Weaning off antidepressants? A fierce battle hampers much-needed research into it

Read also: ‘After a crisis, patients have to reduce their psychotropic drugs to a minimum dose’

The core of the problem: there is still little scientific research into the best ways to taper. To provide some direction, a advice for weaning off all kinds of antidepressants. It complements it earlier advice from 2018 for the two most commonly used types of antidepressants (SSRIs and SNRIs, both serotonin reuptake inhibitors). The latest document deals with the remaining antidepressants, including tricyclic antidepressants (TCAs) and MAOIs. Both documents have been drawn up on the basis of the knowledge and experiences of the professional associations of psychiatrists, general practitioners, pharmacists and members of the patient platform MIND and the Depression Association.

The 2018 document has already considerably improved the possibilities for tapering off some antidepressants. A number of manufacturers have since been supplying tablets in different dosages for tapering purposes. But for some patients, the tapering has to be done in smaller steps, sometimes one or even a quarter of a milligram. Manufacturers do not supply such low doses, so pharmacists have to prepare these pills themselves or order them from colleagues who can make them. On the website of the pharmacist organization KNMP it says which ‘large preparers’ do that. These preparations are reimbursed by health insurers and are used in two phase-out outpatient clinics in Amsterdam and Noord-Holland-Noord, which have recently been opened.

Sexual problems

There have also been so-called tapering strips since 2013: strips of dozens of bags of pills with a 5 percent lower dose of the drug for each day than the day before (tapering comes from the English word for tapering, to taper). There is only one pharmacy in the Netherlands that makes them, the Rainbow Pharmacy in Bavel. Proponents are waging a fierce battle to get them reimbursed for those strips. Only few insurers reimburse them in full; they first want better scientific evidence that this fine-meshed reduction works better.

A quarter of a million people in the Netherlands use long-term antidepressants. These drugs often help against anxiety disorders and severe depression. But they also have long-term side effects, such as emotional blunting, sexual problems and weight gain. This can be a reason for patients to want to cut down or even stop altogether.

Anyone who notices that the treatment does not work, or that it works very well, can also decide to stop. The guideline is: you can stop after a first depressive episode if the symptoms have disappeared for six months, after a second episode after a year.

We don’t see the people who are doing well with tapering off

Eric Ruhe psychiatrist and epidemiologist

Simply stopping the medication can lead to withdrawal symptoms (the antidepressant discontinuation syndrome, or ADS). A patient then suffers from a flu-like feeling, sleeping problems, stomach or intestinal complaints, restlessness, dizziness or strange sensations. It is not known who will be affected, or how large that group is. “We don’t see the people who are doing well with the reduction. Estimates of the percentage of people who develop withdrawal symptoms are between 26 and 80 percent,” says Eric Ruhé, psychiatrist and epidemiologist at Radboud university medical center in Nijmegen, and one of the authors of both recommendations. “The risk appears to be greater for people who take antidepressants for many years.”

The tricky thing is: those withdrawal symptoms can also be mistaken for a relapse. “But we must be careful not to create fear of reduction,” says Ruhé. “English research shows that 50 percent of long-term users were able to successfully taper off.” The new document explains how you can tell the difference between the two. Ruhé: “Withdrawal symptoms usually occur within a week after switching to a lower dose, and disappear as soon as you go back to the previous dose. With complaints after a week or more, there is a greater chance that it is a relapse. Then you should consider restarting the treatment with the original dose.”

Ultimate solution

It is also not yet known for how many patients the reduction must be more gradual than usual, says Ruhé. That is why he and psychiatrist Christiaan Vinkers of the Amsterdam UMC started a major study, the Tempo study. It was set up according to the highest standard in drug research: a randomized, double-blind study. Participants are assigned to a group by lottery, patients and practitioners do not know who will receive which tapering schedule. The recruitment of 200 patients started at the beginning of this year – the participants are people who take long-term paroxetine or venlafaxine, two drugs that often cause withdrawal symptoms. Half will taper off in 16 weeks using a conventional strategy, the other half through more gradually tapering doses.

You would think that everyone involved would be eagerly awaiting the results of this study. But the advocates of tapering strips don’t. Psychiatrist Jim van Os, chairman of the Brain Division at UMC Utrecht, is conducting research into tapering strips in the User Research Center at UMC Utrecht, together with Peter Groot, researcher and expert by experience. He thinks it is “a totally unnecessary study”. For him, tapering strips offer the ultimate solution, and the question of whether they work has, in his view, already been answered in studies that he and Groot did. “More than 10,000 people have used these comics in the Netherlands. Our four studies show that tapering strips help 70 percent of long-term users who experienced withdrawal symptoms on previous attempts to stop. A resounding success!” says Van Os.

He was one of the founders of tapering medication, and I have a lot of respect for that

Christian Vinkers psychiatrist

But these studies have limitations. “The participants in these studies are always several hundred people who had ordered and used tapering strips, and who had returned an accompanying questionnaire. The fact that 70 percent of those were successfully reduced is very nice, but it says nothing about the large group that did not respond, and there is no control group, so there is an unknown placebo effect. The findings can therefore not simply be extrapolated to what is the best way to taper off for the hundreds of thousands of people who want to stop taking antidepressants every year,” says Ruhé. The advisory documents have been written for the entire group.

Van Os is also not satisfied with the latest advisory document. In a fierce letter submitted on May 21 Fidelity, which he drew up with Groot and Pauline Dinkelberg, chair of the Association for Afbouwmeditatie, he writes that it is full of ‘gratuitous open-door recommendations that GPs, psychiatrists and patients in practice cannot use’. They are upset that their tapering strips are not mentioned – although it does say that small dosage units via ‘magistral preparation’ (by a pharmacist) can be considered if severe withdrawal symptoms occur.

A pinprick

It is Groot who in 2013 addressed the use of the fine-meshed tapering strips for paroxetine and venlafaxine among psychiatrists in an opinion piece in the Journal of Psychiatry. “That article played an important role,” says Vinkers. “He was one of the founders of tapering medication, I have a lot of respect for that.” Around that time, Groot finds Paul Harder, the pharmacist of the Rainbow Pharmacy, willing to make the comics. All these years, the group of champions of tapering strips remains strongly intertwined. The User Research Center, where Peter Groot and Van Os conduct their research into the tapering strips, has been receiving donations from the Rainbow Pharmacy via the Friends of the UMC for years. With this, Van Os pays for Groot’s research appointment.

The tapering proponents go far in their fight. For example, Vinkers and Ruhé had to choose a different name for their studies. Vinkers: “Initially, the study was called Taper-ad, but that web domain name turned out to be claimed and now links to the site where you can order tapering strips.” That is just a pinprick in the fierce legal battle that the Association Afbouwmeditatie and the Rainbow Pharmacy are waging to get reimbursed for the tapering strips, via countless lawsuits and dozens of letters to MPs, the Ministry of Health, Welfare and Sport, insurers, working group members and other stakeholders. For example, the association has requested the full study protocol via the Open Government Act (WOO). “That is why we now regularly go to court,” says Vinkers. “The protocol is public, except for the exact description of the ways in which we taper. If it becomes public, participants may be able to determine which reduction schedule they will receive and all the money and work will be for nothing.”

I’d say give that man a prize. It is one of the most important scientific developments in psychopharmacology

Jim van Os psychiatrist

It has become a political issue, says Van Os. “Paul Harder, the pharmacist of the Rainbow Pharmacy, is a brilliant figure, but completely inappropriate in communication. He insults everything and everyone and files lawsuits all the time, sometimes in a very personal way. That is a pity, because in the end the patient does not always benefit from this.” Impossible or not, Van Os has Harder in mind. “I would say: give that man a prize. It has been one of the most important scientific developments in psychopharmacology in the last 50 years.” (About these claims by Van Os, Paul Harder says when asked: “Completely correct, not a word of a lie.”)

Van Os says that he disagrees with all the WOO requests and lawsuits that the Rainbow Pharmacy and the Association for Afbouwmeditatie are filing. “But I understand it from the perspective of the patients. That’s how it has been in psychiatry for 50 years. There are always groups of angry psychiatric patients who use ‘unreasonable’ behavior to draw attention to things that are not right. They are held back for a long time, but at a certain point it breaks open and is incorporated into psychiatry. That will also happen here.”

Vinkers and Ruhé hope that the parties will be able to further advance the research field together one day. “In fact, we aim for the same thing,” says Ruhé, “the best treatment for patients. I am therefore absolutely not against tapering strips, which are a form of the proposed tapering medication. But it is not necessary for every patient. With the advice we have drawn up, many patients can draw up a tapering plan locally, with their own GP or psychiatrist and their own pharmacy.”