Antihypertensive Selection in Patients on Lithium and Multiple Antipsychotics

Primary Recommendation: RAS Inhibitors and Diuretics

• The International Society of Hypertension recommends starting with RAS inhibitors (ACE inhibitors or ARBs) as first-line agents due to their lower rate of pharmacological interactions with antidepressants and antipsychotics 1, 2, 3, 4
• Thiazide-like diuretics (not thiazide diuretics) should be added as second-line therapy for their superior efficacy and lower interaction profile 1, 2

Alternative First-Line Agents

• Dihydropyridine calcium channel blockers (DHP-CCBs) represent an excellent alternative with minimal drug interactions 1, 2, 3
• Use DHP-CCBs with caution if the patient has orthostatic hypotension from antipsychotics 1, 2

Special Indications

• Beta-blockers (excluding metoprolol) should be used when antipsychotics cause drug-induced tachycardia 1, 2, 4
• Monitor for additive sedation and hypotension when using beta-blockers 1

Agents to Avoid or Use with Extreme Caution

• Alpha-1 blockers should be avoided in patients on multiple antipsychotics due to the high risk of additive orthostatic hypotension 1, 2
• Standard thiazide diuretics require intensive monitoring if used, and thiazide-like agents (chlorthalidone, indapamide) are preferred at the lowest effective doses 1, 2

Practical Treatment Algorithm

• Initial therapy: Start ACE inhibitor or ARB at low dose, and monitor lithium levels at baseline, 1 week, and 2 weeks, then monthly 1, 2
• If BP remains uncontrolled, add DHP-CCB before adding diuretic 1, 2, 3
• If a third agent is needed, add thiazide-like diuretic with intensive lithium monitoring 1, 2
• If drug-induced tachycardia is present, substitute or add beta-blocker (not metoprolol) 1, 2

Essential Monitoring Parameters

• Lithium levels should be checked at baseline, 1-2 weeks after any antihypertensive change, then monthly, although the exact frequency may vary 1
• Orthostatic vital signs should be assessed at each visit given antipsychotic use 1
• ECG monitoring should be considered at baseline and periodically given QTc prolongation risk with antipsychotics 1, 2
• Renal function and electrolytes should be checked every 3-6 months minimum 1