For Researchers

OPERA is the Netherlands Study of Optimal, PERsonal Antidepressant use

Over 1 million Dutch people currently get an antidepressant prescribed, with depression as the main indication. Despite the growing advocacy to reduce antidepressant use, the prescription rates are not declining. Research shows that maintenance treatment after depression remission can decrease relapse. However, long-term antidepressant use can also result in side effects, medicalization, reduced autonomy and may contrast with patients’ preferences. Current treatment guidelines state that antidepressant use should be continued until at least 6 months after remission of a first depressive episode. However, after this period, it is not clear whether, when and in whom discontinuation of antidepressants is effective. The OPERA project will provide evidence to address this uncertainty.

The aims of this study are to investigate:

  • the course and predictors of remission in depressed adults that recently started with antidepressants
  • in depressed patients who reach a 6-month stable depression remission after antidepressant treatment whether, when and in whom discontinuation of antidepressant medication is possible.

OPERA is coordinated by the departments of primary care and psychiatry of 5 University medical centers throughout the Netherlands (Amsterdam UMC location VUmc, UMC Groningen, Radboud UMC, Erasmus MC, Leiden UMC), and collaborates with general practitioners, psychiatrists, pharmacists, patient organizations and professional organizations.

OPERA consists of two parts. This first part is OPERA-monitor. In OPERA-monitor, 2000 patients with depression (18-75 year) that recently started with antidepressant medication (for this study citalopram or sertraline) will be invited to complete bi-monthly online questionnaires to monitor depressive symptoms. Participants for the OPERA-monitor cohort will be recruited in general practices, specialized mental health care facilities and pharmacies. From this cohort, we select persons who reach stable depression remission, and invite them to participate in the second part: the randomized discontinuation trial (OPERA-discontinuation). OPERA-discontinuation is a multi-center double-blind randomized clinical trial in which 400 patients will be randomly allocated to an early discontinuation (n=200) vs. later discontinuation group (n=200). In both groups, antidepressant dosages are tapered off during an 8-week period (an 8 week period for higher antidepressant daily doses and a 4 week period for regular to low daily antidepressant daily doses of citalopram and sertraline). Main outcome is sustained remission time of depression. Secondary outcomes include functioning, quality of life, severity of mood, anxiety and somatic (e.g. side-effects and withdrawal) symptoms and (cost) effectiveness. In addition, an external reference group of patients that reached stable remission in OPERA-monitor but refuse randomization (n=200) will be recruited and serve as care as usual group to evaluate internal validity and generalizability of the trial sample and study outcomes.

This study started in 2019 and will continue until 2025. OPERA is supported by The Netherlands Organization for Health Research and Development (ZonMW; grant number 848040001).

Contact: dr. Mariska Bot, project coordinator (