What are the common side effects of lithium therapy?

Lithium Side Effects

Lithium therapy causes predictable adverse effects across multiple organ systems, with the most clinically significant being renal (polyuria/nephrogenic diabetes insipidus in 10-40% of patients), thyroid (hypothyroidism with 6-fold increased risk), gastrointestinal (nausea, diarrhea), neurological (tremor in 4-20%), and weight gain (approximately 30% of patients gain 4-10 kg). 1, 2, 3

Common Side Effects During Initiation and Maintenance

Early/Mild Effects (Often Transient)

• Fine hand tremor, polyuria, and mild thirst typically occur during initial therapy and may persist throughout treatment 1
• Transient nausea and general discomfort appear during the first few days but usually subside with continued treatment or temporary dose reduction 1
• Gastrointestinal symptoms including diarrhea, vomiting, and anorexia are common early signs 1, 2

Persistent Common Side Effects

• Tremor affects 4-20% of patients as a fine postural and/or action tremor, worsened by high caffeine consumption and concomitant psychotropic agents 2
• Weight gain of 4-10 kg occurs in approximately 30% of lithium-treated patients 2, 3
• Polyuria and polydipsia result from reduced urinary concentrating ability, with concentrating capacity reduced by 15% of normal maximum 2, 3

Organ System-Specific Side Effects

Renal Effects

• Nephrogenic diabetes insipidus develops in 10-40% of patients, presenting with polyuria and polydipsia 2, 4
• Glomerular filtration rate reduction averages -6.22 mL/min, though this is not always clinically significant 3
• End-stage renal failure occurs rarely, with only 0.5% (18 of 3,369) of patients requiring renal replacement therapy 3
• Morphologic changes including glomerular and interstitial fibrosis have been reported with chronic therapy 1

Thyroid Effects

• Clinical hypothyroidism occurs with a 5.78-fold increased odds ratio compared to placebo 3
• Thyroid-stimulating hormone (TSH) increases on average by 4.00 IU/mL 3
• Euthyroid goiter may develop with or without hypothyroidism 1
• Hyperthyroidism has been reported paradoxically in rare cases 1

Parathyroid and Calcium Effects

• Hyperparathyroidism is consistently found with lithium therapy 3
• Serum calcium increases on average by 0.09 mmol/L 3
• Parathyroid hormone (PTH) increases by an average of 7.32 pg/mL 3
• Calcium concentrations should be checked before and during treatment due to the high prevalence of hyperparathyroidism 3

Neurological Effects

• Cognitive disturbances include statistically significant negative effects on memory, vigilance, reaction time, and tracking 2
• Muscular weakness and lack of coordination may indicate early toxicity 1
• Rare serious effects include extrapyramidal symptoms, pseudotumor cerebri (increased intracranial pressure and papilledema), and cerebellar symptoms 2
• Severe neurological sequelae are exceptional but can occur 2

Dermatological Effects

• Psoriasis exacerbation is frequently associated with lithium treatment 1, 2, 4
• Hair changes including drying, thinning, and alopecia occur 1
• Skin effects include anesthesia of skin, chronic folliculitis, and xerosis cutis 1

Cardiovascular Effects

• ECG changes include reversible flattening, isoelectricity, or inversion of T-waves 1
• Cardiac arrhythmias and hypotension can occur, particularly in toxicity 1
• Sinus node dysfunction with severe bradycardia may result in syncope 1

Monitoring Requirements

Baseline Assessment

• Complete blood cell counts, thyroid function tests, urinalysis, blood urea nitrogen, creatinine, serum calcium levels, and pregnancy test in female adolescents should be obtained before lithium initiation 5

Ongoing Monitoring

• Serum lithium levels should be monitored twice per week during acute treatment until stabilized 6
• Renal function, thyroid function, and urinalysis every 3-6 months during long-term therapy 5
• Lithium levels, electrolytes, and renal function require regular monitoring to prevent toxicity 6

Early Warning Signs of Toxicity

• Tremor, nausea, diarrhea, and polyuria-polydipsia are early signs requiring immediate evaluation 6, 5
• Drowsiness, muscular weakness, and lack of coordination may indicate toxicity even at levels below 2 mEq/L 1
• Patient and caregiver education about these early signs is essential for rapid intervention 7, 6

Special Populations and Precautions

Pregnancy

• Lithium is FDA Category D (positive evidence of risk) and should be avoided during the first trimester unless benefit exceeds risk 1, 2
• Cardiac anomalies, especially Ebstein's anomaly, have increased incidence based on lithium birth registries 1
• The risk of congenital malformations is uncertain; the balance of risks should be considered before withdrawal during pregnancy 3

Situations Requiring Temporary Suspension

• Intercurrent illness, planned IV radiocontrast administration, bowel preparation, or prior to major surgery warrant temporary lithium suspension 6, 5
• Dehydration increases risk of lithium retention and toxicity 1

Drug Interactions

• NSAIDs should be avoided as they increase lithium levels 6
• Adequate hydration must be maintained, especially during illness 6

Critical Pitfalls to Avoid

• Do not assume mild symptoms mean low toxicity in chronic users: Patients on chronic maintenance therapy who develop toxicity are more likely to have severe symptoms than those with acute overdose, even at similar serum levels 8
• Monitor for progressive renal changes: Even changes within the normal range indicate need for treatment reevaluation 1
• Check calcium levels routinely: The consistent finding of hyperparathyroidism necessitates calcium monitoring before and during treatment 3
• Educate about maintaining hydration: Dehydration is a major precipitant of toxicity 6, 1