Introduction
This topic covers acute poisoning with antidepressants, the most common cause of serious drug overdose in adults, usually in deliberate self-harm. The main emphasis is on tricyclic antidepressants (TCAs), which are the most dangerous class, with shorter notes on SSRIs, SNRIs and MAO inhibitors. Key areas are the mechanisms of toxicity, the clinical syndromes, ECG-guided diagnosis and treatment.
Classes and mechanisms
Antidepressants are grouped by their action on monoamine neurotransmitters, mainly serotonin (5-HT) and noradrenaline. Their toxicity depends on how each class acts.
Tricyclic toxicokinetics
- TCAs are well absorbed orally, highly lipophilic, highly protein bound and have a large volume of distribution.
- Absorption can be erratic and delayed in overdose, because their anticholinergic action slows gut motility. Peak levels may come later than 6 hours.
- They are metabolised in the liver by CYP2D6, CYP2C19 and CYP1A2 to active metabolites, for example nortriptyline from amitriptyline and desipramine from imipramine. Elimination half-lives are long, often more than 24 hours, so toxicity can persist and recur.
- Because of high tissue binding, haemodialysis and haemoperfusion are not useful. Serum levels correlate poorly with severity, so the ECG is the main guide.