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Research · Medication

Lamotrigine

Pooled trials found lamotrigine lowered bipolar mood relapse against placebo and nearly doubled the share of people with drug-resistant focal epilepsy whose seizures halved. Its effect on bipolar depression was modest. Nerve pain and borderline personality disorder trials found no benefit. A boxed warning covers serious rash, seen in 0.1% to 0.3% of adults in trials.

Add to Bio HackChecked 2026-11-13
Status
Prescription drug in the US. FDA-approved as add-on treatment for partial-onset seizures, primary generalized tonic-clonic seizures and Lennox-Gastaut syndrome seizures from age 2, for conversion to single-drug treatment of partial-onset seizures from age 16, and for maintenance treatment of bipolar I disorder to delay mood episodes. The label states it is not approved for acute mania or mixed episodes and carries a boxed warning for serious skin rashes.
Also called
lamotrigine, Lamictal, Lamictal XR, Lamictal ODT, LTG
Taken for
bipolar disorder, bipolar depression, mood stabilizer, epilepsy, seizures, depression, nerve pain, migraine prevention, borderline personality disorder

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help4

Reported risks16

What people take it for, and what was found

Shown to help4

Strong

Preventing mood episodes in bipolar disorder

Shown to lower relapse in bipolar disorder against placebo, by about 16% to 22% in pooled trials, while preventing mania less well than lithium.

Compared with placebo [1][2][3][4]; lithium [1][2]

The numbers and sources
Effect
In a Cochrane review, clinical worsening that needed added treatment was less likely on lamotrigine than placebo (RR 0.82, 95% CI 0.70 to 0.98), and so was a return of manic symptoms at one year (RR 0.67, 95% CI 0.51 to 0.87). Against lithium, manic symptoms returned more often on lamotrigine (RR 2.13, 95% CI 1.32 to 3.44), while fewer people had at least one adverse effect (RR 0.70, 95% CI 0.51 to 0.96) [1]. A second meta-analysis found a lower relapse or recurrence rate than placebo (RR 0.84, 95% CI 0.71 to 0.99) and no difference from lithium (RR 1.06, 95% CI 0.89 to 1.25) [2]. A third found fewer new depressive episodes than on placebo (RR 0.78, 95% CI 0.63 to 0.98) [3]. In the two 18-month label trials, lamotrigine delayed the next mood episode, and a combined analysis found the effect stronger for depression than for mania [4].
Population
2,314 adults with bipolar disorder in 11 trials, 1,146 on lamotrigine [1]; 20 RCTs and 20 cohort studies, 1,166 lamotrigine users in the RCTs [2]; 24 trials with 2,257 patients and 2,320 controls [3]; adults with bipolar I disorder stabilized on lamotrigine and then randomized for up to 18 months [4].
Sources
[1], [2], [3], [4]
Caveats
The Cochrane review rated the evidence low to moderate certainty and found unclear risk of bias in every study [1]. The main trials enrolled only people who had already responded to lamotrigine before randomization [4].
Strong

Bipolar depression

Shown to improve bipolar depression modestly against placebo, with response about 1.27 times as likely, and in one pooled analysis only in more severe depression.

Compared with placebo [5][2][3][6]; lithium, olanzapine with fluoxetine, citalopram and inositol [6]

The numbers and sources
Effect
In individual data from five trials, response on the Hamilton depression scale was more likely on lamotrigine than placebo (RR 1.27, 95% CI 1.09 to 1.47). The gain was seen in people with Hamilton scores above 24 (RR 1.47, 95% CI 1.16 to 1.87) and not in those at 24 or below (RR 1.07, 95% CI 0.90 to 1.27) [5]. Added to other treatment, lamotrigine lowered depression scores more than placebo (SMD -0.30, 95% CI -0.51 to -0.10) [2]. As a single drug it beat placebo by a small margin (SMD 0.155, 95% CI 0.005 to 0.305) [3]. Across unipolar and bipolar trials pooled together, response was more likely than on placebo (RR 1.42, 95% CI 1.13 to 1.78), and lamotrigine did not differ from lithium, olanzapine with fluoxetine, citalopram or inositol [6].
Population
1,072 adults in five placebo-controlled trials [5]; trials within 20 RCTs [2]; 24 trials [3]; 18 studies with 2,152 people, 14 of them in bipolar depression [6].
Sources
[5], [2], [3], [6]
Caveats
The pooled effects are small. The label states that effectiveness in acute mood episodes has not been established and lamotrigine is not approved for this use [4].
Moderate

Drug-resistant focal epilepsy, added to other seizure drugs

Shown to make a halving of seizure frequency about 1.8 times as likely as placebo when added to other drugs in drug-resistant focal epilepsy.

Compared with placebo added to existing seizure drugs [7][4]

The numbers and sources
Effect
A 50% or greater fall in seizure frequency was more likely on add-on lamotrigine than add-on placebo (RR 1.80, 95% CI 1.45 to 2.23), and withdrawal from treatment for any reason did not clearly differ (RR 1.11, 95% CI 0.91 to 1.37) [7]. In one label trial, median partial seizure frequency fell 36% at 500 mg a day, 20% at 300 mg and 8% on placebo. In a children's trial, it fell 36% against 7% [4].
Population
1,806 infants, children and adults in 14 trials lasting 8 to 36 weeks [7]; 216 adults in one trial and 199 children aged 2 to 16 in another [4].
Sources
[7], [4]
Caveats
The trials were short and give no long-term evidence [7]. Only the 500 mg dose separated from placebo in the adult label trial [4].
Limited

Newly diagnosed focal epilepsy, compared with other first drugs

One trial found lamotrigine matched or beat levetiracetam and zonisamide for 12-month seizure remission in newly diagnosed focal epilepsy, with fewer adverse reactions.

Compared with levetiracetam and zonisamide [8]; a low dose of valproate [4]

The numbers and sources
Effect
Levetiracetam did not meet the trial's non-inferiority test against lamotrigine for time to 12-month remission (HR 1.18, 97.5% CI 0.95 to 1.47), while zonisamide did (HR 1.03, 97.5% CI 0.83 to 1.28). In the per-protocol analysis, remission was more likely on lamotrigine than levetiracetam (HR 1.32) or zonisamide (HR 1.37). Adverse reactions were reported by 33% starting lamotrigine, 44% starting levetiracetam and 45% starting zonisamide [8]. In a label trial of switching to a single drug, 42% on lamotrigine and 69% on low-dose valproate met the criteria for leaving the trial [4].
Population
990 people aged 5 or older with newly diagnosed focal epilepsy in an open-label UK trial followed for at least 2 years [8]; 156 adults with partial-onset seizures [4].
Sources
[8], [4]
Caveats
The main trial was open label. The label states that its valproate arm used a deliberately low dose, so that trial does not show lamotrigine beats an adequate valproate dose [4].

Mixed results2

Moderate

Depression without bipolar disorder

Mixed results: a 2025 meta-analysis with unpublished trials found no benefit over placebo in unipolar depression, while an earlier one pooled it with bipolar depression and found a small gain.

Compared with placebo, alone or added to an antidepressant [3][6]; lithium [6]

The numbers and sources
Effect
With three unpublished studies included, lamotrigine did not beat placebo in unipolar depression, either alone or added to other treatment. No maintenance trials in unipolar depression were found [3]. An earlier meta-analysis found no difference in effect between unipolar and bipolar patients and pooled them, finding lower depression scores than placebo (SMD -0.15, 95% CI -0.27 to -0.02) [6].
Population
24 trials, the unipolar ones including three unpublished [3]; 4 studies with 187 people with unipolar depression within 18 studies [6].
Sources
[3], [6]
Caveats
The earlier analysis had few unipolar participants and did not report a unipolar estimate on its own [6]. Lamotrigine is not approved for depression.
Moderate

Migraine prevention

Mixed results: a Cochrane review found lamotrigine no better than placebo for migraine frequency, while a network meta-analysis listed it among drugs with fewer than three positive trials.

Compared with placebo [10][11]

The numbers and sources
Effect
In placebo-controlled trials, lamotrigine did not lower headache frequency per 28 days and did not raise the share of responders [10]. A network meta-analysis of migraine preventive drugs listed lamotrigine among drugs that beat placebo in fewer than three trials, without giving its effect size in the abstract [11].
Population
Adults with episodic migraine in 10 trials of nine seizure drugs, lamotrigine among them [10]; adults in randomized trials of migraine preventive drugs [11].
Sources
[10], [11]
Caveats
Few lamotrigine trials exist, and neither abstract gives their number or size.

Not shown to help2

Moderate

Nerve pain and fibromyalgia

Not shown to relieve nerve pain in adults at 200 to 400 mg a day, in a Cochrane review of 12 trials. Almost 10% on lamotrigine reported a rash.

Compared with placebo [9]

The numbers and sources
Effect
No study gave first-tier evidence for an efficacy outcome, and the review found no convincing evidence of pain relief at doses of 200 to 400 mg daily. Almost 10% of participants taking lamotrigine reported a skin rash [9].
Population
1,511 adults with diabetic nerve pain, HIV-related nerve pain, post-stroke pain, spinal cord injury pain, chemotherapy nerve pain, trigeminal neuralgia or mixed nerve pain, in 12 studies mostly 8 weeks or longer [9].
Sources
[9]
Caveats
No fibromyalgia trial was found, so the fibromyalgia part of the question rests on no data [9].
Limited

Borderline personality disorder

One trial found lamotrigine did not improve borderline personality disorder symptoms at 52 weeks compared with placebo.

Compared with placebo added to usual care [12]

The numbers and sources
Effect
At 52 weeks the mean symptom score was 11.3 on lamotrigine and 11.5 on placebo (adjusted mean difference 0.1, 95% CI -1.8 to 2.0). No secondary outcome differed, including depression, self-harm and social functioning [12].
Population
276 adults with borderline personality disorder in six English mental health services, 195 followed to 52 weeks [12].
Sources
[12]
Caveats
Adherence was low: 36% on lamotrigine and 42% on placebo were taking it at 52 weeks [12].

Doses studied

In the bipolar maintenance trials, the target dose was 200 mg a day, reached by slow titration. The label lists 100 mg a day with valproate and 400 mg a day with carbamazepine, phenytoin, phenobarbital, primidone or rifampin, and states that 400 mg added no benefit over 200 mg in the trials [4]. The adult epilepsy trials used target doses of 300 to 500 mg a day, and the children's trials about 5 mg/kg a day with valproate and 15 mg/kg a day without it [4]. The nerve pain trials used about 200 to 400 mg a day [9]. The borderline personality trial used up to 200 mg a day, or up to 400 mg in women taking combined birth control pills [12]. The label describes a slow escalation schedule because exceeding it raises the risk of rash [4].

Risks

Reported risks15

ModerateVery common

Dizziness, double vision, unsteadiness, nausea and sleepiness in epilepsy trials

Shown to raise dizziness, double vision, unsteadiness and nausea when added to other seizure drugs, with dizziness in 38% against 13% on placebo.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In pooled add-on epilepsy trials, dizziness occurred in 38% on lamotrigine and 13% on placebo, headache 29% and 19%, double vision 28% and 7%, unsteadiness (ataxia) 22% and 6%, nausea 19% and 10%, blurred vision 16% and 5%, sleepiness 14% and 7%, and vomiting 9% and 4%. Dizziness, double vision, ataxia, blurred vision, nausea and vomiting rose with dose [4]. In a Cochrane review the risk ratios were 3.34 for ataxia, 1.76 for dizziness, 1.81 for nausea and 3.79 for double vision, with no difference in fatigue (RR 0.82) [7].
Population
711 adults on lamotrigine and 419 on placebo, added to 1 to 3 other seizure drugs [4]; 14 trials with 1,806 participants [7].
Sources
[4], [7]
Caveats
These trials added lamotrigine to other seizure drugs, which raises these effects. Rates were lower in the bipolar trials, where it was taken alone [4].
ModerateVery common

Side effects in bipolar trials

Shown to raise nausea, insomnia, fatigue and back pain slightly in bipolar trials, with nausea in 14% against 11% on placebo. Overall adverse effects matched placebo.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In two 18-month bipolar trials, nausea occurred in 14% on lamotrigine and 11% on placebo, insomnia 10% and 6%, sleepiness 9% and 7%, back pain 8% and 6%, fatigue 8% and 5%, and dry mouth 6% and 4%. 13% stopped lamotrigine for an adverse reaction, against 16% on placebo and 23% on lithium [4]. A Cochrane review found the share with any adverse effect similar to placebo over 6 to 12 months (RR 0.97, 95% CI 0.77 to 1.23) [1].
Population
227 adults on lamotrigine, 190 on placebo and 166 on lithium [4]; 756 participants in 4 studies [1].
Sources
[4], [1]
Caveats
During the open-label dose escalation, before randomization, headache (25%), rash (11%) and dizziness (10%) were more frequent [4].
ModerateCommon

Any rash

Shown to raise rash against placebo in label trials, 10% against 5% in epilepsy, though a meta-analysis found no clear difference from comparison drugs.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In placebo-controlled epilepsy trials, rash occurred in 10% on lamotrigine and 5% on placebo. In bipolar trials, nonserious rash occurred in 7% against 5% [4]. Across 122 randomized trials, 8.3% of patients had a skin reaction [13]. A meta-analysis found rash in 9.98% in prospective studies and 2.09% in postmarketing reports. Pooled across 21 prospective studies, the odds of rash did not differ significantly from comparison groups, which included placebo, lithium and other seizure drugs, while lamotrigine had higher odds than non-aromatic seizure drugs in retrospective studies [14].
Population
Adults in label trials [4]; 18,698 patients [13]; 4,447 patients in prospective studies, 2,977 in retrospective studies and 26,126 in postmarketing reports [14].
Sources
[4], [13], [14]
Caveats
Comparison groups in the meta-analysis mixed placebo and other drugs that also cause rash [14].
LimitedCommon

Interaction with valproate

The label states valproate more than doubles lamotrigine levels, and rash needing hospitalization occurred in 1% of trial patients taking both against 0.16% without valproate.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Valproate raised lamotrigine concentrations slightly more than twofold. In epilepsy trials, 6 of 584 patients (1%) taking lamotrigine with valproate were hospitalized with rash, against 4 of 2,398 (0.16%) without it. In children, serious rash occurred in 1.2% with valproate and 0.6% without [4].
Population
Adults and children in epilepsy trials and volunteers [4].
Sources
[4]
Caveats
Not randomized by valproate use.
ModerateUncommon

FDA boxed warning: serious skin rashes

FDA states lamotrigine has caused life-threatening rashes, including Stevens-Johnson syndrome, in about 0.3% of adults in epilepsy trials and 0.08% to 0.13% in bipolar trials.

The numbers and sources
How common
Uncommon: between 1 in 1,000 and 1 in 100 people.
Effect
The label's boxed warning states that life-threatening serious rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis, and rash-related deaths have been caused by lamotrigine. Rash needing hospitalization occurred in 0.3% (11 of 3,348) of adults in epilepsy trials, 0.08% of adults starting it alone and 0.13% adding it to other drugs in mood disorder trials, and about 0.3% to 0.8% of children aged 2 to 17. Taking it with valproate, exceeding the starting dose and escalating faster than labeled raise the risk [4]. Across 122 randomized trials of lamotrigine alone, Stevens-Johnson syndrome or toxic epidermal necrolysis occurred in 0.04% [13].
Population
Adults and children in the manufacturer's clinical trials, as reported in the label [4]; 18,698 patients in 122 randomized trials [13].
Sources
[4], [13]
Caveats
The label states rash-related deaths in postmarketing use are too few to estimate a rate, and that a benign rash cannot be told apart early from a serious one [4].
ModerateUncommon

Suicidal thoughts and behavior (seizure drug class warning)

The label warns that seizure drugs as a group raised suicidal thoughts or behavior to 0.43% against 0.24% on placebo, about one extra case per 530 treated.

The numbers and sources
How common
Uncommon: between 1 in 1,000 and 1 in 100 people.
Effect
In FDA's pooled analysis of 199 placebo-controlled trials of 11 seizure drugs, suicidal thinking or behavior occurred in 0.43% on a drug and 0.24% on placebo (adjusted RR 1.8, 95% CI 1.2 to 2.7), about 1 extra case for every 530 people treated. The rise appeared within a week of starting and lasted through the trials. There were 4 suicides on drug and none on placebo, too few for a conclusion [4].
Population
27,863 people on a seizure drug and 16,029 on placebo, median treatment 12 weeks [4].
Sources
[4]
Caveats
The analysis pools 11 drugs and is not specific to lamotrigine. Most trials lasted no more than 24 weeks [4].
LimitedRare

Drug reaction with organ involvement (DRESS) and liver failure

The label reports multiorgan hypersensitivity reactions, some fatal, and deaths from organ or liver failure in 2 of 3,796 adults and 4 of 2,435 children in trials.

The numbers and sources
How common
Rare: fewer than 1 in 1,000 people.
Effect
Multiorgan hypersensitivity (DRESS) has occurred, presenting with fever, rash or swollen lymph nodes alongside hepatitis, kidney inflammation, blood abnormalities or heart or muscle inflammation. Deaths from acute multiorgan failure and liver failure occurred in 2 of 3,796 adults and 4 of 2,435 children in epilepsy trials. Isolated liver failure without rash has also been reported [4].
Population
Adults and children in epilepsy trials, and postmarketing reports [4].
Sources
[4]
Caveats
Trial deaths are counted without a placebo comparison.
ModerateHow often is not known

Serious rash and the HLA-B*1502 gene variant

Linked to about 2.9 times the odds of Stevens-Johnson syndrome or toxic epidermal necrolysis on lamotrigine in people carrying HLA-B*1502, mostly studied in Asian populations.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
A meta-analysis found a pooled odds ratio of 2.88 (95% CI 1.60 to 5.17) for HLA-B*1502 and lamotrigine-induced Stevens-Johnson syndrome or toxic epidermal necrolysis [15]. The label states that case-control studies in people of certain Asian ancestry, such as Han Chinese and Thai, found a risk about 2 to 3 times higher, and that these reactions also occur in people without the variant [4].
Population
Case-control studies of people with lamotrigine-induced severe skin reactions [15][4].
Sources
[15], [4]
Caveats
Only HLA-B*1502 data could be pooled. The label states that many carriers never develop the reaction [4].
LimitedHow often is not known

Hemophagocytic lymphohistiocytosis

The label reports a life-threatening immune overactivation syndrome in children and adults, starting 8 to 24 days after lamotrigine was begun. It gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label reports hemophagocytic lymphohistiocytosis, a syndrome of extreme systemic inflammation with high mortality if not recognized, with fever, rash, enlarged liver and spleen, organ dysfunction and blood cell abnormalities, reported 8 to 24 days after starting treatment [4].
Population
Postmarketing reports in children and adults [4].
Sources
[4]
Caveats
Reports, with no denominator.
LimitedHow often is not known

Blood cell disorders

The label reports low white cells, low platelets, anemia and, rarely, aplastic anemia, with or without a hypersensitivity reaction. It gives no rate.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Reports include neutropenia, leukopenia, anemia, thrombocytopenia, pancytopenia and, rarely, aplastic anemia and pure red cell aplasia [4].
Population
Reports summarized in the label [4].
Sources
[4]
Caveats
No rate or comparison group.
LimitedHow often is not known

Aseptic meningitis

The label states lamotrigine raises the risk of aseptic meningitis, with symptoms starting 1 day to 6 weeks after it was begun and returning quickly on restarting.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Postmarketing cases presented with headache, fever, nausea, vomiting and neck stiffness. Most resolved after stopping. Re-exposure brought symptoms back within 30 minutes to 1 day, often more severe. Some affected people had lupus or other autoimmune diseases [4].
Population
Postmarketing reports in children and adults [4].
Sources
[4]
Caveats
Reports, with no denominator.
LimitedHow often is not known

Seizures after stopping abruptly

The label reports seizures in 2 people with bipolar disorder shortly after stopping lamotrigine abruptly. Other adverse reactions did not rise after abrupt stopping in the bipolar trials.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
In the bipolar development program, 2 patients had seizures soon after abrupt withdrawal. In the two controlled bipolar trials, abrupt stopping did not raise the incidence, severity or type of adverse reactions. In epilepsy, the label states seizure frequency may rise [4].
Population
Adults with bipolar disorder in clinical trials [4].
Sources
[4]
Caveats
Two cases, with no denominator given for the whole program.
LimitedHow often is not known

Interaction with estrogen-containing birth control

The label states estrogen-containing birth control pills lowered lamotrigine levels by about 50%, and levels can double during the pill-free week.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
A pill containing 30 mcg ethinylestradiol and 150 mcg levonorgestrel lowered lamotrigine concentrations by about 50%, and lamotrigine lowered levonorgestrel by 19%. During the pill-free week, lamotrigine levels are expected to rise, up to double by the end of the week, with possible dizziness, unsteadiness and double vision. Other estrogen products, including menopausal hormone therapy, were not studied [4].
Population
Drug interaction studies described in the label [4].
Sources
[4]
Caveats
Measured as blood levels, with no rate of harm given.
LimitedHow often is not known

Drugs that lower lamotrigine levels

The label states carbamazepine, phenytoin, phenobarbital, primidone and the antibiotic rifampin lower lamotrigine levels by about 40%, and some HIV protease inhibitors by 32% to 50%.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Carbamazepine, phenytoin, phenobarbital and primidone each lowered lamotrigine concentration by about 40%, rifampin lowered exposure by about 40%, lopinavir with ritonavir by about 50% and atazanavir with ritonavir by about 32%. The label also states lamotrigine can raise levels of drugs cleared by the kidney transporter OCT2, such as dofetilide [4].
Population
Drug interaction studies described in the label [4].
Sources
[4]
Caveats
Changes in blood levels, with no rate of harm given.
LimitedHow often is not known

False positive drug tests

The label reports that lamotrigine can cause false positive results on some rapid urine drug screens, especially for PCP.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Lamotrigine has been reported to interfere with some rapid urine drug screens, producing false positive readings, particularly for phencyclidine (PCP). The label calls for a more specific method to confirm a positive result [4].
Population
Reports summarized in the label [4].
Sources
[4]
Caveats
No rate is given.

Mixed results1

ModerateStudied in pregnancyCommon

Pregnancy and birth defects

Mixed results: major birth defects in 2% to 3% of exposed infants, a rate one review found higher than in women without epilepsy and others found similar to comparison groups.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
Pregnancy registries reported major malformations in 2.2% (95% CI 1.6 to 3.1) of 1,558 infants exposed to lamotrigine alone in the first trimester, 2.0% of 1,562 in a second registry and 2.9% of 2,514 in a third, against a US background of 2% to 4%. One registry found isolated oral clefts at 3.2 per 1,000, a threefold rise, not seen in other registries [4]. A Cochrane review found a higher risk than in children of women without epilepsy in cohort studies (RR 1.99, 95% CI 1.16 to 3.39, about 1% more), but not against women with untreated epilepsy (RR 1.04, 95% CI 0.66 to 1.63) or in health record studies (RR 1.19, 95% CI 0.86 to 1.64) [16]. A network meta-analysis found no raised risk against unexposed controls (OR 0.96, 95% CrI 0.72 to 1.25) [17].
Population
Infants in pregnancy registries [4]; 49 studies, with over 2,700 lamotrigine-exposed children in one comparison [16]; 96 studies with 58,461 patients [17].
Sources
[4], [16], [17]
Caveats
Most exposed pregnancies were in women with epilepsy. The label notes that lamotrigine lowered fetal folate in rats and that its blood levels fall during pregnancy [4].

Checked, no increase found1

Limited

Mania or hypomania

Mania or hypomania was reported in 5% on lamotrigine, 4% on lithium and 7% on placebo in the 18-month bipolar trials, with no excess over placebo.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
In the two 18-month bipolar trials, manic, hypomanic or mixed episodes reported as adverse reactions occurred in 5% on lamotrigine, 4% on lithium and 7% on placebo. Across all controlled bipolar trials, the rates were 5%, 3% and 4% [4].
Population
227 on lamotrigine, 166 on lithium and 190 on placebo, and 956, 280 and 803 across all controlled bipolar trials [4].
Sources
[4]
Caveats
Counts from the manufacturer's trials, with no confidence intervals.

Possible, not studied in people1

Untested

Heart rhythm in people with heart disease

Not studied in people. In the lab, lamotrigine slowed heart conduction like a class IB drug, and the label predicts arrhythmia risk in people with heart disease.

No study in people. This rests on lab studies.

The numbers and sources
Effect
In vitro testing showed class IB antiarrhythmic activity at therapeutic concentrations. From this, the label states lamotrigine could widen the QRS interval and cause arrhythmias, including sudden death, in people with structural or functional heart disease, and that other sodium channel blockers may add to the risk [4].
Population
Laboratory testing described in the label [4].
Sources
[4]
Caveats
The warning rests on lab findings. No rate in people is given.

Claims tested and not found

  1. That lamotrigine relieves nerve pain. A Cochrane review of 12 trials in 1,511 adults found no convincing evidence of relief at 200 to 400 mg a day [9].
  2. That lamotrigine helps borderline personality disorder. In a trial of 276 adults, symptom scores at 52 weeks did not differ from placebo (adjusted mean difference 0.1, 95% CI -1.8 to 2.0) [12].
  3. That lamotrigine treats unipolar depression. With unpublished trials included, it did not beat placebo alone or as an add-on [3].

Related

SSRIs

Sources

  1. Hashimoto Y, Kotake K, Watanabe N, et al. Lamotrigine in the maintenance treatment of bipolar disorder. Cochrane Database of Systematic Reviews. 2021. https://doi.org/10.1002/14651858.CD013575.pub2
  2. Haenen N, Kamperman AM, Prodan A, et al. The efficacy of lamotrigine in bipolar disorder: A systematic review and meta-analysis. Bipolar Disorders. 2024. https://doi.org/10.1111/bdi.13452
  3. Arnone D, Östlundh L, Mosa M, et al. Efficacy of Lamotrigine in the Treatment of Unipolar and Bipolar Depression: Meta-Analysis of Acute and Maintenance Randomised Controlled Trials. Pharmaceuticals. 2025. https://doi.org/10.3390/ph18101590
  4. U.S. Food and Drug Administration. LAMICTAL (lamotrigine) tablets, tablets for oral suspension and orally disintegrating tablets, prescribing information. 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d7e3572d-56fe-4727-2bb4-013ccca22678
  5. Geddes JR, Calabrese JR, Goodwin GM. Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials. The British Journal of Psychiatry. 2009. https://doi.org/10.1192/bjp.bp.107.048504
  6. Solmi M, Veronese N, Zaninotto L, et al. Lamotrigine compared to placebo and other agents with antidepressant activity in patients with unipolar and bipolar depression: a comprehensive meta-analysis of efficacy and safety outcomes in short-term trials. CNS Spectrums. 2016. https://doi.org/10.1017/S1092852916000523
  7. Panebianco M, Bresnahan R, Marson AG. Lamotrigine add-on therapy for drug-resistant focal epilepsy. Cochrane Database of Systematic Reviews. 2023. https://doi.org/10.1002/14651858.CD001909.pub4
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  9. Wiffen PJ, Derry S, Moore RA. Lamotrigine for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews. 2013. https://doi.org/10.1002/14651858.CD006044.pub4
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