Depression impacts many individuals with autism spectrum disorder (ASD), carrying increased risk of functional impairment, hospitalization, and suicide. Prescribing medication to target depression in patients with ASD occurs despite limited available systematic data describing medication management of depression in this population. Drawing from a large clinical database describing the prescribing practices in patients with ASD, we identified 170 individuals with ASD (mean age 16.2±8.7 years old) who received medication targeting symptoms of depression. We report prescribing rates for specific drugs, drug treatment duration, and reasons for drug discontinuation when applicable. Sertraline, mirtazapine, and fluoxetine were the three most commonly prescribed medications to treat comorbid depression for this patient population. Among 247 drug starts, 121 (49%) drug treatments were continued at the final reviewed follow-up visit (average treatment duration of ±0.72 years). The most common reason for discontinuation across all medications prescribed was loss of or lack of effectiveness. This study raises concern that standard of care pharmacological treatments for depression in individuals with ASD may be less effective than in neurotypical populations. There remains a need to develop effective interventions for depression specifically tailored to the needs of individuals with ASD.