Tricyclic antidepressants (TCAs) may increase the risk of seizures in patients who are at risk for these, including those with epilepsy. Selective serotonin reuptake inhibitors (SSRIs) and selective serotonin and norepinephrine reuptake inhibitors (SSNRIs) are generally the safest to use in patients with a history of seizures.

The U.S. Food and Drug Administration (FDA) in 2005 instructed all manufacturers of antidepressants to add warnings to their labeling about certain dangers associated with these medications. These dangers include increased risk of suicidal thoughts and behavior in children and adolescents.

In addition, the FDA issued a public health advisory to inform patients and healthcare providers about the link between antidepressants and increased risk of suicidal thoughts and behavior in adults. According to the advisory, adults who take antidepressants should be carefully monitored for an increase in feelings of depression and suicidal thoughts, especially if they are taking a medication for the first time or its dosage has recently been adjusted. Adults who take antidepressants and experience an increase in feelings of depression should seek immediate medical attention.

It should be noted that there is no information demonstrating that there is an increase in suicidal thoughts when antidepressants are used to manage pain in patients who are not depressed.

The agency also directed manufacturers to include information from pediatric and adult trials in the packaging of antidepressant medications.

Patients should consult a physician if they have concerns about taking these medications in light of the FDA’s recent recommendations.

Some recent studies including the Diabetes Prevention Program have found a possible link between antidepressants and elevated glucose (blood sugar) or risk of developing diabetes. Further research would be needed to establish a connection. 

TCAs are commonly used for the relief of pain. Patients who have been diagnosed with heart disease should inform their physician of this fact before taking TCAs. In addition, TCAs may exacerbate glaucoma in some patients. Glaucoma is a group of eye diseases that damage the optic nerve and usually involve abnormally high fluid pressure inside the eye. Glaucoma can result in partial to complete loss of vision.

Other conditions of concern in regard to use of TCAs include:

• Alcoholism
• Bipolar disorder
• History of seizures
• Enlarged prostate (benign prostatic hyperplasia) or history of urination difficulties
• High blood pressure
• Heart problems including arrythmias
• Schizophrenia
• Kidney disease
• Liver disease
• Overactive thyroid gland (hyperthyroidism)
• Stomach or intestinal problems

Some of these, such as arrhythmias and prostate enlargement, are contraindications for the use of TCAs, but others, such as kidney or liver disease, may merely affect the dosage.

The SSNRIs have much more benign side-effect profiles than the TCAs.  Duloxetine can be associated with nausea and can exacerbate liver disease. Venlafaxine can, in rare cases, exacerbate high blood pressure.