ANTIDEPRESSANT TOXICITY AND THE NEED FOR IDENTIFICATION AND CONCENTRATION MONITORING IN OVERDOSE

Antidepressant drugs are among the most commonly encountered causes of self-poisoning, These drugs include tricyclics, tetracyclics, bicycli cs and monocyclics, as well as monoamine oxidase (MAO) inhibitors and selective serotonin reuptake inhibitors (SSRIs). Of these, the tricycl ic antidepressants (TCAs) are generally more toxic in overdose, with m ajor toxicity usually manifesting within the first 6 hours after overd ose. Various studies indicate that patients at risk of toxicity from T CA overdose may be identified by neurological, cardiovascular and elec trocardiography status, together with a quantitative estimate of the p lasma drug concentration. While there are various methods available fo r such chemical estimations, the most satisfactory appears to be fluor escence polarisation immunoassay which gives rapid quantitative result s for a variety of TCAs. The selective MAO-A inhibitor antidepressants and the SSRIs are relatively nontoxic when taken alone. However, over doses of combinations of MAO inhibitors and either SSRIs or TCAs with serotonin reuptake blocking activity may result in a serotonin syndrom e with a severe or fatal outcome. Features of this syndrome include hy perpyrexia, disseminated intravascular coagulation, convulsions, coma and muscle rigidity, which may not develop until 6 to 12 hours after o verdose. While qualitative chemical identification of these drugs foll owing overdose is helpful in confirming the diagnosis, it is not manda tory. The increasing use of MAO-A inhibitors and SSRIs in the treatmen t of depression suggests that careful clinical observation is required when combination overdoses are suspected.