Selective serotonin reuptake inhibitors (SSRIs) commonly produce CNS depression in overdose, and may lead to serotonin syndrome Overdose is generally well tolerated with isolated SSRI ingestions Monoamine oxidase inhibitors are highly toxic, which may manifest as a result of food-drug interactions, drug-drug interactions, or MAOI overdose MAOI toxicity produces hypertension, hyperpyrexia, skeletal muscle rigidity, cardiac arrhythmias, myoclonus, seizures, rhabdomyolysis, and death Patients should be observed for at least 24 hours after concerning exposure Current Evidence Besides the tricyclic antidepressants, numerous mood elevating agents are prescribed The chemical structure of these agents and their profile of toxicity are diverse Major groupings of nontricyclic antidepressants include (i) the selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, fluoxetine, sertraline), (ii) the monoamine oxidase inhibitors (MAOIs; e.g., phenelzine, tranylcypromine), and (iii) other atypical antidepressants (e.g., bupropion, venlafaxine) SSRIs most commonly produce CNS depression in overdose Seizures may occur after large ingestions Life-threatening events from acute overdose are rare The serotonin syndrome, manifested by the triad of autonomic instability, neuromuscular changes (myoclonus, rigidity especially in the lower extremities), and altered mental status, is potentially lethal Citalopram and its enantiomer escitalopram cause both QTc interval prolongation and seizure activity that are thought to be dose related Bupropion, prescribed for both depression and in smoking-cessation programs, prevents reuptake of biogenic amines, is highly epileptogenic, and in large overdose, may cause QRS widening and lifethreatening cardiotoxicity Bupropion’s amphetamine nucleus accounts for the positive toxicology screens seen in patients with therapeutic use as well as in overdose settings The α-adrenergic antagonism of trazodone may lead to hypotension The MAOIs, although pharmacologically effective and therapeutically important, are some of the most toxic medications known Acute single overdoses of as little as mg/kg have been associated with a fatal outcome In addition, because of their irreversible inhibition of the enzyme monoamine oxidase, which is responsible for the degradation of most biogenic amines, MAOIs possess several important interactions with foods and other medications that can lead to