Redressing long-term antidepressant use (RELEASE): Pragmatic cluster randomised controlled trial in general practice
The RELEASE pragmatic cluster randomised controlled trial demonstrated that inviting general practitioners to review long-term antidepressant users and providing shared decision-making resources with hyperbolic tapering guidance significantly increased cessation and dose reduction rates at 12 months compared to usual care, without causing adverse effects or symptom relapse.
Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). This is an AI-generated explanation of a preprint that has not been peer-reviewed. It is not medical advice. Do not make health decisions based on this content. Read full disclaimer
For decades, millions of people around the world have taken daily medication to manage depression and anxiety. These drugs, known as antidepressants, are often prescribed for short periods, but in many cases, people continue taking them for years, sometimes for decades. While these medications can be life-saving, long-term use carries risks, including weight gain, sexual dysfunction, and a higher chance of falls. Medical guidelines generally suggest reviewing the need for these drugs after a year, yet in the real world of family doctors, this review rarely happens. A major reason people stay on these medications is the fear of stopping. Many believe their condition is a permanent chemical imbalance that requires a permanent fix, and others fear that stopping will cause a return of their original symptoms or trigger severe withdrawal effects. Withdrawal symptoms, which can include dizziness, nausea, and intense anxiety, often occur when the body is forced to adjust too quickly to the absence of the drug. Because of these fears and the lack of clear, safe ways to stop, many patients remain on medication they might no longer need.
A team of researchers in Australia set out to test a simple, low-cost strategy to help people stop these medications safely. They conducted a large study across twenty-six general practices, involving nearly five hundred adults who had been taking antidepressants for more than a year. The researchers did not select people who were already desperate to quit; instead, they included anyone taking the medication, regardless of whether they wanted to stop or how severe their symptoms were. This approach mirrored real life, where many patients are unaware that stopping is an option. The study compared two groups: one group received their usual medical care, while the other group received a specific intervention. This intervention involved a personal invitation from their doctor to discuss stopping the medication, accompanied by a set of easy-to-read guides. These guides explained how to make shared decisions about stopping and provided a detailed, step-by-step plan for reducing the dose very slowly. This slow reduction, called hyperbolic tapering, involves making smaller and smaller cuts to the dose over many months, allowing the brain to adjust gradually and minimizing withdrawal symptoms.
The results showed that this gentle, information-based approach worked. After one year, nearly fifteen percent of the people who received the invitation and the guides had successfully stopped taking their antidepressants completely. In the group that received usual care, only about nine percent had stopped. This means the intervention nearly doubled the likelihood of a patient quitting the medication. The study also found that many more people in the intervention group reduced their dose by at least three-quarters, even if they had not stopped entirely. Crucially, the people who stopped or reduced their doses did not suffer from a return of depression or anxiety, nor did they experience more withdrawal symptoms than those who stayed on their medication. The researchers found no evidence that the intervention caused harm or led to a worsening of mental health conditions.
The study highlights that the biggest barrier to stopping was not a lack of willpower, but a lack of clear guidance and a safe path forward. While the absolute number of people who stopped was modest, the researchers argue this is a significant success given the difficulty of the task. The average participant had been taking the medication for over fourteen years, and many had tried to stop before and failed. The fact that a simple letter and a set of instructions could help so many people move toward stopping suggests that the problem was not the patients' ability to quit, but the absence of a supportive framework. The intervention did not involve therapy, extra appointments, or psychological support; it simply empowered patients with information and a clear plan, then invited them to talk to their doctor.
Despite the success, the study also revealed the limits of this approach. Many patients who received the guides discussed stopping with their doctors but did not follow through with the full plan. The researchers noted that the final stages of stopping, where the dose becomes very small, are the most difficult. This is partly because the tiny doses required are not always available in standard pharmacies and must be specially prepared, which can be expensive or inconvenient. The study suggests that while providing information and a plan is a powerful first step, future efforts may need to address these practical barriers, such as the availability of small-dose formulations, to help more people finish the process. Ultimately, the research demonstrates that in the everyday setting of a family doctor's office, a respectful invitation combined with clear, safe instructions can help people end long-term antidepressant use without causing them harm.
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