Lithium: Monitoring Tests, Side Effects, and Toxicity

What You Need to Know to Take Lithium Safely?

lab test being done to monitor drug levels
What are the side effect of lithium and what should you know about lithium toxicity?. Getty Images - Cultura - Rafe Swan

Lithium is a mood stabilizer that can be helpful with bipolar disorder and other conditions, but is well known for causing side effects and toxicity. That said, when tests are performed regularly to monitor levels, and people are familiar with the proper use of the drug, it can be very effective in controlling moods. What do you need to know to use lithium safely?

Lithium: A Mood Stabilizer With Side Effects Like All Drugs

Lithium was the first mood stabilizer medication used for bipolar disorder, having been first used for the treatment of the inflammatory condition gout.

We are just starting to learn the mechanism by which this medication works at a biological level.

Possible Side Effects of Lithium Therapy

As with many medications, lithium can come with a number of side effects, both short term and long term and both mild and serious.

The most common side effects of lithium tend to be more annoying than dangerous. These include:

  • Increased thirst
  • Frequent urination
  • Nausea
  • Diarrhea
  • Tremor (a tremor which is made worse by attempting delicate hand movements.
  • Weight gain - Lithium is well known for its role in weight gain. On average, people tend to gain 13.5 pounds on the medication, but roughly 20 percent of people gain more than this. A 2016 study found that the medication Metformin may be of benefit in reducing or preventing weight gain for some people on lithium therapy.
  • Swelling (edema)
  • Hair loss

Organs most affected (and which should be monitored) include the:

  • Kidneys - Most of the time kidney dysfunction is mild, though sometimes this can be progressive.
  • Thyroid - Lithium can affect thyroid function in many ways. It can cause hypothyroidism, a goiter, or autoimmune thyroiditis. Lithium therapy has also been linked with hyperthyroidism in some people.
  • Parathyroid - Parathyroid dysfunction has been recognized more recently as a side effect of lithium use.

    More serious side effects include:

    • Kidney dysfunction
    • Nephrogenic diabetes insipidus - Nephrogenic diabetes insipidus is a condition in which the kidneys are unable to concentrate the urine resulting in excess urination (polyuria) and excess thirst (polydipsia.)
    • Cognitive dysfunction - The exact role that lithium plays in cognitive functioning is difficult to study due to the presence of the mood disorder as well as possibly hypothyroidism. A 2017 study did find that lithium had a significant impact on psychomotor speed, though it did not appear to have an impact on attention. Its effect on memory, intellectual abilities, and executive functioning is still unclear.

    Lithium Toxicity—Acute and Chronic

    Lithium toxicity can take different forms and includes acute, chronic and acute on chronic toxicity.

    Early signs of lithium toxicity include diarrhea, vomiting, drowsiness, muscular weakness, and lack of coordination. More severe symptoms include ataxia (failure or irregularity of muscle action), giddiness, tinnitus (ringing in the ears), blurred vision, and a large output of dilute urine. Severe lithium toxicity is a medical emergency which can result in encephalopathy and cardiac arrhythmias.

    Drug Interactions With Lithium

    There are several drugs which can result in increased lithium levels in the blood. These include:

    • Non-steroidal anti-inflammatory drugs such as Advil (ibuprofen) and Aleve (naproxen.)
    • Diuretics (water pills.)
    • Angiotensin-converting enzyme inhibitors (ACE inhibitors) such as Vasotec (enalapril) and Prinivil (lisinopril.)
    • Angiotensin II receptor antagonists (ARBs) such as Diovan (valsartan) and Cozaar (losartan.)

    There are many more possible drug interactions with lithium and it's important to talk to your doctor before starting any new medication or if you discontinue a medication you are taking.

    Caffeine and theophylline, in contrast, can result in lower lithium levels.

    Monitoring Tests Before and During Lithium Therapy

    Blood tests are monitored both before a person begins lithium therapy, and periodically for the duration the medication is taken.

    Monitoring Lithium levels

    Before treatment is started, tests are ordered to assess both kidney function and thyroid function. Lithium is excreted from the body by the kidneys, so if the kidneys are malfunctioning to any degree, levels of lithium can build up in the blood.

    Lithium levels should be monitored after treatment has begun, and then after every dosage change. Blood levels are often done 5 days after a dosage change as it takes some time for the levels to stabilize.. Levels should also be checked if any new medications are added or discontinued, as many medications interact with lithium. Lithium has a very "narrow therapeutic window" which means that the level of the drug needed to have a therapeutic effect is very close, and sometimes even overlaps, with that which causes toxicity.

    The therapeutic level of lithium is usually between 0.8 and 1.1 mmol/L, though some people may need a level anywhere from 0.5 to 1.2 mmol/L to be therapeutic. Levels toward the higher side are sometimes needed to control mania.

    Toxicity begins at around 1.5 mmol/L. Initial symptoms of toxicity often include a significant worsening of the tremor, nausea, diarrhea, and blurry vision. As levels get higher, symptoms of being unsteady, slurred speech, muscle twitches and weakness, and confusion appear.

    A level of 2.0 mmol/L is a medical emergency and immediate care is needed. Symptoms can include severe neurological signs such as delirium and unconsciousness. Heart arrhythmias may also occur, which if, untreated, can be fatal.

    Thyroid tests

    It's important to note that anyone diagnosed with bipolar disorder should have thyroid tests monitored frequently even if not on lithium since abnormal levels of thyroid hormones can cause symptoms which mimic (or precipitate) both mania and depression. Thyroid levels should be tested at least every 6 months.

    Calcium levels

    A serum calcium level should be checked yearly as lithium may cause hypoparathyroidism.

    Kidney tests

    A BUN and creatinine (kidney function tests) should be drawn at the beginning of treatment, regularly during treatment, and if any symptoms of kidney disease become evident.

    Other tests

    Other tests such as blood chemistries and an EKG may be needed depending on many factors.

    Coping With Lithium Side Effects and Toxicity

    There are several ways in which the risk of side effects and toxicity can be reduced. One is to minimize the dose so that blood levels are on the lower side of the therapeutic window. Timing of the dose may also be helpful. Certainly, monitoring of blood levels is important on a regular basis as well as if any new symptoms should arise. In some cases, medications can be used to reduce the symptoms of side effects.

    Bottom Line on Lithium Side Effects and Toxicity

    Lithium can be an excellent drug for people with bipolar disorder and is thought to be the drug of choice for elderly people with bipolar disorder. It has been found to decrease the rate of suicide, a significant risk among people with the condition.

    At the same time, careful monitoring of levels is critical to reducing the potential for toxicity, and the consequences of toxicity. Side effects are common, and many of these are more annoying than dangerous. Careful monitoring of lab tests (and cardiac function especially in the elderly) is needed due to the risk of kidney dysfunction, and thyroid and hypothyroid side effects.

    With monitoring, however, and a careful understanding of the early symptoms of toxicity, many people have been able to enjoy the benefits of this medication without significant risks.

    Sources:

    Baird-Gunning, J., Lea-Henry, T., Hoegberg, L., Gosselin, S., and D. Roberts. Lithium Poisoning. Journal of Intensive Care Medicine. 2017. 32(4):249-263.

    Finley, P. Drug Interactions with Lithium: An Update. Clinical Pharmacokinetics. 2016. 55(8):925-41.

    Gitlin, M. Lithium Side Effects and Toxicity: Prevalence and Management Strategies. International Journal of Bipolar Disorder. 2016. 4(1):27.

    Paterson, A., and G. Parker. Lithium and Cognition in Those with Bipolar Disorder. International Clinical Psychopharmacology. 2017. 32(2):57-62.

    Continue Reading