Management of tricyclic antidepressant poisoning

Although a number of more recent substances with fewer side effects have become available for the treatment of depression, tricyclic antidepressants (TCA) are still commonly used. In addition, they are used for the treatment of neuropathic pain. The common basic mechanism of action is inhibition of reuptake of different neuromediators at the presynaptic terminal in both the central nervous system (CNS) and peripheral tissues, with the subsequent prolongation of their effect on the post-synaptic membrane. The earliest drug of this class was imipramine. Despite a phenothiazine-like structure it was not effective for the treatment of schizophrenia; quite unexpectedly, it improved depressive symptoms. Consequently, these substances and the derived TCAs became the first line of treatment for depression until the development of the selective serotonin reuptake inhibitors (SSRI). Although all TCAs share the same mechanisms of action, there are some differences in terms of the mediator involved. Whereas imipramine and some of its derivates, including amitriptyline and doxepin, block the reuptake of noradrenaline and serotonin at the presynaptic terminals, clomipramine has a more selective action on serotonin. After oral administration, TCAs are promptly absorbed and achieve peak blood concentrations in 2–6 hours; their absorption is reduced by antacids and drugs with anticholinergic effects. Being highly lipophilic, TCAs are rapidly taken up by the CNS. They are metabolized in the liver through oxidation and glucoronization. Although they undergo a relevant enterohepatic circulation, they are primarily eliminated through the kidney, with a half-life of 12–24 hours depending on the specific drug.