Overview and Use of Tricyclic Antidepressants

All About Trycyclic Antidepressants for Bipolar Disorder and Depression

Doctor explaining prescription medication to patient in clinic
Tricyclic Antidepressants. Hero Images / Getty Images

Your doctor may have recommended a tricyclic antidepressant medication to treat your depression, bipolar disorder, or for another condition such as pain. How do these medications work? What drugs are considered tricyclic antidepressants, and what are some common side effects of which you should be aware?

What are Tricyclic Antidepressants?

Tricyclic antidepressants have been around for a long time, with the first drugs in this class of antidepressants having been developed in the 1950's.

Although newer medications (often with fewer side effects and a lower risk of overdose) are now available, tricyclic antidepressants still have a place in the treatment of bipolar disorder, depression, as well as for other conditions such as chronic pain.

The first of the tricyclic antidepressants, Tofranil (imipramine) was an important discovery and actually helped psychiatrists to formulate their ideas about how depression occurs. Tricyclic antidepressants are named for the chemical structure of many of the drugs in the class—the drugs are made up of three rings of atoms.

How Do Tricyclic Antidepressants Work?

Since the discovery of tricyclic antidepressants, we've been learning more about how a chemical imbalance in the brain underlies many episodes of depression. This is likely not surprising to those who have lived with depression, as they've realized that depression symptoms may occur even when everything in life seems to be going well.

Having friends and family understand the biochemical nature of depression and other mental illnesses is helpful, lest they make hurtful comments such as "just snap out of it." Comments such as these are no different than telling someone with diabetes and a high blood sugar level to just snap out of it.

Communication between different nerve cells in the brain takes place via chemicals known as neurotransmitters. These chemicals are released from the end  of one nerve cell, into a space between the cells (the synapse), and then taken up into the next nerve cell as a method of transmitting information.

Tricyclic antidepressants work by increasing the level of the neurotransmitters serotonin and norepinephrine (by preventing your body from breaking down these chemicals.) Since they increase levels of both of these neurotransmitters, they are considered "dual action" antidepressants.

In addition to effects on serotonin and norepinephrine, tricyclic antidepressants also work by blocking the action of another neurotransmitter, acetylcholine.

In contrast to tricyclic antidepressants, some of the newer antidepressants work primarily by their actions on serotonin. For example, the selective serotonin reuptake inhibitors (SSRI's) such as Prozac (fluoxetine) increase the level of serotonin in the brain but not the level of norepinephrine. (The actual actions of antidepressants are more in depth than this, so this example is used as a simple comparison.)

Overall, it's felt that higher levels of serotonin and norepinephrine in the brain result in a better mood.

(Learn more about the chemistry of depression.)

What Conditions are Tricyclic Antidepressants Used For?

Tricyclic antidepressants may be prescribed either "on label" or "off label." On label uses include those for which the medication is currently FDA-approved. "Off label" use of many drugs is quite common, and refers to the use of a drug which has been approved by the FDA, but for an indication different than that for which it was approved.

On label uses of tricyclic antidepressants include:

Off label uses for tricyclic antidepressants include:

Doctors vary in how comfortable they are prescribing medications such as these "off label" though, especially in the case of chronic pain management and bedwetting, there have been many studies supporting this use.

How Long Does it Usually Take These Medications to Work?

Tricyclic antidepressants, like other antidepressants, often take several weeks (often six to eight weeks) before they work to decrease depression. For this reason, doctors often recommend continuing a medication for two to three months before switching to another type of medication. The reason is thought to be that all of these drugs take time to restore a chemical balance in the brain. This does not mean that there is nothing you can do while waiting. Many people find other therapies such as psychotherapy very helpful for the treatment of conditions such as depression and bipolar disorder, and these may begin to help depression symptoms before a mediation "kicks in."

Medications Classified as Tricyclic Antidepressants

Some of the medications which are classified as tricyclic antidepressants include:

  • Elavil (amitryptyline)
  • Ascendin (amoxapine)
  • Anafranil (clomipramine)
  • Pamelor (nortryptyline)
  • Norpramin (desipramine)
  • Tofranil (imipramine)
  • Vivactil (protryptyline)
  • Surmontil (trimipramine)
  • Sinequan (doxepin)

Common Side Effects of Tricyclic Antidepressants

Although each of the tricyclic antidepressants is slightly different from the others, they share similar side effects. Common side effects include:

If you have had a bad reaction to Tegretol (carbamazepine), or any previous psychiatric medication, make sure you tell this to your doctor if she suggests you take a tricyclic antidepressant.

In addition, there are reports of babies having problems when their mothers took tricyclic antidepressants at the end of the pregnancy. Tricyclics do pass into breast milk. If you are pregnant, nursing or plan to become pregnant, discuss the benefits vs risks of tricyclic antidepressants with your doctor.

Drug Interactions with Tricyclic Antidepressants

Some of the side effects of tricyclic antidepressants can be intensified by other drugs. Your doctor should know what other drugs you are taking, including prescription medications, over-the-counter drugs, and street drugs. For example:

  • Tricyclics can cause cardiac arrhythmias—a fast, pounding or irregular heartbeat. Drugs that can make this worse include amphetamines, diet pills, decongestants, allergy medications, and asthma medications.
  • Sleeping pills, antipsychotic medications, muscle relaxants, antihistamines, tranquilizers and alcoholic beverages can increase the sedating properties of tricyclics.

Other drugs that can cause problems when taken with tricyclic antidepressants include, but are not limited to:

  • Psychiatric medications
  • Blood-thinning drugs
  • Medications for overactive thyroid
  • Tagamet (cimetidine)
  • Certain blood pressure medications

Finally, serious, even fatal complications can occur when combining tricyclic antidepressants with another type of antidepressants known as MAO inhibitors, or when switching from one to the other. Taking these two types of drugs together or within two weeks of each other may cause sudden high body temperature, extremely high blood pressure, severe convulsions, and death. Your doctor may prescribe them together, but this situation should be under the doctor's close supervision.

Bottom Line on Antidepressants

While there are many newer antidepressant medications that work for many people, often with fewer side effects, these drugs still have a role in the treatment of depression. As such, they are sometimes able to control symptoms of depression that have not been controlled on the newer medications. In addition, they appear to have a role in the treatment of conditions such as chronic pain.

That said, tricyclic antidepressants should be used with caution in the elderly due to their side effect profile, especially sedative properties and anticholinergic side effects such as dizziness, blurred vision, and constipation.

No matter what medication you are prescribed, it's important that you be an active participant in your care and advocate for your medical needs. Talk to your doctor if your symptoms are not controlled with your medication, and mention any side effects that you experience. Every person is different, and the only way that your doctor knows how you are feeling with your medication is if you share your thoughts. Conditions such as bipolar disorder and depression can be difficult to manage and often require some hit or miss to find the right treatment regimen. Yet with time, many people are able to obtain good control of their symptoms with minimal side effects.

Suicide Warning Signs

In any discussion about depression, it would be amiss to not mention suicide. Unfortunately, suicide attempts and successful suicides are far too common among those with depression. If you or a loved one have suffered with depression, bipolar disorder, or any mental illness, review the ​warning signs of suicide. And know that there is help out there 24 hours a day, seven days a week. Call the National Suicide Prevention Hotline if you have any concerns at all.


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