Tricyclic Antidepressant Drugs - Information Sheet

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What is a tricyclic?

Tricyclics are a class of antidepressants named for the drugs’ molecular structure, which contains three rings of atoms.

Tricyclic Antidepressant Description:

Tricyclic antidepressants (TCAs) were first used in the 1950s. The first, imipramine, was developed in 1959 by Ciba-Geigy by accident while searching for a new antipsychotic. Initially used for treatment of psychotic disorders such as schizophrenia, it proved insufficient, but through clinical trials its antidepressant qualities became evident.

It was then extensively used as standard antidepressant and later served as a prototype for subsequent tricyclics for antidepressant and other uses.

Tricyclic Treatment and usage:

For many years, tricyclics were the first choice for treating clinical depression. Though still considered effective, they have been increasingly replaced by SSRIs and other newer medications. These newer drugs are believed to have fewer side effects and thought to be less likely to be used to commit suicide, as the treatment and lethal doses are farther apart than with tricyclic antidepressants.

Tricyclics are sometimes used to treat refractory depression that has not responded to standard SSRI therapy. They are not found to be addictive and are preferable to MAOIs. They have been shown effective in treating attention deficit hyperactivity disorder (ADHD) as well as being an effective analgesic (painkiller) and treatment for enuresis (bedwetting) in children over age 7.

Tricyclic Method of action:

TCAs’ exact mechanism of action is not well understood, but it is generally believed that TCAs work by blocking the re-uptake of norepinephrine, dopamine or serotonin by nerve cells. This pharmacologic effect occurs immediately, but often the patient’s symptoms do not respond for several weeks.

In analgesic use, the precise method of action is unknown, but the belief is that the drugs modulate opioids systems in the central nervous system (CNS) via an indirect serotonergic route.

Warnings or dangers associated with tricyclics:

Cyclic antidepressants produce alpha blocking, sedation, anticholinergic and quinidineliie effects. In the central and peripheral nervous systems, dopamine, norepinephrine and 5-hydroxytryptamine (5-HTP) are blocked. Ingestion of tricyclics is a serious problem in children and adolescents due to the availability of these in the home when prescribed for bed wetting and depression. TCA poisoning is a leading cause of death. The CNS and heart are the two main systems affected. Symptoms of TCA poisoning include disorientation, hallucinations, hypotension following hypertension, arrhythmias, seizures, coma and delirium.

Seizures normally resolve without treatment. Patients completely asymptomatic after 6 hours of observation may be discharged. Seizures and arrhythmias are the most important life threatening complications.

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Tricyclic Side effects:

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There are many side effects of TCAs related to anti-muscarinic properties, including blurred vision, constipation and dry mouth.

Patients should develop at least partial resistance to these effects within a couple of weeks. They may be beneficial; as they do indicate they drugs are having some effect. Other side effects may include anxiety, restlessness, urinary retention or difficulty urinating, weight gain, somnolence (drowsiness), muscle twitches, weakness, sweating, nausea, dizziness, cognitive and memory difficulties, increased heart rate, and rarely, irregular heart rhythms.

Since TCAs are extensively metabolized by the cytochrome P450 hepatic enzymes, while taking them it is important to avoid taking Cimetidine (Tagamet®) due to dangerous interactions that can lead to death.
If other side effects are noted, patients should consult their physician promptly.

Tricyclic Overdose and withdrawal:

Tricyclic overdose can lead to the involvement of many organ systems but mainly affects the heart and brain. In 1995, over 20,000 cases of TCA overdoses were reported in America, and of those, nearly 2% of patients died from the overdose. Most of the cases were intentional and not accidental.

TCA overdose can be controlled if the patient received emergency medical care before life-threatening symptoms occur. Symptoms of TCA overdose include lethargy, seizures, muscle twitching, agitation and jerking movements. Overdose can quite easily lead to coma and extremely low blood pressure with rapid heart rate. Life-threatening heart rhythm disturbances (ventricular tachycardia) can occur. TCAs can substantially decrease the heart’s ability to pump, leading to shock and death.

The treatment of this type of drug overdosage is generally similar to treatment for any poisoning. Once life-threatening emergencies are controlled, activated charcoal is routinely administered to prevent further absorption of the drug through the stomach. In addition, magnesium citrate can be given to speed up the removal of the drug from the gastrointestinal tract.

There is no real antidote for TCAs. Some doctors may try sodium bicarbonate to help block the drug’s effect on the heart and its electrical system.

Precautions with tricyclics in children and the elderly:

Research has indicated that tricyclics should be used with caution in the elderly, and that SSRIs and even MAOIs are more appropriately used in this age group than tricyclics. TCAs have a high side effect burden for the elderly and of particular worry are the anti-cholinergic side effects, considering the adverse effects on cognition. As well, postural hypotension is a common side effect of most tricyclics and this is of concern in the aged where falls can easily result in serious fractures, especially of the hip.

Clinical trial data has shown tricyclics, effective in treating adult depression, to have no real effect on adolescent/pediatric depression.

TCAs do not seem useful for treating prepubescent children, and have only moderate effect on adolescent depression. The drugs are effective in treating adults, but it is not clear whether they are safe or effective for children or adolescents, though the drug has proven effective in reducing night-time enuresis (bedwetting) in children. It should be noted, however, that there may be some adverse side effects with these medications that may or may not balance the risk with the need.

Types of tricyclics:

Common TCAs include Adapin (doxepin), Endep (amitriptyline), Norpramin (desipramine), Anafranil (clomipramine), Pamelor (nortryptyline), Sinequan (doxepin), Tofranil (imipramine), Vivactil (protriptyline), Elavil (amitriptyline), Pamelor (nortryptyline), Pertrofrane (desipramine) and Surmontil (trimipramine).

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