To avoid withdrawal symptoms, patients should slowly decrease doses of antipsychotics over months or even years

Withdrawing from antipsychotics may require months or even years, and patients need to gradually reduce to very low doses, according to a new analysis led by UCL and King's College London academics.

The review, published in Schizophrenia Bulletin, is the first-ever scientific paper outlining how exactly antipsychotic medication should be reduced in order to minimize both withdrawal effects and the risk of relapse.

Withdrawal symptoms can be severe, and may include psychotic symptoms similar to the underlying condition, which can result in patients being advised to remain on the medication indefinitely, even though the new symptoms might have been avoidable with a carefully-managed withdrawal.

Lead author Dr. Mark Horowitz (UCL Psychiatry) said: "Surprisingly, there are no published guidelines on how to come off antipsychotics. From my own experience I know how hard it can be to wean off psychiatric medications—so we set out to write guidance on how to withdraw safely from antipsychotics. Stopping medications is an important part of the job of a psychiatrist, yet it has received relatively little attention."

Antipsychotics are one of the fastest growing classes of drugs being prescribed in England, growing from 660,000 people (9.4 million prescriptions) in 2015/2016 to 750,000 people in 2019/2020.

Antipsychotics are often recommended life-long for people diagnosed with schizophrenia or other serious mental illnesses because they are effective at controlling psychotic symptoms in the short term and might reduce the risk of relapse. These drugs are also increasingly prescribed for conditions like insomnia and anxiety 'off-label' (without being licensed for these conditions by the UK's MHRA).

However, some people find the drugs do not help them or that the side effects (which can sometimes contribute to long term health complications) outweigh the benefits, while many people who then stop taking antipsychotics experience withdrawal effects, which can be severe. Some patients say they are helpful in the short-term but harmful in the long-term.

Currently there are no established guidelines on how to stop taking antipsychotics, which is partly why psychiatrists are reluctant to do so. The authors of this proposal reviewed existing evidence into antipsychotic withdrawal, and the mechanisms of the drugs themselves. They describe research, which finds that people with schizophrenia who are slowly taken off their antipsychotics, have twice the chance of functioning well than those who stay on the same dosage, with no worsening in their symptoms.

These new guidelines on how to reduce antipsychotics align with guidelines the same researchers published recently on how to stop taking antidepressants safely. The principles are similar: doing so cautiously by small amounts, and ensuring patients are stable (with suggested three-to-six month intervals between dose reductions) before making further reductions. Liquid versions of the drug or small dose formulations will be needed to help patients to do this, to avoid having to crush up the tablets themselves.

In parallel, the first study in England to look at the effect of slowly reducing antipsychotics in people with a diagnosis of schizophrenia, called RADAR, is currently being undertaken, led by Professor Joanna Moncrieff (UCL Psychiatry).

The reason for stopping drugs gradually is that our brains adapt to long-term use of drugs like antipsychotics (as they do to nicotine, caffeine or opioids). If drugs are stopped too quickly, people can get withdrawal symptoms (which for antipsychotics can include insomnia, tremors and sometimes psychotic symptoms) or can be de-stabilized by the process of coming off.

Dr. Horowitz said: "In clinical practice, I often see patients perking up when they reduce their antipsychotic medication and telling me that they 'feel more themselves." It is also true that some people get worse when their drugs are reduced. What we need is more research to work out who benefits and who doesn't. We also need to take patients seriously when they tell us that medications are doing them more harm than good."

Co-author Professor Sir Robin Murray (King's College London) said: "Some psychiatrists are reluctant to discuss reducing antipsychotics with their patients. Unfortunately the consequence is that patients suddenly stop the medication by themselves with the result that they relapse. Much better that psychiatrists become expert in when and how to advise their patients to slowly reduce their antipsychotic."

Senior author Professor David Taylor (King's College London) said: "Antipsychotics are so familiar to prescribers that it is tempting to assume that they are both effective and innocuous. While they are perhaps the most useful treatment for serious mental illness such as schizophrenia, their toxic nature makes them unsuitable for less severe conditions. Antipsychotics induce long-lasting changes to nerve cells in the brain and they need to be withdrawn very slowly (and in a particular way) to allow time for the brain to re-set."

Sandra Jayacodi, who is part of the lived experience advisory panel member of the RADAR trial, said: "The side effects of antipsychotic drugs are extremely unpleasant, and it reduced the quality of my life, and chances are that my life expectancy will be reduced too. Sometimes it feels like a life sentence."

Stephen Buckley, Head of Information at Mind said: "Antipsychotic medication can help lots of people who experience psychosis to manage their mental health. Should someone decide to come off their medication then ideally their doctor should be able to support them through the withdrawal process, but we know many clinicians feel they don't have the guidance or experience to do this with confidence.

"People should be treated as a whole person, so as well as welcoming more research and evidence into how people can withdraw from antipsychotics safely, it's really important when someone does come off their medication they have some control in their treatment, and are offered trauma informed and culturally relevant treatment options—this could include things like talking or creative therapies, social prescribing, and peer support. Key to this is looking at people's broader life experiences and making sure people have adequate social support to help them achieve their goals and integrate back into the community, this includes support with loneliness and isolation, finances, unemployment, and housing."