Objective: To investigate the demographic and clinical factors associated with antidepressant use for depressive disorder in a psychiatric healthcare setting using a retrospective cohort study design. Setting: Data were extracted from a de-identified data resource sourced from the electronic health records of a London mental health service. Relative risk ratios (RRRs) were obtained from multinomial logistic regression analysis to ascertain the probability of receiving common antidepressant treatments relative to sertraline. Participants: Patients were included if they received mental healthcare and a diagnosis of depression with antidepressant treatment between March and August 2015 and exposures were measured over the preceding 12 months. Results: Older age was associated with increased use of all antidepressants compared with sertraline, except for negative associations with fluoxetine (RRR 0.98; 95% CI 0.96 to 0.98) and a combination of two selective serotonin reuptake inhibitors (SSRIs) (0.98; 95% CI 0.96 to 0.99), and no significant association with escitalopram. Male gender was associated with increased use of mirtazapine compared with sertraline (2.57; 95% CI 1.85 to 3.57). Previous antidepressant, antipsychotic and mood stabiliser use were associated with newer antidepressant use (ie, selective norepinephrine reuptake inhibitors, mirtazapine or a combination of both), while affective symptoms were associated with reduced use of citalopram (0.58; 95% CI 0.27 to 0.83) and fluoxetine (0.42; 95% CI 0.22 to 0.72) and somatic symptoms were associated with increased use of mirtazapine (1.60; 95% CI 1.00 to 2.75) relative to sertraline. In patients older than 25 years, past benzodiazepine use was associated with a combination of SSRIs (2.97; 95% CI 1.32 to 6.68), mirtazapine (1.94; 95% CI 1.20 to 3.16) and venlafaxine (1.87; 95% CI 1.04 to 3.34), while past suicide attempts were associated with increased use of fluoxetine (2.06; 95% CI 1.10 to 3.87) relative to sertraline. Conclusion: There were several factors associated with different antidepressant receipt in psychiatric healthcare. In patients aged >25, those on fluoxetine were more likely to have past suicide attempt, while past use of antidepressant and non-antidepressant use was also associated with use of new generation antidepressants, potentially reflecting perceived treatment resistance.