By Joanna Moncrieff.

Long-term antipsychotic treatment remains the standard recommended treatment for people who have psychotic episodes or a diagnosis of schizophrenia. People who have had just one episode may be supported to try and discontinue treatment, but most people with recurrent episodes are recommended to stay on antipsychotic medication for the rest of their lives. Mental health services put in a great deal of effort to ensure that people are ‘compliant’ or ‘adherent’ with this strategy. 

However, as described in another blog, the evidence base for these recommendations has important. The main problems are that previous studies consist of discontinuation studies that compare continued treatment with discontinuation, yet do not address the potential complications of discontinuation. As well as a causing a withdrawal syndrome characterised by symptoms such as agitation and insomnia, which may be mistaken for relapse, antipsychotic discontinuation may increase the risk of a genuine relapse. Since most randomised trials of long-term antipsychotic treatment last only a few months, and few last longer than a year, it is likely that trial results reflect, at least in part, the adverse effects of withdrawal rather than the benefits of long-term treatment per se. there is also an inherent limitation in studying a long-term or lifelong treatment for a few months, because you cannot assume that the effects achieved in the early days will be the same as the effects further down the line. Another problem is that most trials have focused exclusively on relapse, so there is little information about other outcomes, such as quality of life or functioning, which may mean more to some people.  

A Dutch trial of gradual antipsychotic discontinuation versus maintenance treatment in people following a first episode of psychosis clearly illustrates these problems. The study was ground-breaking because it involved gradual and supported withdrawal of antipsychotics, rather than abrupt cessation, as occurs in most other trials, it looked at social functioning as well as relapse and, most importantly, a long-term follow-up was conducted, seven years after the initiation of the trial. At the initial follow-up at eighteen months, people randomised to antipsychotic discontinuation were more likely to relapse and showed no benefits in terms of social functioning, but by the long-term follow-up, relapses had evened up, and people who had been randomised to the antipsychotic reduction arm showed considerably better social functioning. 

As well as problems with research on the effectiveness of long-term treatment, evidence is mounting about the adverse effects of antipsychotics. We have known for a long time that these include serious and debilitating complications such as tardive dyskinesia, cardiac problems, hormonal abnormalities, weight gain, diabetes and sexual dysfunction. Recent evidence confirms earlier suspicions that they also reduce brain size and volume. 

Moreover, many people with psychotic disorders want another option. ‘Being told you have to take tablets for life is disempowering in the extreme,’ one service user told me. Many patients and their relatives sense the impairment the drugs can cause, and are desperate to see if they can do without them.  Some find a sympathetic psychiatrist who is prepared to help them, but many don’t.

This is what a carer wrote a couple of years ago:

 “If someone wants to stop antipsychotics, they are refused help, so it’s very difficult in spite of feeling of unease and worry about antipsychotic. It makes one feel helpless and more vulnerable. I worry about my son. It appears that more help is offered to newly diagnosed patients, but those suffering most are surely those diagnosed many years ago… [who] appear to be written off and expected to continue antipsychotics regardless of problems.”

It was for these reasons that the RADAR study was set up. It is a randomised trial comparing people who have a supported and gradual programme of antipsychotic reduction followed by, with discontinuation if possible, with people who remain on their antipsychotics as per ‘usual care’. The main outcome is social functioning, but relapse rates will also be measured, along with symptom levels, adverse effects, quality of life, ‘recovery’, costs and neuropsychological performance. The main follow-up for the first part of the trial is at 2 years, but I hope to conduct a longer-term follow-up after that. The Dutch study suggests that social outcomes do not improve until longer term follow-up, and that relapse rates may be higher among those who are randomised to reduction for the first 3 years. 

The study is funded by the National Institute for Health Research (NIHR), the research funding arm of the UK’s National Health Service. It is supported by a team of highly experienced researchers, including some well-known and eminent UK psychiatrists, all of whom are fully committed to the need for further evidence. There is also a dedicated group of service users and carers with experience of the effects of antipsychotic medication who are supporting the project. 

Several similar studies are currently taking place in other countries involving people with a first episode of psychosis, including the HAMLETT trial in the Netherlands, the Reduce trial in Australia and TAILOR study in Denmark.  

The RADAR trial has now finished recruitment, with 253 people successfully recruited and randomised to antipsychotic reduction or maintenance treatment. The antipsychotic reduction programme is being implemented, and people are gradually finishing the two-year follow-up assessments. The final two-year follow-up is scheduled for January 2022, and results will be available after that. 

As well as the 253 people who have entered the study, and the management group, a huge number of clinicians, patients and carers have helped support the study. Although it has had its critics, the fact that so many have welcomed the research, and that similar studies are taking place worldwide, is a good sign that attitudes to long-term treatment may be changing, and that clinicians are increasingly willing provide people with more choice over their treatment.