EULAST: No clear benefits in prescribing long-acting over oral antipsychotics for early-phase schizophrenia

Long-acting injectable antipsychotics (LAIAs) showed no substantial advantage over oral antipsychotics in terms of time to discontinuation in patients with early-phase schizophrenia, the EULAST trial has demonstrated.

Medication discontinuation is by far the most important reason for schizophrenia relapse. However, almost half of schizophrenia patients take <70 percent of their oral antipsychotic medication. Theoretically, switching patients from oral antipsychotics to LAIAs may enhance medication adherence, thereby reducing the risk of relapse. [Lancet Psychiatry 2023;doi: 10.1016/S2215-0366(23)00005-6]

To compare all-cause discontinuation rates with oral antipsychotics vs LAIAs, the researchers conducted the EULAST trial in 15 European countries and Israel. “To our knowledge, it is the first large, pragmatic, open-label randomized clinical trial comparing LAIAs with their oral equivalents in patients with early-phase schizophrenia,” wrote the researchers.

In EULAST, a total of 511 patients with schizophrenia (mean age, 30.5 years; female, 33 percent) who experienced their first psychotic episode from 6 months to 7 years before screening were randomized 1:1:1:1 to receive the LAIAs paliperidone or aripiprazole, or the respective oral formulations, and followed up for up to 19 months.

After 19 months of treatment, all-cause discontinuation rates were 71 percent and 64 percent in the combined oral antipsychotic and the combined LAIA groups, respectively. “We did not find a difference in time to all-cause discontinuation between the combined oral and combined LAIA groups [hazard ratio, 1.16; 95 percent confidence interval, 0.94–1.43; p=0.18],” reported the researchers.

Reasons for all-cause discontinuation were further divided into three major categories: discontinuation due to efficacy, safety issues, or other reasons (eg, loss to follow-up, patients no showing up at study visits after one reminder, treatment refusal, withdrawal due to time investment, patients preferring another or no medication, manic episode, suicide attempt, and death).

“[Among these categories], we only found a significant difference in favour of LAIAs for other reasons [49 percent vs 34 percent; HR, 1.51; 95 percent CI, 1.15–1.98; p=0.0034],” noted the researchers. Among patients who discontinued antipsychotics for other reasons, LAIA recipients showed significantly longer continued use of medication vs oral antipsychotic recipients (log-rank test X²=8.84 [df 1]; p=0.0029). However, these results are difficult to interpret, given the wide variety of reasons for discontinuation captured in this category, which hindered an informative subgroup analysis.

To conclude, results of the EULAST trial indicated that there is no reason to prescribe LAIAs instead of oral antipsychotics in patients with early-phase schizophrenia if the goal is to prevent antipsychotic medication discontinuation. “The use of LAIAs should be carefully considered on an individual benefit-risk basis,” noted the researchers.