Tricyclic antidepressants (often abbreviated to TCAs) are a group of medicines that all have a similar structure and all work in a similar way. They may be used for the treatment of other conditions, not only depression.

Experts are not sure exactly how TCAs work to relieve depression. Historically, it was believed to be due to an increase in levels of neurotransmitters in the brain, such as norepinephrine and serotonin, but this does not appear to be the case. Norepinephrine helps with attention and modulates emotional response. Serotonin is often referred to as the “feel good hormone”. It carries messages between brain cells and contributes to well-being, good mood, and appetite, as well as helping to regulate the body’s sleep-wake cycle and internal clock. TCAs may also block the actions of other neurotransmitters, such as acetylcholine and histamine.

Some TCAs affect these neurotransmitters more than others which explains why some TCAs work better for conditions other than depression, such as pain, or are more likely to cause side effects such as constipation, dry mouth, and sedation.

Antidepressants is the name given to all medicines that relieve the symptoms of depression. TCAs are just one of several classes of antidepressant. Other types include norepinephrine and dopamine reuptake inhibitors (NDRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), serotonin antagonist and reuptake inhibitor (SARIs),  tetracyclic antidepressants (TeCAs), and the miscellaneous antidepressants.

What are tricyclic antidepressants used for?

Tricyclic antidepressants were among the first antidepressants developed. They have largely been superseded by newer antidepressants that have less side effects, although they may still suit certain people or be effective when other antidepressants have been ineffective.

In addition to depression, TCAs may also be used to treat a range of other conditions, for example:

• Anxiety
• Bed-wetting
• Chronic nerve-related pain
• Migraine prevention
• Obsessive-compulsive disorder
• Panic attacks
• Post-traumatic stress disorder (PTSD).

Some reduction in symptoms may be noticed within one to two weeks; however, it may take six to eight weeks of treatment before the full effects are seen.

What are the differences between tricyclic antidepressants?

Although all TCAs are thought to act in the same way, with some slight variations in their effect on certain neurotransmitters, there are differences between individual TCAs with regards to how long they remain in the body, how they are metabolized, and their propensity for interactions with other medications, and their side effects.  For example, amitriptyline, doxepin, imipramine and trimipramine are more likely to cause sedation than nortriptyline and desipramine.

Amitriptyline, doxepin, and imipramine have been associated with more weight gain than some other TCAs; nortriptyline and desipramine may be better tolerated.

Some TCAs, such as amoxapine, are often listed as a TCA, but are in fact tetracyclic antidepressants.

Are tricyclic antidepressants safe?

When taken at the recommended dosage, tricyclic antidepressants are considered safe. However, they have been associated with a few severe side effects, some potentially fatal, such as:

• An increase in suicidal thoughts and behaviors, particularly in children and young adults under the age of 25 years. This is most likely to occur when starting therapy
• Serotonin syndrome – this is caused by excessive levels of serotonin in the body and is more likely to occur with higher dosages of SSRIs or when SSRIs are administered with other medications that also release serotonin. Symptoms include agitation, confusion, sweating, tremors, and a rapid heart rate
• The precipitation of a manic episode in people with undiagnosed bipolar disorder
• An increased risk of seizures in people with a history of seizures
• An increased risk of arrhythmias, heart attacks, stroke, and other cardiovascular effects, particularly in people with pre-existing heart disease
• The triggering of an angle closure attack in people with angle-closure glaucoma.

TCAs may also not be suitable for people with hyperthyroidism or receiving thyroid medications, or in those who use alcohol excessively.

What are the side effects of tricyclic antidepressants?

Some of the more commonly reported side effects with tricyclic antidepressants include:

• A drop-in blood pressure when moving from a sitting to standing position
• Blurred vision
• Constipation
• Disorientation or confusion
• Drowsiness
• Dry mouth
• Excessive sweating
• Increased or irregular heart beat
• Sexual dysfunction (such as reduced desire or erectile dysfunction)
• Tremor
• Urine retention
• Weight loss or weight gain.

For a complete list of side effects, please refer to the individual drug monographs.