What indicates stopping Lithium (lithium carbonate) therapy in a patient with a history of psychiatric conditions, such as bipolar disorder?

Indications for Stopping Lithium Therapy

Lithium should be discontinued in patients with significant renal or cardiovascular disease, severe debilitation or dehydration, sodium depletion, or those receiving diuretics, as the risk of lithium toxicity is very high in these situations. 1

Absolute Contraindications Requiring Immediate Discontinuation

• Significant renal disease with progressive renal impairment necessitates lithium discontinuation, as a small but measurable percentage of lithium-treated patients will show progressive renal insufficiency 1, 2
• Severe cardiovascular disease represents an absolute contraindication, particularly given lithium's association with bradycardia, T wave changes, and AV-block 3, 1
• Severe debilitation or dehydration requires immediate cessation, as lithium decreases sodium reabsorption by renal tubules which could lead to sodium depletion 1
• Sodium depletion from any cause mandates stopping lithium, as the distribution space of lithium approximates total body water and renal excretion is proportional to plasma concentration 1
• Concurrent diuretic use generally contraindicates lithium therapy, as sodium loss reduces renal clearance of lithium and increases serum levels with risk of toxicity 1

Clinical Signs of Lithium Toxicity Requiring Discontinuation

Patients must discontinue lithium therapy immediately and contact their physician if clinical signs of lithium toxicity occur, including diarrhea, vomiting, tremor, mild ataxia, drowsiness, or muscular weakness. 1

• Early toxicity signs include fine tremor, nausea, and diarrhea, which should prompt immediate medical evaluation 4, 1
• Advanced toxicity signs such as coarse tremor, confusion, or ataxia require emergency discontinuation and medical attention 4, 1
• Encephalopathic syndrome characterized by weakness, lethargy, fever, tremulousness, confusion, extrapyramidal symptoms, leukocytosis, and elevated serum enzymes necessitates immediate cessation, particularly when combined with haloperidol or other antipsychotics 1

Relative Indications for Discontinuation

Progressive Renal Impairment

• Interstitial nephropathy occurring mostly after 10-20 years of lithium administration represents the most important negative long-term effect 5
• Progressive renal insufficiency infrequently requires lithium discontinuation, but when present, alternative mood stabilizers must be considered 2
• Regular monitoring of renal function (BUN, creatinine, urinalysis) every 3-6 months is essential to detect early renal changes 4, 3

Intolerable Side Effects

• Severe weight gain that is distressing to patients and difficult to manage may warrant discontinuation, as it is more likely to be associated with lithium nonadherence 2
• Significant cognitive impairment that interferes with daily functioning represents a valid reason for discontinuation, as this tends to be more distressing to patients than other side effects 2
• Protracted sweating or diarrhea with inability to maintain adequate fluid and salt intake may necessitate temporary reduction or cessation 1

Treatment Failure or Inadequate Response

• Systematic 6-8 week trial at therapeutic doses (0.8-1.2 mEq/L for acute treatment) without adequate response should prompt consideration of alternative agents 4, 3
• Rapid cycling patients may not benefit from lithium for preventing recurrences, though lithium improves clinical symptoms as efficiently as in non-rapid cycling persons 6

Critical Safety Considerations When Discontinuation is Necessary

If lithium must be discontinued, taper gradually over 2-4 weeks minimum, never abruptly, as withdrawal is associated with dramatically increased relapse risk, with over 90% of noncompliant patients relapsing versus 37.5% of compliant patients. 4, 3

• Rebound mania risk is highest within 6 months following discontinuation, particularly with abrupt cessation 4, 3
• Tapering schedule should involve 10-20% reduction in the original dose every 1-2 weeks, extending over a minimum of 2-4 weeks total 4
• Slower tapers extending 4-8 weeks may be prudent for patients with history of rapid relapse or severe episodes 4
• High suicide risk patients should not have lithium discontinued without extreme caution, as lithium reduces suicide attempts 8.6-fold and completed suicides 9-fold 4, 3

Special Circumstances Requiring Caution

• Pregnancy represents a Category D indication, where lithium should generally not be given except in life-threatening psychiatric situations where benefits outweigh risks 1
• Nursing mothers should not undertake nursing during lithium therapy except in rare circumstances, as lithium is excreted in human milk 1
• Children under 12 years should not receive lithium, as safety and effectiveness information is not available for this age group 1
• Concomitant infection with elevated temperatures may necessitate temporary reduction or cessation of medication 1

Common Pitfalls to Avoid

• Never discontinue lithium abruptly in patients with high suicide risk without extreme caution, and consider maintaining lithium therapy indefinitely in patients with history of serious suicide attempts 4
• Do not stop lithium solely based on common but manageable side effects like thirst, excessive urination, nausea, or mild tremor, as these are typically no more than annoying and can be managed with timing adjustments and dose optimization 2
• Avoid premature discontinuation before completing an adequate 6-8 week trial at therapeutic doses, as inadequate trial duration leads to unnecessary medication changes 4
• Do not discontinue without a transition plan to alternative mood stabilizers, as maintenance therapy must continue for at least 12-24 months after mood stabilization 4, 3