[4] Atypical depression has high comorbidity with anxiety disorders, carries more risk of suicidal behavior, and has distinct personality psychopathology and biological traits.

[11] The diagnosis of atypical depression is based on the criteria stated in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).

[12] Currently, antidepressants such as SSRIs, SNRIs, NRIs, and mirtazapine, are considered the best medications to treat atypical depression due to efficacy and fewer side effects than previous treatments.

[13] Bupropion, a norepinephrine–dopamine reuptake inhibitor (NDRI), may be uniquely suited to treat the atypical depression symptoms of lethargy and increased appetite in adults.

This class of medication fell in popularity with the advent of the aforementioned selective agents, due to concerns of interaction with tyramine-rich foods (e.g., some aged cheese, certain types of wine, tap beer and fava beans) causing a hypertensive crisis[15] and some – but not all – sympathomimetic drugs, as well as the risk of serotonin syndrome when concomitantly used with serotonin reuptake agents.

Despite these concerns, they are still used in treatment-resistant cases, when other options have been exhausted, and usually show greater rates of remission compared to previous pharmacotherapies.

[16] There are also newer selective and reversible MAOIs, such as moclobemide, which carry a much lower risk of tyramine potentiation and have fewer interactions with other drugs.

[12] One pilot study suggested that psychotherapy or cognitive behavioral therapy (CBT) may have equal efficacy to MAOIs for a subset of patients with atypical depression, although the sample size was small and statistical significance was not reached.

[2] Patients with atypical depression have shown to have higher rates of neglect and abuse in their childhood as well as alcohol and drug disorders in their family.

Some studies suggest that the older class of antidepressants, monoamine oxidase inhibitors (MAOIs), may be more effective at treating atypical depression.