Lithium

# Lithium ## Overview - **Classification**: Mood stabilizer, anti-manic agent. - **Mechanism**: Complex, involves effects on ion transport, neurotransmitter systems (serotonin, dopamine, norepinephrine), and intracellular signaling pathways (e.g., GSK-3 inhibition). ## Primary Indications 1. **Bipolar Disorder** - Acute mania and maintenance treatment. 2. **Major Depressive Disorder** - Augmentation therapy for unipolar depression. 3. **Schizoaffective Disorder** - Adjunctive treatment. ## Adult Dosing ### Standard Dosing **Acute Mania** - **Dose**: Initial **300-600 mg** (IR) BID/TID or **600-900 mg** (ER) BID. Titrate to desired level. - **Frequency**: BID or TID (IR), BID (ER). - **Route**: Oral. - **Target Level**: **0.8-1.2 mEq/L**. **Maintenance/Bipolar Depression** - **Dose**: Initial **300 mg** (IR) BID/TID or **600-900 mg** (ER) daily. - **Frequency**: BID/TID (IR), daily (ER). - **Route**: Oral. - **Target Level**: **0.6-1.0 mEq/L**. ### Dose Adjustments - **Renal Impairment**: CrCl <30 mL/min: Generally **contraindicated** or requires significant dose reduction and very close monitoring. CrCl 30-60 mL/min: Reduce dose by **25-50%**. - **Hepatic Impairment**: No specific adjustments; lithium is primarily renally eliminated. - **Elderly Patients**: Start with lower doses (e.g., **300 mg daily**) and titrate slowly due to decreased renal function and increased sensitivity. Target lower end of therapeutic range (**0.4-0.8 mEq/L**). ## Pediatric Dosing ### Neonates (0-28 days) - **Not recommended**: Generally avoided due to immature renal function and high risk of toxicity. - **Special Notes**: Limited data; severe adverse effects including cardiac defects have been reported with in utero exposure. ### Infants (1-12 months) - **Not recommended**: Limited data; typically avoided due to safety concerns and lack of established efficacy. - **Special Notes**: Higher risk of toxicity due to renal immaturity. ### Children (1-12 years) - **Indication**: Bipolar disorder (off-label, typically after other agents fail). - **Dose**: Initial **15-20 mg/kg/day** (IR) divided BID or TID, or **300-600 mg/day**. - **Frequency**: BID or TID. - **Route**: Oral. - **Maximum**: Titrate to desired serum level (**0.6-1.2 mEq/L**). Do not exceed adult maintenance doses. - **Special Notes**: Close monitoring of renal, thyroid, and cardiac function is essential. ### Adolescents (13-18 years) - **Indication**: Bipolar disorder. - **Dose**: Similar to adult dosing. Initial **300 mg BID/TID** (IR) or **600-900 mg daily** (ER). - **Frequency**: BID/TID (IR), daily (ER). - **Route**: Oral. - **Maximum**: Up to **1800-2400 mg/day** for acute mania, depending on level and tolerability. - **Special Notes**: Target serum levels **0.8-1.2 mEq/L** (acute), **0.6-1.0 mEq/L** (maintenance). ## Safety Information ### Contraindications - **Absolute**: Severe renal impairment, significant cardiovascular disease (e.g., sick sinus syndrome), severe dehydration, sodium depletion. - **Absolute**: Hypersensitivity to lithium. - **Relative**: Pregnancy (especially 1st trimester), breastfeeding, patients on low-sodium diets or diuretics without close monitoring. ### Common Adverse Effects - **Very Common (>10%)**: Fine hand tremor, polyuria, polydipsia, weight gain, nausea, diarrhea, fatigue. - **Common (1-10%)**: Hypothyroidism, muscle weakness, dry mouth, acne, mild cognitive impairment. - **Serious but Rare**: Lithium toxicity (severe tremor, ataxia, confusion, seizures, coma), nephrogenic diabetes insipidus, severe cardiac arrhythmias, irreversible renal damage. ### Key Drug Interactions - **Thiazide Diuretics**: **Increased lithium levels** and toxicity due to reduced renal clearance. Reduce lithium dose or discontinue. - **NSAIDs (e.g., ibuprofen, naproxen)**: May **increase lithium levels** by reducing renal clearance. Monitor levels closely. - **ACE Inhibitors/ARBs**: May **increase lithium levels**. Monitor levels closely. - **Serotonergic Agents (e.g., SSRIs, SNRIs)**: Increased risk of **serotonin syndrome**. Monitor for symptoms. - **Neuroleptics (e.g., haloperidol)**: Increased risk of **neurotoxicity** (encephalopathy, EPS) especially with higher doses. Use with caution. - **Caffeine/Theophylline**: May **decrease lithium levels** due to increased renal excretion. ## Monitoring & Follow-up - **Before Treatment**: Baseline renal function (BUN, creatinine, eGFR), thyroid function (TSH), electrolytes, urinalysis, ECG (especially >50 years or with cardiac risk factors), pregnancy test. - **During Treatment**: - **Lithium levels**: 5 days after initiation/dose change, then weekly until stable, then every **3-6 months**. (Draw **10-12 hours post-dose**). - **Renal function**: Every **6-12 months** (BUN, creatinine, eGFR). - **Thyroid function**: Every **6-12 months** (TSH). - **Electrolytes/calcium**: Periodically. - **Clinical Signs**: Monitor for toxicity (e.g., coarse tremor, ataxia, confusion, severe N/V/D). ## Clinical Pearls - 💡 **Hydration is key**: Advise patients to maintain adequate fluid and sodium intake to prevent lithium toxicity. Dehydration significantly increases levels. - 💡 **Consistent dosing time**: Always draw lithium levels **10-12 hours after the last dose** (trough) for accurate interpretation and to guide dose adjustments. - 💡 **Initial side effects**: Nausea, diarrhea, and fine tremor often subside after the first few weeks of treatment. - 💡 **Warning signs**: Educate patients about symptoms of lithium toxicity and to seek immediate medical attention if they occur. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.