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01.12.2019 | Primary research | Ausgabe 1/2019 Open Access

Annals of General Psychiatry 1/2019

All-cause mortality in patients with treatment-resistant depression: a cohort study in the US population

Annals of General Psychiatry > Ausgabe 1/2019
Gang Li, Daniel Fife, Grace Wang, John J. Sheehan, Robert Bodén, Lena Brandt, Philip Brenner, Johan Reutfors, Allitia DiBernardo
Wichtige Hinweise

Supplementary information

Supplementary information accompanies this paper at https://​doi.​org/​10.​1186/​s12991-019-0248-0.

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Treatment-resistant depression (TRD) may represent a substantial proportion of major depressive disorder (MDD); however, the risk of mortality in TRD is still incompletely assessed.


Data were obtained from Optum Clinformatics™ Extended, a US claims database. Date of the first antidepressant (AD) dispensing was designated as the index date for study entry and 6 months prior to that was considered the baseline period. Patients with MDD aged ≥ 18 years, index date between January 1, 2008 and September 30, 2015, no AD claims during baseline, and continuous enrollment in the database during baseline were included. Patients who started a third AD regimen after two regimens of appropriate duration were included in the TRD cohort. All-cause mortality was compared between patients with TRD and non-TRD MDD using a proportional hazards model and Kaplan–Meier estimate with TRD status being treated as a time-varying covariate. The model was adjusted for study year, age, gender, depression diagnosis, substance use disorder, psychiatric comorbidities, and Charlson comorbidity index.


Out of 355,942 patients with MDD, 34,176 (9.6%) met the criterion for TRD. TRD was associated with a significantly higher mortality compared with non-TRD MDD (adjusted HR: 1.29; 95% CI 1.22–1.38; p < 0.0001). Survival time was significantly shorter in the TRD cohort compared with the non-TRD MDD cohort (p < 0.0001).


Patients with TRD had a higher all-cause mortality compared with non-TRD MDD patients.
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