Gradual Antipsychotic Dose Reduction May Increase Relapse risk in Psychotic Disorders

A recent study led by Dr. Joanna Moncrieff from University College London suggests that reducing or discontinuing antipsychotic medication in patients with schizophrenia or other psychotic disorders may increase the risk of severe relapse. The study published in The Lancet aimed to determine if lowering antipsychotic drug dosages could be safely done to mitigate adverse effects associated with these medications.

Antipsychotic drugs, while effective in treating psychotic disorders, are known to have adverse effects, including an increased risk of diabetes, heart disease, tardive dyskinesia, sedation, akathisia, emotional blunting, and sexual dysfunction. To assess the potential benefits of reducing antipsychotic dosages, researchers conducted the RADAR trial, an open-label, randomised study involving patients from 19 National Health Service Trusts in England.

The RADAR trial was conducted across 19 National Health Service (NHS) Trusts in England. Eligible participants were adults aged 18 years and older who had received a diagnosis of recurrent, non-affective psychotic disorder and were currently prescribed antipsychotic medication. Individuals who had experienced a mental health crisis or hospitalization within the preceding month, those deemed to pose a significant risk to themselves or others by their treating clinicians, and individuals mandated to take antipsychotic medication under the Mental Health Act were excluded from the trial.

Participants were randomly assigned to one of two groups using an independent internet-based system, with a 1:1 allocation ratio. The study groups included those who underwent a gradual and flexible reduction in antipsychotic medication under the supervision of their treating clinicians (reduction group) and those who continued with their current maintenance dose (maintenance group). Both participants and clinicians were aware of the treatment allocations they received, but the assessors responsible for evaluating the study's outcomes were kept unaware of this information.

The follow-up period for participants lasted for two years. The primary outcome measure was social functioning, assessed using the Social Functioning Scale. The principal secondary outcome was the occurrence of severe relapse, defined by the need for admission to a hospital due to worsening mental health symptoms. All data analysis was performed while keeping group identities concealed, using the intention-to-treat approach.

• In this study, a total of 4,157 individuals were initially screened to participate. Out of these, 253 participants were randomly assigned to the study groups.
  
• Among the participants, there were 168 (66%) men, 82 (32%) women, and 3 (1%) individuals who identified as transgender.
• The average age of the participants was 46 years, with a standard deviation of 12 years, and the age range spanned from 22 to 79 years.
• In terms of ethnicity, 171 (67%) of the participants identified as White, 52 (21%) as Black, 16 (6%) as Asian, and 12 (5%) as belonging to other ethnic backgrounds.
• The analysis revealed no significant difference in social functioning between the two groups, as indicated by a beta coefficient of 0.19, with a 95% confidence interval ranging from -1.94 to 2.33 and a p-value of 0.86.

The study's findings suggest that gradually reducing antipsychotic medication does not result in improved long-term social functioning. This information can help guide decisions about the use of long-term antipsychotic medication in individuals with schizophrenia or recurrent psychotic disorders. The study highlights the importance of carefully weighing the benefits and risks of antipsychotic treatment and tailoring treatment approaches to individual patient needs.

Reference:

Moncrieff J, Crellin N, Stansfeld J, et al. Antipsychotic dose reduction and discontinuation versus maintenance treatment in people with schizophrenia and other recurrent psychotic disorders in England (the RADAR trial): an open, parallel-group, randomised controlled trial [published online ahead of print, 2023 Sep 28]. Lancet Psychiatry. 2023;S2215-0366(23)00258-4. doi:10.1016/S2215-0366(23)00258-4