Antipsychotics for relapse prevention less effective a second time

Among patients with first-episode psychosis, the effectiveness of antipsychotics for relapse prevention decreased significantly after the second occurrence, according to a register-based cohort study published in The Lancet Psychiatry.

“The most effective antipsychotic doses for relapse prevention in first-episode schizophrenia and how they evolve during the course of illness are not known,” Heidi Taipale, PhD, of the department of forensic psychiatry at the University of Eastern Finland, and colleagues wrote. “We therefore aimed to study the evolution of antipsychotic dose and the risk of severe relapse, indicated by psychiatric rehospitalization, associated with use vs. non-use of antipsychotics and with specific dose categories in first-episode schizophrenia in a Finnish nationwide cohort.”

Using the nationwide Hospital Discharge register in Finland, Taipale and colleagues identified inpatients with first-episode schizophrenia aged 45 years or younger who were followed for 5 years of illness or until a fifth relapse episode. Rehospitalization due to psychosis served as the primary measure. The investigators defined a next relapse as time between relapses of at least 30 days.

They derived antipsychotic use from the prescription register, summed the dose from all concomitant antipsychotics and studied antipsychotic effectiveness for preventing rehospitalization using within-individual analyses to remove selection bias.

Taipale and colleagues analyzed data from 5,367 patients (64.2% men; mean age, 29.5 years at the start of follow-up). A total of 3,058 (57%) required hospitalizations. Among those who did, the mean dose increased gradually following every new relapse, from 1.22 defined daily doses per day (95% CI, 1.18-1.26) prior to the first relapse to 1.56 defined daily doses per day (95% CI, 1.48-1.64) prior to the fifth relapse. Researchers noted an increase in adjusted HR for rehospitalization with antipsychotic use vs. non-use from 0.42 (95% CI, 0.35-0.51) prior to the second relapse to 0.78 (95% CI, 0.62-0.99) following the second relapse, which suggested a significant decrease in effectiveness.

Analyses of specific dose categories revealed the lowest rehospitalization risk during use of the standard dose (0.9 to less than 1.1 defined daily doses per day) prior to but not following the second relapse. Low dose (less than 0.6 defined daily doses per day) correlated with significantly higher rehospitalization risk (aHR = 1.54; 95% CI, 1.06-2.24) compared with standard dose prior to the second relapse but not following the second relapse (aHR = 1.11; 95% CI, 0.76-1.62), which was related to the reduced effectiveness of all doses following the second relapse.

“The first relapse should be considered as the first marker of a more severe and potentially chronic course of schizophrenia needing enhanced interventions to prevent subsequent relapses,” Taipale and colleagues wrote. “Thus, all patients after their first relapse should receive a sufficient antipsychotic dose and enhanced efforts to prevent relapses, including psychoeducation and long-acting antipsychotic injections.”