Tricyclic Antidepressants: Do They Work?

The use of tricyclic antidepressants has expanded since the drug’s accidental discovery in the 1950s.

tricyclic antidepressants

Don't mix tricyclic antidepressants with alcohol, cimetidine (Tagamet), certain bowel-prep products, or St. John’s Wort.

© Katarzyna Bialasiewicz |

Tricyclic antidepressants were one of the original drugs prescribed for depression and obsessive-compulsive disorder. “Tricyclic” refers to the presence of three rings, or atoms, in the chemical structure of these drugs. Tricyclic antidepressants also are used for anxiety, fibromyalgia, and chronic pain. Physicians may prescribe tricyclic antidepressants for diabetes, shingles, migraines, panic disorders, and phantom limb pain, according to

Tricyclic antidepressants were found by accident in the 1950s, according to Swiss scientists were searching for a treatment for schizophrenia and found a drug that tweaked the balance neurotransmitters (norepinephrine and serotonin), which sent patients into spells of euphoria.

While the drug worsened schizophrenia, it was quickly recognized as an aid for depression. The release of imipramine (marketed as Tofranil in 1958), the first drug in the tricyclic antidepressants category, was heralded as a “miracle cure” for depression.


Tricyclic antidepressants include:

  • Amitriptyline
  • Amoxapine
  • Clomipramine
  • Desipramine
  • Doxepin
  • Imipramine
  • Nortriptyline
  • Protiptyline
  • Tripramine

Side Effects of Tricyclic Antidepressants

No drug is without side effects, and they vary with the individual. Caution needs to be used, with full disclosure to your physician about other drugs or supplements you use. Tricyclic antidepressants shouldn’t be mixed with alcohol, cimetidine (Tagamet), some bowel-prep products, or St. John’s Wort. Prescription medicines, including MOAIs, may also cause dangerous interactions with tricyclic antidepressants.

A new study shows there may be an increased risk of cardiovascular disease (CVD) with tricyclic antidepressants. The University College London (UCL) study, published in the European Heart Journal, showed that tricyclic antidepressants were associated with a 35 percent increased risk of CVD. They found no increased risk with the newer anti-depressants, such as the selective serotonin reuptake inhibitors (SSRIs), say the researchers.

Mark Hamer, MD, Senior Research Fellow in the Department of Epidemiology and Public Health at UCL, says: “Our findings suggest that there is an association between the use of tricyclic antidepressants and an increased risk of CVD that is not explained by existing mental illness. This suggests that there may be some characteristic of tricyclics that is raising the risk. Tricyclics are known to have a number of side effects; they are linked to increased blood pressure, weight gain, and diabetes, and these are all risk factors for CVD.”

Dr. Hamer advises those taking tricyclic antidepressants not to stop without consulting their physician. “There are two important points to be made,” he says. “First, tricyclics are the older generation of antidepressant medicines and we found no excess risk with the newer drugs (SSRIs). Second, people taking the antidepressants are also more likely to smoke, be overweight, and do little or no physical activity. By giving up smoking, losing weight, and becoming more active a person can reduce their risk of CVD by two- to three-fold, which largely out-weighs the risks of taking the medications in the first place. In addition, physical exercise and weight loss can improve symptoms of depression and anxiety.”

Other documented side effects associated with tricyclic antidepressants include:

  • Abdominal cramps
  • Anxiety
  • Blurred vision
  • Confusion
  • Constipation
  • Dizziness
  • Drowsiness
  • Dry mouth
  • Hypertension
  • Increased appetite
  • Insomnia
  • Nausea
  • Orthostatic hypotension
  • Rapid heartbeat
  • Rash
  • Restlessness
  • Seizures
  • Sexual difficulties (low libido, erectile dysfunction)
  • Sweating
  • Tremors
  • Urine retention
  • Weight gain or loss
  • Vomiting

According to, tricyclic antidepressants, like all prescription antidepressants, carry an FDA-mandated warning about an increased risk of suicidal thinking and behavior in children, adolescents, and young adults associated with use of these medications. Indeed, these drugs are not recommended for those under age 25 or over age 65.

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Nortriptyline (Pamelor, Aventyl) is a tricyclic antidepressant that stops the growth of abnormal proteins that can build up in the brain and lead to the development of Parkinson’s, according to a Michigan State University study published in the journal Neurobiology of Disease. Nortriptyline is used to treat depression and nerve pain.

The researchers were wanted to see if antidepressants could delay the need to go on the standard Parkinson’s therapy called levodopa (Sinemet). Levodopa increases levels of dopamine, a natural chemical in the body that sends signals to other nerve cells and can significantly decrease in cases of Parkinson’s.

“We found that those on a certain class of antidepressant, called tricyclics, didn’t need the levodopa therapy until much later compared to those who weren’t on that type of antidepressant medication,” explains Tim Collier, lead author of the federally funded study and a neuroscientist at MSU.

“What we’ve essentially shown is that an already FDA-approved drug that’s been studied over 50 years and is relatively well tolerated could be a much simpler approach to treating the disease itself, not just the symptoms,” Collier says.

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Cindy Foley

Cindy Foley is the editor of several health reports, including Managing Your Cholesterol, Core Fitness, and Brain Power & Nutrition, among others. Foley has worked in the private medical practice field … Read More

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