OBJECTIVE: To explore the temporal dynamic of antidepressant and antipsychotic co-prescribing in real-life conditions. METHODS: The study was performed using reimbursement data from the French Insurance Healthcare system in a cohort of 118,454 persons with at least one dispensing of antidepressants and/or antipsychotics over the period 2006-2016. Latent class analyses were used to identify homogeneous groups of persons following similar multi-trajectories of antidepressant and/or antipsychotic dispensing. Multivariate polynomial logistic regression models were used to explore the characteristics independently associated with distinct trajectories. RESULTS: Five multi-trajectories of antidepressant and/or antipsychotic dispensing were identified: more than half of the sample (58%) had very low antidepressant and antipsychotic use; two groups had chronic (12%) or decreasing (11%) antidepressant use with very low antipsychotic use; two groups used both antidepressants and antipsychotics simultaneously either in an increasing (12%) or chronic (7%) way. Persons with chronic antidepressant-antipsychotic use presented with markers of poor social and mental health conditions. CONCLUSIONS: Most persons using antipsychotics over the follow-up also used antidepressants over the same period. The benefit/risk ratio of these prescribing practices should be further explored as the long-term efficacy of antidepressant-antipsychotic polypharmacy is poorly documented, while this combination increases the risk of adverse effects. This article is protected by copyright. All rights reserved.< Réduire