Psychiatrists caring for older adults regularly face two questions: 1) Are symptoms psychiatric or cardiac? And 2) which psychotropics are safe to use? Cardiovascular disease (CVD) is the leading cause of mortality worldwide and a major cause of death in people with serious mental illness (Chin K et al, Front Psychiatry 2023;14:1110361). Metabolic side effects from psychotropics compound that risk. Depression and anxiety worsen cardiac outcomes, driving decreased medication adherence, increased hospitalizations, and lower quality of life.

Background
Depression affects 15%–20% of patients with coronary disease or acute myocardial infarction (MI) and 20%–25% of those with heart failure. About 30% of patients with heart failure report clinically significant anxiety, though only 13% meet formal diagnostic criteria, roughly the same as the general population (Shapiro P. Heart Disease. In: Levenson JL, ed. Textbook of Psychosomatic Medicine and Consultation-Liaison Psychiatry. 3rd ed. Washington, DC: American Psychiatric Association Publishing; 2019:465–508). The bigger concern is subsyndromal anxiety: symptoms that fall short of a formal diagnosis but still drive higher mortality and rehospitalization. Cardiac surgery adds delirium risk, which in older adults extends hospitalization and increases mortality. Across all these conditions, untreated psychiatric comorbidity worsens outcomes.

When heart medications cause psychiatric symptoms
Before attributing psychiatric symptoms to a new diagnosis, review the medication list. Cardiac drugs are a frequently overlooked cause of depression, fatigue, psychosis, and delirium, and the symptoms won’t resolve until the offending agent is addressed. For more on side effects, visit: www.thecarlatreport.com/CardiacPsychotropicMeds.

What’s cardiac and what’s psychiatric?
Fatigue, dyspnea, sleep disruption, and palpitations can all reflect cardiac illness or depression and anxiety. Ask when symptoms began relative to the medical illness to help untangle the picture. To monitor symptom severity, you can use the PHQ-9 or GAD-7 in outpatient settings, but these lose validity in inpatient settings, where somatic items are confounded by illness.

Know before you prescribe
Consider these cardiac side effects before starting a psychotropic in patients with heart disease.

QT prolongation
The most encountered cardiac concern during inpatient psychiatric consultations, prolonged QT can lead to torsades de pointes (TdP), a potentially fatal arrhythmia. Many antidepressants and antipsychotics carry this risk. Refer to CredibleMeds.org for regularly updated drug-by-drug risk classifications.

Electrolyte abnormalities, common in older adults due to dehydration, diuretics, and certain psychotropics, independently raise QT prolongation risk.

Antipsychotics

• Lowest risk: Aripiprazole is safest, with minimal QT prolongation; lurasidone and brexpiprazole are also cardiac-safe (Beach SR et al, Psychosomatics 2013;54(1):1–13; Bordet C et al, Psychopharmacology 2023;240(1):199–202).
• Low to moderate risk: Olanzapine, risperidone, and quetiapine produce modest QTc increases (2–6 ms), but quetiapine’s real-world data tell a different story: Over 10% develop severe QT prolongation (QTc > 500 ms or a > 60 ms increase), particularly older patients with heart failure or hypokalemia (Wang CL et al, Heart Rhythm 2024;21(3):321–328).
• Higher risk: Ziprasidone prolongs QTc by ~16 ms at therapeutic doses. Iloperidone is comparable, and the risk nearly doubles with CYP2D6 or CYP3A4 inhibitors. Clozapine also carries significant risk.
• For agitation or psychosis requiring an IM antipsychotic: Olanzapine IM has the lowest prolongation risk. Avoid IV haloperidol in patients with prolonged QT, which carries higher TdP risk than oral.

Antidepressants

• Lower risk: Sertraline, fluoxetine, paroxetine, fluvoxamine, SNRIs, bupropion, and mirtazapine have minimal or no QT prolongation effects.
• Moderate risk: Citalopram prolongs QTc by ~8 ms at 20 mg/day and ~17 ms at 60 mg/day, prompting the FDA to cap the dose at 40 mg/day (or 20 mg/day in patients over age 60). Escitalopram carries similar risk.
• Highest risk: TCAs (~7 ms more than SSRIs) and trazodone (dose-dependent: ~4.5 ms at 20 mg, ~12 ms at 60 mg, and ~20 ms at 140 mg) should be avoided in patients with a prolonged QT at baseline (Tellone V et al, J Clin Pharmacol 2020;60(11):1483–1495).

Mood stabilizers

• Lithium can prolong QT and cause T-wave abnormalities.
• Valproate has no significant prolongation effects.
• Lamotrigine carries a 2020 FDA warning for QT prolongation and conduction slowing in structural or functional heart disease.

Benzodiazepines
Benzodiazepines do not appear to prolong QT, even at high doses or with long-term use.

Hypotension and orthostasis
Medications with alpha-1 antagonism (SGAs, low-potency FGAs, TCAs, trazodone, and MAOIs) can cause hypotension and orthostasis, raising fall and syncope risk in older adults. The risk is even higher in patients already on antihypertensives or diuretics. Among SGAs, clozapine, quetiapine, and risperidone carry the highest orthostasis risk. Aripiprazole, lurasidone, and brexpiprazole are safest.

Metabolic syndrome
SGAs can cause all three components of metabolic syndrome (hyperglycemia, dyslipidemia, and hypertension), which drives CVD, already the leading cause of death in patients on SGAs (Zergaw M et al, Cureus 2024;16(8):e67913).

Olanzapine and clozapine carry the highest metabolic risk. Aripiprazole, lurasidone, and ziprasidone are most favorable. Monitor fasting glucose (or HbA1c) and lipids at baseline, 12 weeks, and annually; check weight and blood pressure at each visit. Switch to a lower-risk agent (or add metformin) if changes emerge.

Myocarditis and cardiomyopathy
Myocarditis risk is specific to clozapine, most likely in the first six weeks; cardiomyopathy can emerge later. Monitor troponin and CRP weekly for the first four weeks of titration, as both catch myocarditis early with good sensitivity. Watch for unexplained tachycardia, dyspnea, chest pain, or fever. If either marker spikes, stop clozapine and involve cardiology immediately.

Antipsychotics in dementia
The FDA black box warning on antipsychotics for older adults with dementia reflects a real signal for increased mortality, stroke, and cerebrovascular events. This warning applies to all currently marketed antipsychotics except Cobenfy (xanomeline/trospium), which targets muscarinic rather than dopamine receptors and is unstudied in dementia. Antipsychotics can still be appropriate here, but the risk-benefit conversation must be explicit and documented.

Practical prescribing in cardiac patients
Treat psychiatric symptoms when they persist beyond two weeks, impair functioning, or interfere with cardiac recovery or adherence. Safe options exist.

Antidepressants
SSRIs are first line. Sertraline and escitalopram have the strongest cardiac safety evidence, supported by the SADHART and EsDEPACS trials, respectively (Glassman AH et al, JAMA 2002;288(6):701–709; Kim JM et al, JAMA 2018;320(4):350–358). Citalopram and escitalopram are well tolerated in cardiac populations, but in older adults, use lower maximum doses (citalopram ≤ 20 mg; escitalopram ≤ 10 mg) given the dose-dependent risk of QT prolongation. Avoid TCAs, as QRS/QT prolongation, anticholinergic effects, and arrhythmia risk make them a poor choice in cardiac disease.

From the Clinical Update
“Update on Psychocardiology for Older Adults”
by Roy Williams, MD, MPH
The Carlat Geriatric Psychiatry Report, Volume 5, Number 7 & 8
October/November/December 2026
www.thecarlatreport.com

Antipsychotics
Aripiprazole and lurasidone have the most favorable cardiac profiles among SGAs, with minimal QT effect and lower metabolic burden. Note that EPS risk rises with aripiprazole in older adults. If QTc > 500 ms, avoid QT-prolonging agents or consult cardiology before proceeding.

Non-pharmacologic interventions
Cognitive behavioral therapy (CPT) and problem-solving therapy work well for distorted illness beliefs (“I’ll never recover,” “I’m a burden”) and reduce post-MI depression while improving quality of life (for more, see the “Brief Behavioral Interventions for Older Adults” article on page 1 and our research update on CBT on page 10).

Interpersonal therapy suits patients adapting to role transitions, such as a former household provider now needing care.

Cardiac rehabilitation includes exercise training, cardiovascular risk factor management, nutrition counseling, and psychological support, which improve cardiopulmonary function and are associated with reduced mortality and hospitalizations (Thomas RJ, N Engl J Med 2024;390(9):830–841). Emerging evidence also suggests cognitive benefits. Advocate for enrollment in eligible patients (post-MI, PCI, CABG, valve surgery, stable angina, or heart failure). Fewer than 30% of eligible patients participate, yet rehab is one of the few interventions that addresses both cardiac and psychiatric outcomes.

CARLAT VERDICT
Untreated mental illness worsens cardiac outcomes. When medications are needed for depression or anxiety, start with sertraline or escitalopram. Among antipsychotics, aripiprazole and lurasidone have the most favorable cardiac profiles, but check QTc and orthostasis risk before prescribing. Don’t overlook cardiac rehab, as it’s one of the few interventions that improves both cardiac and psychiatric outcomes.