How Does Lamictal Work on Depression?


Lamictal is the brand name for lamotrigine, a drug marketed to treat seizures and bipolar disorder. Its use in treating depression extends from its use in the treatment of bipolar disorder, one pole of which is depression.

First studied for epilepsy

The drug was first investigated for use in epileptic patients and it acts on nerve transmission in the brain. This is a different mechanism than typical anti-depressants and more nearly akin to lithium, which also finds use as a stabilizer in bipolar patients. It was this similarity that led to lamotrigine being used in bipolar disorder and it has been found to reduce the swings from mania to depression, extending the “normal” period between these states.

The drug has not been approved by the FDA for use in depression alone, but can be prescribed for depression as an “off label” use. It is unknown exactly how Lamictal helps with depression when not accompanied by mania. This type of unipolar depression is traditionally treated with serotonin reuptake inhibitors (SRIs).

Side Effects

Because the side effects from Lamictal are mostly benign (with the exceptions below), it is sometimes used when regular antidepressants have failed. It is referred to in this use as a “mood stabilizer” rather than an antidepressant and if it works, the idea is that the patient must be suffering from a depression that differs from the serotonin imbalance we currently associate with unipolar depression.

There are two significant side effects, but neither happen frequently. The first is an increased risk of suicide, something seen with antidepressants as a class. The second is a type of malignant rash which can be fatal. Although up to 10% of patients who take the drug may develop a rash, the serious, life threatening type only happens in about 1 in 50,000 patients. Finally, there is a risk of aseptic (without infection) meningitis. Patients are warned to contact their doctor if they have any of the following symptoms while on the drug: headache, fever, nausea, vomiting, stiff neck, unusual sensitivity to light, muscle pains, chills, confusion, or drowsiness.

Because Lamictal has a different mechanism of action (non-SRI), it is currently being used as an augmentation in refractory cases of depression. This simply means adding a second drug to an antidepressant when the antidepressant alone doesn’t seem to be helping. Other drugs, including other seizure medications and even thyroid medications are already used in this manner and the practice is normal. Doctors evaluate patients after some time on an antidepressant and decide whether a trial with Lamictal is warranted.

Studies so far seem to show Lamictal is at least as effective as lithium and safer to use.


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