Successful tapering of antipsychotics could take ‘years’, say researchers

Tapering of antipsychotics should be carried out over a period of months or years, and by reducing the dose gradually at intervals of three to six months, according to a major review carried out by researchers at King’s College London.

According to the researchers, there are currently no published guidelines on how to wean patients off antipsychotics, despite the challenge it presents for prescribers. Symptoms of withdrawal can be severe, ranging from insomnia and depression to auditory hallucinations and delusions, but are avoidable with a carefully managed withdrawal, the researchers said.

“The process of stopping antipsychotics may be causally related to relapse, potentially linked to neuroadaptations that persist after cessation, including dopaminergic hypersensitivity,” the authors said.

“Therefore, the risk of relapse on cessation of antipsychotics may be minimised by more gradual tapering.”

After examining existing evidence into antipsychotic withdrawal and the mechanisms of the drugs themselves, the researchers recommended that withdrawal of antipsychotics should be “done gradually (over months or years) and in a hyperbolic manner”.

For example, the most recent dose of antipsychotic could be reduced by one quarter, or one half, in a sequential manner so that reductions become smaller in size as the total dose decreases, at intervals of three to six months, depending on the tolerance of the individual.

“Some patients may prefer to taper at 10% or less of their most recent dose each month. This process might allow underlying adaptations time to resolve, possibly reducing the risk of relapse on discontinuation,” the researchers said, adding that the final dose before complete cessation of the antipsychotic may need to be as small as one 40th of a therapeutic dose.

“Antipsychotics are so familiar to prescribers that it is tempting to assume that they are both effective and innocuous,” said David Taylor, professor of psychopharmacology at King’s College London and senior author of the study.

“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“Antipsychotics induce long-lasting changes to nerve cells in the brain and they need to be withdrawn very slowly (and in a particular way) to allow time for the brain to reset.”

Oliver Howes, chair of the Psychopharmacology Committee at the Royal College of Psychiatrists, said: “Antipsychotic medication can help treat mental illnesses including psychosis, severe depression and bipolar disorder, and many people benefit from taking them long-term.

“Patients who want to stop treatment should consider the risk of relapse as well as side-effects and get support and advice from their doctor.

“These guidelines are useful to help doctors advise patients who want to stop treatment on the best way to do this.”

According to statistics reported by the NHS Business Services Authority in September 2020, 12.6 million items of antipsychotics were prescribed in 2019–2020; a 14.3% increase from 11.0 million items in 2015–2016. 

The researchers, who have also produced aligning guidelines on stopping antidepressants, said that the hypothesis put forward in their paper should be tested in further tapering trials of antipsychotics, and that formal guidelines for tapering antipsychotics were required.

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