Introduction

An atypical antidepressant is any antidepressant medication that acts in a manner that is different from that of most other antidepressants.

Refer to Second-Generation Antidepressant, Tricyclic Antidepressant, and Tetracyclic Antidepressant.

Background

Atypical antidepressants include agomelatine, bupropion, mianserin, mirtazapine, nefazodone, opipramol, tianeptine, and trazodone. The agents vilazodone and vortioxetine are partly atypical. Typical antidepressants include the SSRIs, SNRIs, TCAs, and MAOIs, which act mainly by increasing the levels of the monoamine neurotransmitters serotonin and/or norepinephrine. Among TCAs, trimipramine is an atypical agent in that it appears not to do this. In August 2020, Esketamine (JNJ-54135419) was approved by the US Food and Drug Administration (FDA) for the treatment for treatment-resistant depression with the added indication for the short-term treatment of suicidal thoughts.

Buprenorphine/Samidorphan (ALKS-5461) is an antidepressant with a novel mechanism of action which is under development and is considered an atypical antidepressant. They act faster than available antidepressants.