What are the side effects of lithium (lithium carbonate)?

Side Effects of Lithium

Lithium has numerous side effects ranging from common mild symptoms to rare but serious toxicity, with the likelihood of toxicity increasing with higher serum lithium levels, particularly above 1.5 mEq/L. 1

Common Side Effects

• Gastrointestinal effects: Nausea, vomiting, diarrhea, anorexia, and abdominal discomfort 1, 2
• Neurological effects: Fine hand tremor (occurs in 4-20% of patients), dizziness, drowsiness, and muscle weakness 1, 2
• Renal effects: Polyuria, polydipsia, and nocturia due to reduced urinary concentrating capacity 1, 2
• Weight gain: Approximately 30% of patients experience weight gain of 4-10 kg 2
• Cognitive effects: Mild impairment of memory, vigilance, reaction time, and tracking at therapeutic serum concentrations 2

Endocrine Side Effects

• Thyroid abnormalities: Increased risk of hypothyroidism (OR 5.78) and goiter due to inhibition of thyroid hormone release 1, 3
• Parathyroid effects: Hyperparathyroidism with elevated calcium levels (+0.09 mmol/L) and parathyroid hormone (+7.32 pg/mL) 3
• Metabolic effects: Transient hyperglycemia 1

Dermatological Side Effects

• Hair changes: Drying and thinning of hair, alopecia 1
• Skin effects: Chronic folliculitis, xerosis cutis (dry skin), and exacerbation of psoriasis 1

Cardiovascular Side Effects

• Cardiac arrhythmia: Including sinus node dysfunction with severe bradycardia 1
• ECG changes: Reversible flattening, isoelectricity, or inversion of T-waves 1
• Circulatory effects: Hypotension and peripheral circulatory collapse in severe cases 1

Serious Toxicity (Serum Levels >2 mEq/L)

• Neurological toxicity: Ataxia, confusion, slurred speech, blurred vision, seizures, and coma 1, 4
• Renal toxicity: Progressive renal insufficiency in approximately 0.5% of patients requiring renal replacement therapy 3
• Cerebellar symptoms: Including downbeat nystagmus and acute dystonia 1
• Neurological sequelae: Permanent brain damage possible with prolonged intoxication with levels >2 mEq/L 5

Special Populations

• Pregnancy: Lithium is FDA pregnancy category D due to risk of fetal harm 1
• Breastfeeding: Lithium transfers into breast milk; safety during breastfeeding is controversial due to risk of toxicity in newborns 2

Monitoring and Prevention of Toxicity

• Regular serum monitoring: Measure lithium levels twice per week during initial treatment until stabilized 6
• Target therapeutic range: Maintain serum levels below 1.5 mEq/L to minimize toxicity risk 1
• Thyroid function: Regular monitoring of thyroid function is necessary due to high risk of hypothyroidism 1
• Calcium levels: Should be checked before and during treatment due to high prevalence of hyperparathyroidism 3
• Renal function: Monitor for declining glomerular filtration rate (average reduction of 6.22 mL/min) 3

Drug Interactions

• Diuretics and ACE inhibitors: Can increase lithium levels by reducing renal clearance 1
• NSAIDs: Can significantly increase steady-state plasma lithium concentrations 1
• Haloperidol: Combined use has been associated with an encephalopathic syndrome 1
• Neuromuscular blocking agents: Lithium may prolong their effects 1

Management of Toxicity

• Discontinuation: Patients must discontinue lithium and contact their physician if signs of toxicity appear 1
• Hemodialysis: Treatment of choice for severe lithium toxicity, particularly with serum levels ≥3.5 mEq/L 4
• Supportive care: Includes fluid management and monitoring of vital signs 4

Important Considerations

• Chronic vs. acute toxicity: Patients with toxicity during maintenance therapy often have more severe symptoms than those with acute overdose, even at similar serum levels 4
• Therapeutic benefit: Despite side effects, lithium remains effective in lowering suicide risk in mood disorders, independent of its mood-stabilizing effect 7