Tricyclic antidepressants (TCAs)

Tricyclic antidepressants (TCAs)

Tricyclic antidepressants (TCAs) are nonselective uptake inhibitors of noradrenaline and serotonin. They are absorbed rapidly after oral administration and they are extensively metabolised in the liver. The major metabolites of some are active compounds. Because of the long half-life these compounds can be given once-daily, usually in the evening. There are marked interindividual variations in steady-state plasma concentrations at the same dosage but plasma concentration measurements may be of value in some circumstances. Individual dosage adjustment is required to achieve optimum therapeutic effects.

TCAs show affinity for a wide range of postsynaptic receptors which correlates with their adverse effect potential . Common adverse effects include anticholinergic (dry mouth, blurred vision, constipation, urinary retention) and alpha-adrenergic (sedation, postural hypotension, sexual dysfunction, weight gain) effects and sedation. Compounds that are more sedating are amitriptyline, doxepin, dothiepin and trimipramine. Anticholinergic effects are most often seen with amitriptyline and clomipramine, and are less frequent with nortriptyline. Older persons are more susceptible to these effects, and to confusion and delirium and special caution should be observed. Alcohol may potentiate the sedative effects of TCAs and patients should be warned that this may affect their ability to drive and operate machinery safely. 

Patients satisfactorily maintained on TCAs should not be changed unnecessarily to newer drugs.

In children, TCAs can impair cardiac conduction and cause potentially fatal arrhythmias. In patients with pre-existing cardiac conduction defects, they may cause impairment of cardiac conduction. At higher doses, tricyclic antidepressants can prolong the QTc interval, which can lead to life-threatening arrhythmias. Cardiac toxicity is also the main cause of the high lethality in TCA overdose and all patients with significant overdose should have cardiac monitoring.

There is the possibility of a serotonin syndrome occurring when tricyclic antidepressants are combined with other serotonergic medications.

TCAs can lower the seizure threshold and should be used with caution in patients with epilepsy