A single dose of lamotrigine causes subtle changes in emotional memory

A single dose of lamotrigine, a drug often prescribed to prevent depressive episodes in people with bipolar disorder, was found to shift emotional memory in a more positive direction in a group of healthy volunteers. The research, published in Psychological Medicine, suggests that lamotrigine may influence how people recall self-relevant emotional information, but does not appear to broadly alter emotional processing or mood in the short term.

Lamotrigine is an anticonvulsant medication that has been approved for the long-term maintenance treatment of bipolar disorder, particularly to help prevent future episodes of depression. Unlike many treatments used for bipolar disorder, which are more effective in controlling mania, lamotrigine has shown more consistent results in reducing depressive relapses. Despite its established role in clinical practice, little is known about how lamotrigine affects the psychological processes that might contribute to mood regulation, especially emotional memory and perception.

The motivation behind this new study was to examine how lamotrigine might affect emotional cognition in people without mood disorders. The idea is based on findings from research on antidepressants, which have been shown to shift emotional biases toward the positive end of the spectrum—such as remembering more positive than negative words or facial expressions—sometimes even before changes in mood are noticeable. Since lamotrigine is also used to stabilize mood and prevent depression in bipolar disorder, the researchers wanted to know if it could produce similar effects on emotional information processing.

To explore this question, researchers from the University of Oxford and the University of Minho recruited 36 healthy adults aged 18 to 40. None of the participants had a history of psychiatric or neurological illness, and all underwent medical and psychological screening before being included in the study. The participants were randomly assigned to receive either a single 300 milligram dose of lamotrigine or a placebo. The study was double-blind, meaning neither the participants nor the researchers knew who received which treatment until after the experiment was completed.

Three hours after taking the dose, participants completed a series of computerized tasks from the Oxford Emotional Test Battery. These tasks are designed to measure how people perceive and remember emotionally charged information, such as facial expressions, emotionally toned words, or emotionally relevant memories. Participants also filled out questionnaires throughout the experiment to track their mood, anxiety, and any physical side effects.

The central finding of the study came from a task that tested how many emotional words participants could recall. In an earlier part of the test battery, participants had been shown a series of personality-related words—some positive, like “kind,” and some negative, like “bossy”—and were asked to imagine someone using these words to describe them. Later, they were asked to recall as many of those words as possible. The participants who received lamotrigine recalled more positive words than negative ones, whereas the placebo group did not show this same bias. This shift in memory recall suggests that lamotrigine may promote a more positive interpretation of self-relevant emotional content, at least temporarily.

This effect is consistent with a growing body of research on how antidepressant medications seem to work. Some studies suggest that improving how people process emotional information—especially information about themselves—is an early step in how these medications help lift mood over time. The theory is that people with depression often focus more on negative information, and reversing that tendency may help change their outlook and reduce symptoms. If lamotrigine also produces a similar positive bias, this could offer insights into why it is helpful in managing depression in bipolar disorder.

Notably, lamotrigine did not produce broader changes across other tasks in the emotional battery. There were no significant effects on how participants recognized facial expressions, categorized emotional words, or shifted attention toward emotional content. The drug also did not affect self-reported mood or anxiety during the course of the experiment. This pattern suggests that the observed effect was specific to emotional memory, rather than a general change in emotional perception or subjective feeling.

Although the study found a statistically significant effect on emotional memory, the researchers acknowledge that the results should be interpreted with caution. The sample size was relatively small, and the positive memory bias was the only significant effect among a larger group of emotional tasks. The researchers did not adjust their statistical analysis to account for testing multiple outcomes, which increases the chance of false positives. In addition, the group that received lamotrigine reported more side effects, even before taking the drug, and showed higher levels of trait anxiety. These imbalances between groups may have influenced the results, although the researchers conducted follow-up analyses to control for them.

Importantly, the study was conducted in healthy participants, not people with bipolar disorder or depression. While using a healthy sample allows researchers to examine the direct effects of a drug without the confounding influence of illness, it also means the findings may not fully translate to clinical populations. Emotional processing in people with mood disorders may be shaped by different mechanisms, and drugs like lamotrigine could work differently in those contexts.

Even so, the study offers an initial look at how lamotrigine might affect emotional cognition, supporting the idea that its antidepressant-like effects could involve a subtle reshaping of memory processes. In particular, the increase in recall of positive self-descriptive words may reflect a short-term cognitive shift that, over time, could help reduce vulnerability to depressive thinking. Previous research in patients with bipolar disorder has found that depressive episodes are often accompanied by a focus on negative self-concepts and difficulty recalling positive personal memories. A drug that helps tip the balance back toward positive emotional content could contribute to more stable mood regulation.

There is also support from animal and human studies suggesting that lamotrigine may have effects on learning and memory. In mice, the drug has been shown to improve memory performance in certain tasks. In clinical settings, children and adults with bipolar disorder have shown improvements in working memory after extended treatment with lamotrigine. The current findings build on this earlier work by suggesting that the drug may also influence emotional aspects of memory, at least in the short term.

Future research will need to explore whether this positive memory bias extends beyond healthy participants and whether it is seen with repeated dosing. It will also be important to determine whether these cognitive shifts are linked to real-world clinical benefits, such as reduced depressive symptoms or fewer relapses in people with bipolar disorder. To answer those questions, larger studies in clinical populations using longer treatment periods and broader cognitive testing will be necessary.

The study, “A single dose of lamotrigine induces a positive memory bias in healthy volunteers,” was authored by Tarek Zghoul, Pilar Artiach Hortelano, Alexander Kaltenboeck, Lucy Wright, Guy M. Goodwin, Liliana P. Capitão, and Catherine J. Harmer.