Quick Summary Zoloft (sertraline) and Lexapro (escitalopram) are two of the most widely prescribed SSRIs for anxiety and depression. Both work by increasing serotonin levels and show similar effectiveness in clinical trials. Prescription data shows Zoloft with about 39.9 million U.S. prescriptions in 2024 and Lexapro with about 30.8 million, reflecting their strong use and reliability. Zoloft has broader FDA approvals , including panic disorder, PTSD, OCD, and social anxiety