A new life-threatening warning was added to lamotrigine in 2018
Fifteen years after the bipolar approval. Onset is usually in the first month.
Top of the evidence hierarchy, independently funded. how we score evidence
In June 2018 the FDA added a subsection to the lamotrigine label that had not existed before: hemophagocytic lymphohistiocytosis, or HLH. It is a syndrome of runaway immune activation, and the label calls it life-threatening, with high mortality if it is not recognised early and treated. Reported signs include fever, rash, an enlarged liver or spleen, swollen lymph nodes, neurological symptoms, low blood counts, and abnormal liver and clotting results. Symptoms have been reported 8 to 24 days after starting the medication.
Two things about this are worth sitting with. It arrived in 2018, and lamotrigine was approved for bipolar maintenance in 2003 and has been marketed since 1994 — this was not in the approval package. It came from people taking the drug afterwards. And the label gives no rate for it. That is not sloppiness: reports like these arrive voluntarily from a population of unknown size, so a frequency cannot honestly be calculated. What the label does say is that it has occurred, in both children and adults, across the conditions lamotrigine is used for.
This is not a reason to stop, and stopping lamotrigine abruptly carries its own risk. It is a reason to know what the first month should not look like.
Worth asking
What exactly should I watch for in the first three or four weeks, who do I call if I get a fever and a rash at the same time, and is there anything in my history that makes this more likely.
What it is FDA approved for
Read off the label. Trial duration and approval year are shown only where they were recorded — never inferred.
- Maintenance treatment of bipolar I disorder (to delay time to occurrence of mood episodes, after acute stabilization)
- Epilepsy, adjunctive therapy (partial-onset seizures, primary generalized tonic-clonic seizures, Lennox-Gastaut syndrome; ages 2+)
- Epilepsy, conversion to monotherapy for partial-onset seizures (ages 16+)
Source
LAMICTAL (lamotrigine) safety-related labeling change, 27 June 2018 (SUPPL-57): Warnings and Precautions 5.2, Hemophagocytic Lymphohistiocytosis — new subsection added — U.S. Food and Drug Administration (2018)
Regulator or national health body
How this was scored
- Study design
- Regulatory safety determination
- Funding
- No external funding
- Published in
- Regulator or national health body
- Sample size
- not recorded
- Preregistered
- No
- Conflicts disclosed
- Yes
- Independent of proponent
- Yes
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published August 5, 2026. Last verified August 19, 2026.
Questions
How strong is the evidence behind this?
Resolv rates this source "gold standard". Top of the evidence hierarchy, independently funded. It scores 86 out of 100 on our published rubric. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
LAMICTAL (lamotrigine) safety-related labeling change, 27 June 2018 (SUPPL-57): Warnings and Precautions 5.2, Hemophagocytic Lymphohistiocytosis — new subsection added — U.S. Food and Drug Administration (2018). Published in: Regulator or national health body. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Regulatory safety determination. Funding: No external funding. The researchers were independent of whoever benefits from the result. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is lamotrigine (Lamictal) FDA approved?
Yes — FDA approved for Maintenance treatment of bipolar I disorder (to delay time to occurrence of mood episodes, after acute stabilization), Epilepsy, adjunctive therapy (partial-onset seizures, primary generalized tonic-clonic seizures, Lennox-Gastaut syndrome; ages 2+), Epilepsy, conversion to monotherapy for partial-onset seizures (ages 16+). Approval is for a specific indication, not for everything the drug is prescribed for.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.