Fill in the blank _______ antidepressants block voltage-sensitive sodium channels in the brain (top) and heart (bottom). In overdose, this action can lead to coma, seizures, arrhythmia, and even death.

A. Monoamine Oxidase Inhibitors: MAOIs work by inhibiting the enzyme monoamine oxidase, increasing levels of serotonin, norepinephrine, and dopamine. They do not block voltage-sensitive sodium channels and are not associated with sodium channel–mediated cardiotoxicity in overdose. B. Serotonin Antagonists and Reuptake Inhibitors: These agents primarily modulate serotonergic neurotransmission and do not significantly affect cardiac or neuronal sodium channels. Their overdose risks are usually related to serotonin syndrome rather than arrhythmias. C. Tricyclic: Tricyclic antidepressants block voltage-sensitive sodium channels in both the brain and heart. In overdose, this can lead to CNS depression (coma, seizures) and cardiac conduction abnormalities (arrhythmias), which can be life-threatening. D. Selective Serotonin Reuptake Inhibitors: SSRIs selectively inhibit serotonin reuptake without significant sodium channel blockade. While overdose can cause serotonin syndrome or mild CNS effects, they rarely produce the severe cardiotoxicity seen with TCAs.