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Lithium side effects and how to avoid them

Weight gain is a common side effect of lithium, but it can also cause serious reactions like serotonin syndrome or toxicity. Learn the warning signs of lithium side effects.

Common lithium side effects | Weight gain | Serious side effects | Serotonin syndrome | Toxicity | How long do side effects last? | Warnings | Interactions | How to avoid side effects

Lithium carbonate is a prescription medication used to treat symptoms associated with bipolar disorder. Lithium carbonate is available as a tablet, capsule, extended-release tablet, and liquid. Lithium is not an over-the-counter medication. Brand names for lithium carbonate include Eskalith and Lithobid.

The World Health Organization (WHO) has classified lithium as an “essential medicine,” and therefore, one of the most important medications for doctors worldwide in the treatment of bipolar disorder. Lithium is often used to treat mania and manic episodes which occur during the elevated phase of bipolar disorder. The U.S. Food and Drug Administration (FDA) has approved lithium for use in both adults and children as young as 7 years old. 

Lithium is in a class of medications known as mood stabilizers. Mood stabilizers are used in the field of psychiatry to treat mood disorders such as bipolar disorder that have sustained and elevated mood shifts. Elevated mood states such as mania are thought to be caused in part by irregular levels of proteins and neurotransmitters in the brain. 

Lithium works by a complex set of interrelated and sophisticated pathways that ultimately decrease levels of excitatory neurotransmitters and increase levels of inhibitory neurotransmitters in the brain. It has been used for decades to improve mental health and provide neuroprotective effects for individuals with bipolar disorder. It’s also used in some individuals with schizophrenia for the treatment of psychotic symptoms, aggression, and affective symptoms. This article will discuss lithium side effects, drug interactions, and how to avoid them. 

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Common side effects of lithium

As with any medication, you may experience common, non-serious side effects while taking lithium. If any of these common side effects are bothersome, notify your healthcare provider. 

  • Polyuria (excessive urination) and polydipsia (excessive thirst)
  • Problems with appetite and weight including weight gain and anorexia 
  • Gastrointestinal symptoms including nausea, vomiting, and diarrhea 
  • Nervous system effects including cognitive impairment, impaired coordination, blurry vision, dizziness, tremors, and muscle weakness
  • Skin concerns such as rashes, acne, psoriasis, or exacerbation of psoriasis 
  • Xerostomia (dry mouth) 
  • Fatigue or drowsiness 
  • Alopecia (hair loss)
  • Reversible leukocytosis (elevated white blood cell count) 
  • Edema 
  • Hyponatremia (elevated sodium)
  • Chronic tubulointerstitial nephropathy (injury to the tubules in the kidney)

Lithium weight gain

Lithium use is very commonly associated with unwanted weight gain in the first few years of beginning treatment. A review article in the International Journal of Bipolar Disorders notes that studies vary in reporting the amount of weight someone taking lithium might gain, however many studies suggest individuals taking lithium who experience weight gain may gain at least 10 pounds. Other studies cited in the review have shown that throughout the course of treatment, people taking lithium gain about 8% of their body weight on average.

Weight gain while taking lithium is correlated to three important factors:

  1. Your baseline weight. The more you weigh before starting treatment, the more weight you are likely to gain.
  2. The dose of lithium and/or the levels of lithium in the blood. The higher the dose of medication or higher the concentration of lithium in the blood, the more weight you are likely to gain. 
  3. The use of multiple psychotropic medications, which is very common in individuals with bipolar disorder, is associated with increased weight gain. Several antipsychotics are widely known to cause weight gain (olanzapine and quetiapine) and the effects of that weight gain can be amplified when taking multiple psychotropic medications simultaneously. In some cases, your healthcare provider may be able to switch your medication to one that is less associated with weight gain (aripiprazole or lurasidone) or to one associated with weight loss (topiramate). 

Individuals taking lithium usually have their weight routinely monitored and see their prescribing healthcare provider frequently. If you have experienced excessive weight gain while taking lithium, discuss options for weight loss or weight management with your healthcare provider. Most strategies for weight loss or management are centered around healthy eating and drinking habits and encouraging exercise when appropriate. 

RELATED: List of antipsychotic medications

Serious side effects of lithium

Lithium is associated with several very severe adverse effects. If any of these effects occur while taking lithium, a healthcare provider should be notified right away.

  • Coma
  • Seizures
  • Syncope (fainting or a temporary loss of consciousness from low blood pressure)
  • Serious cardiac rhythm events including ventricular arrhythmia, severe bradycardia, Brugada syndrome unmasked (abnormal ECG findings that could lead to sudden death)
  • Metabolic derangements or dysfunction leading to goiter, hypothyroidism, elevated calcium, hyperparathyroidism, or nephrogenic diabetes insipidus 
  • Drug reaction with eosinophilia and systemic symptoms (DRESS), a severe autoimmune drug reaction
  • Pseudotumor cerebri
  • Raynaud phenomenon (decreased blood flow to the fingers and sometimes ears, toes, nipples, and nose causing a blue or white appearance) 
  • Serotonin syndrome (potentially life-threatening elevated serotonin levels from serotonergic drugs)

Serotonin syndrome 

Lithium increases a chemical in the brain called serotonin. Many medications that are used to treat depression also elevate serotonin in the brain; these are called selective serotonin reuptake inhibitors (SSRIs). Antidepressants are very commonly used in a variety of mental health conditions, and lithium is sometimes used to treat major depressive disorder. It is important to use caution if you are taking antidepressants and lithium at the same time. Too much serotonin in your brain could lead to serotonin syndrome, a potentially life-threatening syndrome characterized by symptoms such as mental status changes, muscle rigidity or twitching, fever and sweating, dilated pupils, and agitation.

Examples of antidepressants that increase serotonin levels include fluoxetine, escitalopram, and sertraline. There are other medications that are not antidepressants but are known to “boost” the effect of some antidepressants by increasing the reuptake of serotonin. These medications should also be used with caution when taken concomitantly with antidepressants and lithium. 

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Lithium toxicity

It is possible to experience an overdose while taking lithium. The FDA has issued a black box warning regarding lithium toxicity. Lithium has a very narrow therapeutic window (the range of drug doses that can be administered and treat disease effectively without having toxic effects). Lithium is rapidly absorbed, and lithium toxicity is closely related to lithium concentrations and can occur even at doses close to therapeutic concentrations. Serum lithium concentrations should be monitored by your healthcare provider when starting treatment and routinely throughout the duration of treatment. 

The symptoms associated with lithium toxicity are broad and may include tremor, difficulty walking, hyperreflexia, uncontrolled eye movements, poor kidney function, and altered consciousness. Lithium toxicity can occur from either too much ingestion of medication or impaired excretion of the medication. 

Impaired excretion could be caused by sodium or volume depletion from a number of conditions including excessive sweating, diarrhea, vomiting, febrile illness, renal insufficiency, water restriction, low sodium diet, and heart disease including congestive heart failure. All of these states affect lithium absorption and excretion. 

The severity of lithium intoxication is often divided into the following three grades: mild, moderate, and severe. 

Lithium intoxication grades

Symptoms Serum lithium concentration
Mild intoxication
  • Nausea
  • Vomiting
  • Lethargy
  • Tremor
  • Fatigue
1.5-2.5 mEq/L
Moderate intoxication
  • Confusion
  • Agitation
  • Delirium
  • Tachycardia
  • Hypertonia
2.5-3.5 mEq/L
Severe intoxication
  • Coma
  • Seizures
  • Hyperthermia
  • Hypotension
Higher than 3.5 mEq/L

Before beginning treatment with lithium, it is important to give your healthcare provider a full health history and for you to have access to an accurate and rapid lithium testing facility. 

How long do lithium side effects last?

Side effects associated with lithium use vary in the length of time they occur. Most neurologic symptoms such as tremor, hyperreflexia, or difficulty walking are reversible, however, it is not uncommon for symptoms to persist for more than 12 months and some may not resolve. 

Most of the common side effects of lithium use are self-limiting (they resolve on their own) after several weeks of treatment. 

Lithium contraindications and warnings

Abuse and dependence

Lithium is contraindicated for use in individuals who have known hypersensitivity to the medication. Lithium is not habit-forming or addictive. Individuals who discontinue lithium therapy do not experience withdrawal, however, there are some individuals who may develop severe mood destabilization if the medication is discontinued. This medication should not be discontinued without first speaking with your healthcare provider. 

Restrictions

For some specific populations of people, lithium should be avoided, used with caution, or strictly monitored. Caution should be used in individuals who:

  • Have a condition that puts them at risk for dehydration
  • Have severe debilitation
  • Have cardiovascular disease
  • Have a thyroid disorder
  • Are taking a CNS depressant
  • Use alcohol
  • Are at risk for Brugada syndrome
  • Have renal impairment
  • Are elderly
  • Are pregnant

Pediatric use

Lithium is not FDA-approved for use in children younger than 7 years of age. The safety and effectiveness of lithium have not been established in pediatric patients younger than 7 years of age. 

Geriatric use

Clinical studies of lithium carbonate tablets did not include sufficient numbers of individuals older than 65 to determine whether they respond differently than younger subjects. Lithium is known to be substantially excreted by the kidneys. The risk of intoxication with this medication may be greater in seniors as older patients are more likely to have decreased renal function. Care should be taken in dose and patient selection for those older than 65 years of age.

Pregnancy

Lithium may cause harm when administered to pregnant women. There is an increase in cardiovascular malformations like Ebstein’s anomaly associated with lithium use. The risk of adverse effects on the fetus is especially prominent within the first trimester of pregnancy. In the United States, there is a background risk of major birth defects and miscarriage of 15% to 20%. Other medications should be considered in the first trimester of pregnancy and a fetal echocardiogram is recommended between 16 to 20 weeks of gestation. 

It is also possible for there to be maternal and/or neonatal toxicity in the postpartum period. Pregnant women should be advised of the potential risks to the fetus and the risk/benefit ratio discussed when deciding if and when to administer lithium in pregnancy. If lithium use is continued or initiated during pregnancy, serum lithium concentrations should be monitored closely and lithium dosage lowered or discontinued two to three days prior to delivery. 

Breastfeeding

Breastfeeding is not recommended with maternal lithium use. Lithium carbonate is known to be present in human breast milk. Infants exposed to lithium in breast milk may have signs and symptoms of lithium toxicity including hypertonia, hypothermia, cyanosis, and ECG changes. 

If a woman chooses to breastfeed while taking lithium, the infant should have thyroid function tests performed and blood levels of lithium monitored closely for signs of lithium toxicity. Breastfeeding should be immediately discontinued if a breastfed infant develops any signs or symptoms of lithium toxicity. 

Renal impairment

As lithium is primarily eliminated through the kidney, lithium clearance from the body is decreased in individuals with abnormal renal function and kidney disease, and the risk of lithium intoxication is increased. Lithium should not be used in severe renal insufficiency (creatinine clearance less than 30 ml/min). 

Lithium interactions

Lithium is known to result in drug interactions with many other medications. It is important to discuss all medications you are taking or have taken prior to taking lithium and for the duration of lithium treatment. 

Lithium is contraindicated for use with the following medications:

  • Cidofovir
  • Tranylcypromine

Lithium and angiotensin-converting enzyme (ACE) inhibitors

The use of ACE inhibitors such as enalapril in combination with lithium has been warned against due to a potential increased risk of lithium toxicity. While there is historical precedent against this combination, more recent case reports suggest potential negative effects could be offset with adequate hydration and avoidance of hydrochlorothiazide (HCTZ). While this is promising data, it is important to discuss any potential side effects associated with taking these medications together with your healthcare provider before taking ACE inhibitors with lithium. 

How to avoid lithium side effects

  1. Follow medical advice while taking this medication. Take only the dose prescribed by a healthcare professional. Do not take more or less medication than prescribed. Take all of the doses how and when they are prescribed. If you miss a dose, take the next dose as soon as you remember. Patients should continue taking the medication as prescribed even if they feel better after the first few doses.
  2. Patients should disclose a full medication list, health history, and allergies before taking lithium. This includes all medications and supplements, any medical conditions the patient has, or any allergic reactions they have had to medications in the past. 
  3. Store the medication correctly. Lithium should be stored at room temperature (68 to 77 degrees Fahrenheit).
  4. Swallow the tablet or capsule whole or take the liquid exactly as it was prepared. Do not crush, break or chew the tablet or dilute the liquid.
  5. Avoid excessive intake of caffeinated beverages or supplements while taking lithium. Lithium is known to cause tremors. Excessive intake of caffeine from coffee, tea, soda, energy or pre-workout drinks or supplements may increase the severity or likelihood of unwanted tremors occurring. Caffeine is also a diuretic that may increase the concentration of lithium in the blood.
  6. Minimize sugary or sweetened beverages while taking lithium. Weight gain is a known unwanted side effect associated with lithium use. Limiting caloric intake from beverages can help avoid or keep weight gain to a minimum. Lithium can make you very thirsty. Replace sugary drinks or juices with water, flavored waters, or other low- to no-calorie beverages. 
  7. Avoid alcohol use and abuse while taking lithium. Alcohol can increase the serum levels of lithium. Alcohol consumption while taking lithium can result in unwanted sedation and other negative side effects. 
  8. Avoid low sodium diets and states of dehydration. Low sodium and dehydration can increase the levels of lithium in the blood increasing the chance of negative side effects occurring from lithium toxicity.
  9. Minimize taking non-steroidal anti-inflammatory drugs (NSAIDs) while taking lithium. Most NSAIDs (ibuprofen, naproxen) moderately increase lithium levels in the blood which can increase the potential for unwanted side effects. This risk is increased with high doses and long-term treatment.
  10. Have blood tests for lithium levels when recommended by your healthcare provider. It is important that lithium dosing is maintained at a level where the medication is effective without causing negative side effects. Checking the levels of lithium in your blood will inform your healthcare provider if dose adjustments need to be made. 
  11. Immediately seek medical care for symptoms of allergic reaction or serotonin syndrome or lithium toxicity. Allergic responses, serotonin syndrome, and lithium toxicity could be fatal and should be reported and treated as early as possible.