Tricyclic Antidepressants


Category: Medical Options

What is it?

Tricyclic antidepressants (TCAs) are a class of antidepressant drugs first used in the 1950s. For many years TCAs were the first choice for pharmacological treatment of depression, and were among the first drugs used for PTSD patients. They are used for a variety of other conditions including neuropathic pain and bed wetting. TCAs have been increasingly replaced by SSRIs and other newer drugs which are thought to have fewer side effects.

There are several TCAs available which each have slightly different chemical makeup and effect. Tricyclic medications include:

  • Amitriptyline (trade names Elavil, Endep, Tryptanol, Trepiline, Amyzol)
  • Amoxapine (trade names Asendin, Asendis, Defanyl, Demolox, Moxadil)
  • Clomipramine (trade name Anafranil)
  • Desipramine (trade name Norpramin, Pertofrane)
  • Dosulepin hydrochloride (trade names Prothiaden, Thaden)
  • Doxepin (trade names Adapin, Sinequan)
  • Imipramine (trade names Tofranil, Janimine)
  • Iprindole
  • Lofepramine (trade name Gamanil)
  • Nortriptyline (trade names Aventyl, Pamelor, Noritren)
  • Opipramol (trade names Opipramol-neuraxpharm, Insidon)
  • Protriptyline (trade names Vivactil, Rhotrimine)
  • Trimipramine (trade name Surmontil)

How does it work?

In the brain, messages are passed between nerve cells via a synapse, a small gap between the cells. Naturally occurring chemicals, known as neuro-transmitters (of which norepinephrine and serotonin are two), allow the messages to pass across that gap. It is believed that incorrect levels of neuro-transmitters in some people lead to symptoms such as depression. The exact mechanism of action is not well understood, however it is thought that TCAs improve the level of norepinephrine and serotonin neuro-transmitters available and thus help to normalise brain function.

Is it effective?

A large body of evidence exists on the use of TCAs to treat depression and has found that TCAs are effective in reducing symptoms of depression but that their side-effects are not well tolerated by many patients. There is very little research evidence regarding the use of TCA medications for the treatment of PTSD symptoms and none which show that TCAs are effective for this condition.

Are there any disadvantages?

Side effects from TCA usage are not uncommon and include drowsiness, anxiety, restlessness, cognitive difficulties, dizziness, nausea and dry mouth. Other side effects are possible and health practitioners should be made aware of any changes.

Where do you get it?

Tricyclic antidepressants can only be prescribed by registered health practitioners.

What are the evidence limitations?

The evidence base for tricyclic antidepressant use in PTSD is poor. Methods of diagnosing PTSD were not reported in the review literature. Therefore interpreting this evidence should be undertaken with caution.


Based on current limited evidence tricyclic antidepressants cannot be recommended for the routine treatment of PTSD. It is important that any drug treatment is provided by a registered health professional, with appropriate assessment carried out prior to treatment as well as ongoing monitoring during the course of treatment.

Key References

Bisson, JI 2007, ‘Pharmacological treatment of post-traumatic stress disorder’, Advances in Psychiatric Treatment, vol. 13, pp. 119–126.

Cooper, J, Carty, J & Creamer, M 2005, ‘Pharmacotherapy for posttraumatic stress disorder: empirical review and clinical recommendations’, Australian and New Zealand Journal of Psychiatry, vol. 39, pp. 674–682.

Guaiana, G, Barbui, C, Hotopf, M 2007, ‘Amitriptyline for depression. Cochrane Database of Systematic Reviews’, Issue 3. Art. No.: CD004186. DOI: 10.1002/14651858.CD004186.pub2

Ipser, J, Seedat, S & Stein DJ, 2006, ‘Pharmacotherapy for post traumatic stress disorder - a systematic review and meta-analysis’, South African Medical Journal, Vol. 96, no. 10, pp. 1088-96.

Schoenfeld, F, Marmar, C & Neylan, T 2004, ‘Current concepts in pharmacotherapy for posttraumatic stress disorder’, Psychiatric Services, vol. 55, pp. 519–531.

Stein, DJ, Ipser, JC & Seedat, S 2006,‘Pharmacotherapy for post traumatic stress disorder (PTSD)’ Cochrane Database of Systematic Reviews 2006, Issue 1. Art. No.: CD002795.
DOI: 10.1002/14651858.CD002795.pub2.

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