Lamictal Depression: How Can Lamictal Treat Depression?

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Lamictal (generic name: lamotrigine) is a drug originally approved for use as an antiepileptic, later approved in 2003 as a mood stabilising treatment for bipolar disorder. It was found to be particularly effective in increasing the interval between depressive episodes. In both of the above cases, it was approved as a treatment for people who had not responded to the more usual courses of treatment. Lamictal is now becoming increasingly popular as an off-label (i.e. unofficial) therapy for people with treatment resistant unipolar depression.

What is treatment resistant unipolar depression?

Treatment resistant depression does not have one set definition. It can be defined as depression that has not responded to 1/2/3 Selective Serotonin Reuptake Inhibitors, depression that has not responded to at least two different types of antidepressant, or depression that has been alleviated but not cured completely.

Initial Lamictal depression trials have been encouraging. A 2002 study published in the Journal of Clinical Psychiatry found that over 40 percent of participants (patients with long term, treatment resistant depression) were found to be much improved and over 21 percent were found to be mildly improved after treatment with Lamictal.

How does it work?

It is still not clear how Lamictal can treat depression. The exact mechanism of action is not known, although there is in vitro evidence that it works on the voltage-sensitive sodium channels in neuronal membranes, normalising activity. This is thought to then alter the release of some neurotransmitters, with glutamate being considered one of the most important of these. It works in a completely different way to the other antiepileptic and antidepressant drugs, which makes its mechanism of action even more difficult to understand.

Lamictal is usually prescribed as an add on to more traditional antidepressants, intended to boost the effect of the original medication. Lamictal has no sexual side effects and has been found to improve sleep stability. It also has no weight related side effects, which is unusual for a medication with antidepressant effects.

Therapeutic doses and side effects

Therapeutic doses vary widely between patients, and depend on sex, other drugs, race and age. The manufacturers of Lamictal state that a mood lifting effect may be felt at a dose of 25-100 mg, while mood stabilising effects are expected at doses of 100-200 mg.

In contrast to the majority of antiepileptic drugs, women usually suffer from more side effects than men, and these side effects are more severe. The oral contraceptive pill reduces levels of Lamictal in the body, and so women on the oral contraceptive pill may find they require a higher dose than they would otherwise.

In general, white people require 25-33pc higher doses than non white people in order to feel a therapeutic effect. Rashes are a relatively common side effect of Lamictal, with about 10 percent of people experiencing a rash of some sort. In rare cases a rash may indicate a serious reaction, known as Stevens-Johnson Syndrome, and so it is advised that any rash is reported to a doctor immediately.

As with all medications you should consult your doctor first. This article is not intended to replace the medical advice of a professional physician.


Curia G, Biagini G, Perucca E, Avoli M (2009). “Lacosamide: a new approach to target voltage-gated sodium currents in epileptic disorders”. CNS Drugs, 23 (7), 555-568.

Barbee, J. G. Jamhour, N. J. (2002). “Lamotrigine as an augmentation agent in treatment resistant depression.” Journal of Clinical Psychiatry, 63 (8), 737-741.

Rapport, D. J., Calabrese, J. R., Clegg, K. et al. (1999). Lamotrigine in unipolar major depression. Primary Psychiatry, 6 (4), 41-42.