Background: Post-stroke depression (PSD) is the most frequent mental illness after stroke, affecting about 30% of stroke survivors and hampering rehabilitation outcome. While current guidelines recommend monitored antidepressant treatment (ADT) in PSD, the limited precision between the use and need of ADT in clinical practice remains underassessed and poorly understood. Methods: Depression according to DSM criteria and ADT was assessed in n = 294 stroke survivors from two German rehabilitation centers about one, six, and twelve months after stroke. At each measurement occasion, PSD and current use of ADT was assessed, leading to four subgroups: PSD (yes/no) and ADT (yes/no). Frequencies of ADT and PSD were examined and analyzed with regard to depression severity (minor/major). Intra-individual trajectories were used to assess the persistence in ADT over- and undertreatment from a longitudinal perspective. Results: After one, 6 and 12 months, 36.7%, 31.1% and 25.5% of stroke survivors fulfilled the criteria for depression. Across all measurement occasions, 53% of depressed stroke survivors did not receive ADT, while 12% of the non-depressed did. ADT between stroke survivors with major or minor depression differed at baseline but not thereafter. Between 15–40% of the depressed without ADT experienced persisting undertreatment and 25–50% the non-depressed with ADT had not fulfilled depression criteria at an earlier time point. Conclusions: Depression occurred in one in three stroke survivors. Among these, only one in two received ADT, irrespective of PSD severity after discharge. In contrast, one in eight stroke survivors without depressive disorder received ADT, about half of them in the absence of earlier PSD. In conclusion, we found evidence of both under- and overtreatment of PSD with ADT, which emphasizes the need for a more stringent implementation of current PSD guideline recommendations.