Tricyclic Antidepressants

Tricyclic antidepressants have been in use since the 1960's and are considered to be the gold standard for effectiveness in antidepressant therapy. They are not used as much as they used to be because newer antidepressants have been developed to have the same effect with fewer side effects. There are still many indications for tricyclic antidepressants today.

How tricyclic antidepressants work

The exact mechanism of action of tricyclics is unknown, but they probably normalize brain chemistry by inhibiting reuptake of serotonin, dopamine and norepinephrine. They also have histaminic and cholinergic effects.


Tricyclics are used for a number of neuropsychological conditions, such as:

Side effects

Most people who take tricyclic antidepressants experience some side effects. These are often mild and temporary, but sometimes are serious enough that you need to decrease the dose or stop taking the medication. The most common side effects are:


Tricyclic antidepressants interact with a number of other medications, especially those that:

Serotonin syndrome: Serotonin syndrome is a toxic reaction caused by excessive serotonergic action. This can happen with an overdose, but it is more likely when you are taking an antidepressant and you take another medication that affects serotonin. Mild serotonin toxicity can make you feel ill, sweaty, twitchy and anxious. Later you may experience tremors and muscle spasms or seizures, confusion, delirium, hallucinations, very high fever, rapid heart rate, high blood pressure, seizures and coma. Serotonin syndrome can result in death.

Make sure your doctor and pharmacist know about all medications that you take, including over the counter preparations, herbs and things you only take occasionally.


Tricyclic antidepressants should be used with caution if you have any of the following conditions:


One of the reasons tricyclics are not used as much anymore is because they have a narrow therapeutic window, making it easier to overdose on them. There is some evidence that there are more overdoses with tricyclics than other antidepressants, and there are definitely more fatalities. Only narcotics cause more fatal overdoses than tricyclic antidepressants. Fatalities are usually due to neurological or cardiovascular toxicity.


Abrupt withdrawal from tricyclic antidepressants can result in "discontinuation syndrome." The withdrawal symptoms can be very uncomfortable, and they include sweating, tremors, twitching, muscle spasms, seizures, anxiety, nervousness, confusion, agitation, restlessness, nightmares and sleep problems. Tricyclics must be tapered and withdrawn slowly to minimize these side effects.

Suicide precaution

There is an increased risk of suicide with depression and with antidepressant use, especially in the first few weeks of therapy. People who are beginning antidepressant therapy should be monitored closely for unusual thoughts or behaviors, anxiety, agitation, restlessness, hostility, aggression, deepening depression and thoughts of harming themselves or others.

Because tricyclic antidepressants have the potential for fatal overdose, people who are at risk for suicide should only have access to a few pills at a time.


Tricyclics can expose and trigger mania in untreated bipolar depression. The mania can be mild or severe, and can lead to paranoia and psychosis or rapid cycling. People with new depression should be screened for the possibility of bipolar disorder prior to treatment with antidepressants.