Long-term D2 blockade not to blame for relapse in patients with first-episode schizophrenia

Continuous dopamine D2 receptor blockade does not appear to increase the risk of breakthrough psychosis in patients with first-episode schizophrenia, as shown in a study. 

Nearly half of these patients, however, will relapse despite continuous D2 blockade because of “nondopaminergic elements of the pathophysiology of the illness,” according to the researchers. 

The study used data from a Finnish nationwide cohort involving individuals aged ≤45 years with first-episode schizophrenia from 1996 to 2014. The researchers determined whether the incidence of breakthrough psychosis was accelerated among previously relapse-free patients receiving continuous D2 antagonist treatment beyond 5 years. 

The primary outcome was a severe relapse leading to hospitalization among individuals treated with long-acting injectable (LAI) antipsychotics, while the secondary outcome was the incidence rate ratio (IRR) of relapse during years 2–10, with year 1 as the reference. 

Overall, 305 patients used LAI during the first 30 days of follow-up. In Kaplan-Meier analysis, the cumulative probability of relapse stood at 45 percent (95 percent confidence interval [CI], 35–57) during the 10-year follow-up. 

The annual relapse incidence per person-year showed a significant drop from 0.26 (95 percent CI, 0.20–0.35) during the first year to 0.05 (95 percent CI, 0.01–0.19) during the fifth year. This corresponded to an IRR of 0.18 (95 percent CI, 0.04–0.74). 

From year 6 to 10, only four relapses were recorded for 128 person-years. This corresponded to an IRR of 0.12 (95 percent CI, 0.03–0.33) compared to year 1.