TEMPO

Research project

Trial Examining Methods for Antidepressant Discontinuation

TEMPO (Trial Examining Methods For Antidepressant Discontinuation) is a multi-centered double-blind randomized controlled trial of two different discontinuation strategies of paroxetine and venlafaxine.

Annually, over 1 million Dutch people currently get an antidepressant prescribed, with depression as the main indication. Despite the growing advocacy to reduce antidepressant use, sometimes it appears difficult to actually stop antidepressants. Subjects might experience antidepressant discontinuation symptoms (ADS), also referred to as antidepressant withdrawal symptoms. It is currently unknown at which rate, which people will experience ADS and how to counter these symptoms to achieve successful cessation of antidepressants. Moreover, it might be difficult to distinguish ADS from a relapse of the original disorder. The limited studies to date either applied randomized tapering strategies over very short time-periods or were open studies (e.g. unblinded, non placebo-controlled), with inherent risks of selection bias, placebo and nocebo effects biasing the outcomes of those studies.

With the TEMPO project we aim to investigate:

• Do different discontinuation schemes result in differences in efficacy to actually stop the antidepressant?
• Who will experience ADS when an antidepressant is discontinued, what is the frequency of these ADS and how severe are the ADS?
• Do different discontinuation schemes result in different relapse/recurrence rates of depression during a 1 year follow-up?
• What is the best guidance patients can receive from a multidisciplinary team of psychiatrists, general practitioners, pharmacists to collaborate when stopping antidepressants?

TEMPO will recruit 200 patients (100 paroxetine users and 100 venlafaxine users), age 18-75 years, who are in stable remission from a (unipolar) depressive episode for at least 6 months and who are using paroxetine or venlafaxine for at least 6 months, while the patient and their physician want to discontinue the antidepressants. Discontinuation will take place over a period of 14-26 weeks with placebo-controlled tapering to ensure blinding of patients, physicians and researchers for the moment of discontinuation and discontinuation strategy.
Should participants be unable to successfully discontinue antidepressants during the period of placebo-controlled administration of paroxetine or venlafaxine, we will –if wanted- offer an alternative approach to help them discontinue the antidepressant and follow up this secondary attempt.

TEMPO is coordinated by the departments of primary care and psychiatry of the Amsterdam UMC, location VUmc and Radboud UMC and collaborates with general practitioners, psychiatrists, pharmacists, patient organizations and professional organizations. The study is broadly supported by the Dutch Association of Psychiatry, the College of General Practitioners, the Royal College of Pharmacists, Patient organisations and healthcare insurance companies.

This study started in March 2021, the start of active enrollment is planned for 2022. The study will continue until 2027. TEMPO is supported by The Netherlands Organization for Health Research and Development (ZonMW; grant number 80-86600-98-19026).