Treating psychiatric symptoms in patients with serious medical illness is challenging. The goal is to relieve symptoms without worsening the medical condition. Adjust medication doses carefully, watch for drug interactions, and monitor closely to prevent toxicity. Below are practical tips for prescribing safely in this population.

Cardiovascular conditions
Patients with heart disease are particularly vulnerable to the cardiotoxic effects of several psychotropics. Be especially careful in those with risk factors for QT prolongation:

• Female sex
• Age > 65
• Electrolyte disturbances (hypokalemia, hypomagnesemia)
• Concomitant QT-prolonging medications
• Comorbid hypertension, diabetes, or stroke

Antidepressants

• Tricyclic antidepressants (TCAs), particularly amitriptyline and imipramine, pose the highest cardiac risk, prolonging the QT interval by 7–18 msec, increasing heart rate by ~6 bpm, and raising arrhythmia risk (Rochester MP et al, Ther Adv Drug Saf 2018;9(6):297–308).
• Selective serotonin reuptake inhibitors: Citalopram has the highest dose-related risk for QT prolongation. The Beers criteria recommend limiting doses to 20 mg/day in patients over 60. Sertraline remains the gold standard even in patients who have had a heart attack, starting at 25 mg daily.
• Serotonin/norepinephrine reuptake inhibitors: Venlafaxine and duloxetine can increase blood pressure, especially at higher doses. Monitor blood pressure in patients with hypertension.
• Be alert for orthostatic hypotension with trazodone and TCAs.

Antipsychotics

• Highest QT risk: Ziprasidone (~10–20 msec), chlorpromazine, thioridazine, IV haloperidol (30+ msec) increasing risk of torsades de pointes (Harrigan EP et al, J Clin Psychopharmacol 2004;24(1):62–69)
• Safest for QT: Lurasidone, brexpiprazole, aripiprazole (Bordet C et al, Psychopharmacology (Berl) 2023;240(1):199–202)
• Clozapine: Lower QT risk but additional myocarditis risk (~10% show troponin or C-reactive protein [CRP] elevations); obtain baseline and weekly troponin and CRP during first month
• Monitor orthostatic hypotension: Clozapine, quetiapine, ­olanzapine

Stimulants
Stimulants may elevate the heart rate by about 3–4 bpm and blood pressure by about 2 mmHg (systolic and diastolic). These effects persist with ongoing use and are usually clinically relevant only in those with uncontrolled hypertension or coronary artery disease (Chan M et al, Cochrane Database Syst Rev 2025;3(3):CD007896). In patients with cardiovascular disease or risk factors, start at half the typical starting dose and monitor blood pressure and pulse weekly for the first month.

Lithium
Lithium can slow sinoatrial node conduction and occasionally cause AV block or sinus bradycardia. Monitor ECG in patients who have preexisting cardiac conduction disease or are on AV-nodal-blocking drugs.

Pulmonary diseases
Patients with respiratory conditions (eg, chronic obstructive pulmonary disease, asthma) or sleep apnea face increased complications from sedating medications.

Highest-risk medications 
Benzodiazepines (BZDs), barbiturates, and opioids cause a dose-dependent reduction in respiratory drive, leading to carbon dioxide retention and hypoxemia. Avoid or use with great caution.

Aspiration risk
Many antipsychotics impair swallowing and cause sedation; clozapine carries the highest risk of aspiration (hypersalivation + sedation + dysphagia).

Management strategies

• Minimize sedatives
• Consider home pulse oximetry
• Maintain current vaccinations (influenza, COVID-19, ­pneumococcal)
• Emphasize infection prevention precautions

Renal disease
Chronic kidney disease (CKD) can significantly alter psychotropic clearance, with greater impact once glomerular filtration rate (eGFR) falls below 60 mL/min. Many medications may need dose adjustments even when eGFR is < 90 mL/min, including: 

• Topiramate
• Paliperidone
• Gabapentin
• Bupropion

Lithium is of greatest concern in patients with renal impairment since it’s entirely renally excreted and has a narrow therapeutic index. In patients prescribed lithium with reduced renal function:

• Monitor lithium levels and eGFR every three to six months
• Decrease lithium dose and/or frequency
• Use immediate-release formulation
• Medications requiring dose adjustment in advanced CKD (eGFR < 30 mL/min):
• All medications listed above and memantine (max 10 mg/day)
• Duloxetine, mirtazapine (adjust dose or avoid)
• Choose hepatically metabolized drugs when possible, but watch for toxicity since many of them still rely partly on renal excretion.

Hepatic disease
Hepatic impairment increases exposure to medications metabolized by the liver—including most psychotropics. General dose adjustment guidance (Verbeek AK, Eur J Clin Pharmacol 2008;64(12):1147–1161):

• Mild impairment: Reduce 25%–50%
• Moderate impairment: Reduce ~50%
• Severe impairment: Reduce ~75% or avoid

The Child-Pugh score is an imperfect proxy for metabolic capacity. Whenever possible, use drug-specific pharmacokinetic data, as some antidepressants, antipsychotics, or mood stabilizers may require specific adjustment that differs from the general rule.

Valproate poses the highest hepatotoxicity risk. Check liver enzymes while titrating and periodically thereafter. Stop the medication if aspartate/alanine transaminase (AST/ALT) exceed three times the upper limit of normal or if symptoms develop (jaundice, nausea, right upper quadrant pain, confusion, disorientation). Check ammonia levels for encephalopathy signs. Carbamazepine carries a similar hepatotoxicity risk and requires routine liver enzyme monitoring, but the risk of hyperammonemia is much lower than with valproate.

Antipsychotics, antidepressants, and BZDs have variable hepatic metabolism. Use lower, less frequent doses and avoid long half-life agents when possible (eg, fluoxetine, diazepam). Note: Aripiprazole has a long half-life but is a highly effective augmentation option in late-life depression; titrate and monitor carefully.

Carlat Take
Managing psychiatric symptoms in medically complex older patients requires a fundamentally different approach than treating healthy younger adults. Know the highest-risk medications: TCAs in cardiac disease, antipsychotics and BZDs in pulmonary disease, lithium in renal disease, and valproate in hepatic disease. Prioritize nonpharmacologic options or safer alternatives, tailor monitoring to the patient’s organ function, and coordinate care with internists and specialists.