Tricyclic antidepressants

Other names: TCAs

What are Tricyclic antidepressants?

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.

The TCA cycle starts when the two-carbon molecule acetyl-CoA combines with four-carbon oxaloacetate to form citrate, a reaction catalyzed by citrate synthase (CS). Citrate is then converted to isocitrate by aconitase 2 (ACO2).

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.

TCAs are considered “first-generation” antidepressants, and SSRIs are considered “second-generation” antidepressants. They’re both effective in improving the symptoms of major depressive disorder. But healthcare providers more commonly prescribe SSRIs than TCAs because TCAs cause more significant adverse side effects.