Anything else?

Lamotrigine can rarely cause hair loss. Even more unlikely: Aseptic meningitis, kind of a really bad headache. In combination with quetiapine (Seroquel), lamotrigine will lower blood levels of quetiapine by 60%. Sometimes it seems to make things worse, sometimes it doesn't work at all. If you are taking lamotrigine, don't supplement with folate as this might blunt lamotrigine's effect. 

How does lamotrigine work?

I would like to give you a smart answer but the smartest thing to write is "we don't know", which means that I don't know either.

Dosing schedule for Bipolar Depression

Week   1 = 12.5 mg daily

Week   2 =    25 mg daily

Week   3 = 37.5 mg daily

Week   4 =    50 mg daily

Week   5 =    50 mg daily

Week   6 =    75 mg daily

Week   7 =  100 mg daily

Week   8 =  100 mg daily

Week   9 =  125 mg daily

Week 10 = 150 mg daily

Week 11 = 175 mg daily

Week 12 = 200 mg daily

Treatment for bipolar depression is off-label. That means that while thousands of patients are on this medication for exactly this indication, the manufacturer has not asked for FDA approval for this indication. Compared to the manufactures dosing schedule, I prefer to go even slower. If you are anywhere on the bipolar spectrum, specifically with bipolar II, you have been dealing with this for a much longer time than the 12 weeks it would take you to get to a maintenance dose of 200mg per day. Please keep in mind that some patients take higher doses - clinical trials have evaluated up to 400mg per day. However, if you look at guidelines, such as the WFSBP 2010, the recommended dose range is from 50 to 200mg per day. Even though most of my patients are at doses higher than that, you can be at an effective maintenance dose of 50mg daily in week 4 of starting with lamotrigine. 

How Do You Stop Taking It?

By letting your psychiatrist know and decreasing it by ~50% every week, taking a minimum of 2 weeks unless you are worried about a rash, which would require a more rapid withdrawal.

Restarting Lamotrigine after Stoping it

Professional guidelines recommend a complete restart from the lowest (starting) dose after you have not taken the medication for more than 5 half-lives. What that means in plain English and in real life: If you have stopped lamotrigine for more than 3 days, you will have to start with the dosing schedule as outlined above again. If you were on 200mg 4 days ago, you will have to start with 12.5mg again and work yourself up to 200mg. 

Lamotrigine While Being on Oral Contraceptives

If you take an oral contraceptive (birth control pill), your lamotrigine dose may need to increase twofold over the target dose, i.e. if your target dose was 200mg daily before taking the pill, your new target dose might be up to 400mg daily. After talking to your psychiatrist about this, your lamotrigine dose should increase when you are starting to take the contraceptive. Titrate up to clinical response but not faster than 50 to 100mg per week. Once you discontinue an estrogen-containing oral contraceptive, you will have to decrease the Lamotrigine dose by 50% but do not do this faster than 25% of the total daily dose over a 2-week period. Lastly, if you take any of these medications -carbamazepine, phenytoin, primidone, rifampin, lopinavir/ritonavir, atazanavir, ritonavir - forget about what I just wrote because no dose adjustment is needed.