Maintenance Discontinuation After First Episode Psychosis May Increase Treatment Non-Responsiveness: 10-Year Follow-Up of an RCT

Abstract

Background: Clinical decision to discontinue antipsychotics in patients remitted from first-episode psychosis is important. Existing short-term evidence suggests that patients who discontinued antipsychotics had more relapses. Data on long-term outcomes are lacking; with only one open-label study suggesting better long-term recovery outcome in patients who had early medication discontinuation. We compared the long-term clinical and functional outcomes at 10 years of remitted first-episode psychosis patients who had either discontinued or continued their antipsychotic medications in the early stage of the illness under a randomized controlled trial (RCT). Methods: We followed up 178 first-episode psychosis patients who participated in a 1-year RCT on medication discontinuation. In the RCT, patients were randomized into receiving either a medication maintenance group (MT) or a placebo discontinuation group (PL). In this follow-up study, 142 subjects were successfully traced and assessed at 10 years on their clinical, functional and cognitive outcomes. Results: There were no differences between patients who were included (n = 142) and excluded (n = 36) from the study with regard to their baseline demographics, clinical and functioning. At 10 years, patients in the PL group had more residual delusion as defined using PANSS P1 item score (15%) than those in the MT group (4%; P = .028). PL group also had more treatment refractory (as defined using residual delusion or on clozapine; 24%) than the MT group (8%; P = .011). Specifically, PL started to take clozapine significantly earlier than MT during the follow-up period (P = .04). We found no significant differences between MT and PL in terms of functioning, cognitive functioning, quality of life, and medication taken after 10 years. Conclusion: This is the first study to examine the long-term impacts of medication discontinuation during early phase of psychotic disorders. Our findings show that early decision to stop medication in remitted first-episode psychosis may result in less symptomatic remission and more treatment nonresponsiveness. The decision to discontinue medication during the early phase of psychosis should be considered carefully.