What is a significant concern when combining SSRIs with MAOIs?

Combining selective serotonin reuptake inhibitors (SSRIs) with monoamine oxidase inhibitors (MAOIs) presents a significant concern due to the risk of serotonin syndrome. Serotonin syndrome is a potentially life-threatening condition that occurs when there is an excess of serotonin in the brain. This can lead to a cluster of symptoms including confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, and in severe cases, it can be fatal.

SSRIs increase serotonin levels by inhibiting its reuptake in the brain, while MAOIs block the enzyme that breaks down serotonin. When taken together, the combined effects can lead to dangerously high serotonin levels, triggering serotonin syndrome. Due to this significant risk, healthcare providers generally recommend a washout period between discontinuing an MAOI and starting an SSRI to prevent this severe interaction.

While other options such as increased risk of weight gain, increased sedation, and serious allergic reactions can be concerns with SSRI or MAOI use, they are not as acutely dangerous or as well-established in relation to drug interactions as serotonin syndrome. Thus, the risk of serotonin syndrome stands out as the primary and most critical concern when these medications are combined.