Background: Guidelines recommend fluoxetine as a first-line medication for youths diagnosed with major depressive disorder (MDD). However, little is known about the long-term effectiveness of different antidepressants in juveniles in the real world. This study aimed to compare the effectiveness of antidepressants in youths with MDD.

Methods: Youths (<20 years old) with a diagnosis of MDD who were new users of antidepressants were selected from a nationwide population-based cohort in Taiwan between 1997 and 2013. We divided a total of 16,981 users (39.9% male; mean age: 16.6 years) into 10 different antidepressant groups (fluoxetine, sertraline, paroxetine, venlafaxine, citalopram, escitalopram, bupropion, fluvoxamine, mirtazapine and moclobemide). Regarding treatment outcomes (hospitalisation and medication discontinuation), Cox proportional hazards regression models were applied to estimate the hazards of such outcomes.

Results: Compared with the youths treated with fluoxetine, the bupropion-treated group demonstrated lower rates of hospitalisation and discontinuation. Mirtazapine-treated group demonstrated a higher hospitalisation risk mainly when administered for single depressive episodes. Furthermore, patients treated with sertraline and fluvoxamine had higher discontinuation rates. Among the younger teenage subgroups (< 16 years), significantly higher rates of discontinuation were observed in those treated with sertraline, escitalopram and fluvoxamine. Among the older teenage subgroups (⩾ 16 years), bupropion was superior to fluoxetine in preventing hospitalisation and discontinuation.

Conclusion: We concluded that bupropion might surpass fluoxetine with regard to hospitalisation prevention and drug therapy maintenance among youths with MDD, while mirtazapine users demonstrated a higher hospitalisation risk. Our findings might serve as a reference for clinicians in future studies.