The results from the RADAR trial have been discussed in several comments and blogposts, and in our case, in a letter in Lancet Psychiatry calling for attention to the dignity of risk-taking. The RADAR trial, the largest study in the field to date, led by Professor Joanna Moncrieff, tested the hypothesis “…. that antipsychotic reduction would improve social functioning with only a small increase in relapse rate.”
They concluded that no differences in social functioning were found between the group randomized to dose reduction compared to those randomized to maintenance treatment, but the risk of severe relapse was significantly increased in the dose reduction group.
Here, we will highlight some methodological limitations and elaborate on the dignity of risk-taking.
Limitations of causal inference from randomized clinical trials
We fully support the need for studies exploring gradual tapering. Studies with too fast or abrupt stopping will conflate withdrawal symptoms and relapses and may lead to inflated effect estimates of relapses. However, as much as we welcome the new wave of trials exploring the effect of open-label, gradual antipsychotic tapering, we will draw the attention to some methodological limitations associated with the causal contrasts in these studies. While the aim in these trials to provide data on the causal effect of maintenance treatment versus dose reduction, the low adherence to the allocated treatment arm may profoundly limit the casual inference.
RADAR, while by far the most rigorous study on the topic to date, has some of the methodological weakness as the other open-label tapering studies. In the maintenance arm, 10% stopped medication during the study period (many of these may be abrupt), compared to 27% in the dose reduction arm. On the other hand, people in the dose reduction arm may not have continued the process out of fear of relapse, or may have had their doses increased after a relapse. This leaves the two arms with rather similar levels of medication (200 versus 300 cpz equivalents), just as was the case in Wunderink’s study and the Danish Tailor trial.
In the most extreme case, the causal contrast may compare abrupt stopping in the maintenance arm with gradual reduction in the experimental arm. One solution may be to make a per protocol analyses, which means that only individuals who adhered to the protocol will be included in the analyses. However, this will introduce confounding by indication, and therefore approximate the same weaknesses as the purely observational data that Harrow published.
In the case of RADAR, we therefore cannot conclude that dose reduction does not affect social functioning but rather that being randomized to dose reduction did not affect social functioning compared to being randomized to maintenance treatment. This is the answer to a pragmatic real-life trial, as opposed to an explanatory trial where adherence would be optimized.
Further, it has been suggested that RADAR investigated if gradual dose reduction could decrease risk of relapse. This was not the case, as that hypothesis would need a trial comparing two different tapering strategies: rapid compared to gradual.
Dignity of risk-taking
Results from relapse prevention studies are often reported as relative numbers, such as relative risks or odds ratios, which convey little useful information for decisionmakers. Some have reported the relapse risk in RADAR to be doubled. This is not wrong, but it is important to add that 75% of those who had a trial of dose reduction did not have a severe relapse, and 10% were completely off medication. There were no signs of symptomatic or cognitive worsening in this group, opposing earlier studies suggesting a substantial risk of treatment resistance.
The primarily contribution and value of this finding is that it helps inform the potential risk during shared decision-making. For some people, a 25% risk of relapse may be too high, while for others the burden of medication is so heavy, they are willing to take the risk to find out if they belong to the fortunate subgroup that can discontinue completely and do not relapse. In most cases, people have the capacity to understand and weight the information and make their own personal choices about their lives including medication use, and it is crucial to support the dignity of risk-taking.
The concept of the dignity of risk finds its roots in the late 20th century, primarily attributed to Robert Perske, an advocate for the rights of people with disabilities. It underscores the notion that individuals, including those with mental health challenges, should have the freedom to make choices involving uncertainty or potential failure, emphasizing respect for autonomy and the inherent role of risk-taking in personal growth. While the disability rights movement, including Perske’s contributions, has significantly influenced the idea of dignity of risk, this concept has lately gained prominence in mental health.
The deinstitutionalization era marked a shift toward community-based mental health care, highlighting the importance of individual choice and self-determination. However, we contend that taking risks is an intrinsic part of human dignity, and buzzwords like empowerment and shared decision-making ring hollow if individuals are not allowed to make choices that involve an element of risk.
In our response to the RADAR study, we argued that the dignity of risk associated with dose reduction must be preserved. Here, we would like to extend the responsibility of healthcare professionals to include the risk of staying on medication. Choosing to stay on medication is also a form of risk-taking, considering uncertainties about the long-term effects on physical health and the potential for iatrogenic psychosis. The dignity of this type of risk-taking must be preserved, which may call for the recovery movement to keep a nuanced rhetoric strategy about medication.
At the same time, if we are sincere and honest in our aspirations to support people in their own risk taking, we must also defend (running a different risk—that of stating the obvious) the right to choose medication, as a part of the personal path to recovery. Choosing to take medication is an absolutely legitimate and often very helpful choice and we are truly disturbed and sadden when we encounter subtle messages of a recovery hierarchy. Recovery, as we all know, is personally defined and whether a person chooses to use or not use medication does not make one’s recovery more or less real!
Is a secondary deinstitutionalization necessary?
Regardless of the results from RADAR, the reluctance and sometimes even unwillingness of psychiatrist to support people who share their wish to taper or, alternatively, services that are contingent upon adherence poses a problem. Register-based studies reveal that less than 10% of people diagnosed with schizophrenia take medication regularly and continuously as prescribed. We also know that many stop without support, which makes the process much riskier.
According to the Danish OPUS studies, as much as one-third can stop medication without a relapse. This suggests that expressing the desire and/or choosing to taper is totally reasonable and certainly does not signify a lack of insight or impaired reasoning capacity. Another group is the 20% who never experienced a positive effect of medication, which is reported in many long-term studies. Few guidelines have suggested what good clinical care could be for this subgroup. To our knowledge, only one, the Danish guideline on antipsychotic treatment, recommends considering tapering off medication for these people as it makes no sense to add side effects, when they have no effect.
In reality, however, it seems like few people have the experience of their psychiatrists willing to do that, as any unfortunate events happening during tapering are likely to be attributed to discontinuation process. The combination of the collective striving for a shared illusion or delusion of certainly and predictability (don’t we all wish there was a simple and correct “answer”) together with the justified fear and concern about being blamed, held responsible and accountable for any possible future events sustains a situation in which psychiatrists often prefer not to be involved in tapering.
We will emphasize that most tragic happenings in society have nothing to do with mental illness. However, when it happens, psychiatric organizations are often the first to take responsibility, and claim they made a mistake, and this mistake could have been avoided if more economic resources was allocated to treatment. A Danish shooting in a shopping mall in 2022 is a good example, where a leading Danish psychiatrist claimed the event was caused by medical undertreatment.
While we understand the urge to use any occasion to fight for more resources, this rhetorical strategy gives rise to two paradoxes: 1) The societal impression that medication is necessary to keep “the mentally disordered” from being unpredictable and dangerous may further increase stigma, exclusion and marginalization. This increased stigma paradoxically increase the risk of these “deaths of despair”, as people are further driven away from meaningful participation in society. 2) If individual psychiatrists are blamed by colleagues for these types of tragic events, they are unlikely to support the next person who present with a wish to taper. This could paradoxically lead to more people stopping abrupt without support, increasing their risk of relapse.
To create a mental health system truly based on the ideology of recovery, self-determination and human rights there needs to be a change. We must therefore find a way to rise to the occasion and create a system that will truly respect people’s right to make choices about their lives including supporting the deprescribing phase of treatment when people choose.
Many psychiatrists are aware of the effect long-term use of antipsychotics often has on one’s sense of self and identity, vitality, energy, functioning and physical health. However, it seems like these risks are much more acceptable than the risks associated with tapering. There are never headlines in the news about people not being supported in a tapering process, and that they therefore developed obesity, diabetes and suffered a heart attack. We have been speculating that a lawsuit against a psychiatrist neglecting a wish to taper may be necessary to balance this imbalance.
“Talking about a revolution”, it is time that society in large and mental health and legal policy more specifically, create an infrastructure that will enable to accept and support choices including those that involve risk. The process of deinstitutionalization has been seen as one of the revolutions in mental health care. We suggest here, however, that there is a need for a second revolution. Where deinstitutionalization was an important step to acknowledge that people “even” with a mental illness are part of society and should have the right to live in their environment of choice (and certainly not locked in an institution), the next step is to accept that they cannot be medicated into normality, and if we will pay more than lip service to human rights, we must accept that some people prefer to live a life with psychotic symptoms or a risk for relapse if they feel anything like a zombie, a “dead man walking” or simply place more value on their sexual functioning, creativity or physical health.
As we navigate the complexities of risk discourse, we advocate for an inclusive discussion that recognizes the dignity of risk in mental health. The exploration of medication adherence, shifting towards patterns of use and tolerating ambiguity and uncertainty, and challenging societal perceptions, attitudes and stigma is essential for shaping policies that genuinely support individuals on their personal paths of recovery and well-being.
The RADAR study is the most rigorous study to date and its findings have made a major contribution to the field. Yet. We need to stop and ask: Do we really need more, stringent and larger studies like RADAR comparing dose reduction to maintenance? We are not sure this is the most urgent next step. Findings will most likely be replicated, with increased risk for those who stop medication. Perhaps rather than doing more of the same we need to consider trials comparing tapering strategies, exploring if there is indeed a need for manufacturing of smaller doses to avoid withdrawals and if psychosocial support can further decrease the risk.
The goal may not be to eliminate risk, but to respect the risk that people are willing to take, and then, from the professional perspective, develop interventions during tapering that makes it as safe as possible.
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