Population-based prevalence and pharmacotherapy sequences of treatment resistant depression in Germany

AI Summary

TRD occurred in 6.46% of moderate-to-severe depression cases and 17.49% of patients receiving continuous pharmacological treatment.
Guideline adherence was poor: 27.20% received combination or augmentation after first-line failure, rising to 38.35% in third-line therapy.
SSRIs predominated across all therapy lines with frequent cycling back to failed classes; ECT remained critically underused.

Eur Neuropsychopharmacol. 2026 May 12;110:112846. doi: 10.1016/j.euroneuro.2026.112846. Online ahead of print.

ABSTRACT

Treatment-resistant depression (TRD) represents a significant clinical challenge, yet data on its epidemiology and real-world therapy patterns remain limited. This study aimed to estimate TRD prevalence and analyze treatment patterns using claims data. This retrospective analysis used the German Analysis Database for Evaluation and Health Services Research (DADB), encompassing 2.47 million statutory health insurance beneficiaries in 2019. TRD was operationally defined as a claims-based proxy for patients with moderate-to-severe depression receiving at least three consecutive antidepressant prescriptions involving two or more changes of therapeutic strategy (switch, combination, augmentation, or ECT) using claims data. Among 360,344 individuals diagnosed with depressive episodes, 98,577 (27.36%) had moderate-to-severe depression and received pharmacological treatment. Of these, 12,054 patients met our operational TRD definition, representing 6.46% of all moderate/severe depression cases and 17.49% of those receiving continuous pharmacological treatment. Treatment patterns revealed suboptimal guideline adherence: only 27.20% of patients received combination or augmentation therapy after failure of first-line therapies, and 38.35% in third-line treatment. SSRIs dominated across all therapy lines, with frequent class-level cycling back to previously failed medication groups. ECT remained critically underused. This study provides the first large-scale, real-world evidence on epidemiology and treatment patterns of TRD in Germany. TRD affects a substantial proportion of patients with moderate-to-severe depression. As first large-scale, real-world evidence on TRD in Germany, these findings highlight urgent needs for improved clinical decision-making and better access to specialized care to address the substantial burden and suboptimal treatment trajectories of TRD in Germany.

PMID:42119282 | DOI:10.1016/j.euroneuro.2026.112846

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