Lithium: Stabilizing Mood with Precision Neurochemical Action
Lithium
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Synonyms
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Lithium remains a cornerstone in the pharmacological management of bipolar disorder, offering a unique mechanism of action that stabilizes mood fluctuations with well-documented efficacy. As a mood stabilizer, it modulates neurotransmitter activity, reduces manic episodes, and decreases the risk of suicide in affected populations. Its use is supported by decades of clinical research and is often considered a first-line treatment for acute mania and long-term prophylaxis. Proper monitoring and dosing are essential to maximize therapeutic benefits while minimizing adverse effects.
Features
- Active ingredient: Lithium carbonate or lithium citrate
- Available in immediate-release and extended-release tablet formulations, as well as oral solution
- Standard strengths: 150 mg, 300 mg, 450 mg tablets; 8 mEq/5 mL liquid
- Half-life: approximately 24 hours in adults
- Therapeutic serum concentration range: 0.6–1.2 mmol/L for acute mania; 0.6–0.8 mmol/L for maintenance
- Renal excretion as the primary elimination pathway
Benefits
- Effectively reduces the frequency and severity of manic episodes in bipolar I disorder
- Demonstrates robust anti-suicidal properties, lowering mortality rates in high-risk populations
- Provides long-term mood stabilization, preventing relapse into both manic and depressive phases
- May enhance the efficacy of adjunctive antidepressants when used in bipolar depression
- Offers a well-established safety profile with decades of clinical use and research
- Contributes to neuroprotective effects, potentially mitigating progressive neurostructural changes associated with bipolar disorder
Common use
Lithium is primarily indicated for the treatment of bipolar I disorder, specifically for the management of acute manic episodes and as maintenance therapy to prevent recurrent manic and depressive episodes. It is also used as an augmenting agent in treatment-resistant major depressive disorder, though this is an off-label application. In some cases, it may be prescribed for schizoaffective disorder or cluster headache prophylaxis. Its use requires careful patient selection, considering renal function, cardiovascular status, and capacity for adherence to monitoring protocols.
Dosage and direction
Dosage must be individualized based on clinical response, serum lithium levels, and patient tolerance. For adults initiating therapy, a typical starting dose is 300 mg two to three times daily, or 450 mg twice daily of extended-release formulations. Titration should occur gradually, with serum levels checked 5–7 days after each dosage adjustment. The target therapeutic range is 0.6–1.2 mmol/L for acute mania and 0.6–0.8 mmol/L for maintenance therapy. Serum levels should be drawn 12 hours after the last dose. Dosage adjustments are often necessary in elderly patients or those with renal impairment. Consistent daily timing of administration is critical to maintaining stable serum concentrations.
Precautions
Regular monitoring of serum lithium levels, renal function (e.g., serum creatinine, estimated GFR), thyroid function, and electrolytes is imperative. Patients should maintain adequate and consistent fluid intake—especially during illness, exercise, or hot weather—to avoid dehydration and lithium toxicity. Caution is advised in patients with cardiovascular disease, sodium depletion, or those taking diuretics. Lithium may impair cognitive or motor performance; patients should exercise caution when driving or operating machinery. Education on early signs of toxicity (e.g., tremor, nausea, drowsiness) is essential.
Contraindications
Lithium is contraindicated in patients with severe renal impairment, significant cardiovascular disease, severe debilitation or dehydration, or sodium depletion. It should not be used during pregnancy unless clearly needed and under close supervision, due to risks of cardiac malformations (e.g., Ebstein’s anomaly). Lithium is also contraindicated in patients with known hypersensitivity to any component of the formulation.
Possible side effect
Common side effects include fine hand tremor, polyuria, polydipsia, mild nausea, and weight gain. Less frequently, patients may experience diarrhea, vomiting, drowsiness, muscle weakness, or acneiform eruptions. Long-term use may be associated with renal concentration defects, hypothyroidism, or leukocytosis. Serious adverse effects include lithium toxicity (see Overdose), nephrogenic diabetes insipidus, and sinus node dysfunction.
Drug interaction
Lithium interacts significantly with several medication classes. Diuretics (especially thiazides) can increase lithium levels and risk of toxicity. NSAIDs, ACE inhibitors, and ARBs may also elevate lithium concentrations. Concomitant use with antipsychotics may increase the risk of extrapyramidal symptoms or neurotoxicity. Serotonergic drugs (e.g., SSRIs, SNRIs) may increase the risk of serotonin syndrome. Caution is advised with metronidazole, topiramate, and caffeine, which may alter lithium levels.
Missed dose
If a dose is missed, it should be taken as soon as possible unless it is nearly time for the next scheduled dose. In that case, the missed dose should be skipped, and the regular dosing schedule resumed. Doubling doses is not recommended, as it may increase the risk of toxicity. Patients should inform their clinician if multiple doses are missed, as retitration may be necessary.
Overdose
Lithium overdose may be acute or chronic and can be life-threatening. Symptoms include severe diarrhea, vomiting, drowsiness, slurred speech, coarse tremor, ataxia, seizures, and coma. Serum levels >1.5 mmol/L indicate toxicity, and levels >2.5 mmol/L constitute a medical emergency. Treatment involves discontinuation of lithium, aggressive hydration with saline infusion, and in severe cases, hemodialysis. Continuous cardiac and neurological monitoring is essential.
Storage
Store at controlled room temperature (20–25°C or 68–77°F), in a tightly closed container, away from light, moisture, and heat. Keep out of reach of children and pets. Do not use beyond the expiration date printed on the packaging. Oral solution formulations should not be frozen.
Disclaimer
This information is intended for educational purposes and does not replace professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider before starting, changing, or discontinuing any medication. Individual patient needs and responses may vary. Not all uses, precautions, or interactions are listed here.
Reviews
“Lithium has been transformative in managing my bipolar disorder. The stability it provides is worth the required blood tests and dietary vigilance.” — Patient, 42
“A cornerstone therapy with unparalleled anti-manic and anti-suicidal efficacy. Requires discipline in monitoring but offers profound benefits for appropriate candidates.” — Psychiatrist, 15 years experience
“While side effects like weight gain and thirst are challenging, the preventive effect on mood episodes is undeniable. Patient education is key to adherence.” — Clinical Pharmacist
“After trying several other mood stabilizers, lithium provided the most consistent control over my cycles. The regular monitoring keeps me engaged in my treatment.” — Patient, 35