New Research into Antipsychotic Discontinuation And Reduction: the RADAR programme

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.

 

 

Reference List

(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

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14 thoughts on “New Research into Antipsychotic Discontinuation And Reduction: the RADAR programme

  1. Hello,
    I would like to contact you. I am in my early 30s, and was on antipsychotic medications for over 10 years for bipolar disorder. I now have a serious neurological movement disorder, which neurologists believe to be caused by medication. I experience pretty debilitating episodes, and believe in the short term benefits of this type of medication, but believe long term use should be illegal. Is there a way I can contact you?

  2. Trying to wean off Latuda my son was prescribed a Year ago 100 mg twice daily…it got him almost végétative and it doesn’t get rid of his voices…moving to another City trying to get him help to wean off…and to attend voice hearer groups…fighting thé system alone and against his shrink who has refuséd to meet with me for thé past 6 years…

  3. I believe that our 31 year old son would be a perfect candidate to take part in this study having been diagnosed with schizo affective disorder 6 years ago. He has a couple of times tried to stop his Clozapine with side effects deemed psychosis and is currently back in hospital while they get his meds back up.

    • Dear Amanda, we will be only running the study in certain Mental Health Trusts. If your son’s local Trust takes part in the RADAR trial, then your son should get to hear about it and have the chance to be assessed to see if he is eligible.

      • Thank you very much for replying. I’ll find out if NSFT is getting involved.

  4. Pingback: Royal College of Psychiatrists still not interested in discussing important evidence on long-term antipsychotic treatment | Joanna Moncrieff

  5. Dr Grace Jackson talks about psychiatric drug induced dementia 6-14 fold increase on antipsychotics, hopefully someone will pass this video around… it needs to be seen, plus her book is a great piece of research work and very disturbing at the same time:

  6. Pingback: Why I don’t like the idea that mental disorder is a disease | Joanna Moncrieff

  7. Pingback: Por que eu não gosto da ideia que o transtorno mental é uma doença | Mad In Brasil

  8. Pingback: Why I Don’t Like the Idea that Mental Disorder is a Disease – EcoGreenData

  9. Is there any update for public on this trial ? Is it still recruiting ? We have had one attempt at withdrawing but it was a ‘cold turkey’ all or nothing reaction. Withdrawal began in earnest several months after-symptoms of ‘relapse’ severe agitation and seizures praying lost appetite eye rolls . I recorded many many symptoms by video. I would urge any carer parent partner or doctor to be vigilant to recording symptoms. Our experience was traumatic. My son walked for miles hands held in prayer eyes rolling pale ill agitated and unable to control any of this. He almost died. I had to call ambulance several times but they dismissed his severe symptoms as ‘same as a drunk on a Sat night’, a GP failed to see how far beyond controlling his psychosis he was and also a Psychiatrist who let him go home from a clinic in withdrawal and making no sense. It took 4 1/2 months to get an admittal while he wasted away unable to sleep eat stop pacing praying etc
    Currently maintained on new lower dose depot at my request and anti epileptic meds. Ive added cbd oil and a well researched nutritional program with swim every day and he is taking relaxation/ yoga classes started in Hospital as rehabilitation.
    Norway has just recently designated some beds in psychiatry to medication free treatment. A lot of birthing pains still with their effort but officially it seems they are agreed in provision of alternatives alongside Open Dialogues etc.

  10. Another Q. How do you measure social functioning post illness/treatment when a knock on effect is withdrawal of social contact by peers -particularly among younger patients where onlookers to the predicament of the affected person have their own issues -safety, fears, lack of understanding.
    Patients who are younger can become isolated by exclusion while ill,when there are perceived changes to their presentation of self. Social avoidance is unavoidable for them. Idiosyncratic or unusual tics mannerisms involuntary movements slowness of mental clarity responses may be less of an affliction socially if public had clearer understanding of difference between a symptom of mental disturbance and a side effect of medication. Visited my son for 6 months every day for many hours and saw how easily it is to confuse these two issues.
    I think nutritional support is necessary in tapering off anti psy medications – we are supplementing the lower dose with B Complex , Coconut oil, fresh green juices, cold water swims and time for silliness and space to regress if needed. My son wrote that what he needed was kindness most of all.
    We posted small updates to his FB to give an idea of the journey he is on and what made it easier or put him at ease….ppl were v positive and helpful once they had some grasp of the issue. A lot of bridges have to have their foundations laid first by carers etc to provide roadmap to inclusivity..

  11. I was just watching this video again, certainly… it’s applicable to drugs, maybe not anti-psychotic drugs, but it’s an interesting correlation. Exaggerating reality to counter the boredom of our reality is ‘hard wired’ in us.

    “Hanking after something more human than human”

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