Tricyclic Antidepressants – How Do They Work and What are the Side-effects?

Tricyclic Antidepressants

Tricyclic antidepressants (TCAs) were discovered by accident. In the 50s a Swiss physician prescribed imipramine. People, who were taking it, experienced good mood. Later scientists realized that imipramine can beat depression. It was named – tricyclic – because of its structure, which is based on a triple carbon bond. This group of drugs includes imipramine, nortriptyline and amiltriptilin.

Tricyclic AntidepressantsTricyclic antidepressants increase the amount and boost the transfer of both norepinephrine and serotonin between neurons of the brain. These antidepressants, along with neurotransmitters, also affect other systems (cholinergic, histaminergic, muscarinic, and others.). Earlier the use of tricyclic antidepressants was wide enough: endogenous, psychogenic, somatogenic depression, depression with diseases of the central nervous system. In addition to the therapy of depressive phases (bouts), there were attempts of continuous use of these medications in the treatment of chronic depression (dysthymia), as well as a means of prevention of recurrent attacks of the disease.

A number of scientists consider tricyclic antidepressants to be appropriate for treatment of severe depressive conditions with high risk of suicide and depression that is resistant to other antidepressants.

Tricyclic Antidepressants clomipramineIn the 80-s of the twentieth century it was thought that while taking tricyclic antidepressants, such as clomipramine or amitriptyline, improvement can be noticed in 60% of cases of previously untreated patients with endogenous depression. In the practice of the psychiatrist the difference in the clinical picture of depression is the foundation for the choice of an antidepressant. For example, it was believed that the effect of imipramine is the best choice for the motor and intellectual retardation, and the effect of amitriptyline is better for anxiety. At the same time it was proved that while taking tricyclic antidepressants 30% of patients have to stop treatment due to the severity of side effects, whereas in the case of the prescription of new drugs only 15% of patients have to stop taking medications.

Tricyclic antidepressants are available only with a physician’s prescription and are sold in tablet, capsule, liquid, and injectable forms.

How do tricyclic antidepressants work?

Tricyclic antidepressants block the reuptake of serotonin and norepinephrine, brain chemicals that are related to mood. By blocking the reabsorption of these chemicals, tricyclic antidepressants enhance the levels of serotonin and norepinephrine. This helps improve mood.

Tricyclic antidepressants also affect the action of acetylcholine, a brain chemical that affects muscle movement and the automatic (also known as autonomic) functions of the body, including secretions and digestion. Tricyclic antidepressants block the effects of histamine, too. Neither of these actions is believed to affect depression; however, they explain some of the more troublesome side effects associated with tricyclic antidepressants.

The role these chemicals have in causing, or treating, depression is still unclear.

How long do tricyclic antidepressants take to work?

Tricyclic Antidepressants medicationTCAs can take some period of time to have an effect so you may not feel better immediately when you start taking tricyclic antidepressants. You may experience an effect on your mood within two weeks, however, the full benefits of treatment with TCAs may not occur for a further two to four weeks. It is important to keep taking meds even if you think it is not working at first. If you notice your depression has got worse, or if you have any distressing thoughts or feelings in these first few weeks, then you should speak with your doctor.

Side effects of tricyclic antidepressants

Side effects often limit the possibility to take adequate doses. Thus, up to 80% of patients receive insufficient treatment. In addition, an acute phase of depression may become a chronic depression because of treatment with low doses. To stop taking tricyclic antidepressants suddenly can lead to anxiety, restlessness, insomnia, autonomic disorders, the occurrence of muscle pain, vomiting.
The most common side effects of tricyclic antidepressants include:

  • apathy and sleepiness (go away after the first week of taking antidepressants);
  • dry mouth – 85% of patients has it; in order to get rid of this unpleasant symptom it is recommended to rinse your mouth frequently, to sip, to eat various sugar-free candies);
  • dry eye and/or blurred vision;
  • Tricyclic Antidepressants dizzinessconstipation – 30% experiences it, balanced diet is advisable, in case of its inefficiency – laxatives;
  • increased sweating (25%);
  • dizziness – 20%, in this case it is recommended to lie for an hour after taking meds;
  • increased heart rate;
  • decreased potency;
  • weakness;
  • nausea;
  • problems with urination;
  • drowsiness;
  • weight gain (it is recommended to go on a diet).

It is important to mention that if a dose is increased gradually then side effects occur less frequently.

What are the available tricyclic antidepressants in the U.S.?

The following are approved TCAs in the U.S.:

  • amitriptyline (Elavil),
  • clomipramine (Anafranil),
  • doxepin (Sinequan),
  • imipramine (Tofranil),
  • trimipramine (Surmontil),
  • amoxapine (Amoxapine Tablets),
  • desipramine (Norpramin),
  • nortriptyline (Pamelor, Aventyl), and
  • protriptyline (Vivactil).









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