Atypical depression is picky about its treatment. Doctors discovered decades ago that, unlike other forms of depression, it didn't respond to tricyclic antidepressants (TCAs) and electroconvulsive therapy (which has a bad rap but can be very helpful for people with treatment-resistant depression). Rather, atypical depression seemed to respond only to one type of drug: monoamine oxidase inhibitors, or MAOIs.
MAOIs work. Sometimes, they're the only thing that works for people whose depression has defied every other type of pill on the market. The problem is their side effects. They can cause very high blood pressure, leading to cardiac arrhythmia, brain hemorrhage and even heart failure. People on MAOIs have to follow a very strict diet absent of all foods containing an amino acid called tyramine, which includes, among many others, miso soup, sauerkraut, pepperoni, powdered protein supplements, pickled herring, cheese, Chianti, draft beer and vermouth (just to give you an idea of what to serve at a bizarre, tyramine-themed dinner party) [sources: Hall-Flavin; UPMC].
Because of the potential side effects, MAOIs have largely gone out of fashion and are no longer considered a first-line treatment. Luckily, newer antidepressants, such as selective serotonin-reuptake inhibitors (SSRIs) like fluoxetine (Prozac, Sarafem, Rapiflux, Selfemra) and sertraline (Zoloft), work for atypical depression.
If they don't cut it, however, MAOIs are still available. Phenelzine (Nardil) is the only one that's indicated specifically for atypical depression, and in studies, it's the drug that's shown the greatest effectiveness.
Treatment isn't all pills, either. An important double-blind, placebo-controlled (as in, the best kind) study from 1999 showed that cognitive therapy was just as effective as phenelzine in bringing relief to those with major depressive disorder and atypical depression [source: Jarrett]. (Cognitive therapy focuses on changing a person's distorted perceptions and creating new behavior patterns.) This is great news for someone resistant to taking medication, but psychotherapy should ideally be included in any treatment depression treatment plan, pills or no.