Randomised controlled trial of gradual antipsychotic reduction and discontinuation in people with schizophrenia and related disorders: the RADAR trial (Research into Antipsychotic Discontinuation and Reduction)

Abstract

IntroductionAntipsychotic medication is effective in reducing acute symptoms of psychosis, but it has a range of potentially serious and debilitating adverse effects and is often disliked by patients. It is therefore essential it is only used when benefits outweigh harms. Although multiple trials conducted with people with schizophrenia indicate an increased risk of relapse in the short-term following abrupt antipsychotic discontinuation, there is little evidence about the long-term outcome of a gradual process of reduction and discontinuation on social functioning, relapse and other outcomes.Methods and analysisThis is a multicentre, randomised controlled trial involving people with schizophrenia and related disorders who have had more than one episode. Participants are randomised to have a clinically-supervised, gradual reduction of antipsychotic medication, leading to discontinuation when possible, or to continue with maintenance treatment. Blinded follow-up assessments are conducted at 6, 12 and 24 months and the primary outcome is social functioning, measured by the Social Functioning Scale at 24 months. A minimum of 134 evaluable participants provides 90% power to detect a five-point difference, and 206 to detect a four-point difference. Secondary outcomes include severe relapse (admission to hospital) and the study is also intended to detect a minimum 10% difference in severe relapse, which requires 402 participants, assuming a 15% loss to follow-up. Other secondary outcomes include all relapses, as identified by an independent and blinded endpoint committee, symptoms measured by the Positive and Negative Syndrome Scale, quality of life, adverse effects, self-rated recovery and neuropsychological measures. Enrolment started in 2016. The trial is scheduled to finish in June 2022.Ethics and disseminationEthical approval was initially obtained on 27 October 2016 (UK Research Ethics Committee reference 16/LO/1507). Results will be published in peer-reviewed journals and disseminated to the public.Trial registration number ISRCTN90298520. EudraCT: 2016-000709-36. Pre-results.

Pharmacological treatment algorithms for the acute phase, agitation, and maintenance phase of first‐episode schizophrenia: Japanese Society of Clinical Neuropsychopharmacology treatment algorithms

“…The algorithm does not recommend discontinuation of antipsychotics for the following reasons. First, it is reported that the discontinuation of antipsychotics is associated with a higher risk of relapse even in first‐episode schizophrenia or psychosis (Kishi et al., 2019 ; Leucht et al., 2012 ), several studies are ongoing to address this topic (Begemann et al., 2020 ; Liu et al., 2021 ; Moncrieff et al., 2019 ; Stürup et al., 2017 ; Weller et al., 2019 ). Second, there are no established clinical predictors for successful discontinuation of antipsychotics (Bowtell et al., 2018 ).…”

Clozapine discontinuation withdrawal symptoms in schizophrenia

“…From a preventative approach, the optimal tapering regime to minimise the risk of withdrawal symptoms has also not been explored empirically; however, studies are underway. 93 Whilst a patient-rated scale to measure the success of antipsychotic and antidepressant discontinuation has recently been developed, 94 the scale does not differentiate between the withdrawal symptoms described in this review, which may also be present with other psychotropics. 11 Finally, the role of medication to prevent and treat clozapine-withdrawal symptom is largely unknown.…”

The role of trust and hope in antipsychotic medication reviews between GPs and service users a realist review

“…This review is part of a wider NIHR funded programmethe RADAR trial on antipsychotic medication reduction. LG, NC and JM are also affiliated with the RADAR trial [21] and members of he trial's LEAP (Lived Experience Advisory Panel), which included mental health service users and carers, were involved in discussing the initial aims of the study and reviewing theories on two occasions.…”