Cyproheptadine is a widely prescribed first-generation antihistamine, and due to its unique chemical structure, it has a popular off-label choice for a range of clinical conditions. Its efficacy is widely debated in the literature, but there are reports of hepatotoxicity as a rare adverse effect. Its benefits in migraine prophylaxis and appetite stimulation also underscore a highly overlapping clinical pathway that requires additional assessment and evaluation. The evidence suggests a baseline metabolic profile before initiation and assessment for co-occurring mental health conditions may improve overall response with evidence-based mental health interventions.