Raja_2026_Ther.Adv.Drug.Saf_17_20420986261418947

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.