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- Lithium is a medication used to treat certain mental illnesses such as bipolar disorder.
- For some people, lithium can help decrease abnormal activity in the brain, manic episodes and suicidal feelings.
- Short-term side effects can include shaking, fatigue, headache and gastrointestinal problems, while a long-term side effect can be weight gain.
- If you take lithium your doctor will monitor your kidney function, thyroid function and how much lithium is in your blood.
- Lithium is just one treatment option, usually prescribed initially by a psychiatrist. Your doctor will decide if it’s right for you.
What is lithium?
Lithium is a chemical element found in nature that is sometimes used in medicines to treat certain mental illnesses, such as bipolar disorder. Lithium can treat acute mania, or 'highs', and help with longer-term mood stabilisation.
It's also used in treating some types of depression and other types of mental illness.
If you have a mental illness, your doctor will decide if medication is the right treatment for you. Lithium is just one option.
How does lithium work?
Lithium works by changing the release of chemicals in the brain.
It can take some time to get the dosage right and it may be weeks or even months before it affects your mood. If you take lithium, you will need regular appointments with your doctor to make sure you are not taking too little or too much lithium.
What are the benefits of lithium?
Lithium helps reduce the severity and frequency of mania — the elevated, euphoric end of the mood scale — and may help to treat bipolar depression.
If you have been at risk of suicide, lithium may help reduce these feelings. Lithium also helps prevent manic and depressive episodes occurring in the future. Therefore, your doctor may prescribe it over long periods of time to prevent relapse.
Important things to remember when taking lithium
- Tell your doctor or pharmacist if you have any allergies.
- If you are taking diuretics (water pills), tell your doctor since these may need to be carefully monitored.
- Tell your doctor about any other medicines, supplements or complementary medicines you are taking, as they may interact with lithium.
- If you are pregnant, planning to become pregnant or breastfeeding, tell your doctor straight away. Lithium may cause harm to a fetus or baby.
- Tell your doctor first if you have any heart or kidney problems.
- Lithium can cause drowsiness, so it is important to consider this if driving or operating heavy machinery
Short-term side effects
You may have some short-term side effects when starting treatment with lithium or changing dose. It's important to weigh up these short-term side effects with the benefit lithium may have for the symptoms of the mental illness.
Short-term sides effects can include:
These side effects usually go away after a few days. If side effects continue or are worrying you, see your doctor. If they suddenly get worse, it may be a sign of 'lithium toxicity', or too much lithium in your body (see below). If this happens, call your doctor immediately.
Long-term side effects
Taking lithium for long periods can affect your kidneys and your thyroid. Lithium can also cause drowsiness.
Your doctor will carry out blood tests regularly to monitor how much lithium is in your blood. They will also monitor your kidney function, your thyroid gland and your parathyroid gland.
Some people who take lithium for long periods gain weight. A healthy diet and regular exercise can help you keep your weight under control. Talk to your doctor about managing your weight.
Women who take lithium are usually advised to use other medicines while pregnant.
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What is lithium toxicity?
You can develop lithium toxicity suddenly if you take too many tablets at once or combine lithium with certain other medicines.
If you are on a steady dose of lithium, you may get chronic lithium toxicity when your kidneys stop working properly.
Lithium toxicity can cause:
If you think you or someone you care for may have lithium toxicity, it's important to talk to a doctor immediately.
See healthdirect's medicines section for more information about lithium.
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Last reviewed: June 2020
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Start Your Symptom CheckValproic acid may cause serious or life-threatening damage to the liver that is most likely to occur within the first 6 months of therapy. The risk of developing liver damage is greater in children who are younger than 2 years of age and are also taking more than one medication to prevent seizures, have certain inherited diseases that may prevent the body from changing food to energy normally, or any condition that affects the ability to think, learn, and understand. Tell your doctor if you have a certain inherited condition that affects the brain, muscles, nerves, and liver (Alpers Huttenlocher Syndrome), urea cycle disorder (an inherited condition that affects the ability to metabolize protein), or liver disease. Your doctor will probably tell you not to take valproic acid. If you notice that your seizures are more severe or happen more often or if you experience any of the following symptoms, call your doctor immediately: excessive tiredness, lack of energy, weakness, pain on the right side of your stomach, loss of appetite, nausea, vomiting,, dark urine, yellowing of your skin or the whites of your eyes, or swelling of the face.
Valproic acid can cause serious birth defects (physical problems that are present at birth), especially affecting the brain and spinal cord and can also cause lower intelligence and problems with movement and coordination, learning, communication, emotions, and behavior in babies exposed to valproic acid before birth. Tell your doctor if you are pregnant or plan to become pregnant. Women who are pregnant or who are able to become pregnant and are not using effective birth control must not take valproic acid to prevent migraine headaches. Women who are pregnant should only take valproic acid to treat seizures or bipolar disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods) if other medications have not successfully controlled their symptoms or cannot be used. Talk to your doctor about the risks of using valproic acid during pregnancy. If you are a woman of childbearing age, including girls from the start of puberty, talk to your doctor about using other possible treatments instead of valproic acid. If the decision is made to use valproic acid, you must use effective birth control during your treatment. Talk to your doctor about birth control methods that will work for you. If you become pregnant while taking valproic acid, call your doctor immediately. Valproic acid can harm the fetus.
Valproic acid may cause serious or life-threatening damage to the pancreas. This may occur at any time during your treatment. If you experience any of the following symptoms, call your doctor immediately: ongoing pain that begins in the stomach area but may spread to the back nausea, vomiting, or loss of appetite.
Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your response to valproic acid.
Talk to your doctor about the risks of taking valproic acid or of giving valproic acid to your child.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with valproic acid and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (//www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer's website to obtain the Medication Guide.
Lamotrigine can be used to treat the following partial seizures, primary generalized tonic-clonic seizures, bipolar I disorder maintenance and Lennox-Gastaut syndrome. Off-label uses include treating acute bipolar depression, fibromyalgia, schizophrenia, and unipolar depression. This activity covers lamotrigine, including mechanism of action, pharmacology, adverse event profiles, eligible patient populations, contraindications, monitoring, and highlights the interprofessional team's role in managing lamotrigine therapy.
Objectives:
Explain the mechanism of action of lamotrigine.
Identify both approved and off-label indications for lamotrigine.
Summarize the potential drug-drug interactions for lamotrigine.
Describe interprofessional team strategies for improving care coordination and communication to use lamotrigine to enhance patient outcomes.
Lamotrigine is an anti-seizure/anti-epilepsy drug first approved for use in the USA in 1994. It is considered a first-line treatment for primary generalized tonic-clonic seizures (including simple and complex partial seizures and focal-onset tonic-clonic seizures) and Lennox-Gestault syndrome.[1][2][3]
Off-label uses include treatment of rapid-cycling bipolar depression, bipolar disorder type I maintenance, prophylaxis for basilar migraine with aura, panic disorder, and binge eating disorder.[4][5][6] Some research has pointed towards using lamotrigine use in managing trigeminal neuralgia.[7]
The mechanism of action for lamotrigine is not entirely understood. It is a triazine, and research has shown that lamotrigine selectively binds and inhibits voltage-gated sodium channels, stabilizing presynaptic neuronal membranes and inhibiting presynaptic glutamate and aspartate release. Researchers have not demonstrated that lamotrigine has significant effects on other neurotransmitters such as serotonin, norepinephrine, or dopamine.[8] There is a theory that lamotrigine may interact with voltage-activated calcium-gated channels, contributing to its broad range of activity. In vitro studies have also shown that lamotrigine inhibited dihydrofolate reductase, potentially contributing to concerns for its teratogenicity. Lamotrigine follows first-order kinetics with a half-life of 29 hours.
Lamotrigine is available as tablets, chewable tablets, and orally disintegrating tablets. It is available in formulations of 25 mg, 100 mg, 150 mg, and 200 mg tablets in tablet form. A chewable, dispersible tablet form is available in 2 mg, 5 mg, and 25 mg dispersible tablets. The orally disintegrating tablets are available in formulations of 25 mg, 50 mg, 100 mg, and 200 mg. All formulations should be stored at room temperature and need protection from light.
It also is available in 5-weeks starter "convenience packs" with different color coding: the blue pack contains 35 tablets of 25 mg, the green pack contains 84 tablets of 25 mg and 14 tablets of 100 mg, and the orange pack contains 42 tablets of 25 mg and 7 tablets of 100 mg.
Lamotrigine dosing requires alteration if given concurrently with carbamazepine, phenytoin, phenobarbital, primidone, rifampin, lopinavir/ritonavir, atazanavir, ritonavir, and valproic acid.
If it is necessary to discontinue lamotrigine, it should be done in a step-wise fashion over two weeks, if possible. There is a possibility of withdrawal seizures when discontinuing lamotrigine, which lessens if the drug is tapered rather than stopped quickly.
For Seizures
If not used concurrently with carbamazepine, phenytoin, phenobarbital, primidone, rifampin, lopinavir/ritonavir, atazanavir, ritonavir, and valproic acid, dosing instructions are as follows. Initially, dosing is 25 mg given daily. At week three, the dose should increase to 50 mg daily. At week five, increase by an additional 50 mg each week or every other week. The typical maintenance ranges from 225 mg to 375 mg in two divided doses.
If being used concurrently with valproic acid, dosing instructions are as follows. Initially, dosing is 25 mg given every other day. At week three, the dose should increase to 25 mg daily. At week 5, increase the dose by an additional 25 mg to 50 mg every week or every other week. Typical maintenance varies from 100 mg to 200 mg daily in one or two divided doses if given with valproic acid alone or 100 mg to 400 mg in one or two divided doses if given with other medications that induce glucuronidation.
If used concurrently with carbamazepine, phenytoin, phenobarbital, primidone, rifampin, lopinavir/ritonavir, atazanavir, or ritonavir, dosing instructions are as follows. Initially, the dose is 50 mg given daily. At week three, the dose should increase to 100 mg daily in 2 divided doses. At week five, increase by an additional 100 mg every week or every other week. Typical maintenance ranges from 300 mg to 500 mg to two divided doses.
For Bipolar I
Maintenance is from 200 mg to 400 mg, with additional consideration given to medication given concurrently with lamotrigine.
Renal and Hepatic Dosing:
In cases of renal impairment, the immediate-release formulation dose should be reduced by 25% if CrCl is between 10 and 50. If Creatinine clearance is below 10, the maximum dosing is 100 mg every other day. For hemodialysis patients, dosing is 100 mg for a single dose after each dialysis with no supplement. For patients on peritoneal dialysis, dosing is 100 mg every other day. For the extended-release formulation, clinicians are advised to reduce the usual dose in instances of significant renal impairment.
For hepatic impairment, dosing should reduce the dose by 25% in severe impairment; if the patient has severe impairment with ascites, the dose reduction is 50%.
United States Boxed Warning: Lamotrigine can cause serious rashes requiring hospitalization and discontinuation of this medication. Rash severity varies but includes a risk for Stevens-Johnson syndrome. The incidence of Stevens-Johnson syndrome in the pediatric population is 0.3% to 0.8% and 0.03% to 0.08% in adult populations. The number of cases associated with toxic epidermal necrolysis is too low to report an estimated incidence. Nearly all cases of a rash occur 2 to 8 weeks after the initiation of lamotrigine. It should also bear mentioning that the discontinuation of lamotrigine may not prevent a rash from becoming life-threatening. Patient education should include continuous monitoring of the rash for improvement after discontinuing the medication.[9][10]
Other serious adverse effects include multi-organ sensitivity, hemophagocytic lymphohistiocytosis, blood dyscrasias, suicidal behavior/ideations, aseptic meningitis, status epilepticus, and sudden unexplained death in epilepsy.[11][12]
Side Effects
Nausea, vomiting
Chest pain, back pain
Xerostomia
Edema
Dysmenorrhea
Weight changes
Constipation
Abdominal pain
Pain, weakness
Insomnia, drowsiness
Dizziness, ataxia, diplopia.
Headache
Anxiety, irritability
Visual disturbances
Hypersensitivity to lamotrigine or its ingredients is the primary contraindication for the administration of lamotrigine.
Evaluating gender, age, and contraceptive use is essential when considering starting lamotrigine. While some studies in humans have not shown an increased risk for congenital malformations during lamotrigine therapy during pregnancy, animal studies have demonstrated that an increased risk exists. The drug is pregnancy risk factor C; animal studies have shown the risk for congenital malformations. Clinicians should recommend their pregnant female patients to enroll in the North American Antiepileptic Drug Pregnancy Registry.[13]
Lamotrigine is present in breast milk and is detectable in the blood of breastfed infants. Symptoms of lamotrigine in infants include poor feeding, drowsiness, rash, and apnea. These symptoms can improve with the discontinuation of lamotrigine. If the benefits outweigh the risks in treating epilepsy during lactation/breastfeeding, clinicians should consider monitoring infant lamotrigine levels.
Consideration for other drugs' effects on glucuronidation merit consideration, as glucuronic acid conjugation primarily metabolizes lamotrigine.
Drugs that induce lamotrigine glucuronidation include carbamazepine, phenytoin, phenobarbital, rifampin, lopinavir/ritonavir, atazanavir/ritonavir, and primidone.
Valproic acid inhibits lamotrigine glucouronidation.
Concurrent use with central nervous system (CNS) depressants may increase the potency of CNS depression.
Lamotrigine reportedly interferes with urine drug screening and can cause false-positive readings of phencyclidine.
The value of monitoring lamotrigine concentrations remains unestablished to date. Due to the pharmacokinetics between lamotrigine and other drugs and their effect on lamotrigine concentration, clinical judgment must be exercised during concomitant use if there are concerns regarding lamotrigine levels. Dofetilide can have a severe interaction with lamotrigine, and the combination is strongly discouraged. Other drugs with potential serious interactions include valproic acid, rifampin, estrogen-containing contraceptives, and estrogen replacement therapy medications, as well as certain barbiturates.
Labs should include pertinent serum levels of concurrent anticonvulsants, liver function testing, and renal function assessments. Clinical team staff should spend ample time educating patients on monitoring themselves for hypersensitivity, particularly rashes or other skin changes occurring near or on the mucosa. Patient education should also include discussing how to monitor for changes in seizures and their frequency and duration. Patients should also monitor for changes in suicidality, including suicidal thoughts and increased desire to commit suicide. Finally, patients should receive counsel on how to watch for signs/symptoms of aseptic meningitis.
With excessive lamotrigine overdoses, some reportedly as high as 16 g, fatalities have occurred following complications, including seizures, coma, and conduction abnormalities. Immediate-release lamotrigine is rapidly absorbed, and inducing emesis may not be the appropriate intervention indicated in this instance. However, hospitalization and supportive care are indicated, as well as the usual precautions to protect the airway. As of this writing, there is no known specific antidote for lamotrigine toxicity.[14]
Lamotrigine is best prescribed, administered, dispensed, and managed by an interprofessional healthcare team. This team includes all clinicians (physicians, specialists, and mid-level practitioners (i.e., PAs and NPs)), nursing staff, and pharmacists. The drug is often prescribed by the primary care provider/nurse practitioner, internist, neurologist, and pain specialist to treat several other disorders besides seizures. However, all prescribers should be aware of the United States Boxed Warning, which states that lamotrigine can cause serious rashes requiring hospitalization and discontinuation of this medication. Rash severity varies but includes a risk for Stevens-Johnson syndrome. It also bears mentioning that the discontinuation of lamotrigine may not prevent a rash from becoming life-threatening. Patient education should instruct the patient to continuously monitor for the outbreak for improvement after discontinuing the medication.[15] Pharmacists need to monitor the patient's medication record, alert the prescriber to possible drug-drug interactions, verify appropriate dosing, and offer patient counsel about their medication. Nursing can serve as an additional patient counseling resource and coordinate activities between the various clinicians and other specialties involved in patient care.
All interprofessional team members need to engage in open communication and patient data sharing so that everyone on the team is operating from the same accurate, up-to-date information. This interprofessional team approach will help yield optimal patient outcomes and reduce the potential for adverse events. [Level 5]
Review Questions
1.
Jansen AC, Andermann E. Progressive Myoclonus Epilepsy, Lafora Type. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Mirzaa GM, Amemiya A, editors. GeneReviews® [Internet]. University of Washington, Seattle; Seattle (WA): Dec 28, 2007. [PubMed: 20301563]
2.Brigo F, Igwe SC, Lattanzi S. Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents. Cochrane Database Syst Rev. 2019 Feb 08;2:CD003032. [PMC free article: PMC6367681] [PubMed: 30734919]
3.Brigo F, Jones K, Eltze C, Matricardi S. Anti-seizure medications for Lennox-Gastaut syndrome. Cochrane Database Syst Rev. 2021 Apr 07;4:CD003277. [PMC free article: PMC8095011] [PubMed: 33825230]
4.Köhler-Forsberg O, Sylvia LG, Thase M, Calabrese JR, Tohen M, Bowden CL, McInnis M, Iosifescu DV, Kocsis JH, Friedman ES, Ketter TA, McElroy SL, Shelton RC, Fung V, Ostacher MJ, Nierenberg AA. Lithium plus antipsychotics or anticonvulsants for bipolar disorder: Comparing clinical response and metabolic changes. Aust N Z J Psychiatry. 2022 Feb 15;:48674221077619. [PubMed: 35164524]
5.Ranganathan LN, Ramamurthy G, Kanthimathinathan S. Preventive Oral Treatment of Episodic Migraine: An Overview. Neurol India. 2021 Mar-Apr;69(Supplement):S51-S58. [PubMed: 34003148]
6.Besag FMC, Vasey MJ, Sharma AN, Lam ICH. Efficacy and safety of lamotrigine in the treatment of bipolar disorder across the lifespan: a systematic review. Ther Adv Psychopharmacol. 2021;11:20451253211045870. [PMC free article: PMC8504232] [PubMed: 34646439]
7.Bendtsen L, Zakrzewska JM, Abbott J, Braschinsky M, Di Stefano G, Donnet A, Eide PK, Leal PRL, Maarbjerg S, May A, Nurmikko T, Obermann M, Jensen TS, Cruccu G. European Academy of Neurology guideline on trigeminal neuralgia. Eur J Neurol. 2019 Jun;26(6):831-849. [PubMed: 30860637]
8.Verrotti A, Striano P, Iapadre G, Zagaroli L, Bonanni P, Coppola G, Elia M, Mecarelli O, Franzoni E, Liso P, Vigevano F, Curatolo P. The pharmacological management of Lennox-Gastaut syndrome and critical literature review. Seizure. 2018 Dec;63:17-25. [PubMed: 30391662]
9.Tomson T, Battino D, Perucca E. Teratogenicity of antiepileptic drugs. Curr Opin Neurol. 2019 Apr;32(2):246-252. [PubMed: 30664067]
10.Hou S, Huh B, Kim HK, Kim KH, Abdi S. Treatment of Chemotherapy-Induced Peripheral Neuropathy: Systematic Review and Recommendations. Pain Physician. 2018 Nov;21(6):571-592. [PubMed: 30508986]
11.Kanner AM, Ashman E, Gloss D, Harden C, Bourgeois B, Bautista JF, Abou-Khalil B, Burakgazi-Dalkilic E, Park EL, Stern J, Hirtz D, Nespeca M, Gidal B, Faught E, French J. Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs II: Treatment-resistant epilepsy: Report of the American Epilepsy Society and the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Epilepsy Curr. 2018 Jul-Aug;18(4):269-278. [PMC free article: PMC6145395] [PubMed: 30254528]
12.Di Stefano G, Truini A, Cruccu G. Current and Innovative Pharmacological Options to Treat Typical and Atypical Trigeminal Neuralgia. Drugs. 2018 Sep;78(14):1433-1442. [PMC free article: PMC6182468] [PubMed: 30178160]
13.Li Y, Meador KJ. Epilepsy and Pregnancy. Continuum (Minneap Minn). 2022 Feb 01;28(1):34-54. [PMC free article: PMC9642109] [PubMed: 35133310]
14.Wood KE, Palmer KL, Krasowski MD. Data on the relationship between lamotrigine and levetiracetam serum/plasma levels and toxicity: Experience at an academic medical center. Data Brief. 2021 Dec;39:107555. [PMC free article: PMC8603012] [PubMed: 34825027]
15.Demir M, Akarsu EO, Dede HO, Bebek N, Yıldız SO, Baykan B, Akkan AG. Investigation of the Roles of New Antiepileptic Drugs and Serum BDNF Levels in Efficacy and Safety Monitoring and Quality of Life: A Clinical Research. Curr Clin Pharmacol. 2020;15(1):49-63. [PMC free article: PMC7497568] [PubMed: 30864528]