OBJECTIVES: Studies evaluating prices of antidepressant drugs before and after generic competition are lacking. This study assessed pricing strategies before and after generic entry of oral antidepressants drugs approved by the US Food and Drug Administration (FDA) in the period 1988-July 2015. METHODS: Regulatory information was collected from the FDA. Average wholesale prices (AWP) per unit at market entry were derived from the RedBook (Truven Health Analytics). The FDA recommended daily dose (DDD) for adult patients was obtained from the FDA-approved labels. Prices were converted to 2015 US dollars using the consumer price index. Descriptive statistics and trends analysis were performed in the analysis. RESULTS: The FDA approved 9 new oral antidepressants drugs in the study period that experienced generic competition. The median AWP per DDD increased over time. Entry prices of four new oral antidepressants were below the median prices of the already marketed oral antidepressants drugs. Trends in prices varied by drug: fluoxetine (entry year=1988; CPI-Adjusted 30-DDD AWP= $81.13; median prices of drugs already available in the market=NA), sertraline (1992; $95.82; 101.3%), paroxetine (1993; $93.67; 103.6%), bupropion SR (1996; $99.26;94.5%), venlafaxine (1997; $104.59; 96.7%), citalopram (1998; $99.76; 103.3%), escitalopram (2002; $106.67; 104.4%), bupropion XL (2003; $119.56; 90.7%), and duloxetine hydrochloride (2004; $128.33 ;94.7%). The AWP annual compound growth rate (CARG) for the drugs included in the study was significantly higher from approval to generic entry (median 4.5%; range 0.5%-8.1%) than from generic entry to July 2015 (median 8.2%; range -1.5%-28.0%). CONCLUSIONS: The prices of oral antidepressants drugs included in the study increased faster than the inflation rate during the study period. Entry prices of new oral antidepressants were in some cases often below the median prices of the drugs already marketed. The introduction of generic drug competitors into the market significantly accelerated the increase in prices of branded oral antidepressant drugs.