Cardiovascular disease (CVD) is one of the leading causes of death in patients with severe mental illness (SMI), being ~3.3 times higher than in the general population. The adverse cardiovascular effects of psychiatric medications have short- and long-term consequences that contribute to higher rates of cardiovascular death in patients experiencing SMI. By understanding these adverse effects, clinicians can better address cardiovascular health inequalities in patients with SMI from a pharmacological perspective. This review highlights both the short- and long-term adverse cardiovascular effects of psychiatric medications. These adverse effects include QTc prolongation and torsades de pointes (TdP), which are phenomena associated with certain selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs) and antipsychotics. Increasing QT dispersion and induction of Brugada phenotype, both associated with serious cardiac arrhythmias and sudden death, can occur with certain antipsychotics (e.g. trifluoperazine), certain TCAs (e.g. amitriptyline), certain SSRIs (e.g. fluoxetine), methylphenidate and particular mood stabilisers (e.g. lithium). Antipsychotics themselves are associated with increased risk of myocarditis, cardiomyopathy, tachycardia, cardiometabolic derangement, hypertension, orthostatic hypotension and bradycardia. Attention deficit Hyperactivity disorder (ADHD) medications contribute to CVD and tachycardia. Acetylcholinesterase inhibitors (AChEIs) contribute towards bradycardia. Hypertension risk is elevated with serotonin-norepinephrine reuptake inhibitors (SNRIs), norepinephrine-dopamine reuptake inhibitors (NDRIs), monoamine oxidase inhibitors (MAOIs), reversible inhibitors of monoamine oxidase A (RIMA) and psychostimulants. Conversely, orthostatic hypotension is associated with certain psychiatric medications, namely TCAs and serotonin antagonist and reuptake inhibitors (SARIs). It is important to note that pharmacokinetic drug-drug interactions, such as inhibition of the cytochrome P450 (CYP450) system, can affect the pharmacodynamic profile of psychiatric medications, thereby increasing the risk of their associated adverse cardiovascular effects. By understanding the main adverse cardiovascular effects of psychiatric medications and prescribing appropriately, clinicians can reduce potential harm in patients with SMI.
Keywords: Brugada phenotype; QT dispersion; QTc prolongation; bradycardia; cardiometabolic derangement; cardiomyopathy; cytochrome P450 interactions; hypertension; myocarditis; orthostatic hypotension; psychiatric medications; tachycardia; torsade de pointes (TdP).
Improving treatment of hearts and minds: understanding the adverse cardiovascular effects of psychiatric medications Patients with severe mental illness are around three times more likely to die from cardiovascular disease than those without mental illness. Some psychiatric medications for severe mental illness are associated with potentially harmful effects on the heart and blood vessels. By better understanding these effects, we can learn to improve drug choice and dosing to help reduce the risk of death caused by heart disease in patients with severe mental illness. This review explains how certain psychiatric medications for severe mental illness can affect the heart and blood vessels in these patients. Some medications can cause problems with a patient’s heart rate and rhythm, while others may lead to long-term issues like weight gain and a higher risk of diabetes. These changes can increase the chances of having a heart attack or other serious health problems. These issues can be made worse when patients are given certain combinations of medications. By understanding the problems that can be caused by individual or a combination of psychiatric medications for severe mental illness, healthcare professionals can work towards improved drug therapies to help reduce the unusually high risk of heart disease amongst this vulnerable patient group.
© The Author(s), 2026.