29 October 2020

How do you reduce the use of antidepressants safely and without major problems? That is a question that concerns many patients and physicians. Radboudumc and Amsterdam UMC in the Netherlands are going to investigate this with a ZonMw grant of 1.5 million euros. This TAPER-AD study is the first robust study worldwide to directly compare two tapering methods.

Researcher and psychiatrist Christiaan Vinkers, Amsterdam UMC: “Many patients stop taking their antidepressant at some point. For example because they have been going well for some time or because they suffer from side effects”. Co-researcher and psychiatrist Eric Ruhé, Radboudumc adds: “Hardly any research has been done on how to discontinue antidepressants best in order to stop. That is actually quite strange when you consider how many people use these medications."

More than a million

Worldwide millions of people are prescribed antidepressants. Alone in the Netherlands, more than a million people are prescribed antidepressants every year. Not everyone has to take these drugs for a long time. A large proportion of patients therefore stop taking antidepressants at some point. For some of the patients who want to taper, this is not without problems. Especially at lower doses, patients develop discontinuation symptoms that might resemble a relapse or recurrence of depression.

Lack of knowledge about the best way to discontinue antidepressants

“These tapering problems are common with the commonly used antidepressants paroxetine and venlafaxine,” says Vinkers. “However, doctors and patients lack the knowledge to taper down properly and patients the idea of stopping their medication may increase insecurity and fear of symptomatic deterioration ” Through a multidisciplinary document recently published in the Netherlands and internationally, there are recommendations for tapering off antidepressants, but real scientific support is lacking so far.

Two strategies, two drugs

The researchers are now, in collaboration with - among others - the Dutch patient-organization for depression, the Depression Association, going to look at the best way to taper down. Ruhé: “We compare a usual and slower tapering strategy for paroxetine and venlafaxine. These two commonly used antidepressants are the most difficult to taper off. For example, we are investigating whether one way of tapering off causes more discontinuation symptoms than another. But also whether it is more likely that with one of the two tapering strategies the depression will return in the longer term. We also look at effectiveness, quality of life and cost-effectiveness. This knowledge will be of great help to patients, physicians and policymakers.”

Big knowledge gap

The Dutch Depression Association is pleased with this study. They are also amazed that so remarkably little is known about the withdrawal of antidepressants. Spokesperson Bart Groeneweg: “More knowledge is really needed about the best way to phase out. We know that it is now problematic for a group of patients. They report complaints such as dizziness, nausea, lethargy, tremor, anorexia and headache. This research can fill a large gap in knowledge about discontinuation of antidepressants. Many patients will be able to benefit from this.” Also insurance companies in the Netherlands are pleased with this unique study. This will allow doctors and patients to jointly choose the right care when discontinuing antidepressants on the basis of scientific research, they say.

Broad collaboration

The TAPER-AD study uses the infrastructure that the national OPERA study has already built up. OPERA examines who can stop antidepressants and when, while TAPER-AD looks at how to stop. Three other universities (UMC Groningen, UMC Leiden and Erasmus MC) are also involved in TAPER-AD through the collaboration with OPERA. In addition, the Dutch College of General Practioners (NHG), the Dutch Association of Psychiatry (NVvP), the Royal Dutch College of Pharmacy (KNMP) and The Dutch Knowledge Center for Anxiety and Depression (NedKAD) support the research.

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