Can lithium be initiated in a patient taking Angiotensin Receptor Blockers (ARBs)?

Lithium Initiation in Patients on ARBs

Yes, lithium can be initiated in patients taking ARBs, but this requires intensive monitoring due to significant risk of lithium toxicity from reduced renal clearance. 1

Critical Drug Interaction Warning

The FDA label for lithium explicitly states: "Caution should be used when lithium and diuretics or angiotensin converting enzyme (ACE) inhibitors are used concomitantly because sodium loss may reduce the renal clearance of lithium and increase serum lithium levels with risk of lithium toxicity." 1 While this specifically mentions ACE inhibitors, ARBs share the same mechanism of renin-angiotensin system inhibition and carry similar risks. 2

Mechanism of Interaction

• ARBs suppress angiotensin stimulation, which can lead to sodium loss and reduced renal lithium clearance 2
• Lithium itself decreases sodium reabsorption by renal tubules, compounding this effect 1
• Case reports document lithium intoxication occurring 3-4 months after ARB initiation, even with stable lithium doses 3
• The interaction can develop insidiously, with toxicity manifesting weeks to months after starting the ARB 3

Practical Management Algorithm

Before Initiating Lithium

Baseline Assessment (Mandatory): 1

• Serum creatinine and calculated GFR
• Serum sodium and potassium
• Thyroid function tests (TSH, free T4)
• Pregnancy test in women of childbearing age
• Blood pressure including orthostatic measurements 2

Dosing Considerations

Start with reduced lithium doses when ARBs are present, as the standard empirical titration method may lead to toxicity 1, 4

• Begin at the lower end of typical starting doses (e.g., 300 mg daily rather than 300 mg twice daily) 1
• The patient must maintain normal salt intake and adequate fluid intake (2500-3000 mL daily) 1
• Consider that lithium tolerance is greater during acute mania and decreases as symptoms subside 1

Monitoring Protocol (More Intensive Than Standard)

First Month: 1

• Check lithium level, renal function, and electrolytes at 5-7 days after initiation
• Repeat at 2 weeks after any dose adjustment
• Weekly monitoring is prudent during initial titration when ARBs are present

After Stabilization: 1

• Lithium levels every 2-4 weeks for the first 3 months
• Then monthly for 3 months
• Then every 2-3 months long-term (more frequent than standard monitoring)
• Renal function and electrolytes should accompany each lithium level check

Signs of Lithium Toxicity to Monitor

Instruct patients to discontinue lithium immediately and contact physician if these occur: 1

• Diarrhea or vomiting
• Tremor (beyond fine hand tremor)
• Mild ataxia or unsteady gait
• Drowsiness or confusion
• Muscular weakness
• Myoclonus 3

Special Precautions with ARBs

Volume Status Considerations: 2

• Patients with systolic BP <80 mm Hg require especially close surveillance 2
• Those with low serum sodium are at higher risk 2
• Diabetes mellitus and pre-existing renal impairment increase risk 2

Avoid Triple Therapy: The combination of lithium with both an ACE inhibitor/ARB AND an aldosterone antagonist creates compounded risk of hyperkalemia and renal dysfunction 2

Common Pitfalls to Avoid

• Do not use standard lithium dosing protocols without accounting for the ARB interaction 1, 3
• Do not rely on stable lithium levels from months prior—the interaction can develop gradually over 3-4 months 3
• Do not overlook subtle early signs like progressive tremor or mild GI symptoms, which may herald toxicity 3
• Do not assume the interaction only occurs with ACE inhibitors—ARBs carry equivalent risk through the same renin-angiotensin mechanism 2, 1, 3

Alternative Considerations

If the clinical situation allows, consider whether:

• The ARB is absolutely necessary or could be replaced with a different antihypertensive class (e.g., calcium channel blocker) that doesn't affect lithium clearance 1
• Alternative mood stabilizers might be appropriate if the interaction risk is deemed too high for the individual patient

The key principle: lithium can be initiated with ARBs present, but only with dose reduction, intensified monitoring, and clear patient education about toxicity warning signs. 1, 3