Lamotrigine

 

Lamotrigine (Brand names: Lamictal, Lamictal CD, Lamictal ODT, Lamictal XR)

Like other mood stabilizers, lamotrigine was originally developed as an anticonvulsant to treat seizures and is often used with other medications in the treatment of bipolar (manic-depressive) disorder. For the latest information on the use of lamotrigine, Psycom spoke with Joseph Goldberg, MD, Clinical Professor of Psychiatry at the Icahn School of Medicine at Mount Sinai in New York, and co-author of Managing the Side Effects of Psychotropic Medications, 2nd Ed, a textbook published by American Psychiatric Association Publishing and Christopher Aiken, MD, the director of the Mood Treatment Center in North Carolina.

Lamotrigine is the only mood stabilizer that calms mood swings by lifting the depression rather than suppressing the mania, says Dr. Aiken. “That makes it a great choice for the bipolar spectrum, where the depressive symptoms usually outweigh the manic ones. Its greatest benefit is in prevention. It can prevent both the depressive and manic side, but its benefits are much stronger for depression and it does not treat active mania or hypomania.”

Dr. Aiken adds that part of the reason patients prefer lamotrigine is that it’s generally free of side effects. “In the original research studies people reported more side effects on the placebo than on lamotrigine. That may sound impossible, but it’s likely that lamotrigine helped them feel better physically by treating their depression,” explains the mood disorder expert adding that lamotrigine is also largely free of the “medicated” feelings that people dislike with mood stabilizers. “People don’t tend to feel dull, flat, or groggy on it.”

In some research studies comparing a placebo to the medicine, the results were exceptional. “Lamotrigine is the only medicine we know of where patients were unable to tell they were taking the medication,” he explains. “It didn’t make them feel medicated, and its benefits built up very gradually. After 2 years, people taking lamotrigine had half as many days of depression as those who did not take it.”

Which conditions are treated with lamotrigine?

Although lamotrigine is not considered an antidepressant, it is used as a maintenance treatment for bipolar I disorder to help stabilize mood changes. (Bipolar I disorder is characterized by manic episodes.) 1,2

“The drug manufacturer’s original studies of lamotrigine in bipolar depression found that improvements were stronger in bipolar 1 than bipolar II disorder,” Dr. Goldberg recalls. (Bipolar II disorder is characterized by longer episodes and more frequent occurrence of major depression and hypomania.) Newer research suggests, however, that lamotrigine may be even more effective as a mood stabilizer in preventing relapses in treating bipolar II disorder.2

There are also conditions lamotrigine treats off-label including borderline personality disorder, schizoaffective disorder, and obsessive-compulsive disorder (OCD), Dr. Aiken says.

How does lamotrigine work?

 Lamotrigine delays the time between mood changes and manic or depressive states in people with bipolar disorder by decreasing the intensity of irregular electrical activity in the brain. People with bipolar disorder are at high risk of experiencing recurrent and relapsing episodes of mood change. Maintenance treatment with lamotrigine helps reduce the risk by preventing or delaying these recurrences and relapses.

“Many clinicians think that lamotrigine helps achieve and sustain even moods over time by virtue of its antidepressant properties, rather than anti-manic (mood-stabilizing) properties,” says Dr. Goldberg. “It works with mood stabilizers like lithium and Divalproex, but it’s not interchangeable with these drugs and cannot be used in their place.”

Lamotrigine is used over time as a preventative medication. Clinical trials that looked at lamotrigine’s potential for treating acute (in-the-moment) episodes of mania found no difference between the medication and placebo.2

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Is there a typical dose of lamotrigine?

Your doctor will initially prescribe a low dose of lamotrigine and gradually increase your dose every week or two for several weeks, until you reach an effective dose level.

“Treatment guidelines for target blood levels of lamotrigine have not been established for conditions other than epilepsy,” Dr. Goldberg points out. “In relapse prevention studies conducted by its manufacturer, however, 200 mg/day was found to be a better target dose than 50 mg/day, while higher doses (400 mg/day) did not provide greater benefit against relapse.”

The dosing regimen of lamotrigine can depend on which other medications you are taking to treat bipolar disorder, and is adjusted when you wean off and discontinue other medications.

“Some medicines slow down the metabolism of lamotrigine (notably, Divalproex), requiring a slower rate of increase and a lower target dose,” notes Dr. Goldberg.  “Others speed up its metabolism (notably, carbamazepine), requiring a faster-than-usual dose increase and a higher-than-usual target dose.”

Lamotrigine comes in several forms for treating bipolar disorder: Tablets, chewable tablets, dissolving tablets. Your doctor may tell you to take tablets once a day, twice a day or every other day.

If you miss a dose of lamotrigine, take the missed dose as soon as you remember. If it is close to the time of your next dose, however, skip the missed dose and continue with your usual schedule. Never take a double dose of lamotrigine.

How long does it take to work?

In certain cases, the antidepressant and antimanic benefits of lamotrigine are noticed pretty early on in the treatment cycle, says Dr. Aiken. “For some other patients, though, effects are seen after about a month of being on lamotrigine treatment. But there will always be others that take a bit longer to experience the positive effects.”

Cost of Lamictal/Lamotrigine

When ordered in lots of 100 tablets, here is the breakdown in pricing for one tablet of the medication in the following doses (Note: pricing information generated April 2011):

  • $4.83 for 25 mg tablet
  • $5.43 for 100 mg tablet
  • $5.93 for 150 mg tablet
  • $6.67 for 200 mg tablet

Generic cost (lamotrigine) is as follows:

  • $0.3 for 25 mg tablet
  • $0.3 for 100 mg tablet
  • $0.53 for 150 mg tablet
  • $0.53 for 2000 mg tablet

Advantages of Lamotrigine

Dr. Aiken reports there are some major advantages of lamotrigine including:

  • It’s effective in a majority of bipolar patients
    Almost two-thirds of patients who are suffering from bipolar mood disorders have responded extremely well to lamotrigine.
  • It’s ideal for mixed states
    People who, due to mania switches during intense cycling, have not been able to rely on other antidepressants have responded well to lamotrigine when given in therapeutic doses.
  • It’s good for patients who respond to nothing else
    Patients who fail to respond to any other mood stabilizers and lithium have shown good results when treated using lamotrigine.
  • There are minimal side effects
    Lamotrigine has minimal side effects that usually fade away after some time.

Who can (and cannot) take lamotrigine for bipolar disorder?

Doctors may prescribe lamotrigine to adults or adolescents who are otherwise being treated for bipolar disorder or weaning off other medications used to treat bipolar disorder. Older adults may be more sensitive to the effects of lamotrigine and prescribed lower doses. “When people respond to lamotrigine, they often say they can see things in perspective better and are less reactive under stress. They usually still have days of depression, but these tend to be shorter and less frequent,” says Dr.  Aiken.

Children under age 18 are at higher risk of developing a skin rash from lamotrigine if dosed too rapidly. In spite of the potential side effects, however, Dr. Goldberg points out that many studies support the use of lamotrigine for treating bipolar disorder in youth.

Definitive information about the safety of lamotrigine in pregnancy is not available, but according to Dr. Goldberg, many doctors perceive it to be among the safer options when treatment is required, especially in women who are more prone to depression than mania.  Like many psychotropic drugs, lamotrigine is secreted into breast milk, so women are advised to discuss with their doctors the risk and benefits of breastfeeding while taking lamotrigine.

Lamotrigine Side Effects 

Some people who take lamotrigine may experience adverse reactions or side effects. In approximately 8 in 10,000 people, lamotrigine can cause severe, life-threatening rashes and other skin disorders, typically between the second and eighth weeks of treatment. The risk of rash increases with higher starting doses, higher escalating doses and use of lamotrigine in combination with valproate.  Early clinical trials and follow-up research showed that the overall incidence of any skin disorders was 11 to 12% in both bipolar I and bipolar II patients treated with lamotrigine. 2

“Most of these skin issues are benign,” Dr. Goldberg emphasizes. “Serious rashes from lamotrigine are not due to an allergy, but rather, a systemic reaction that also usually includes fever, sore throat, swollen glands, and other physical symptoms.”

But as with any medication, Dr. Goldberg adds, allergic reactions to lamotrigine can occur. Get immediate emergency help if you show any signs of an allergic reaction, such as hives, facial or throat swelling, or difficulty breathing. Notify your doctor if you develop a skin rash, especially if it occurs within your mouth or on soft body tissue such as eyelids or around nasal openings, and if it is blistering, peeling, painful, burning, or involves a fever or sore throat. Be sure to report all medications you are taking to medical staff.

Serious side effects that should be reported immediately to your doctor include:

  • Any skin rash, blistering or peeling of skin
  • Painful (burning) sores in or around the mouth, eyes or genitals
  • Jaundice (yellowish skin or eyes)
  • Swollen gland, fever, severe muscle pain
  • Weakness, drowsiness, confusion
  • Stiff neck, headache
  • Increased sensitivity to light
  • Mood or behavior changes, such as depression, anxiety, agitation, hostility, restlessness, mental or physical hyperactivity, suicidal thoughts

Common side effects of lamotrigine that are not emergencies but should also be reported to your doctor include:

  • Headache or dizziness
  • Blurred or double vision
  • Dry mouth
  • Gastrointestinal distress such as nausea, vomiting, diarrhea or stomach pain
  • Fever, sore throat, runny nose
  • Drowsiness or fatigue
  • Tremor
  • Insomnia

Lamotrigine Rash

The biggest risk with lamotrigine is a rare allergic reaction called Stevens-Johnson Syndrome, which can be fatal if left untreated. Many medications can cause this reaction, including antibiotics like Bactrim and penicillin and over-the-counter medications like Tylenol and Motrin. The risk of getting the rash can be prevented if the following precautions are followed:

  1. Dosing increases must be raised very slowly.
  2. It should be stopped if any new rash or skin changes occur while you’re starting the medication. (After the first 3 months the risk of Stevens-Johnson Syndrome declines to almost zero).
  3. To avoid false-alarm rash confusion, the use of new soaps, getting a sunburn, exposure to poison ivy and starting any other new medications should be avoided during the first 3 months of starting lamotrigine.

With those steps, the risk of this severe rash is about 1 in 3,000; without them, it’s more like 1 in 100. “Unfortunately, there is still a high risk of non-serious, benign rashes (10% chance), so many people have to stop lamotrigine to be on the safe side,” Dr. Aiken explains. “If you responded to lamotrigine but had to stop it because of a rash, it may be possible to restart at a lower dose.”

Does lamotrigine interact with any medications or other substances?

Certain other drugs can affect the way lamotrigine works in your body by decreasing its effectiveness or delaying its excretion from your body. These include hormonal birth control methods, hormone treatments, seizure medications such as phenobarbital, and valproic acid, which is also used to treat bipolar disorder.

Your doctor will carefully prescribe and monitor your dosage when lamotrigine is taken with other treatments. Avoid alcohol, cannabis, and other substances that can increase dizziness or drowsiness while taking lamotrigine. To rule out dangerous side effects, discuss all other medications or mind-altering substances you consume with your doctor before taking lamotrigine.

One recent British study found that folic acid supplements can cancel out lamotrigine’s benefits (Geddes et al., 2016). “No one expected that result, as folic acid usually helps depression, and other medications, like valproate (a mood stabilizer approved for mania associated with bipolar disorder, seizures/epilepsy, and migraine headaches),” says Dr. Aiken. “More research is needed before we can fully trust this result, but until then, we recommend taking lamotrigine without any folic acid supplements, including those found in multivitamins. Once you’re doing well on lamotrigine, if you decided to add folic acid, watch out for a potential loss of benefits.”

Is it OK to suddenly stop taking lamotrigine?

Consult your doctor before stopping lamotrigine. If you do stop for more than a few days, DO NOT restart at your current dose. Call your doctor to review your dosing schedule.

 

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Last Updated: Oct 13, 2019