Lithium: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on July 4, 2023.

1. How it works

• Lithium may be used to treat mania associated with bipolar disorder.
• Experts are not sure exactly how lithium works but believe it alters sodium transport in nerve and muscle cells which adjusts the metabolism of neurotransmitters within the cell. Lithium is an element found naturally in the environment and our bodies.
• Lithium belongs to the class of medicines known as antimanic agents.

2. Upsides

• May be used to treat acute manic or mixed episodes in people with bipolar 1 or bipolar 2 disorder.
• Considered a first-line agent for the initial treatment of depressive, manic, or mixed episodes in bipolar disorder.
• May be used in combination with an atypical antipsychotic, another mood-stabilizing agent, or an antidepressant to treat rapid cycling or more severe depressive manic or mixed episodes.
• Long-term therapy with lithium prevents or diminishes the intensity of subsequent episodes of mania.
• Has been used off-label for the treatment of depression in people who fail to respond to antidepressants.
• Has limited use for the treatment of schizophrenia or schizoaffective disorder and should only be considered if antipsychotics have failed. Can be added to existing therapy; however, careful monitoring of serum lithium concentrations, side effects, or drug interactions is recommended.
• Other off-label uses include disorders of impulse control, psychiatric disorders in children, neutropenia or anemia, hyperthyroidism, or SIADH; however, its use should only be considered if other agents have been ineffective.
• Non-habit forming and not abusable.
• Generic lithium is available.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Fine hand tremors, frequent urination, and mild thirst commonly occur during lithium initiation. Sometimes these effects may persist throughout treatment.
• Nausea during initiation is common but usually subsides with continued administration.
• Diarrhea, vomiting, drowsiness, muscular weakness, loss of appetite, and coordination difficulties may be an early sign of lithium toxicity. Dizziness, blurred vision, ringing in the ears, and excessive production of dilute urine may occur with higher (toxic) lithium levels. Seek urgent medical advice.
• Lithium may also cause irregular heartbeat, drying and thinning of hair, alopecia, dry mouth, weight gain, itchiness, and other side effects. Long-term use may lead to kidney disease, high blood calcium levels, hyperparathyroidism, hypothyroidism, or other thyroid problems.
• May require multiple daily doses. Conventional tablets, capsules, or oral solution requires 3 or 4 times the daily dosage - less frequent dosing may be associated with gastrointestinal or nervous system effects. Extended-release preparations may be administered 2 to 3 times daily.
• Dosing may be difficult because there is not much of a margin between an adequate dose of lithium and a toxic dose. Facilities should be available that can quickly and accurately monitor serum lithium concentrations.
• If toxicity occurs, temporarily discontinue for 24 to 48 hours then resume at a lower dosage.
• Monitoring is required and should be done twice weekly during therapy initiation and then every two months long-term.
• Not suitable for people with significant renal or cardiovascular disease, who are frail, dehydrated, taking diuretics, with low levels of sodium, or on a sodium-restricted diet. In exceptional circumstances, lithium may be used if the patient's condition is life-threatening and other treatments have failed.
• Not recommended for children aged less than 12. Lithium use may cause an unmasking of Brugada syndrome (a heart disorder characterized by abnormal ECG findings and a risk of sudden death).
• The range of effects of lithium in pregnancy has not been fully determined so experts recommend women avoid lithium, particularly in the first trimester. Lithium has been associated with fetal toxicity, such as cardiac anomalies, especially Ebstein's anomaly. If given during pregnancy, dosages of lithium generally need to be increased but should be reduced 1 week before giving birth or when labor begins.
• May interact with several other medications including diuretics (water pills), NSAIDs, and ACE inhibitors.
• Interaction or overdosage may cause serotonin syndrome (symptoms include mental status changes [such as agitation, hallucinations, coma, delirium]), fast heart rate, dizziness, flushing, muscle tremor or rigidity, and stomach symptoms (including nausea, vomiting, and diarrhea).

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Lithium may be used to treat manic episodes associated with bipolar disorder; however, there is a fine line between too much and too little, and ongoing monitoring is needed to prevent lithium toxicity.

5. Tips

• Lithium is usually taken two to three times daily with food (extended-release preparations) or 3 to 4 times daily with food (conventional tablets/capsules/solution). Administering it with food and more frequently throughout the day has been associated with fewer gastrointestinal effects.
• There is a fine line between too much and too little lithium. Always take lithium exactly as directed and go to your scheduled appointments. Never take any herbal supplements or over-the-counter remedies without consulting your doctor or pharmacist first as many drugs may affect blood levels of lithium.
• If you miss a dose of lithium, take it as soon as you remember. If it is close to your next dose, do not double up on the dose.
• Do not crush or chew extended-release tablets; swallow whole.
• Too much caffeine may decrease the amount of lithium in your body. If you cut out salt from your diet, this can also affect blood levels of lithium.
• Lithium may affect your mental alertness or make you drowsy. Do not drive until you know how lithium will affect you. Avoid alcohol.
• Ensure you keep adequately hydrated while taking lithium and maintain an adequate salt intake (your doctor will discuss this requirement). The risk of side effects of lithium is increased if you are dehydrated, or if you are excessively hydrated. Excessive sweating or diarrhea may also upset the balance of lithium in the blood.
• Contact your doctor if you become ill or have an infection as your dosage of lithium may need to be altered or temporarily discontinued.
• Seek urgent medical attention if symptoms similar to diabetes (such as excessive thirst or excessive urine production) occur.
• Stop lithium and contact your doctor urgently if symptoms of lithium toxicity such as diarrhea, vomiting, tremor, drowsiness, muscle weakness, or confusion occur.
• Seek urgent medical advice if symptoms consistent with serotonin syndrome (such as agitation, hallucinations, fast heart rate, dizziness, flushing, nausea, and diarrhea) develop.
• You will need to go for regular blood tests while you are taking lithium to ensure that the dosage is appropriate for you.
• May affect your mental and physical abilities so be careful driving or operating machinery until you know how lithium affects you.
• Do not take any other medications, including those bought over the counter, without first checking with your doctor or pharmacist that they are compatible with lithium.
• Talk to your doctor if you are thinking about getting pregnant or are already pregnant before you are prescribed lithium. Although lithium can cause fetal harm, sometimes the benefits outweigh the risks. Tell your doctor right away if you inadvertently become pregnant.

6. Response and effectiveness

• Lithium is completely absorbed in the gastrointestinal tract with peak levels occurring 0.25 to 3 hours after oral administration of immediate-release preparations and two to six hours after sustained-release preparations.
• A reduction in manic symptoms should be noticed within 5 to 7 days but the full therapeutic effect may require 10 to 21 days.
• Lithium concentrations should be determined immediately before the next dose (ie, 8 to 12 hours after the previous lithium dose). Total reliance should not be placed on serum lithium levels alone and include a clinical assessment of the patient's response.
• Serum lithium concentrations of 1-1.2 mEq/L are usually required during acute manic episodes (concentrations should not exceed 1.5 mEq/L during the acute treatment phase).
• 5mL of lithium citrate solution contains about 8mEq of lithium and is approximately equivalent to 300mg of lithium carbonate.

7. Interactions

Medicines that interact with lithium may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with lithium. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with lithium include:

• acetazolamide
• aminophylline
• antacids containing sodium bicarbonate
• anticonvulsants, such as carbamazepine, fosphenytoin, phenytoin, phenobarbital, or primidone
• antidepressants, such as tricyclic antidepressants (eg, amitriptyline), monoamine oxidase inhibitors (eg, isocarboxazid, phenelzine, and tranylcypromine), or SSRIs (eg, fluoxetine, sertraline)
• antipsychotics (such as butyrophenones, phenothiazines, or thioxanthenes) and atypical antipsychotics (eg, olanzapine, quetiapine, ziprasidone)
• any medication that may prolong the QTc interval, such as amiodarone or haloperidol
• calcium channel blockers, such as diltiazem or verapamil
• diuretics, such as furosemide or HCTZ
• heart medications, such as digoxin, ACE inhibitors (such as captopril, enalapril, or lisinopril), angiotensin II receptor antagonists (such as candesartan or irbesartan), or beta-blockers (such as atenolol or sotalol)
• iodides
• metronidazole
• migraine medications, such as almotriptan, eletriptan, or sumatriptan
• NSAIDs, such as ibuprofen, diclofenac, or naproxen
• opioids (such as codeine and morphine)
• sodium chloride
• tetracycline
• other medications that affect serotonin, such as amphetamines, dextromethorphan, fentanyl, ondansetron, tramadol, or St. John's Wort.

May prolong the effects of neuromuscular blocking agents (such as pancuronium or succinylcholine).

Avoid drinking alcohol or taking illegal or recreational drugs while taking lithium.

Note that this list is not all-inclusive and includes only common medications that may interact with lithium. You should refer to the prescribing information for lithium for a complete list of interactions.

References

• Lithium. Revised 08/2022. Sun Pharmaceutical Industries, Inc. https://www.drugs.com/pro/lithium.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use lithium only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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