Despite the availability of effective therapies, many patients with major depressive disorder (MDD) develop treatment-resistant depression (TRD).

To evaluate and compare prescribing patterns, contact with specialist services and treatment outcomes in patients with MDD and TRD.

This was a retrospective analysis of linked primary and secondary care National Health Service data in the north-west London Discover-NOW data-set. Eligible patients were adults who had diagnostic codes for depression and had been prescribed at least one antidepressant between 2015 and 2020.

A total of 110 406 patients were included, comprising 101 333 (92%) with MDD and 9073 (8%) with TRD. Patients with TRD had significantly higher risks of suicidal behaviour and comorbidities such as anxiety, asthma, and alcohol or substance misuse (all P < 0.0001). Citalopram, sertraline, fluoxetine and mirtazapine accounted for 83% of MDD and 71% of TRD prescriptions. Use of antidepressant switching (1% MDD, 7% TRD) and combination therapy (1%, 5%) was rare, whereas augmentation occurred more frequently in the TRD group (4%, 35%). Remission was recorded in 42 348 (42%) patients with MDD and 1188 (13%) with TRD (P < 0.0001), whereas relapse was seen in 20 970 (21%) and 4923 (54%), respectively (P < 0.0001). Mean times from diagnosis to first contact with mental health services were 38.9 (s.d. 33.6) months for MDD and 41.5 (s.d. 32.0) months for TRD (P < 0.0001).

There appears to be a considerable difference between treatment guidelines for depression and TRD and the reality of clinical practice. Long-term treatment with single antidepressants, poor remission, and high relapse rates among patients in primary care highlight the need to optimise treatment pathways and access to newer therapies.