The Truth About Lamotrigine

lamotrigine brain

Last Updated on 21 June 2024

Lamotrigine is a drug belonging to the category of antiepileptics, and also used to treat a few types of bipolar disorder. The first truth is that lamotrigine treats only bipolar depression, but not hypomanic or manic mood, in which, initially, its impact may be minimal. Is it really this way? The article just explored all the truth about this particular drug.

Lamotrigine Overview


Lamotrigine was released in the United States in 1994 for the treatment of partial seizures, and in 1998 it was authorized for the treatment of severe forms of epilepsy in children and adults.

During the treatment for epilepsy, patients reported a beneficial sense of wellness, and due to this positive effect, lamotrigine was approved in 2003 for the treatment of bipolar 1, and the maintaining of bipolar 2 disorder, as adjuvant of lithium, a mood stabilizer which, traditionally, was the preferred drug to treat bipolar disorder overall.

Sold with the commercial name of Lamictal, Lamotrigine is mainly contained in chewable dispersible white tablets, with round shape and square angles, and four different dosages of 50, 100, 150 and 200 mg. This is the primary pharmaceutical form sold in Italy and Europe, even though there are other types of Lamictal pills, with extended release, and various dosages.

Over time, physicians have become more and more reluctant to prescribe lithium for bipolar disorders, for its high toxicity on kidneys and thyroid and for the long duration of the treatment, which, classically, lasts for the entire life.

Lamotrigine, hence, took on the role of mood stabilizer, becoming the most prescribed drug to cure bipolar disorder 1. In reality, more than a mood stabilizer, lamotrigine is always an anticonvulsant, and an antidepressant, because it works on the depressive episodes of bipolar disorder, while it seems not be effective on manic or hypomanic episodes. Its low impact on manic episodes prevented lamotrigine from being prescribed to cure bipolar 2, characterized by more frequent episodes of depression and hypomania.

Lamotrigine Mechanism of Action

lamotrigine pills

The action mechanism of the tablets with lamotrigine is not clearly understood, yet, but its high tolerability, the scarce side effects, and the nearly absence of unpleasant interactions with other drugs, pushed doctors to be extremely confident with the prescription of this medicine as antidepressant and mood stabilizer, besides as an antiseizure drug.

This is one of the truths about lamotrigine. As said, for its effects on the control of bipolar depression, the drug is mainly considered as an antidepressant.

The drug, indeed, seems to be ineffective to treat bipolar mania, preventing the relapse of depressive episodes, only. Lamotrigine, in fact, leverages the principle that bipolar disorder is a part of a depressive personality and that by preventing depression, it can relieve manic episodes, as well. In short, mania or hypomania would be the double face of a severe form of depression. And so, the control of the depression over time may result in a long delay of mood swings and a partial or total remission of manic episodes.

Furthermore, Lamotrigine seems to not work very well to treat rapid cycling bipolar disorder, characterized by shorter and more frequent episodes of mania and depression in the course of the day.

But, to verify this aspect, a few studies have been conducted on patients affected by rapid cycling bipolar disorder. These studies, published in Science Direct, found that rapid cycling bipolar disorder is in reality a progression of an untreated condition of classical bipolar disorder. In this case, lamotrigine is prescribed as a maintenance therapy to delay and extend the distance and the relapse of manic and depressive bouts.

Here is why lamotrigine is a good treatment for bipolar 1, characterized by longer distance between episodes of mania and depression.

However, eminent physicians affirmed that, as a mood stabilizer, lamotrigine can’t be considered as a substitute of other classic mood stabilizers, such as lithium or valproate. Hence, why is this new drug so largely prescribed?

Truth About the Large Prescription of Lamotrigine as a Mood Stabilizer

In addition to the reason for less side effects than lithium and the like, lamotrigine is often prescribed in patients who have a comorbidity with a neurological disease. The latter, in fact, is the result of a lack of neurotransmitters in the brain. While other psychiatric drugs worsen the neurologic symptoms, lamotrigine improves them, because it inhibits the reuptake of dopamine, serotonin and noradrenaline, allowing a greater availability of these neurotransmitters in the body. Nerve cells, indeed, usually absorb the neurotransmitters they release, with a detrimental effect on patients who suffer from mental and brain disorders. One of these bad effects may worsen motor symptoms in Parkinson disease, for example, an effect which does not occur with lamotrigine.

That is why lamotrigine can be prescribed in combination with Levodopa, the main medication used to treat Parkinson’s. The two drugs have less interactions and adverse effects when they are administered together.

The fact lamotrigine is frequently prescribed as a mood stabilizer in patients with not to tolerate lithium or with concurrent Parkinson disease could push people to believe that lamotrigine is like the other psychotropic drugs.

Is Lamotrigine a Psychiatric Drug?

Even though it is classified as a psychiatric medication, lamotrigine is not an antipsychotic, nor a tranquiliser, and does not have the effects of other psychoactive drugs, such as bromazepam, diazepam, and the like. It always remains an antiepileptic medication, and a mood stabilizer, which has been considered a psychotropic drug only when it was used to control manic or depressive mood in bipolar disorders.

In reality, lamotrigine works changing the electrical activity in the brain and blocking the sodium channel, and maybe inhibiting synaptic glutamate release and reducing the neuronal activity, which is excessively stimulated in bipolar and other psychiatric disorders.

Glutamate, indeed, is an excitatory neurotransmitter that when it arrives in the extra synaptic regions of the brain has a cytotoxic effect and can cause neuronal death. Moreover, the imbalance of this neurotransmitter is involved in the onset of many psychiatric disorders, such as depression, bipolar, psychosis, stress response, and neurodegenerative diseases.

Upon this aspect, lamotrigine seems to exert a protective role in the neurons, allowing an increased availability of other functional neurotransmitters, such as dopamine, serotonin and noradrenaline. In this sense, lamotrigine has the same action mechanism of reuptake serotonin inhibitors SSRIs, such as fluoxetine, paroxetine and citalopram, but without the adverse effects of the latter, which tend to reduce the availability of dopamine in the brain.

For the capacity to increase the level of serotonin in the brain, lamotrigine is also used to treat obsessive compulsive disorder, but Psychiatrist Antonino Petralia, Professor and Researcher at the University of Catania said that OCD in reality does not exist, because often it is a symptom of other psychiatric conditions, such as bipolar disorder. Anyway, the beneficial action of lamotrigine on the brain, on the neurotransmitter levels, and bipolar conditions often results in a consequent relief of obsessive-compulsive thoughts.

Lamotrigine exerts its action after it has been absorbed in the gastrointestinal tract and metabolized by an enzyme called glucuronidation, a molecule involved in the metabolism of drugs, pollutants, and sexual hormones.

For these features, it remains to discover if lamotrigine can be additive. This is another truth to explore.

Lamotrigine Addiction

While other psychiatric drugs give addiction that, sometimes, can be fairly severe, lamotrigine is considered less addictive, even though a sudden interruption of the therapy may cause bipolar disorder to worsen.

Fortunately, when used for bipolar, lamotrigine can be suspended without reducing the dose, but the decision must always be made by a doctor. Usually, when patients stop taking lamotrigine, they take up to 14 days to get fully detoxified. However, the return of psychiatric and physical symptoms may be challenging, initially, but does not prevent the patient from recovering, while the withdrawal of other psychoactive drugs instead can cause serious and life-threatening symptoms that can even require hospitalization.

However, even the withdrawal of a lamotrigine must always be carried out with extreme caution. Hence, the withdrawal must be prescribed by a doctor who gives precise instructions about how gradually reducing the dose (especially for other psychiatric disorders and epilepsy) to avoid symptoms such as anxiety, mood swings, angry, headaches, joint pain and suicidal thoughts, pancreatitis, anemia and seizures (due to the antiepileptic action of this drug).

Moreover, many wonder if lamotrigine causes weight gain. This is another truth to investigate.

Lamotrigine Weight Gain

Unlike other psychotropic drugs, lamotrigine does not cause weight gain. This side effect may be the result of the same psychiatric disorder, which, alternatively, pushes to binge or avoid food.

A weight gain is probable when lamotrigine is used in combination with other drugs that commonly can cause an increase of weight such as carbamazepine or lithium.

But this event is fairly rare, because often lamotrigine is used in combination with lithium, which, in turn, causes mild weight gain in comparison with other psychoactive substances.

Moreover, some clinical trials tested the weight gain of the usage of lamotrigine for epilepsy and bipolar disorder. As regards the first pathology, the 5% of epileptic patients treated with lamotrigine lose weight, while for bipolar patients treated with lamotrigine, the weight gain has been between the 1% and the 5%. However, the weight gain has been minimal in these patients.

Furthermore, other 13 clinical trials conducted in 2021 found that lamotrigine is weight neutral, that means it does not cause any relevant increase in weight.


As seen, lamotrigine is a drug that nowadays has a wide range of applications, as an anticonvulsant, antidepressant and a mood stabilizer for bipolar disorders. It is often prescribed instead of lithium, especially for patients with concurrent neurological disorders, due to its protective action on the brain, the possibility to get taken along with other medications, the minor side effects (usually headache and nausea), and the minimal risk of weight gain.

I investigated this medication because I was also prescribed with it to treat my bipolar disorder. Due to the fact that, in the past year, I have also been diagnosed with a neurological disease that caused me movement disorders, Lamictal has been the only solution I could take along with Levodopa. Currently, my concurrent disorders have improved. I hope it will be like this in the future, as well.

Author: Rosalba Mancuso
Rosalba Mancuso is a medical journalist, an international content writer credited at the University of Washington and a blogger born in Sicily. She is internationally appreciated for founding a network of four websites in English. On, Rosalba writes well researched and detailed health articles backed by her experience as a medical writer for pharma companies and as a PR assistant for a clinical analysis laboratory. She is also a member of the AHCJ, American Association of Health Care Journalists and Center for Excellence in Health Journalism. Her health magazine survives thanks to spontaneous donations, and sponsorships with brands and clinical organizations.