Courses of treatment and risk factors for treatment-resistant depression in Finnish primary and special healthcare: A nationwide cohort study

Investigate incidence, risk factors and courses of treatment for treatment-resistant depression (TRD) in primary and special healthcare. All patients identified from nationwide registers, aged 16–65 years, diagnosed with depression in Finland during 2004–2016 were included. New antidepressant users were identified with six-month washout period and followed-up for two years to observe for presence of TRD, which was defined as initiation of a third trial after having failed two pharmacological treatment trials with adequate duration. During follow-up, 177,144 persons had their first registered antidepressant treated depression (mean age: 39.5, 62.5% women). Of them, 10.9% (N = 19,322) met TRD criteria. Among the TRD patients, most common first and second antidepressants trials were: SSRIs (44.6%), mirtazapine (19.0%) and SNRIs (16.5%). As the third treatment line, antidepressant monotherapy (44.2% of TRD patients) was most common, followed by a combination of ≥2 antidepressants (32.1%), antipsychotic or mood stabilizer augmentation and an antidepressant (15.8%), both combination of antidepressants and an augmentation with a mood stabilizer or antipsychotic (4.9%), antipsychotic or mood stabilizer monotherapy (2.7%) and ECT (0.3%). Of TRD patients, 16.5% (N = 3188) progressed to the fifth treatment line, in which the most common treatments were antidepressant monotherapy (33.4%), antidepressant combinations (27.5%) and augmentation (24.2%). Factors associated with higher risk of TRD included male gender, younger age, higher initial disease severity and hospitalization at initial onset of depression. Antidepressant monotherapies were still the most common fifth line of depression treatment. Severe depression, hospitalization due to depression, young age and male gender may predispose to TRD. •Up to 11% of depression patients may suffer from treatment resistance.•Pharmacological treatment augmentation is not aggressive enough in depression.•Antidepressant monotherapy is still the most common treatment up until the fifth line.