When should phenelzine be started after stopping paroxetine?

Phenelzine is a monoamine oxidase inhibitor (MAOI), while paroxetine is a selective serotonin reuptake inhibitor (SSRI). When transitioning from an SSRI like paroxetine to an MAOI like phenelzine, it is crucial to allow sufficient time between stopping the SSRI and beginning the MAOI to avoid the risk of serotonin syndrome, a potentially life-threatening condition caused by excessive serotonergic activity in the nervous system.

Starting phenelzine four to six weeks after discontinuing paroxetine is appropriate because this timeframe allows for the complete washout of paroxetine from the body, reducing the risk of serotonin syndrome. Additionally, the half-life of paroxetine, typically around 24 hours, means that residual effects may still be present for several days after stopping the medication, making this cautious approach essential.

In contrast, beginning phenelzine immediately upon stopping paroxetine would pose a significant risk due to the overlap in serotonergic effects. Waiting only 48 hours would also be insufficient given the pharmacokinetics of paroxetine and the risks involved. Concurrently tapering paroxetine while starting phenelzine is inadvisable as it increases the possibility of serotonin syndrome due to overlapping effects and incomplete washout of par