ObjectivesThe current recommended treatment for patients with recurrent episodes of schizophrenia and related conditions is antipsychotic medication. However, many antipsychotic users remain functionally impaired and experience serious physical and mental side effects. This study aims to assess the cost-effectiveness of a gradual antipsychotic reduction and discontinuation strategy compared with maintenance treatment over 24 months from mental health services, health and social care, and societal perspectives. MethodsNineteen mental health trusts recruited patients to the RADAR randomized controlled trial. Quality-adjusted life-years were calculated from patient-reported EQ-5D-5L, with years of full capability calculated from the patient-reported ICECAP-A. Mental health services use and medication was collected from medical records. Other resource use and productivity loss was collected using self-completed questionnaires. Costs were calculated from published sources. ResultsA total of 253 participants were randomized: 126 assigned to antipsychotic dose reduction and 127 to maintenance. There were no significant differences between arms in total costs for any perspectives. There were no significant difference in quality-adjusted life-years (−0.035; 95% CI: −0.123 to 0.052), whereas years of full capability were significantly lower in the reduction arm compared with the maintenance arm (baseline-adjusted difference: −0.103; 95% CI: −0.192 to −0.014). The reduction strategy was dominated by maintenance for all analyses and was not likely to be cost-effective. ConclusionsIt is unlikely that gradual antipsychotic reduction and discontinuation strategy is cost-effective compared with maintenance over 2-years for patients with schizophrenia and other recurrent psychotic disorders who are on long-term antipsychotics.