Lithium
Lithium carbonate is the reference mood stabilizer for bipolar disorder, first-line for acute mania and long-term maintenance, and the only mood stabilizer credited with reducing suicide risk. Dosing is titrated to a trough serum level, targeting 0.8 to 1.2 mEq/L for acute mania and 0.6 to 1.0 mEq/L for maintenance. Its narrow therapeutic index and near-total renal clearance make dehydration, renal impairment, and interacting drugs the leading triggers of toxicity, which is treated with isotonic fluids and, when severe, hemodialysis.
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What this article covers
- Overview
Identity: lithium carbonate is a monovalent cation and the reference mood stabilizer for bipolar disorder, dosed as an immediate-release capsule/tablet or an extended-release tablet.
- Epidemiology
Place in bipolar treatment: guideline-preferred first-line monotherapy alongside lamotrigine and risperidone; combined with an atypical antipsychotic for severe acute mania.
- Risk factors
Renal impairment: lithium is almost exclusively renally excreted, so decreased renal function directly raises the level; significant renal dysfunction is a contraindication.
- Pathophysiology
Mechanism: affects neurotransmission (decreased excitatory, increased inhibitory signaling) and second messenger systems, including G proteins.
- Clinical features
Acute mania: first-line, generally combined with an atypical antipsychotic (for example olanzapine or quetiapine) for severe mania; titrated to a trough of 0.8 to 1.2 mEq/L.
- Differential diagnosis
Alternative mood stabilizers, each chosen instead of lithium in specific circumstances: Valproate: preferred for rapid-cycling or mixed episodes, or when lithium is ineffective, impractical, or…
- Diagnosis
What confirms therapeutic dosing: a trough serum lithium level, drawn 12 hours after the last dose once steady state is reached (about 5 days after starting or changing the dose), targeted to 0.8 to…
- Management
Starting the immediate-release formulation: lithium carbonate 300 mg PO two to three times daily; titrate by 300 mg/day every few days guided by levels to the target trough (0.8 to 1.2 mEq/L acute…
- Complications
Neurologic: dose-related resting tremor and, at toxic levels, ataxia, dysarthria, hyperreflexia, delirium, and seizures.
- Prognosis
With adequate maintenance: lithium lowers relapse frequency and carries an anti-suicide benefit, supporting indefinite continuation in most patients.
- Prevention
Level monitoring schedule: trough serum lithium level 12 hours after the last dose, at steady state (about 5 days after starting or a dose change), targeting 0.8 to 1.2 mEq/L acute mania and 0.6 to 1.0 mEq/L maintenance.
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Related articles
- Bipolar I disorder
Bipolar I disorder is a chronic mood disorder defined by at least one manic episode lasting a week or requiring hospitalization, with three or more DIG FAST symptoms causing marked impairment. Diagnosis is clinical after substances and medical mimics are excluded. Acute mania is treated with lithium or valproate, often with an atypical antipsychotic, and most patients need lifelong mood-stabilizer maintenance.
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Bipolar II disorder requires at least one hypomanic episode (elevated or irritable mood for 4 or more consecutive days without marked impairment, psychosis, or hospitalization) plus at least one major depressive episode, and no lifetime history of a full manic episode; first-line treatment is lithium with careful avoidance of unopposed antidepressants.
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Valproate/divalproex, lamotrigine, carbamazepine, oxcarbazepine, and second-generation antipsychotics are the mood stabilizers used for bipolar disorder when lithium is ineffective, poorly tolerated, or contraindicated. Valproate treats acute mania, mixed episodes, and rapid cycling with an oral loading dose; lamotrigine, titrated slowly to limit serious rash, treats bipolar depression and maintenance but not acute mania; carbamazepine is second-line, limited by agranulocytosis.
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- Chronic kidney disease
Chronic kidney disease is abnormal kidney structure or function present for more than 3 months, staged by the Kidney Disease: Improving Global Outcomes (KDIGO) system using estimated glomerular filtration rate and albuminuria, and managed with blood pressure control, renin-angiotensin blockade, an SGLT2 inhibitor, and correction of its metabolic complications.
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