Fri July 25/2008

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Tricyclic Antidepressants (TCAs)

Tricyclic antidepressants are used in the acute treatment of episodes of depression. They produce a 55–70% response rate with a 10–20 day delay. They are useful in relapse prevention and are effective, but need an adequate dose and there may be problems with compliance. Tricyclic antidepressants are especially useful in patients who are agitated, retarded or have severe illness, but are less useful in elderly patients, patients with psychotic depression or the physically ill.

Tricyclic antidepressants should be avoided in younger patients, elderly patients, patients who drive, when drowsiness is unacceptable, when there is a risk of suicide attempts, when the therapeutic dose is not feasible, when there is preexisting cardiac disease or when long-term treatment is needed.

Tricyclic antidepressants are useful in cases where there has been a previous response to Tricyclic antidepressant treatment and when that previous treatment was well accepted. They are also useful when there is no risk of suicide attempts, when drowsiness is acceptable or preferable and when the patient is able to tolerate a recommended dose.

Tricyclic antidepressants are rapidly absorbed and widely distributed, while there is genetic variation in liver metabolism. Tertiary amines are generally more potent at blocking 5-HT uptake, while secondary amines are more potent at blocking NE uptake. Tertiary amines are metabolized to secondary amines (e.g. amitriptyline to nortriptyline and imipramine to desmethylimipramine). Discontinuation effects (cholinergic hyperfunction) can occur with tricyclic antidepressants.

Side Effects of Tricyclic Antidepressants

Anticholinergic: dry mouth, constipation, urinary retention, accomodation problems, glaucoma

Antihistaminergic: sedation

Alpha blockade: postural hypotension, sedation

Unknown mechanism:weight gain

Cardiotoxic: QT prolongation, ST elevation, AV block, membrane stabilization, arrythmias

Neurotoxic: delirium,movement disorders, convulsions

Problematic Interactions of Tricyclic Antidepressants

  • MAOIs (esp. clomipramine and tranylcypromine)
  • Antiepileptics, barbiturates decrease TCA levels
  • Cimetidine increases TCA levels
  • Warfarin action potentiated
  • Alcohol potentiates TCA sedation

Examples of Tricyclic Antidepressant Drugs

  • Amitryptiline
  • Amoxepine
  • Clomipramine
  • Dothiepin
  • Doxepin
  • Imipramine
  • Lofepramine
  • Nortriptyline
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