The OPERA project: randomized placebo-controlled study of the short- and long term effects of  early versus late discontinuation of antidepressants

OPERA (the Netherlands study of Optimal, PERsonalized Antidepressant use) is a randomized placebo-controlled study of the short- and long term effects of  early versus late discontinuation of antidepressants (AD’s). This project started in 2019. OPERA consists of two parts: the OPERA-monitor and the OPERA-discontinuation study. In OPERA-monitor, 2.000 patients using antidepressants (either citalopram or sertraline) will be recruited in primary care and mental health care institutions. Patients will be monitored to study the course of depression over time, and predictors of remission. Of these 2.000, 400 patients who achieve a stable remission will be randomly allocated to early versus late tapering of ADs, andfollowed during their process of discontinuation in the OPERA-discontinuation study. The trial is complemented with a non-randomized ‘external reference’ patient group (n=200) to evaluate internal validity and generalizability of the trial sample and study outcomes.

Over 1 million Dutch persons currently get an antidepressant (AD) prescribed, with depression as the main indication. Despite growing advocacy to reduce AD use, prescriptions are not declining. Long-term AD use can result in disturbing side effects (such as sexual dysfunction, emotional flattening, dry mouth, head ache, and weight gain), medicalization, and reduced autonomy. Furthermore, not all patients prefer to use ADs for a long time which can lead to non-compliance and risky (often non-supervised and non-tapered) discontinuation.

Currently, there are many uncertainties concerning the optimal AD discontinuation policy. Research shows that AD maintenance treatment after depression remission can decrease relapse. Current treatment guidelines state that AD 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 ADs is effective.  To fill this clinical knowledge gap, OPERA investigates whether, when and in whom tapered discontinuation of AD is possible in depressed patients that have reached a stable depression remission during optimal AD treatment.

OPERA will be carried out by a large consortium existing of the general practice and psychiatry departments of Amsterdam UMC, Leiden UMC, UMC Groningen, Erasmus MC and Radboud UMC, supported by health professionals and patient organizations. Brenda Penninx is the P.I. of OPERA. Mariska Bot is the local project leader for the department of psychiatry of Amsterdam UMC. The OPERA project is funded by the ZonMw program Goed Gebruik Geneesmiddelen.

Contact information

Mariska Bot or Karlijn Joling, project managers OPERA

Email us: opera@vumc.nl