Diagnosis The diagnosis of atypical depression is based on the criteria stated in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The DSM-5 defines atypical depression as a subtype of major depressive disorder that presents with "atypical features", characterized by: Mood reactivity (i.e., mood brightens in response to actual or potential positive events) At least two of the following: Significant weight gain or increase in appetite (hyperphagia); Hypersomnia (sleeping too much, as opposed to the insomnia present in melancholic depression); Leaden paralysis (i.e., heavy feeling resulting in difficulty moving the arms or legs); Long-standing pattern of interpersonal rejection sensitivity (not limited to episodes of mood disturbance) that results in significant social or occupational impairment. Criteria are not met for With Melancholic Features or With Catatonic Features during the same episode. Treatment Due to the differences in clinical presentation between atypical depression and melancholic depression, studies were conducted in the 1980s and 1990s to assess the therapeutic responsiveness of the available antidepressant pharmacotherapy in this subset of patients. 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. Bupropion, a norepinephrine reuptake inhibitor, may be uniquely suited to treat the atypical depression symptoms of lethargy and increased appetite in adults. Modafinil is sometimes used successfully as an off-label treatment option. Before the year 2000, monoamine oxidase inhibitors (MAOIs) were shown to be of superior efficacy compared to other antidepressants for the treatment of atypical depression, and were used as first-line treatment for this clinical presentation. This class of medication fell in popularity with the advent of the aforementioned selective agents, due to concerns of interaction with tyramine-rich foods (such as some aged cheese, certain types of wine, tap beer and fava beans) causing a hypertensive crisis 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. They are also generally better tolerated by many patients. 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. Tricyclic antidepressants (TCAs) were also used prior to the