Phenelzine sulfate is primarily used as an antidepressant in the treatment of major depressive disorder, particularly for patients who do not respond to other types of antidepressants. It belongs to the class of monoamine oxidase inhibitors (MAOIs), which work by increasing the levels of certain chemicals in the brain that help improve mood and reduce anxiety.

This medication is also effective in managing atypical depression, characterized by symptoms such as increased appetite, excessive sleep, and sensitivity to rejection. Additionally, it has been used off-label to treat conditions like social anxiety disorder, panic disorder, and post-traumatic stress disorder (PTSD).

Due to its MAOI properties, phenelzine sulfate requires careful dietary restrictions to avoid interactions with tyramine-rich foods, which can lead to hypertensive crises. It is typically prescribed when other antidepressants have failed, given its potential side effects and the need for close monitoring during treatment.