TRADAR trial completed. Unfortunately, it has been shown that people who gradually taper off their antipsychotic medication are more likely to relapse than those who continue taking it. At 2-year follow-up, there were no differences in social functioning, symptoms, side effects, or quality of life. However, relapse is not inevitable, and qualitative analysis showed that some people felt empowered by the opportunity to receive public support and reduce their medication, regardless of outcome.
execute radar survey This is the most difficult thing I have done in my professional career, and I would like to take the opportunity to publish the results.Moncrieff et al., 2023) Reflect on what you learned from the process, not just the results.
RADAR studies include randomized trials comparing a gradual antipsychotic tapering strategy (withdrawal if possible) to maintenance therapy in people who have recurrent psychotic episodes or have been diagnosed with schizophrenia. It was included.
From the beginning, I was supported by a strong team of experienced psychiatrists and academics, who not only helped me in practical aspects, but also gave credibility to my research. They included people who had worked with drug companies in the past, but all agreed that antipsychotics are unpleasant and potentially harmful, and that research on alternatives to lifelong treatment is critical. I recognized the need. This trial was also supported by a team of people with experience in psychosis and the use of antipsychotics, who generously gave their time and provided constant encouragement.
We learned how difficult it is to conduct randomized trials, especially when the options are fundamentally different from each other. Most clinical trials struggle to recruit enough participants, in part because many people believe that treatment is determined by the roll of the dice (or a computerized randomization program). This is because they don’t like it. However, the RADAR trial, unlike many trials, does not provide people with additional treatment, but with the goal of continuing antipsychotic medication or discontinuing it if tapering has progressed well. It offered people the possibility of receiving two completely different treatment strategies: medication.
Understandably, people who are already taking antipsychotics often have strong opinions about whether they want to continue taking them. Therefore, despite our best efforts, we were not able to recruit as many patients as originally planned. Still, he managed to recruit 253 people. This is thanks to the incredible efforts of my hard-working and dedicated local research team, and his amazing network of NHS research facilities across the UK. The people recruited had on average a long history of contact with mental health services, including a number of hospitalizations, and were comparable to the general population under the care of community mental health services in England with the same problem (diagnosis) profile. was. (Freudenthal et al., 2021).
We ended up enrolling people from 19 different regions and organizations, each with a team of people supporting the project. I was also reminded of how many excellent psychiatrists there are in the UK. Each field needed psychiatrists to support research, a job that required dedication and nerve. Some psychiatrists had to confront colleagues who thought they should not conduct research. They believed that doing so would provide patients with better evidence for treatment and improve their outcomes in the long run.
What will be the result? (see) Moncrieff et al., 2023)? Most trials to date have stopped antipsychotics over a period of days or weeks, and relapses can often consist of symptoms such as agitation and insomnia, which are thought to be due to withdrawal effects. It was defined in this way. When we designed the RADAR study, we expected that slowly tapering antipsychotics would prevent severe relapses (defined as hospitalizations to ensure they reflected significant deterioration). was doing. That wasn’t the case. Those randomly assigned to a weight-loss strategy were more likely to relapse and be hospitalized than those randomly assigned to maintenance therapy (25% vs. 13%). Relapses were full-blown psychotic relapses rather than mild worsening, and those who tapered off their antipsychotics did not show compensatory improvements in social functioning.
On the other hand, people in the reduction group also showed no decline in social functioning by the end of the study, and psychotic symptoms were the same in both groups at this point. At 2 years of follow-up, there were no differences in any outcome measures, including quality of life or side effect measures. It would be interesting to look at the data more closely (which we plan to do in the future), but it seems likely that relapses, even if they require hospitalization, do not lead to the long-term decline that is sometimes suggested. is. .
The results are not surprising and are similar to earlier results from the Wunderlink study conducted in the Netherlands in people with a first episode of psychosis. Wunderink et al. also found increased rates of psychotic relapse and no differences in social functioning at 18-month follow-up (Wonderlink et al., 2007). It was only during the seven-year follow-up that those who were originally randomized to undergo debulking surgery had better social functioning and smoothed out recurrence.Wonderlink et al., 2013).
RADAR’s results show how difficult it is for people to stop taking antipsychotic drugs after taking them for a while. In the RADAR trial, no special additional support was provided to those randomized to reduce their antipsychotic dose, other than more frequent monitoring by a psychiatrist (to do this) (because there were no resources available). Participants from both sectors were able to make referrals to psychotherapy and general social support provided by local services, and also provided information about local support groups. However, I think it would have been nice to have more specific support, and if I were to do this kind of research again, I would definitely like to provide something like this.
About 20 years ago, I wrote about possible ways to explain the adverse consequences after drug discontinuation (Moncrief, 2006a; Moncrieff 2006b), and other prominent researchers agree with my analysis (Tondo and Ballesarini, 2020). One possibility is that the drug was suppressing an underlying pattern of problem behavior that would spike again once the drug was removed. I think there are people like this. Another possibility is that the process of drug withdrawal induces psychotic symptoms, as has been shown to occur in some people without a history of psychosis or mental illness. A phased withdrawal process should make this less likely, but it is difficult to say whether the reduction in RADAR testing has been gradual enough to eliminate it completely. As it turns out, even if you gradually withdraw from benzodiazepines and antidepressants, most people still experience withdrawal symptoms. A related possibility is that the experience of drug withdrawal facilitates the relapse of the underlying problem. Again, gradual withdrawal is expected to reduce this possibility, but not necessarily eliminate it. Qualitative results (also just published) highlight the emotional rebound that can occur after antipsychotic dose reduction or discontinuation, suggesting that it may transform into psychosis or psychotic relapse. and supports this possibility (Morant et al., 2023).
Although we do not intend to downplay the impact of full-blown relapse, our qualitative results indicate that for some people, the process of tapering off antipsychotics was empowering, regardless of the outcome. For some, the RADAR trial was the first time they were offered anything other than continued drug treatment, and the first time they were seriously involved in decisions about their future. Some people had restarted medication but felt they were able to accept it better, while others were looking forward to eventually coming off the medication, even if they had not had success so far. I was there.
Some members of the group of people with lived experiences of mental illness who supported this research were also empowered to seek different approaches to their personal treatment.
The trial showed that stopping or significantly reducing antipsychotic medication increased the chance of relapse, but it did not show that relapse was inevitable. In fact, his 72% (47 people) of those who discontinued antipsychotics in both groups had no severe relapse, and of his 109 who had their antipsychotics reduced by at least 50%, he found that 71 % had no recurrence. Thirteen patients in the dose reduction group and eight patients in the maintenance group stopped taking antipsychotics by the end of the study.
Data from the RADAR trial will allow people to make more informed decisions about antipsychotic treatment. If you finish treatment slowly over a period of 1-2 years, you are more likely to relapse than if you continue taking medication. However, not everyone has a recurrence. Most people can avoid relapse by increasing the dose again or by other means. Approximately 10% may be able to stop the medication completely.
And above all, the fact that the RADAR trial was funded, completed and supported by so many patients and experts shows that antipsychotic treatment is far from ideal and that it will help people who have experienced psychotic conditions. It emphasizes the need to explore alternative methods.
