M.T.I.

MICHAEL T. INGRAM, M.D.

All About Lithium

1) What type of drug is lithium?

Lithium is a cation metal first used in the 19th century to treat gout. Circa 1940, John Cade discovered that lithium was effective as a mood stabilizing medication for patients with bipolar mania. It is now called a mood stabilizer. 

2) What is lithium used for?

Lithium is one of the best medications we have in the treatment of bipolar disorder. It is also used as an “add-on” medication to antidepressants in patients with severe depression. Lithium is probably the best for euphoric-type mania and has been shown effective for chronic suicidal thoughts in patients with both unipolar and bipolar depression. 

Lithium has also been shown effective for aggression and violent behaviors in patients with impulse-control disorders. Lastly, lithium has been used successfully in patients with general mood instability in patients with psychotic disorders such as schizoaffective disorder and schizophrenia.

3) For bipolar disorder, is it used for manic episodes, depressive episodes, or both? Is it taken between episodes or just during episodes?

Lithium is used for both manic and depressive episodes as well as between episodes to prevent mania and depression. 

See tables below

 
 
 
 
 

4) How effective is it in treating mood disorders? 

Lithium is one of the most effective medications we have for preventing both mania and depression in patients with bipolar disorder. Some experts would argue that lithium is best for euphoric mania and less effective for patients experiencing “mixed states” or “rapid cycling” bipolar disorder, but this is controversial. 

During an acute manic episode, lithium is often combined with other medications to help stabilize mood. Unfortunately, lithium prescriptions have declined over the past 20 years due to development of atypical antipsychotics and because lithium has a narrow therapeutic index (meaning that the therapeutic range is narrow, and it is easy to become toxic from lithium if not taken appropriately or if mixed with certain medications). 

5) How does lithium work to stabilize mood? 

This is still unclear. However, we do know that lithium has a number of actions. Lithium’s interactions with the brain are complex and include modulating serotonin neurotransmission, modulating signal transduction within neurons, and altering transcription of certain genes that promote growth and neuron viability. Lastly, it appears that lithium alters metabolism of dopamine, norepinephrine, and epinephrine in ways that are still incompletely understood. 

6) How long does it take for lithium to start working? 

Varies depending on the patient but typically within 1-3 weeks.   

7) How often does someone take lithium and what are common doses? 

Patients are instructed to take lithium every day. Doses vary but typically we want patients to be dosed such that blood lithium levels are between 0.6-1.2 meq/L. For the average person, the dose range of lithium can be anywhere from 300mg-1,200mg per day (or higher if patient has severe mania) in divided doses. There are controlled-release formulations of lithium that allow for once per day dosing, which is preferred as there is some evidence that once daily dosing reduces the risk of long-term kidney problems. 

8) Are there any patients who should avoid taking lithium? 

There is no absolute contraindication to lithium therapy. A careful risk-benefit analysis should be conducted for each patient and should take into consideration their medical history. In general, elderly patients and patients with renal impairment are dosed lower due to decreased renal elimination. 

Patients who are pregnant or actively trying should speak with their medical provider about continuing or discontinuing lithium during pregnancy. It is important to know that lithium is not absolutely contraindicated during pregnancy. However, there are risks associated with lithium use during pregnancy and these risks (and potential benefits) should be discussed on an individual basis with a psychiatrist. 

Risks associated with lithium use in childhood are not well established and therefore it is rarely used in children.  

9) Are there any health conditions that prevent someone from taking lithium? 

In general, patients with severe renal problems, certain cardiac arrhythmias, severe seizure disorders, and pregnant patients should try alternative medications before starting lithium. Also, lithium should be discontinued prior to Electroconvulsive Therapy (ECT) due to risk of prolonged seizures during ECT treatment. Lithium has also been shown to worsen symptoms of acne and psoriasis. 

10) What are some common drug interactions people should look out for?

Hydration status, hyponatremia (low sodium levels), hypernatremia (elevated sodium levels), caffeine, theophylline, blood pressure medications (thiazide diuretics, Angiotensin Converting Enzyme Inhibitors, Calcium channel blockers), Non-steroidal anti-inflammatory drugs, Carbamazepine, Phenytoin, Methyldopa, and metronidazole (Flagyl) may alter lithium levels. Lithium in combination with high potency antipsychotics such as haloperidol may cause neurotoxicity. Lithium has also been associated with serotonin toxicity if used in combination with serotonergic medications but this is very rare.  

11) What percentage of lithium uses experience side effects? What are some common side effects?

The exact percentages are not well established. Up to 20% of patients taking lithium (more often women) develop clinical hypothyroidism. About 5% of lithium treated patients develop some form of renal impairment but the clinical significance of this is unclear.

Common side effects: Weight gain, tremors, sedation, dizziness, nausea, polyuria, polydipsia, cognitive problems, diarrhea, alopecia, and hypothyroidism are common side effects. 

Hypothyroidism is a common side effect of lithium treatment

12) When should you reach out to a doctor about worrisome side effects or changing your dosing? 

Any sign of lithium toxicity should prompt patients to seek medical attention. This includes worsening tremors, ataxia (balance/coordination problems), slurred speech, nausea, or confusion. 

Lithium Toxicity

1) What is lithium toxicity and who is most at risk for experiencing it?
Lithium toxicity occurs with blood lithium levels above 1.5mEq/L and/or symptoms of lithium toxicity.

See table below

2) What percentage of bipolar patients experience lithium toxicity?
This question is difficult to answer as the data is mixed. 

3) What is a safe blood level of lithium?
0.6mEq/L – 1.2mEq/L is the therapeutic range

4) What are the symptoms of lithium toxicity? Do these vary based on whether it is acute or chronic?
Nausea, vomiting, ataxia, course tremors, slurred speech, confusion, seizures, diarrhea are all symptoms of lithium toxicity.

5) When should you see a doctor or seek emergency help?
If you feel lethargic, nauseated, vomiting/diarrhea, new tremors, slurring speech, or feeling confused/disoriented.

6) If you think you might be experiencing lithium toxicity what are the first steps you should take to treat it?
First thing to do is immediately contact your health provider, stop/reduce the dose of lithium, and drink plenty of fluids. 

7) How do doctors treat lithium toxicity?
Typically, lithium toxicity is managed by reducing or stopping the medication, administering IV fluids, and close monitoring of cardiac, neurologic, and renal functioning. In severe cases, hemodialysis is used.

8) Are there lasting side effects of lithium toxicity?
Renal impairment (decreased renal functioning), abnormal involuntary movements, and thyroid/parathyroid problems have been associated with chronic lithium treatment. 

References

  • Cooper, J. R., Bloom, F. E., & Roth, R. H. (2003). The biochemical basis of neuropharmacology (8th ed.). New York, NY, US: Oxford University Press.
  • Iversen, L. L., Iversen, S. D., Bloom, F. E., & Roth, R. H. (2009). Introduction to neuropsychopharmacology. Oxford: Oxford University Press.
  • Puzantian, T., & Carlat, D. J. (2016). Medication fact book: for psychiatric practice. Newburyport, MA: Carlat Publishing, LLC.
  • J. Ferrando, J. L. Levenson, & J. A. Owen (Eds.), Clinical manual of psychopharmacology in the medically ill(pp. 3-38). Arlington, VA, US: American Psychiatric Publishing, Inc.
  • Schatzberg, A. F., & DeBattista, C. (2015). Manual of clinical psychopharmacology. Washington, DC: American Psychiatric Publishing.
  • Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
  • Stahl, S. M. (2014). Stahl’s essential psychopharmacology: Prescriber’s guide (5th ed.). New York, NY, US: Cambridge University Press.
  • Stahl, S. M. (2021). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (5th ed.). New York, NY, US: Cambridge University Press.
  • Whalen, K., Finkel, R., & Panavelil, T. A. (2015). Lippincotts illustrated reviews: pharmacology. Philadelphia, PA: Wolters Kluwer.
  • Charney and Nestler’s Neurobiology of Mental Illness. 5th Ed. Oxford University Press. 2017. 

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