Lithium was the first mood stabilizer medication used for bipolar disorder, having been originally proposed for the treatment of the inflammatory condition gout. We are just starting to learn the mechanism by which this medication works at a cellular level.
Possible Side Effects
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:
DiarrheaFrequent urinationHair lossIncreased thirstNauseaSwelling (edema)Tremor (which is made worse by attempting delicate hand movements)
Another side effect of lithium is weight gain. Although not everyone on the drug will gain weight, the majority will. On average, people tend to gain around 13 pounds. A 2016 study found that the medication Metformin may be of benefit in reducing or preventing weight gain for some people on lithium therapy. Organs most affected (and which should be monitored) include:
Kidneys: Most of the time kidney dysfunction is mild, though sometimes this can be progressive.Parathyroid: Parathyroid dysfunction has been recognized more recently as a side effect of lithium use.Thyroid: Lithium can affect thyroid function in many ways, although it generally leads to hypothyroidism.
Other side effects may include:
Cognitive dysfunction: Although lithium is known to potentially have an impact on cognitive function, the exact role that lithium plays in cognitive functioning is difficult to study due to the cognitive impact of bipolar disorder.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).
Acute and Chronic Toxicity
Lithium toxicity can take different forms and includes acute, chronic and acute on chronic toxicity. Severe lithium toxicity is a medical emergency that can result in encephalopathy and cardiac arrhythmias.
Drug Interactions
There are several drugs that can result in increased lithium levels in the blood. These include:
Angiotensin II receptor antagonists (ARBs): Diovan (valsartan) and Cozaar (losartan)Angiotensin-converting enzyme inhibitors (ACE inhibitors): Vasotec (enalapril) and Prinivil (lisinopril)Diuretics: Water pillsNon-steroidal anti-inflammatory drugs: Advil (ibuprofen) and Aleve (naproxen)
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 During Lithium Therapy
Blood tests are monitored both before a person begins lithium therapy, and periodically for the duration that 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. Blood levels are often done five days after a dosage change as it takes some time for the levels to stabilize. Levels should also be checked if any new medications that can impact lithium levels 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 1.0 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 1.3 to 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.
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.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 that mimic (or precipitate) both mania and depression. Thyroid levels should be tested at least every 6 months.
Other tests such as blood chemistries and an EKG may be needed depending on many factors.
Coping With 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. The 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 certain side effects.
A Word From Verywell
Lithium can be an excellent drug for people with bipolar disorder and can sometimes be a lifesaver, as it has been found to decrease the rate of suicide, a significant risk among people with the condition. Careful monitoring of levels is critical to reducing the potential for toxicity and its consequences. Side effects are common, and many of these are more annoying than dangerous. For more mental health resources, see our National Helpline Database. Lab tests must be monitored to minimize the risk of kidney and thyroid dysfunction. 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.
