I would like to announce the exciting news that the UK government’s National Institute of Health Research (NIHR) has recently agreed to fund a new study to compare a gradual and supported programme of antipsychotic reduction with maintenance treatment. The RADAR research programme (Research into Antipsychotic Discontinuation And Reduction) has just started.
I have already described my worries about long-term antipsychotic treatment, and the flaws and limitations of existing evidence. For a long time I have felt that there just isn’t a good enough and long enough study on the pros and cons of long-term antipsychotic treatment versus reduction and discontinuation in people who have psychotic disorders, including those who are classified as having schizophrenia.
Moreover, there are increasing reasons to be worried about the effects of long-term treatment with antipsychotics. We have known for a long time that these drugs cause a range of serious adverse effects, including 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 (1;2).
While the inhibiting effects of antipsychotics may be useful for someone who is in the throes of an acute psychotic episode, over the longer term it is possible that antipsychotics leave some people in a worse state than they might have been without them. This possibility is supported by evidence from Martin Harrow’s long-term follow-up of people admitted with a psychotic episode (3), and by the seven year follow-up data from the Dutch First Episode randomised controlled trial of antipsychotic reduction (4). The Dutch trial suggested that people who had tried to reduce and discontinue antipsychotic medication, even if they did not succeed, functioned better than those who took it continuously.
Nevertheless, long-term antipsychotic treatment remains the standard recommended treatment for people who have psychotic episodes or a diagnosis of schizophrenia. The National Institute for Health and Care Excellence (NICE) guideline on treating psychosis and schizophrenia assumes that this is what people will have (5). 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.
Yet 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.”
I put this case to the UK’s National Institute of Health Research (NIHR) recently, and proposed that they fund a trial to assess the long-term outcomes of a gradual programme of antipsychotic reduction compared with standard ‘maintenance treatment’. The NIHR agreed that this was an important issue, and that a new trial was urgently needed. The RADAR (Research into Antipsychotic Discontinuation And Reduction) study officially started in January 2016.
The RADAR trial will be similar to the Dutch study, but we will recruit people who have more than one episode of psychosis or schizophrenia, as opposed to people who have had a single or first episode. People who agree to take part in the trial will be randomised to receive maintenance antipsychotic treatment (staying on their current regime) or to have the antipsychotic reduction strategy. Participants who are randomised to the antipsychotic reduction strategy will have their antipsychotics reduced gradually with the support of a psychiatrist. People who want to try and stop the medication altogether will be supported to do so, but for others the aim will be to reduce the medication to a very low dose. The time this process takes will vary between different individuals, but we think it will take anything from 6 months to 18 months.
The main outcome for the study will be people’s levels of social functioning. Most long-term antipsychotic trials focus on symptoms or relapse, and we thought it was important to look at how treatment affects people’s lives more globally. We will, however, also look at relapses, symptoms, side effects of medication, employment and costs. We will be following people up for 2 years within the time-frame of this project, but we hope to follow people up for longer in the future.
Before the trial starts we are conducting a ‘Recruitment study’ to assess how many people would be willing to enter the trial, and how recruitment can best be organised and achieved.
The study is supported by a team of highly experienced researchers, including some well-known and eminent psychiatrists, all of whom are fully committed to the need for further evidence. We have a dedicated group of service users with experience of taking antipsychotic medication who will support the project.
I would personally like to thank the NIHR for supporting this study. The fact that it is being done will, I know, give great hope to many people around the world who feel they have been stuck on these drugs for years without being offered any alternative. The study will help to answer one of the most important practical questions in psychiatry: the question of whether the current approach of keeping people on long-term antipsychotic treatment is really the best thing to do, or whether we should be offering the opportunity to reduce and sometimes discontinue medication with medical support. Whatever the outcome, we need better evidence to inform our choices and recommendations.
(1) Dorph-Petersen KA, Pierri JN, Perel JM, Sun Z, Sampson AR, Lewis DA. The influence of chronic exposure to antipsychotic medications on brain size before and after tissue fixation: a comparison of haloperidol and olanzapine in macaque monkeys. Neuropsychopharmacology 2005 Sep;30(9):1649-61.http://www.ncbi.nlm.nih.gov/pubmed/15756305
(2) Ho BC, Andreasen NC, Ziebell S, Pierson R, Magnotta V. Long-term Antipsychotic Treatment and Brain Volumes: A Longitudinal Study of First-Episode Schizophrenia. Arch Gen Psychiatry 2011 Feb;68(2):128-37. http://www.ncbi.nlm.nih.gov/pubmed/21300943
(3) Harrow M, Jobe TH, Faull RN. Do all schizophrenia patients need antipsychotic treatment continuously throughout their lifetime? A 20-year longitudinal study. Psychol Med 2012 Oct;42(10):2145-55. http://www.ncbi.nlm.nih.gov/pubmed/22340278
(4) Wunderink L, Nieboer RM, Wiersma D, Sytema S, Nienhuis FJ. Recovery in remitted First-Episode Psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy: long-term follow-up of a 2-year randomised clinical trial. JAMA Psychiatry 2013; 70: 913-20. http://www.ncbi.nlm.nih.gov/pubmed/23824214
(5) National Collaborating Centre for Mental Health. Psychosis and schizophrenia in adults: treatment and management. NICE Clinical Guideline. National Collaborating Centre for Mental Health: London 2014. http://www.nice.org.uk/guidance/cg178/evidence/full-guideline-490503565