Sertraline is a strong first-line selective serotonin reuptake inhibitor (SSRI) due to its broad FDA indications, flexible dosing, minimal drug interactions, and good overall tolerability.

Emsam is a transdermal monoamine oxidase inhibitor (MAOI) with fewer dietary restrictions at the 6 mg dose—and possibly even at higher doses. It tends to cause less weight gain and fewer sexual side effects than oral MAOIs.

Dr. Carlat and Dr. Puzantian have no financial relationships with companies related to this material.
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Mirtazapine causes sedation and weight gain, but unlike selective serotonin reuptake inhibitors (SSRIs), it rarely causes sexual or gastrointestinal side effects.

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.

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.