Cost‐Effectiveness of Early Dose Reduction or Discontinuation Versus Antipsychotic Maintenance After First‐Episode Psychosis: Results From the HAMLETT Study

Background After remission from a first episode psychosis (FEP), international clinical guidelines recommend continuation of antipsychotic medication for at least 1 year, although many patients wish to reduce or discontinue medication due to side effects or long‐term health concerns. Evidence on the cost‐effectiveness of early dose reduction or discontinuation compared to continuation remains limited. Methods A trial‐based cost‐utility analysis was conducted alongside the ongoing HAMLETT study, in which 347 remitted FEP participants were randomized to either early guided dose reduction or discontinuation or maintenance treatment for 1 year. Both healthcare and societal perspectives over a 24‐month time horizon were considered. Health outcomes were expressed as quality‐adjusted life years (QALYs) derived from the EQ‐5D‐5L questionnaire using Dutch valuation tariffs. Costs were estimated using patient reported healthcare utilization and administrative pharmacy data. Incremental costs and effects were analysed using seemingly unrelated regression with uncertainty assessed through nonparametric bootstrapping and multiple sensitivity analyses. Results Early dose reduction or discontinuation was associated with lower quality‐adjusted life years and higher or comparable costs compared with maintenance treatment over the 2‐year analysis period. In the base‐case societal perspective analysis, incremental costs were €23,563 and incremental effects were −0.077 QALYs, resulting in an incremental net monetary benefit of ‐€27,430 at a willingness‐to‐pay threshold of €50,000 per QALY at 24 months. Results were consistent across several scenarios with only approximately 9% probability that early dose reduction or discontinuation was cost‐effective at the assumed willingness‐to‐pay threshold. However, a sex‐at‐birth subgroup analysis suggested a small and uncertain positive incremental net monetary benefit among female participants. Conclusion Over a 24‐month period, early dose reduction or discontinuation of antipsychotic medication after remission from a FEP is unlikely to be cost‐effective compared with maintenance treatment from both healthcare and societal perspectives. Whether longer term functional improvements associated with early dose reduction translate into cost‐effective benefits remains uncertain and requires follow‐up. Trial Registration: EudraCT number: 2017‐002406‐12