Last Updated on March 6, 2023 by
Alternative to Meds Editorial Team
Medically Reviewed by Dr John Motl MD
The Prescribers’ Digital Reference on Lamictal® (lamotrigine) provides the drug’s label information detailing over 37,000 words on Lamictal adverse effects ranging from mild to life-threatening, dangerous interactions of Lamictal with other drugs, and other warnings.12 That’s comparable to the size of an Agatha Christie novel — yet, In all of that ocean of material, one single sentence mentions withdrawal. The drug package information directs the patient to cut the dose by 50% for week one, and then do another 50% cut for week 2, and no other direction or guidance is given.
Evidence suggests that attempting such an abbreviated approach may introduce impassable difficulties. At Alternative to Meds Center, we would proceed in a much more nuanced way, tailoring the process to each individual, much slower, and with support in place to soften the withdrawals. More on these protocols used at Alternative to Meds Center will be further described below, and can also be found on our services page.
In other literature, we found one case report by Frey et al that followed 6 patients on Lamictal, where clinically significant withdrawal phenomena were present at “end of dose,” meaning before the patient’s next dose. The authors conclude that these interdose withdrawals caused marked subjective distress, making the continued use of lamotrigine questionable as the withdrawals between doses could hamper successful treatment.15 We also found a case report by Gelisse et al, where psychomotor disturbances, severe depression, tachycardia, and other withdrawal symptoms were observed after a 4-day withdrawal of lamotrigine. The authors concluded, with some surprise, that lamotrigine causes withdrawal symptoms even though it is rarely reported.11 As Cosci and Chouinard observe in their 2020 article published in the Journal of Psychotherapy and Psychosomatics, acute and prolonged Lamictal withdrawals do occur but are seemingly under-reported, under-researched, and even overlooked in medical literature, especially when such medication is prescribed in the treatment of bipolar.,13,14,16,18
People that are being treated with this medication for seizure disorder will also need to exercise additional caution during the withdrawal process and need to be medically monitored in the process. For those with seizure disorders, some have reported seizures and seizures of greater intensity and frequency where withdrawal is too rapid.6 Slow, gradual cessation over several months is suggested according to Cosci and Chouinard’s 2020 article.16
*In a 2005 study comparing withdrawal manifestations of Lamictal and other anticonvulsants, all participants with pharmacoresistant epilepsy experienced seizures of increased intensity during lamotrigine withdrawal.6,7
Lamictal (lamotrigine) is an anticonvulsive medication used in the treatment of seizures in patients aged two years and up and as bipolar maintenance for the delay of recurring episodes of depression, mania, and hypomania.
Below you will find a number of topics for discussion and study, including uses for the drug, Lamictal adverse effects, important notes about safe protocols for withdrawal, and other frequently searched topics of information about Lamictal. There are some special safety notes and warnings that anyone considering starting or stopping Lamictal (lamotrigine) should be aware of.
Even if Lamictal was correctly prescribed during a demonstrable crisis, this does not always mean that a lifetime of drug use is warranted.
Lamictal is used for epileptic seizure prevention and control, and as a mood stabilizer to treat the manic and depressive episodes of adult bipolar disorder.
It is FDA approved for use in children as young as 2 years old as well as for adults as an anticonvulsant medication to prevent epileptic seizures.24
At Alternative to Meds Center, we often see instances where Lamictal has been prescribed as an adjunct to antipsychotic medication. Lamictal is used as a mood stabilizer and when combined with an antipsychotic, creates an inhibition of both glutamate and dopamine. This also leaves a person with Lamictal reactions such as difficulty perceiving natural reward or stimulation, which is why the consumer may be driven to seek lower dosing or non-medicating alternatives.
Lamictal is the brand or trade name for the generic drug lamotrigine. There is no known slang or street name for the drug, and there is no evidence that the drug has been associated with street or illicit use or sale. There are many alternate names for Lamictal, including domestically:
International names include:
In April 2018 the FDA issued a new warning regarding anti-seizure medications including Lamictal precipitating a rare but life-threatening reaction. This reaction is described as a severe immune system inflammation, called HLH or hemophagocytic lymphohistiocytosis which can quickly escalate, and if not treated quickly, can lead to death.1
Some signs of HLH include persistent fever and low or absent natural killer cells, and certain other characteristics in the blood that are markers for HLH. Mortality rates for HLH are 50%, and it occurs in children more often than in adults, which is a concern since Lamictal is approved for patients aged two years of age and older.24
Anti-seizure medication (ASM) may lead to further seizure activity in certain patients, as hypothesized by authors Khateb et al in their 2021 research on the subject. While researchers are looking over this phenomenon more closely, patients taking ASM should be monitored for this potential Lamictal side effect.26
According to the information published by the 2021 Prescriber’s Digital Reference12 and mentioned on the drug insert 24 the following severe Lamictal adverse effects have been reported:
It should be noted that since many very young children are placed on Lamictal for epilepsy disorders, careful monitoring should be ongoing for any signs of these or other unusual or adverse Lamictal reactions, especially because a child may not be able to articulate such experiences easily.
Lamictal should never be stopped abruptly, unless as in the case of HLH, Stevens-Johnson syndrome, or other dire situations as noted above, that require a life-saving medical intervention. These require immediate hospitalization.
According to medical consensus, for the vast majority of cases, a gradual taper is the recommended procedure for coming off Lamictal. Gradual Lamictal cessation can avoid a sudden shock to the body that could leave the person in a worse off state than before the prescription was initiated.25
Lamictal influences two amino acids, aspartate, and glutamate. These are excitatory neurotransmitters, which Lamictal restricts the release of, thereby causing a calming effect. When Lamictal tapering is occurring, more of these excitatory agents may start to release into the system and this may cause rebound excitability. A gradual approach can soften the adverse effects that Lamictal cessation may otherwise cause.
Let’s talk about rebound excitability and why it may occur if the drug is reduced too fast. Lamictal restricts the presynaptic permeability of the excitatory amino acids aspartate and glutamate. When a person is withdrawing from the medication, it is generally accepted that more of these excitatory amino acids, with stimulatory neuromodulating capabilities, will begin to flood into the synapse, and there may be rebound excitability. This can be further compounded if foods containing versions of aspartate and glutamate are consumed during the withdrawal period. Therefore, foods such as diet sodas, processed foods, and artificial sweeteners (which break down into aspartate) should be restricted. One can do a search for foods that contain aspartate and glutamate to avoid these. Modifying the diet in this way may help reduce the flood of excitatory neurotransmitters during Lamictal withdrawal.
Information has been collected here covering some often-asked questions about the drug’s classification, its properties, how it is used in treatments, more information on Lamictal withdrawal symptoms, and several other topics.
Mood stabilizers, like most psychiatric drugs, can create a dependency, most pronouncedly after long-term use. Lamictal dependence can occur over time. There is a lot yet to be learned about how Lamictal and similar drugs work, but it is known that the body can build up a tolerance to a drug. This means that when you stop taking such a drug you will experience withdrawal symptoms.22
Withdrawal symptoms are also found as a component of developed dependence, where uncomfortable symptoms present when the drug is stopped. In the British Journal of Addiction, Goodman proposes a useful definition of addiction that includes powerlessness over the addictive substance and continuing to take the addictive substance despite the negative consequences of doing so. No reports have been found that document Lamictal addiction so defined.23
The decision to come off Lamictal should be carefully assessed in the context of why it was prescribed, whether the drug has or has not increased the health and quality of life of an individual, or whether the burden of Lamictal adverse effects has begun to outweigh the benefits.
Because of the inherent risks involved with Lamictal, withdrawal should only be done under medical supervision so that the process can be done in a safe and controlled way.
When choosing help, be sure to ask if the professionals who you will be working with have specific experience working with patients coming off Lamictal, and medication withdrawal in general.
In addition to the above discussions with your physician, don’t be afraid to ask about the complications that the doctor has personally seen, and how they might have been resolved. Certainly, if he or she has been doing medication withdrawal and has attained competence, there would have been some rough cases along the way. Sometimes, certain cases would lie outside of the outpatient capacity for treatment. Knowing the difference is mastery and sometimes a second opinion is pragmatic.
The prescribing doctor may be reluctant to withdraw a medication that they have invested faith in. A second doctor that specializes in medication withdrawal may have unique viewpoints worth considering. To a physician who is unfamiliar with a particular medication, especially over long-term use, Lamictal withdrawal symptoms may be misinterpreted and may receive erroneous diagnoses and treatment.
These questions would probably be even more important to explore primarily if outpatient treatment is being considered. Antipsychotic medication withdrawal complications may sometimes fall outside the capacity of an outpatient treatment setting. Seek second opinions, and keep asking questions until all the information you need has been provided so a confident treatment decision can be made.
If mental health issues, for example, depression or the beginning signs of mania, were not met with holistic, medical or other drug-free exploratory methods and investigations before prescribing medication, then no real attempt to discover why these symptoms were present ever occurred. Holistic psychiatry would incline toward such investigative work well before prescribing medications.5
An inpatient program that does implement investigative testing might be a considered approach leading to bonafide solutions that do not have to include prescription drugs.
Alternative to Meds Center does offer such investigatory work as part of the usual programs, with a wealth of adjunctive therapies provided in our inpatient program, to ease the process. Safe Lamictal tapering methods are administered by licensed physicians with decades of experience in medication withdrawal, and training in Orthomolecular and Environmental Medicine. We encourage anyone in this difficult situation to become more acquainted with our resources for safe, gradual, and gentle Lamictal withdrawal, and relief of ongoing Lamictal adverse effects.
- FDA. “FDA Drug Safety Podcast: FDA warns of serious immune system reaction with seizure and mental health medicine lamotrigine (Lamictal)” last updated 2018 Apr 30 [cited 2023 Jan 23]
2. Zhou Y, Danbolt NC. Glutamate as a neurotransmitter in the healthy brain. J Neural Transm (Vienna). 2014 Aug;121(8):799-817. doi: 10.1007/s00702-014-1180-8. Epub 2014 Mar 1. PMID: 24578174; PMCID: PMC4133642. [cited 2023 Jan 23]
3. Cunningham MO, Jones RS “The anticonvulsant, lamotrigine decreases spontaneous glutamate release but increases spontaneous GABA release in the rat entorhinal cortex in vitro” abstract, PubMed, 2000 Aug 23 [cited 2022 Mar 21]
4. CDC Body and Mind publication for teachers and students “BAM! Body and Mind” Reviewed Aug 2022 [cited 2023 Jan 23]]
5. Gibbs G DO “What is Holistic Psychiatry?” MadInAmerica, 2016 Dec 3 [cited 2022 Mar 21]
6. Wang-Tilz Y, Tilz C, Wang B, Pauli E, Koebnick C, Stefan H. “Changes of seizures activity during rapid withdrawal of lamotrigine.” Eur J Neurol. 2005 Apr;12(4):280-8. doi: 10.1111/j.1468-1331.2004.01101.x. PMID: 15804245. [cited 2022 Mar 21]
7. Berg AT. Identification of pharmacoresistant epilepsy. Neurol Clin. 2009;27(4):1003-1013. doi:10.1016/j.ncl.2009.06.001 [cited 2022 Mar 21]
8. Frey LC, Strom LA, Shrestha A, Spitz MC. End-of-dose emergent psychopathology in ambulatory patients with epilepsy on stable-dose lamotrigine monotherapy: a case series of six patients. Epilepsy Behav. 2009 Aug;15(4):521-3. doi: 10.1016/j.yebeh.2009.05.008. Epub 2009 Jul 29. PMID: 19643671. [cited 2022 Mar 21]
9. Economou NT, Bonakis A, Ghika A, Ferini-Strambi L, Vassilopoulos D, Kyrozis A. Lamotrigine withdrawal may worsen RBD symptoms. Neurologist. 2011 Sep;17(5):279-81. doi: 10.1097/NRL.0b013e31822c3e5d. PMID: 21881472. [cited 2022 Mar 21]
10. Iranzo A, Molinuevo JL, Santamaría J, Serradell M, Martí MJ, Valldeoriola F, Tolosa E. Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study. Lancet Neurol. 2006 Jul;5(7):572-7. doi: 10.1016/S1474-4422(06)70476-8. PMID: 16781987. [cited 2022 Mar 21]
11. Gelisse P, Kissani N, Crespel A, Jafari H, Baldy-Moulinier M. Is there a lamotrigine withdrawal syndrome? Acta Neurol Scand. 2002 Mar;105(3):232-4. doi: 10.1034/j.1600-0404.2002.1c220.x. PMID: 11886370. [cited 2022 Mar 21]
12. Prescribers Digital Reference “Lamotrigine – Drug Summary” [published online 2021] [cited 2023 Jan 23]
13. Bowden CL, Asnis GM, Ginsberg LD, Bentley B, Leadbetter R, White R. Safety and tolerability of lamotrigine for bipolar disorder. Drug Saf. 2004;27(3):173-84. doi: 10.2165/00002018-200427030-00002. PMID: 14756579. [cited 2023 Jan 23]
14. Goldsmith DR, Wagstaff AJ, Ibbotson T, Perry CM. Spotlight on lamotrigine in bipolar disorder. CNS Drugs. 2004;18(1):63-7. doi: 10.2165/00023210-200418010-00007. PMID: 14731061.[cited 2023 Jan 23]
15. Frey LC, Strom LA, Shrestha A, Spitz MC. End-of-dose emergent psychopathology in ambulatory patients with epilepsy on stable-dose lamotrigine monotherapy: a case series of six patients. Epilepsy Behav. 2009 Aug;15(4):521-3. doi: 10.1016/j.yebeh.2009.05.008. Epub 2009 Jul 29. PMID: 19643671. [cited 2023 Jan 23]
16. Cosci F, Chouinard G: Acute and Persistent Withdrawal Syndromes Following Discontinuation of Psychotropic Medications. Psychother Psychosom 2020;89:283-306. doi: 10.1159/000506868 [cited 2023 Jan 23]
17. Ketter TS, Malow BA, Flamini R, White SR, Post RM, Theodore WH, “Anticonvulsant withdrawal‐emergent psychopathology,” Neurology.org, First published Jan 1, 1994, DOI: https://doi.org/10.1212/WNL.44.1.55, [cited 2023 Jan 23]
18. Baldessarini RJ, Tondo L, Viguera AC. Discontinuing lithium maintenance treatment in bipolar disorders: risks and implications. Bipolar Disord. 1999 Sep;1(1):17-24. doi: 10.1034/j.1399-5618.1999.10106.x. PMID: 11256650. [cited 2023 Jan 23]
19. Hesdorffer DC, Berg AT, Kanner AM. An update on antiepileptic drugs and suicide: are there definitive answers yet?. Epilepsy Curr. 2010;10(6):137-145. doi:10.1111/j.1535-7511.2010.01382.x [cited 2023 Jan 23]
20. Viguera AC, Whitfield T, Baldessarini RJ, Newport DJ, Stowe Z, Reminick A, Zurick A, Cohen LS. Risk of recurrence in women with bipolar disorder during pregnancy: prospective study of mood stabilizer discontinuation. Am J Psychiatry. 2007 Dec;164(12):1817-24; quiz 1923. doi: 10.1176/appi.ajp.2007.06101639. PMID: 18056236. [cited 2023 Jan 23]
21. Barbee JG, Jamhour NJ. Lamotrigine as an augmentation agent in treatment-resistant depression. J Clin Psychiatry. 2002 Aug;63(8):737-41. doi: 10.4088/jcp.v63n0813. PMID: 12197456. [cited 2023 Jan 23]
22. CAMH Information Letter, “Mood Stabilizing Medications.” [published online 2009/2012] [cited 2023 Jan 23]
23. Goodman A. Addiction: definition and implications. Br J Addict. 1990 Nov;85(11):1403-8. doi: 10.1111/j.1360-0443.1990.tb01620.x. PMID: 2285834.[cited 2023 Jan 23]
24. FDA label Lamictal (lamotrigine) tablets for oral use, chewable dispersable tablets for uoral use, orally disintegrating tablets, {online} approval 1994 [cited 2023 Jan 23]
25. Betchel NT, Fariba KA, Saadabadi A. Lamotrigine. [Updated 2022 Feb 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470442/ [cited 2023 Jan 23]
26. Khateb M, Bosak N, Herskovitz M. The Effect of Anti-seizure Medications on the Propagation of Epileptic Activity: A Review. Front Neurol. 2021 May 27;12:674182. doi: 10.3389/fneur.2021.674182. PMID: 34122318; PMCID: PMC8191738. [cited 2023 Jan 23]
27. Rissardo JP, Fornari Caprara AL. Lamotrigine-Associated Movement Disorder: A Literature Review. Neurol India. 2021 Nov-Dec;69(6):1524-1538. doi: 10.4103/0028-3886.333440. PMID: 34979637. [cited 2023 Jan 23]
Originally Published Feb 18, 2021 by Diane Ridaeus
Dr. Motl is currently certified by the American Board of Psychiatry and Neurology in Psychiatry, and Board eligible in Neurology and licensed in the state of Arizona. He holds a Bachelor of Science degree with a major in biology and minors in chemistry and philosophy. He graduated from Creighton University School of Medicine with a Doctor of Medicine. Dr. Motl has studied Medical Acupuncture at the Colorado School of Traditional Chinese Medicine and at U.C.L.A.
Diane is an avid supporter and researcher of natural mental health strategies. Diane received her medical writing and science communication certification through Stanford University and has published over 3 million words on the topics of holistic health, addiction, recovery, and alternative medicine. She has proudly worked with the Alternative to Meds Center since its inception and is grateful for the opportunity to help the founding members develop this world-class center that has helped so many thousands regain natural mental health.
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