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All antidepressants may increase the risk of seizures in certain patients, including those with epilepsy. Selective serotonin reuptake inhibitors (SSRIs) and the non-tricyclic antidepressant serotonin and norepinephrine reuptake inhibitors (SNRIs) are generally the safest to use in patients with a history of seizures.

Patients with prostate conditions (e.g., enlarged prostate), certain forms of glaucoma (an eye disease) or heart conditions are usually not prescribed tricyclic antidepressants (TCAs). An electrocardiogram (records the electrical activity of the heart) is typically required for patients with heart disease or patients over the age of 40 years before they are prescribed TCAs.

The norepinephrine and dopamine reuptake inhibitor (NDRI) bupropion is not recommended in patients with a history of major head trauma, a central nervous system tumor or an active eating disorder. Buproprion can cause seizures even in patients without any history of these.

Monoamine oxidase inhibitors (MAOIs) are usually avoided in patients with congestive heart failure and those with high blood pressure (hypertension). Serotonin modulators are not generally used in patients with heart disease.