Overdose - Clinical Pharmacology of Antidepressants

Overdose

Suicide attempts are a common and unfortunate consequence of major depression. The lifetime risk of completing suicide in patients previously hospitalized with MDD may be as high as 15%. Overdose is the most common method used in suicide attempts, and antidepressants, especially the TCAs, are frequently involved. Overdose can induce lethal arrhythmias, including ven-tricular tachycardia and fibrillation. In addition, blood pressure changes and anticholinergic effects including altered mental status and seizures are sometimes seen in TCA overdoses. A 1500 mg dose of imipramine or amitriptyline (less than 7 days’ supply at antidepressant doses) is enough to be lethal in many patients.

Toddlers taking 100 mg will likely show evidence of toxicity. Treatment typically involves cardiac monitoring, airway support, and gastric lavage. Sodium bicarbonate is often administered to uncouple the TCA from cardiac sodium channels.

An overdose with an MAOI can produce a variety of effects including autonomic instability, hyperadrenergic symptoms, psy-chotic symptoms, confusion, delirium, fever, and seizures. Management of MAOI overdoses usually involves cardiac moni-toring, vital signs support, and lavage.

Compared with TCAs and MAOIs, the other antidepressants are generally much safer in overdose. Fatalities with SSRI overdose alone are extremely uncommon. Similarly, SNRIs tend to be much safer in overdose than the TCAs. However, venlafaxine has been associated with some cardiac toxicity in overdose and appears to be less safe than SSRIs. Bupropion is associated with seizures in overdose, and mirtazapine may be associated with sedation, disori-entation, and tachycardia. With the newer agents, fatal overdoses often involve the combination of the antidepressant with other drugs, including alcohol. Management of overdose with the newer antidepressants usually involves emptying of gastric contents and vital sign support as the initial intervention.