MAOIs are rarely used due to side effects, dietary restrictions, and numerous drug interactions; however, they remain valuable options for patients who do not tolerate or respond to other antidepressants.

Mirtazapine causes sedation and weight gain, but unlike selective serotonin reuptake inhibitors (SSRIs), it rarely causes sexual or gastrointestinal side effects.

Levomilnacipran is the active enantiomer of milnacipran (Savella), which is used for fibromyalgia in the US and for depression in other countries.

Ketamine is an intravenous (IV) agent that appears uniquely effective for patients who need an ultra-rapid antidepressant, such as patients who are acutely suicidal.

Less commonly used SSRI in the US due to sedation, twice-daily dosing, and interaction potential; FDA-approved for OCD but effective for other conditions as well.

Fluoxetine’s wide spectrum of indications and long track record make it a go-to SSRI, often favored for patients who may benefit from its activating profile. Its main drawback is a high potential for drug interactions.

Esketamine is the S-enantiomer of ketamine, given as a nasal spray.

A first-line selective serotonin reuptake inhibitor with strong tolerability and low interaction potential. Preferred over citalopram due to lower QT risk and broader FDA indications.

Duloxetine is the main serotonin/norepinephrine reuptake inhibitor alternative to venlafaxine/desvenlafaxine

May accelerate response in major depression and possibly offer a new option for treatment-resistant cases, but high cost and misuse potential limit its appeal.