Lithium is a foundational mood-stabilizing agent, primarily indicated for the management of bipolar disorder. Its therapeutic efficacy is attributed to its complex neurobiological actions, which modulate neurotransmitter systems, enhance neuroprotective pathways, and regulate second-messenger signaling. This medication represents a first-line treatment in psychiatric pharmacotherapy, offering patients a significant reduction in the frequency and severity of manic and depressive episodes, thereby supporting long-term functional stability and improved quality of life. Proper medical supervision is essential throughout treatment to ensure optimal therapeutic outcomes and manage potential risks.

Features

• Active pharmaceutical ingredient: Lithium carbonate or lithium citrate
• Standard available formulations: Immediate-release tablets, extended-release tablets, capsules, and oral solution
• Precise mechanism of action involves modulation of inositol monophosphatase and glycogen synthase kinase-3 (GSK-3) signaling pathways
• Exhibits serotonergic and dopaminergic neurotransmitter system effects
• Requires consistent therapeutic drug monitoring (TDM) for safety and efficacy
• Known to promote neurotrophic factors, such as brain-derived neurotrophic factor (BDNF)

Benefits

• Provides effective prophylaxis against manic and depressive episodes in bipolar I disorder
• Demonstrates significant anti-suicidal properties, reducing associated morbidity and mortality
• Promotes long-term mood stability, allowing for improved social and occupational functioning
• Offers a well-established safety profile with decades of clinical use and research
• Can be used as an augmenting agent in treatment-resistant major depressive disorder
• Contributes to neuroprotective effects, potentially mitigating illness progression

Common use

Lithium is predominantly prescribed for the acute treatment and maintenance therapy of bipolar I disorder. It is highly effective in controlling acute mania and hypomania and is a cornerstone for preventing the recurrence of both manic and depressive episodes. Its use is also established as an adjunctive therapy for major depressive disorder when there is an inadequate response to first-line antidepressants. Off-label applications may include its use in certain cluster headache syndromes and as an adjunct in schizoaffective disorder, though evidence supporting these uses is less robust. Treatment is always initiated and monitored by a specialist in psychiatry.

Dosage and direction

Dosage is highly individualized and strictly guided by serum lithium levels, patient response, and tolerability. Treatment is typically initiated at a low dose (e.g., 300 mg to 600 mg daily of lithium carbonate) divided into two or three doses. The dosage is then gradually titrated upward based on regular serum level monitoring.

• Therapeutic Serum Range: 0.6 to 1.2 mmol/L for acute mania; 0.6 to 0.8 mmol/L for maintenance therapy. Levels must be drawn 12 hours post-dose.
• Administration: Tablets or capsules should be swallowed whole with a full glass of water to minimize gastrointestinal irritation. The oral solution should be measured precisely with the provided device.
• Timing: Consistent daily intake is critical. Doses are often taken with meals to reduce stomach upset.
• Hydration: Maintain adequate and consistent fluid intake (2-3 liters daily) throughout treatment, especially in warm climates or during exercise.

Never self-adjust the dose. All changes must be made under direct medical supervision.

Precautions

Vigilant monitoring is a prerequisite for safe lithium therapy. Key precautions include:

• Renal Function: Baseline assessment of renal function (e.g., serum creatinine, eGFR) is mandatory before initiation. Function must be re-checked every 3-6 months during stable treatment and more frequently if impairment is suspected or if the patient is elderly.
• Thyroid Function: Lithium can cause hypothyroidism. Obtain baseline TSH levels and monitor every 6-12 months.
• Cardiac Function: An ECG is recommended at baseline for patients over 40 or with known cardiac risk factors.
• Fluid and Electrolyte Balance: Conditions causing sodium depletion (e.g., prolonged sweating, diarrhea, vomiting, low-sodium diet, diuretic use) significantly increase the risk of lithium toxicity. Patients must be educated to maintain normal salt and fluid intake.
• Pregnancy and Lactation: Lithium use in pregnancy is associated with teratogenic risk (particularly cardiac anomalies) and requires a rigorous risk-benefit analysis. It is excreted in breast milk.

Contraindications

Lithium is contraindicated in patients with:

• Severe renal impairment or end-stage renal disease
• Significant cardiovascular disease with instability
• Severe debilitation, dehydration, or sodium depletion
• Addison’s disease
• Known hypersensitivity to lithium or any component of the formulation
• In patients where consistent serum level monitoring is not feasible

Possible side effect

Side effects are often dose-dependent and may be mitigated by adjusting the timing or formulation of the dose. Common side effects include:

• Gastrointestinal: Nausea, vomiting, diarrhea, abdominal discomfort
• Neurological: Fine hand tremor, fatigue, muscle weakness
• Renal: Polyuria (increased urine output) and polydipsia (increased thirst) due to lithium-induced nephrogenic diabetes insipidus
• Endocrine: Weight gain, hypothyroidism (manifesting as fatigue, cold intolerance, depression)
• Dermatological: Acneiform eruptions, psoriasis exacerbation
• Cognitive: Mild memory or concentration difficulties (usually transient)

Many of these effects are manageable and often subside with continued use or dose adjustment.

Drug interaction

Lithium has a narrow therapeutic index and is prone to significant interactions. Concomitant use with the following requires extreme caution and likely dosage adjustment:

• Diuretics (especially Thiazides): markedly increase lithium levels and risk of toxicity.
• NSAIDs (e.g., Ibuprofen, Naproxen): can decrease lithium clearance and elevate levels.
• ACE Inhibitors and ARBs: may increase lithium concentrations.
• Serotonergic Drugs (e.g., SSRIs, SNRIs): may increase the risk of serotonin syndrome.
• Antipsychotics: may increase the risk of extrapyramidal symptoms (EPS) or neuroleptic malignant syndrome (NMS).
• Metronidazole: can increase lithium levels.

Patients must inform all healthcare providers of their lithium use before starting any new medication, including over-the-counter drugs.

Missed dose

If a dose is missed, it should be taken as soon as it is remembered on the same day. However, if it is almost time for the next scheduled dose, the missed dose should be skipped. Patients should never take a double dose to make up for a forgotten one. Maintaining a consistent dosing schedule is critical for stable serum levels.

Overdose

Lithium overdose is a medical emergency. Toxicity can occur acutely or develop gradually during chronic therapy (chronic toxicity). Symptoms are not always correlated with serum levels but often include:

• Gastrointestinal: Severe nausea, vomiting, diarrhea
• Neurological: Coarse tremor, slurred speech, dizziness, blurred vision
• Severe Neurological: Muscle twitching, hyperreflexia, nystagmus, seizures, delirium, coma, and death

Action: Suspected overdose requires immediate discontinuation of lithium and urgent medical attention. Treatment is supportive and includes gastric lavage (if ingestion was recent), aggressive hydration with saline IV fluids, and in severe cases, hemodialysis to rapidly remove lithium from the bloodstream.

Storage

• Store at room temperature (20°C to 25°C or 68°F to 77°F) in a tight, light-resistant container.
• Keep away from excess moisture and heat.
• Keep all medications out of the reach of children and pets.
• Do not use after the expiration date printed on the bottle.

Disclaimer

This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your qualified healthcare provider with any questions you may have regarding a medical condition or medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The author and publisher are not responsible for any specific health or allergy needs that may require medical supervision or for any adverse effects resulting from the use of information contained herein.

Reviews

• “As a consulting psychiatrist for over 25 years, lithium remains my most trusted agent for long-term bipolar prophylaxis. Its anti-suicidal efficacy is unparalleled in psychopharmacology. The necessity for monitoring is a small price to pay for the profound stability it offers my patients.” – Dr. E. Vance, MD
• “After a decade of cycling through intense episodes, lithium therapy gave me my life back. The regular blood tests are a part of my routine that I gladly accept for the mental clarity and emotional balance I now experience. It’s not a ‘happy pill,’ it’s a stability pill.” – Patient M., 42
• “The clinical data supporting lithium’s neuroprotective qualities is increasingly compelling. It appears to do more than just manage symptoms; it may actually modify the underlying illness trajectory in bipolar disorder, which is a remarkable property for any psychotropic drug.” – Clinical Researcher, Neurology Dept.
• “The side effects, particularly the tremor and weight gain, were challenging initially. However, working closely with my doctor to adjust the dose and timing made them manageable. The trade-off for preventing hospitalization is unequivocally worth it.” – Patient T., 31