Vilazodone is essentially an SSRI with added buspirone-like 5-HT1A partial agonist effects.

Venlafaxine may be slightly more effective than SSRIs, but side effects—especially blood pressure elevation and withdrawal symptoms—make it a second-line option.

TCAs are less commonly used today due to side effects and overdose risk but remain a valid option for patients who haven’t responded to other antidepressants.

Trazodone is most often prescribed at low doses (25–50 mg) as a sleep aid.

Thyroid augmentation—usually with T3 (Cytomel)—is sometimes used to treat fatigue and lethargy in depression. It is inexpensive, generally well tolerated, and may help, especially when paired with tricyclic antidepressants.

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.
Full Fact Sheet Editorial Information

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.