Antidepressants (ADs) are the first-line pharmacological treatment of Major Depressive Disorder, a common chronic-recurring disease causing disability worldwide. However, the effectiveness of AD treatment is modest. Only about 60-70% of cases are estimated to be in remission after time-consuming trial-and-error treatment attempts. Unfortunately, relapse rates are constantly high. At the same time, there is some evidence that severe depressions with melancholia/somatic syndrome are more responsive to AD treatment. More clarification of the mechanisms behind AD treatment response and lack thereof are urgently needed to improve treatment.

Discussion: When stratifying participants according to AD response, remitters and responders had significantly higher baseline suPAR levels than non-remitters and non-responders, respectively. Additionally, suPAR levels among AD responders decreased significantly more during treatment than among non-responders. To our knowledge, this is the first study demonstrating that AD treatment response is associated with increased serum suPAR levels which are reduced by remission. The absolute suPAR differences at baseline and changes during AD treatment were small (in the 0.2–0.5 ng/ml range), indicating that serum suPAR levels alone cannot predict AD treatment response. However, given the lack of reliable biomarkers for AD treatment response, suPAR’s association with treatment response is of interest.

Conclusion: In a study of MDD, serum suPAR levels were associated with neurovegetative symptoms but not with overall MDD severity. Higher suPAR levels at baseline were associated with subsequent response to AD treatment with escitalopram and nortriptyline. suPAR levels decreased during treatment only among responders and remitters.