lithium

General Information

Lithium carbonate is a classic mood stabilizer with robust evidence for acute mania, maintenance prophylaxis, and suicide prevention in bipolar disorder.

This profile focuses on bipolar I/II management and emphasizes safe monitoring given lithium’s narrow therapeutic index.

The compare tool, the lithium evidence feed, and the bipolar disorder hub support side-by-side review of antimanic potency, metabolic effects, and maintenance roles when updating long-term plans.

Remains first-line for many patients due to efficacy in mania and maintenance plus anti-suicidal properties; requires ongoing laboratory monitoring for renal, thyroid, and lithium levels.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Lithium modulates intracellular signaling pathways (inositol monophosphatase, glycogen synthase kinase-3) and influences monoamine neurotransmission, circadian rhythms, and neurotrophic factors.

Unlike other mood stabilizers, lithium is not metabolized and depends on renal clearance, creating a narrow therapeutic window.

• Indirect modulation of dopamine, serotonin, and glutamate systems via intracellular second messengers.
• Inhibits inositol recycling and GSK-3, impacting gene transcription and neuroplasticity.

Metabolism and Pharmacokinetics

• Rapidly and completely absorbed (peak 1–2 hours IR, 4–5 hours ER).
• Distributed in total body water (volume ~0.6 L/kg); crosses placenta and enters breast milk.
• Not metabolized; excreted unchanged by the kidneys with 80% tubular reabsorption.
• Half-life 18–24 hours in adults (longer in elderly or renal impairment).
• Steady state reached in ~5 days; elimination closely linked to sodium and fluid balance.

Dosing and Administration

• Acute mania: typical starting doses are 600–900 mg/day divided BID/TID, titrated to serum 0.8–1.2 mEq/L (12-hour trough). Typical total daily dose is 1,200–1,800 mg/day.
• Maintenance: 900–1,200 mg/day (BID or TID IR; BID ER) targeting 0.6–1.0 mEq/L; lower range (0.4–0.8) for older adults or long-term stability.
• Dose adjustments are often made in 300 mg increments with repeat levels 5–7 days later; consistent formulation is typically maintained.
• Renal impairment (CrCl 30–89 mL/min) requires dose reduction and closer monitoring; many references avoid use if CrCl <30 mL/min.

Monitoring & Labs

• Baseline: BMP (BUN/Cr), electrolytes, TSH, pregnancy test if relevant, weight/BMI.
• Level timing: 12-hour trough (or pre-morning dose if BID).
• Level cadence: 5–7 days after each dose change; then every 3–6 months when stable.
• Lithium levels are typically rechecked after dehydration/illness or when starting or stopping interacting medications (NSAIDs, ACE inhibitors/ARBs, thiazides), often within 5–7 days of the change.
• Ongoing: Periodic renal and thyroid function, with assessment for toxicity symptoms.
• Periodic calcium monitoring (hyperparathyroidism risk) and follow-up for urine concentrating symptoms (polyuria/polydipsia) are often part of long-term therapy.
• Education often emphasizes hydration, consistent salt intake, and key interactions (NSAIDs/ACE inhibitors/diuretics).

Sources: FDA label; AGNP TDM consensus; local guidelines. Document the target serum range for the current phase of treatment (acute vs maintenance) and keep draw timing consistent (12-hour trough) so trends are interpretable.

Adverse Effects

Interactions

• Sodium/water depletion (diuretics, dehydration) raises levels—hydration and consistent salt intake are commonly emphasized.
• Thiazide diuretics, ACE inhibitors, ARBs, and NSAIDs increase levels—dose reduction and closer level monitoring are typically needed.
• Caffeine and theophylline can lower levels—dose adjustments may be needed.
• Serotonergic agents rarely cause serotonin syndrome; closer monitoring is common when combining with SSRIs/SNRIs.

Other Useful Information

• Education often covers maintaining hydration, consistent sodium intake, and recognizing toxicity symptoms.
• Chronic NSAID use can raise lithium levels; acetaminophen is often preferred when feasible.
• During pregnancy, lithium levels are monitored more frequently (clearance increases), with risk/benefit discussions that include teratogenic risk; postpartum clearance decreases and dose adjustments may be needed.
• Baseline labs (BMP, TSH, CBC, pregnancy test, ECG as indicated) are obtained, and lithium/renal/thyroid parameters are monitored per guidelines.

References

1. Lithium prescribing information — DailyMed (2024)
2. The CANMAT and ISBD Guidelines for the Management of Patients With Bipolar Disorder: 2021 Update — Bipolar Disorders (2021)Guidelinebipolarclinical
3. Mcknight2012 Lithium Toxicity
4. Gitlin2016 Lithium Side Effects
5. Lithium IN THE Prevention OF Suicide IN Mood Disorders: Updated Systematic Review AND Meta Analysis — BMJ (2013)