Focus on Pharm: Lithium

Lithium is a very common medication that you’ll see regularly in the clinical setting (and on exams if you’re a student!). It’s actually a type of metal found in rocks and is a micronutrient found in many foods including nuts, cereals, cabbage, potatoes, tomatoes, fish and mineral water.

When we use lithium for medical purposes, we use it in its salt forms which are lithium carbonate and lithium citrate. 

Maximize your learning about lithium by reading this article and then listening to this information in episode 248 of the Straight A Nursing podcast. Tune in wherever you get your podcast fix, or straight from the website here.

D: Drug Class

Going through the Straight A Nursing DRRUGS format, we start with the drug class. Lithium is categorized in the therapeutic class as a mood stabilizer – it does not have a pharmacological classification.

How mood stabilizers work is not thoroughly understood. We do know that lithium alters the transport of sodium in nerve and muscle cells and can exert influence on neurotransmitter reuptake (specifically catecholamines and serotonin). The overall mechanism of action is that mood stabilizers decrease abnormal brain activity and bring a sense of “calm” to areas of the brain that are overstimulated or overly active. 

R: Routes of Administration

Lithium comes in PO form only but in several different formats – these are tablets, capsules, extended release tablets and as an elixir.

Lithium carbonate is the most commonly used form. Typical brand names you will see are Lithobid, Eskalith and Eskalith-CR (note that CR is the extended release version). The elixir formulation is Lithium Citrate Syrup which is a clear and colorless liquid with added flavor such as raspberry or cherry.

R: Regular Dose Range of Lithium

Dosing for lithium is highly individualized and will vary from patient to patient. Most adults will take 2 to 3 doses per day. Patients are generally started on a low dose which is then increased slowly over several weeks while watching for both the desired response and signs of toxicity. It’s important for your patient to understand that it can take about one to three weeks for the effects of lithium to be realized. A common maintenance dose is 300 to 600 mg 3 times per day to achieve a serum plasma level approximately 0.6 to 1.2 mEq/L. 

Note that because lithium is excreted solely by the kidneys, reduced renal function will require lower doses. So, as your patient gets older (or if they develop renal insufficiency) they’ll need to have their lithium levels monitored closely and their dose will likely be reduced.

U: Uses of Lithium

Lithium is mainly used to treat the mania associated with bipolar disorder, and is also used in coordination with antipsychotics in the treatment of schizophrenia. In addition, lithium is used off-label as adjunct therapy in major depressive disorder and may also be utilized to prevent cluster headaches. Additionally, because a side effect of lithium is increased neutrophil and white blood cell count, it may be useful for patients who have neutropenia or leukopenia.

G: Guidelines for Lithium Administration

Lithium Toxicity

Because lithium has a narrow therapeutic window, a key safety consideration is to avoid toxic levels. Your patient will have their lithium levels monitored routinely and will need to avoid any drugs that can cause the lithium levels to rise. These include: 

• Diuretics – Thiazide and thiazide-like diuretics increase sodium reabsorption which, in turn, causes decreased clearance of lithium. Furosemide can also affect serum levels and is used with caution in individuals taking lithium. 
• NSAIDs – Non-steroidal anti-inflammatory drugs, especially regular use of aspirin and ibuprofen, can be problematic for individuals taking lithium due to their detrimental effect on glomerular filtration rate (GFR). With lower GFR, lithium can build up to toxic levels.
• ACE inhibitors – Studies have shown that ACE inhibitors, such as lisinopril, can contribute to lithium toxicity through multiple potential mechanisms. One potential cause is that ACE inhibitors can decrease GFR, which leads to higher serum levels of lithium. Another potential cause is increased reabsorption of lithium in the proximal and distal tubules secondary to the decreased aldosterone levels that occur with ACE inhibitors.
• ARBs – Angiotensin receptor blockers, such as losartan, can cause lithium toxicity. It is thought this is due to decreased GFR and hyponatremia, both of which enhance reabsorption of lithium in the renal tubules.
• Metronidazole – This antifungal medication can raise serum lithium levels by decreasing the kidney’s ability to excrete the medication adequately. 
• Others – Other medications that can increase lithium levels are phenytoin, carbamazepine and methyldopa.

Signs of lithium toxicity include: nausea and vomiting, tremor, ataxia, nystagmus, dysarthria, dizziness, altered LOC (ranging from confusion to acute delirium), dry mouth and increased thirst. ECG changes include bradycardia, heart block, sick sinus syndrome and T-wave inversion.

Assessment

• Mood and behavior – Especially when initiating treatment or making dose adjustments.
• Intake – It is important that the patient avoid becoming volume depleted, so a fluid intake of 2 to 3 liters per day is recommended. 
• Output – Increased urine output may be due to diabetes insipidus (see adverse effects below). Excessive output due to vomiting or diarrhea could cause hypovolemia and subsequent decrease in GFR which can lead to lithium toxicity.
• ECG – Lithium can cause bradycardia, heart block and other adverse effects, namely when levels are too high.
• Weight – Lithium can cause weight gain, more commonly in women than in men.

Labs

• Serum lithium levels will be monitored at the initiation of therapy, with any dose changes, with any changes to renal function and periodically throughout therapy (typically every two months).
• Draw serum lithium level immediately prior to dose (this is a “trough” level).
• Normal reference range for maintenance therapy is 0.6 to 1.2 mEq/L, not to exceed 2.0 mEq/L.
• Renal function – Because reduced renal function can contribute to lithium toxicity, you will monitor creatinine, BUN, creatinine clearance and GFR periodically throughout therapy.
• Thyroid function – Lithium can cause both hypothyroidism and hyperthyroidism so levels should be checked at the initiation of therapy and periodically throughout. Note that hypothyroidism is more common.
• Glucose – Lithium can cause hyperglycemia.
• WBC – Lithium can cause elevated leukocytes as well as aplastic anemia.
• Electrolytes – Because lithium is a monovalent cation, it competes with other cations which can cause electrolyte imbalances. Additionally, hyponatremia can cause increased serum lithium levels and lithium itself can cause hyperparathyroidism which can lead to hypercalcemia.

Safe Administration of Lithium

• Lithium is absorbed directly into the gastrointestinal system and should be taken with food or milk to minimize GI irritation.
• Lithium is typically avoided in patients with renal impairment and not recommended in those with cardiovascular disorders due to its effect on cardiac electrophysiology. 
• Lithium is not used in pregnancy as it can cause congenital abnormalities, including cardiac defects. Note that lithium does cross over into breastmilk, so breastfeeding is not advised.
• Lithium has many drug-drug interactions beyond those discussed previously related to lithium toxicity. 
  • Effectiveness of lithium may be decreased with aminophylline and theophylline (which are used to treat asthma) and acetazolamide (a medication used to treat glaucoma, edema in heart failure and seizure).
  • There is increased risk for serotonin syndrome when lithium is taken with any medication that affects serotonin such as TCAs, SSRIs, fentanyl and the herb St. John’s Wort. 
  • Taking lithium along with an antipsychotic can increase the risk of developing encephalopathy
• Food-drug interactions include sodium and caffeine. If the patient is following a low-sodium diet, they are at higher risk for lithium toxicity. Conversely, a drastic increase in sodium intake can cause increased renal excretion of lithium. Additionally, caffeine can decrease serum lithium levels.

Lithium Education

Lithium requires a lot of education and ongoing monitoring. Patients who are unable to adhere to safe administration guidelines will likely be reconsidered for alternate therapy.

• Ensure the patient understands drug and food interactions. A consistent sodium intake is better than drastic fluctuations.
• Teach the patient to drink 2 to 3 liters of water each day to avoid hypovolemia, which can contribute to lithium toxicity.
• Teach the patient to avoid activities that contribute to sodium loss such as hot yoga or working/exercising in hot weather.
• Instruct the patient to follow all administration guidelines and to continue taking the medication even if they are feeling better. 
• Missed doses should be taken as soon as possible unless it is within two hours of the next dose or within 6 hours of an extended-release dose. 
• Lithium can cause drowsiness so teach the patient not to drive or operate heavy machinery until they know how the medication affects them.
• Make sure your patient knows the signs of lithium toxicity and when to seek medical treatment.
• Ensure the patient understands the frequency and purpose of lab tests.
• Discuss lithium’s effect on reproductive health and advise the patient to plan pregnancy and nursing with their physician’s guidance.
• Instruct the patient to NOT abruptly discontinue their medication. If they would like to discontinue lithium, they should consult with their physician and do so gradually over several months. 

S: Side Effects of Lithium

Lithium has a lot of adverse effects, the most common are:

• Weakness and drowsiness
• Tremors
• Headache and difficulty with memory
• Polyuria
• Abdominal pain, diarrhea, nausea, anorexia or weight gain
• Hypothyroidism
• Acne-like rash
• ECG changes

Less common but more serious side effects include:

• DRESS – drug reaction with eosinophilia and systemic symptoms
• Seizures
• Pseudotumor cerebri which is a buildup of pressure in the skull – it is thought to be due to the buildup of CSF
• Serotonin syndrome
• Nephrogenic diabetes insipidus
• Renal impairment
• And then, of course, all the adverse effects of lithium toxicity

TL;DR

I know that was a lot to take in about lithium, so here’s your short but sweet summary highlighting the most important things to know:

Lithium is a mood stabilizer used to treat bipolar disorder. It has a very narrow therapeutic window so patients will need to have serum lithium levels checked periodically throughout therapy. Signs of lithium toxicity are tremor, dizziness, ataxia, nausea and vomiting, altered LOC and ECG changes. Lithium has many drug-drug interactions including thiazide diuretics, ACE-inhibitors and NSAIDs. Volume depletion and low sodium intake can both contribute to excess lithium levels, leading to toxicity.

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References

Abdel-Maksoud, M. B., Nasr, A., & Abdul-Aziz, A. (2009). Lithium treatment in cluster headache: Review of literature. The European Journal of Psychiatry, 23(1), 53–60.

Aksakal, N., Erçetin, C., Özçınar, B., Aral, F., & Erbil, Y. (2015). Lithium-associated primary hyperparathyroidism complicated by nephrogenic diabetes insipidus. Turkish Journal of Surgery/Ulusal Cerrahi Dergisi, 31(3), 166–169. https://doi.org/10.5152/UCD.2014.2859

Alda, M. (2015). LITHIUM IN THE TREATMENT OF BIPOLAR DISORDER: PHARMACOLOGY AND PHARMACOGENETICS. https://doi.org/10.1038%2Fmp.2015.4

Aruna, A. S. (2009). Lithium Toxicity Secondary to Lithium—Losartan Interaction. Journal of Pharmacy Technology, 25(2), 89–93. https://doi.org/10.1177/875512250902500204

Bauer, M., & Giltin, M. (2016). What Is Lithium and How Does It Work?. In: The Essential Guide to Lithium Treatment. Springer, Cham.

Centre for Addiction and Mental Health. (n.d.). 20158 Mood Stabilizing Medications. CAMH. https://www.camh.ca/en/health-info/mental-illness-and-addiction-index/mood-stabilizing-medication

Chokhawala, K., Lee, S., & Saadabadi, A. (2022). Lithium. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK519062/

Corleone, J. (n.d.). What Foods Contain Lithium? LIVESTRONG.COM. https://www.livestrong.com/article/519437-what-foods-contain-lithium/

Cruz, S., & Bunoy, L. (2021). Lithium Intoxication-Induced Myxedema Coma in a Schizophrenic Patient: A Case Report. 8, 1–7. https://doi.org/10.4236/oalib.1108162

Drugs.com. (n.d.). Lithium Citrate Syrup: Package Insert / Prescribing Information. Drugs.Com. https://www.drugs.com/pro/lithium-citrate-syrup.html

Ekbom, K. (1981). Lithium for Cluster Headache: Review of the Literature and Preliminary Results of Long-term Treatment. Headache: The Journal of Head and Face Pain, 21(4), 132–139. https://doi.org/10.1111/j.1526-4610.1981.hed2104132.x

Evans, D. (n.d.). Lithium & Low Potassium Levels. Sciencing. https://sciencing.com/lithium-low-potassium-levels-6630594.html

Maddala, R. N. M., Ashwal, A. J., Rao, M. S., & Padmakumar, R. (2017). Chronic lithium intoxication: Varying electrocardiogram manifestations. Indian Journal of Pharmacology, 49(1), 127–129. https://doi.org/10.4103/ijp.IJP_204_16

Malhi, G. S., Bell, E., Outhred, T., & Berk, M. (n.d.). Lithium therapy and its interactions. Retrieved September 12, 2022, from https://www.nps.org.au/australian-prescriber/articles/lithium-therapy-and-its-interactions

Mayo Clinic. (2022). Lithium ( Oral Route ). Mayo Clinic. https://www.mayoclinic.org/drugs-supplements/lithium-oral-route/proper-use/drg-20064603

MedlinePlus. (n.d.). Lithium. MedLine Plus. https://medlineplus.gov/druginfo/meds/a681039.html

National Alliance on Mental Illness. (2016). Lithium. Https://Cpnp.Org/. https://nami.org/About-Mental-Illness/Treatments/Mental-Health-Medications/Types-of-Medication/Lithium

Paton, C., & Esop, R. (2005). Managing clozapine-induced neutropenia with lithium. Psychiatric Bulletin, 29(5), 186–188. https://doi.org/10.1192/pb.29.5.186

Schneir, A., & Masom, C. P. (2020). Lithium Toxicity from the Addition of an ACE Inhibitor with an Unexpected Type I Brugada Pattern ECG: Case Files of the Medical Toxicology Fellowship at the University of California, San Diego. Journal of Medical Toxicology, 16(3), 321–328. https://doi.org/10.1007/s13181-020-00773-9

Sivan Mauer, Derick Vergne, S Nassir Ghaemi. (2014). Standard and trace-dose lithium: A systematic review of dementia prevention and other behavioral benefits. https://doi.org/10.1177%2F0004867414536932

Szklarska, D., & Rzymski, P. (2019). Is Lithium a Micronutrient? From Biological Activity and Epidemiological Observation to Food Fortification. Biological Trace Element Research, 189(1), 18–27. https://doi.org/10.1007/s12011-018-1455-2