Cochrane Review Calls for More Research on Antidepressant Withdrawal

Researchers find a lack of current literature on safe, effective ways to manage antidepressant withdrawal and make suggestions for future research.


A new Cochrane review examines the current body of research on stopping antidepressant use, finding a major lack in this area. The researchers call for further investigation into safe and effective strategies for stopping antidepressants.

“We know the rise in long-term antidepressant use is a major concern around the world,” says lead review author and Belgian-based researcher Ellen Van Leeuwen.
“As a GP myself, I see first-hand the struggles many patients have coming off antidepressants. It’s of critical concern that we don’t know enough about how to reduce inappropriate long-term use or what the safest and most effective approaches are to help people do this. For example, there are over 1,000 studies looking at starting antidepressants, yet we found only 33 randomized controlled trials (RCTs) around the world that examined stopping them. It’s clear that this area needs urgent attention.”

Antidepressants are commonly used in the treatment of depression and anxiety. Current guidelines suggest that people should continue antidepressant use for at least six months after beginning to feel better and for at least two years if they have experienced multiple depressive episodes. Half of the people prescribed antidepressants are on them for longer than two years.

Surveys of people taking antidepressants show a lack of evidence to support 30-50% of long-term users still being on the drug. Long-term use may cause more harm than benefit, as antidepressant use can cause negative side effects, such as sleep disturbances, weight gain, sexual dysfunction, gastrointestinal bleeding, emotional numbing, among other issues. Additionally, other research has highlighted that antidepressants are, on average, ineffective and potentially harmful.

In the current study, Cochrane researchers looked at the findings from 33 RCTs, the gold standard for evidence-based research, which included 4,995 individuals who had been prescribed antidepressants for 24 weeks or longer. Antidepressant use was stopped suddenly in 13 of the studies examined. In 18 of the studies, antidepressant use was tapered over the course of a few weeks, with most tapering periods lasting about four weeks or less.

The researchers found that the available research does not provide any conclusive evidence of the safest and most effective approach to stopping antidepressants. Although most of the studies resulted in an apparent relapse of depressive symptoms, there was a lack of differentiation between relapse and withdrawal symptoms.

Most studies also included participants who had a history of repeated depressive episodes, further muddying the waters around whether the depressive symptoms that manifested after stopping antidepressants resulted from relapse or withdrawal.

None of the studies used slow, measured approaches to stopping antidepressant use – which has been recommended as a safe way of tapering from SSRIs and antipsychotics. Instead, the studies that included a tapering regimen used a rapid approach, explaining why abrupt discontinuation and tapering resulted in relapse/withdrawal.

Additionally, the current studies do not offer a clear consensus on how long antidepressant use should continue after the individual’s symptoms have abated. The researchers highlight how the current prescribing guidelines are not grounded in research evidence, raising cause for concern, particularly in light of the problematic side effects attributed to antidepressant use.

The researchers make several suggestions for future research into safe discontinuation guidelines. They encourage clinicians to formally monitor how their clients are responding to tapering and eventually discontinuation, as a way to better determine whether the symptoms are withdrawal or relapse, as well as knowing when to slow down the tapering process if symptoms do arise.

Further, they recommend that researchers more clearly delineate between withdrawal and relapse symptoms. They also suggest that slow approaches to tapering be investigated to minimize potential withdrawal symptoms as much as possible.

They call for research that examines the benefits and harms of stopping antidepressant medications, acknowledging the pharmaceutical industry’s and researchers’ lack of investment in the de-prescribing movement. Research investigating de-prescribing, including shared decision-making between client and clinician, effective rates of discontinuation, withdrawal symptoms, and other adversities, and overall quality of life, is needed to provide a clear picture of how to navigate stopping medication in a way that is both safe and successful.

Other key aspects to be addressed include having a more widely represented patient population, including those experiencing milder forms of depression and other psychiatric diagnoses. As most antidepressants are prescribed by general practitioners, research in primary care settings must be conducted, and that general practitioners talk with their clients about continuing and stopping their medication.

Also, gaining a deeper understanding of how general practitioners and other clinicians perceive discontinuation would allow for further awareness of the complexity of the contributors that help and hinder stopping the medication.

Exploration of therapeutic interventions that could assist with discontinuation, like cognitive-behavioral therapy (CBT) or mindfulness-based cognitive therapy (MBCT), in addition to interventions such as online support, psychoeducation, etc., could allow for a clearer picture of how practitioners can best support clients undergoing the process of stopping their medication.

UCL-based researcher and psychiatrist Mark Horowitz emphasizes the importance of further investigation into safe approaches to stopping psychiatric medications:

“For me, this is such a critical issue both from a personal and a professional perspective. I’m one of the hundreds of thousands of people who have had or are having long, difficult, and harrowing battles coming off long-term depressants because of the severity of the withdrawal effects. And yet, rather than being able to find or access any high-quality evidence or clinical guidance in this situation, I could only find useful information on peer support sites where people who had gone through withdrawal from antidepressants themselves have been forced to become lay experts. Since then, the Royal College of Psychiatrists has taken a great step forward in putting out guidance on Stopping Antidepressants in 2020. However, there is still a lack of research and, therefore, evidence in this area on what works for different people. I want other people to have the evidence base to come off without the same trouble I had.”

Looking to the future, Van Leeuwen writes:

“Looking ahead, we await the results of current studies underway that are looking at discontinuing antidepressants, such as the REDUCE trial in the UK, which is testing online and phone psychological support for patients withdrawing from long-term antidepressants, where this is appropriate. We know future studies will be critical in addressing the urgent need for more and better evidence, given the concerning trend of long-term use of antidepressants here in England and around the world.”  




Van Leeuwen E., van Driel M.L., Horowitz M.A., Kendrick T., Donald M., De Sutter A.I.M., Robertson L., Christiaens T. (2021). Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults. Cochrane Database of Systematic Reviews, 4. Art. No.: CD013495. DOI: 10.1002/14651858.CD013495.pub2. (Link)


    • It’s kind of bizarre, Alsotrata, that the “Cochrane Review Calls for More Research on Antidepressant Withdrawal.” When they’re also systemically fighting against, the ethical founder of that organization, for ethically speaking out against the systemic scientific fraud of both the psychiatric and psychological industries.

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      • The appearance of caring and being evidence based is a powerful thing. They are making it appear they want evidence and care so they can justify their denials of the massive harms the evidence says psych is inflicting on humanity.

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  1. May sound odd to say this but I personally could not have quit antipsychotics, and met the onslaught of acute withdrawals, without almost welcoming the waves of chaos as if I were ritualistically meeting a powerful force of nature, or an effigy of death. I turned towards the appalling attacks like I was a martial arts doyen. But to go into martial arts I believe there comes a moment of bowing honour, a steely mutual affection, between opponent versus foe, almost a respect for how intolerable it is, like you might respect a tiger who “is what it is”. Both keeping the sense of “awe” at such a formidable enemy, yet also “accepting” what it is. In a weird way my prior forays into suicidal despair honed my ability to be more detatched about death, but detatched in the right way. It is as if there are two kinds of sucicidalness, a flexible way, like an Olympian athlete of triathlon terror, or a jittery, woosy hysterical way. It has been my noticing that of these two ways of suicidalness, the jittery hysterical suicidal people lose their nerve before they even begin withdrawal. If I were living on another planet with lots of sci fi leeway to innovate I would train the jittery lot to become more like zen masters about mortality before they meet the many challenging reasons for failing at withdrawals. Withdrawals is like walking over burning hot coals, you have to be monstrous to yourself to encourage your own bare soled first steps. And people who are best placed to succeed at that are those who have visited treating themselves monstrously in the past, yet sailed through it becsuse in a way they are still monstrously horrid to themselves. The lilly livered tend to get themselves distraught. Those of us who have gone deep into “distraught” as if it is merely more hot coals, are better able to do the hard task of withdrawal which is keep moving, moving, moving forward through that valley of death.

    Some go on antidepressants to get rid of death once and for all, in a Polyanna pole vault to positivity. Others go on antidepressants as if its ice to numb and sponge clean their wounds between rounds, because they know death will always be around, as a noble tiger, or an oriental dragon. I think these people take being defeated less personally or less to heart, and so they msybe catastrophize less when withdrawal goes a bit draggy. So in other words some people may have a better aptitude for coming off meds ironically if they can embrace being mean to themselves, and even having spent years tackling their suicidalness without wishing it would all go away instantly, which is what the jittery suicdal folks feel like. The wishing it would all go away thought makes them run back to Daddy Psychiatry, who helps it never go away by giving yet more antidepressants. Another way to look at it is like refugees having to keep crossing a mountain peak to save their lives. The stoic keep moving, moving, moving “into” the discomfort. The jittery keep saying “Are we there yet?”. The jittery have a way of being anxious “about” withdrawals that the martial arts stoical heroes do not. Yet both are suffering the same monstrous withdrawal ordeal. I do worry that whilst it is good to taper slowly and make it all as gentle and soft as possible, that this will stop potential quitters from chancing bring “brave” and “enduring”. Bravery requires being a bit monstrous to yourself to get to where you want to get to. The jittery tend to want to want to be kind to themselves right now and soak in a lovely bubble bath. Hot coals are awaiting a very very very globally long queue. I hear alot of jittery people mulling over the start of the path to quitting, brooding over the embers, perhaps fussily wanting to wear metaphorical sandals. Which come in many styles and sizes but invariably are made of the cheap stuff of newer antidepressants.

    None of this is to suggest that other people should be telling anyone how they as individuals should quit. Some may favour healing via gentleness. It is just my observaton that if you are going to go down a shattered tower block using a cascading stairwell, you have to be a bit posessed of enough death wish to walk towards the appallingness of falling concrete rubble that might tumble you free.

    God, I’m tired. Must take a rest from all this commenting.

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  2. I have lost respect for the Cochrane Review. I recently read their research on maintenance therapy with antipsychotics and was stunned by its poor quality. It’s conclusion: “For people with schizophrenia, the evidence suggests that maintenance on antipsychotic drugs prevents relapse to a much greater extent than placebo for approximately up to two years of follow-up.” It failed to mention the problems with the studies that allowed them to reach this finding. One example, it ignores the fact that patients in the placebo groups have often been abruptly withdrawn from treatment, which could lead to relapse. It claimed long term studies could be difficult to interpret because of such things as environmental factors. I wouldn’t trust anything the Cochrane Review comes up with.

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    • The studies don’t even measure symptoms but simply a subjective “relapse”. Once some one relapses because of withdrawal they are relapsed for good in the study. If a person relapses a week after abrupt withdrawal but from years .5-2 have half the symptoms as those on the drugs who don’t relapse they are still considered worse off. Imagine if we used that research method for other things. “Alcohol addiction saves lives. Budweiser studies finds those in placebo get seizures, anxiety, and die at higher rates.” “Tobacco is a safe and effective treatment for depression and lethargy with no negative health effects because Marlboro study finds placebo is worse.” Placebo of course being a group addicted and abruptly withdrawn from the drug.

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  3. The reason there are no meaningful studies on how one can safely withdraw from anti depressants and other psychotropic drugs is because BIG PHARMA will never support such research.

    However thier are a small (but growing) number of holistic psychiatrists who have a large body of real world data in thier own practices successfully guiding patients off all of thier drugs with little to no withdrawal problems.

    My wife (age 57) is one of those success stories who was mistreated by no less than 8 psychiatrists over 2 yrs. At one point she was on 6 drugs after only one inpatient stay and zero previous history of any depression or anxiety issues.

    After being failed miserably by the system we found a kind, compassionate psychiatrist named Alice Lee, MD.

    Over the next 12 months Dr Lee successfully helped my wife withdraw (with ZERO side effects). That’s right ZERO! It can be done safely and effectively with long lasting effect.

    My wife’s story is not a unique one as this psychiatrist has been doing this kind of work for decades. My wife’s story was a extreme case (6 drugs), but it proves it can be done if patient and skilled physician work collaboratively.

    I don’t have time here to provide all the details However but anyone seriously interested in saving a love one or themselves would be well served to study her work and reach out to her via her website.

    I have tremendous compassion for people who’ve been sentenced to a life of horrible side effects and labeling. Many many forgotten and left for dead.

    Here’s the good news- there is HOPE but you need to go outside of main stream psychiatry to get it. The solutions are not coming from psychiatry but rather from renegade physicians like Dr Lee who herself was addicted to drugs early in her career.

    God bless and good luck to all who seek the truth and real life solutions without mind altering addictive and destructive drugs.

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