Antidepressant Toxicity Research Articles

Tricyclic antidepressant poisoning. Management of arrhythmias.

Deaths from tricyclic antidepressant (TCA) overdose are usually due to arrhythmias and/or hypotension. Tricyclic antidepressant toxicity is due mainly to the quinidine-like actions of these drugs on cardiac tissues. Slowing of phase 0 depolarisation of the action potential results in slowing of conduction through the His-Purkinje system and myocardium. Slowed impulse conduction is responsible for QRS prolongation and atrioventricular block, and contributes to ventricular arrhythmias and hypotension. Therapies that improve conduction, e.g. hypertonic sodium bicarbonate, are useful in treating these toxic effects. Other mechanisms contributing to arrhythmias include abnormal repolarisation, impaired automaticity, cholinergic blockade and inhibition of neuronal catecholamine uptake. Toxicity may be worsened by acidaemia, hypotension or hyperthermia. Sinus tachycardia is due to the anticholinergic effects of the tricyclic antidepressants as well as blockade of neuronal catecholamine reuptake. Sinus tachycardia is generally well-tolerated and requires no therapy. Sinus tachycardia with QRS prolongation may be difficult to distinguish from ventricular tachycardia. Electrocardiograms obtained using oesophageal or atrial electrodes may be useful in determining the relationship of atrial and ventricular activity. Although QRS prolongation alone is not compromising, it is a marker for patients at highest risk of developing seizures, arrhythmias or hypotension. Ventricular tachycardia (monomorphic) is a consequence of impaired myocardial depolarisation and impulse conduction. Hypertonic sodium bicarbonate may partially correct impaired conduction and be of benefit in treating ventricular tachycardia. Since hypertonic sodium bicarbonate appears to act by increasing the extracellular sodium concentration as well as by increasing extracellular pH, hyperventilation may be less effective. Hypertonic sodium bicarbonate is of particular benefit in patients who are acidotic, since acidosis aggravates cardiac toxicity. However, administration of hypertonic sodium bicarbonate is beneficial even when blood pH is normal. Lignocaine (lidocaine) may be useful in treating ventricular tachycardia but should be administered cautiously to avoid precipitating seizures. Ventricular bradyarrhythmias are due to impaired automaticity or depressed atrioventricular conduction and can be treated by placement of a temporary pacemaker, or with a chronotropic agent, e.g. isoprenaline (isoproterenol), with or without concomitant vasoconstrictors.(ABSTRACT TRUNCATED AT 400 WORDS)

Prescribing Practices and Knowledge of Tricyclic Antidepressants Among Physicians Caring for Children

We did not find any significant difference between pediatricians and family practitioners with regard to their knowledge of the potentially serious toxicities of the tricyclic antidepressants. One of this group, imipramine, is in widespread use for the treatment of enuresis. A large proportion of the pediatricians (40%) and family practitioners (50%) surveyed use this drug as the first or only approach to enuresis. It is disquieting to discover that, of those physicians choosing to use the drug, one third appear to be unaware of its toxic potential. Other effective treatment modes are available, and it is to be hoped that more physicians will explore them before turning to the more hazardous pharmacologic alternatives. Pediatricians, although not more knowledgeable than family practitioners, exhibited more careful prescribing practices.

Tricyclic Antidepressant Cardiotoxicity

To the Editor.— The article by Robinson and Barker (236:2089, 1976) regarding tricyclic antidepressant (TCA) toxicity has its good and bad features. The good is that the Food and Drug Administration and its advisors are continuing to present their data and views in a general scientific forum. The bad is that this particular article, while providing very useful and timely information, could also mislead the physician on important scientific and regulatory points. In the scientific area, the authors state that unfortunately, plasma TCA levels are too variable from patient to patient to be of value in defining a safe therapeutic range. Evidence suggests that, in fact, minimum and maximum therapeutic plasma levels for TCAs do exist and are useful guides to therapy.1,2 In defining resistant cases of depression as adults failing to respond to 200 mg imipramine hydrochloride daily, the authors ignore evidence that at least 30% of patients

Potentiation of Tricyclic Antidepressant Toxicity by Physostigmine in Mice

Subtoxic doses of physostigmine have been found to potentiate the convulsive toxicity and lethality of amitriptyline and imipramine in CD1 and B6A mice. Neostigmine failed to potentiate the toxicity and lethality of imipramine. Physostigmine tended to protect mice against atropine-induced lethality. These data suggest the site of toxicity of this drug-drug interaction between the tricyclic antidepressants and physostigmine may be occurring in the CNS through a mechanism distinct from the anticholinergic actions of the antidepressants.