In a multicountry, randomized, open-label study of more than 500 adults with schizophrenia, participants received either LAI paliperidone, LAI aripiprazole, or the respective oral formulation of these antipsychotics.
Results showed no significant difference between the combined oral and combined LAI treatment groups in time to all-cause discontinuation.
“We found no substantial advantage for LAI antipsychotic treatment over oral treatment, regarding time to discontinuation in patients with early-phase schizophrenia,” write investigators, led by Inge Winter-van Rossum, PhD, assistant visiting professor at Mount Sinai, New York, and affiliated with King’s College London and UMC Utrecht (the Netherlands).
This indicates that “there is no reason to prescribe LAIs instead of oral antipsychotics if the goal is to prevent discontinuation of antipsychotic medication in daily clinical practice,” they add.
The findings were published online in The Lancet Psychiatry.
Previous conflicting results
Maintenance treatment with antipsychotic medication reduces risk for relapse considerably, with treatment discontinuation being “by far the most important reason for relapse,” the investigators write.
LAIs “seem theoretically to be a way to enhance medication continuation and thereby reduce the risk for relapse,” they add. This is because LAIs enable a rapid response to nonadherence and remove the need for patients to remember to take their medications on a daily basis.
However, previous research has “provided conflicting results,” regarding the effectiveness of LAIs in accomplishing this. Moreover, the subject has not been thoroughly investigated in early-stage schizophrenia, the researchers note.
Therefore, they decided to conduct the EULAST study to compare LAI and oral formulations in terms of all-cause discontinuation.
The trial was conducted at 50 general hospitals and psychiatric specialty clinics located in 15 European countries and Israel and included 511 participants in the intention-to-treat sample (67% men; mean age, 30.5 years).
All were randomly assigned 1:1:1 to receive either LAI paliperidone, LAI aripiprazole, or their respective oral formulations.
The combined OA treatment group consisted of 247 patients; the combined LAI group consisted of 264 patients.
Randomization was stratified by country and illness duration (5 months to 3 years vs. 4-7 years). Participants were followed up to 19 months, with all-cause discontinuation during that time serving as the primary endpoint.
All-cause discontinuation was defined as the allocated treatment was stopped or used at doses outside the allowed range, medication was switched or augmented with another antipsychotic after visit four, the patient missed a monthly visit and did not show up after being reminded, the patient withdrew consent for the study, or the clinician withdrew the patient from the study.
After the baseline visit, patients already taking antipsychotics were also randomly assigned. The next 4 weeks were then used to cross-taper between the prestudy antipsychotic and the agent they would be treated with during the study.
LAIs not superior
Results showed the LAI group did not have lower rates of hospitalization.
In addition, the discontinuation rates between the two combined groups were very similar at 71% for the oral antipsychotics group versus 64% in the LAIs group (hazard ratio, 1.6; 95% confidence interval, 0.94-1.43; P = .18).
Moreover, “no significant difference was found in the time to all-cause discontinuation between the combined oral and combined LAI treatment groups (P = .17),” the researchers report.
Reasons for discontinuation also did not differ significantly between the groups: 12% of patients in the OA group discontinued treatment because of efficacy vs. 17% of patients in the combined LAI group. The difference was not significant and the time to discontinuation also did not differ.
The main reason for discontinuation in both groups was safety concerns, affecting 10% and 13% of the combined OA and LAI groups, respectively, which was not a significant between-group difference.
Illness duration had a significant effect on time to all-cause discontinuation, with patients who had longer illness duration showing a poorer response, compared with those who had shorter duration (HR, 1.26; 95% CI, 1.01-1.56; P = .038).
However, stratifying participants by illness duration showed no significant difference between the subgroups (P = .25 and .34, respectively).
There was a significant between-group difference in discontinuation due to “other reasons,” with 49% vs. 34% of patients in the OA and LAI groups, respectively, discontinuing (HR, 1.51; 95% CI, 1.15-1.98; P = .0034). Moreover, the LAI group showed significantly longer continued use of medication vs the OA group (P = .0029).
“After separating the reasons for discontinuation into no efficacy, safety reasons, and other reasons, we only found a significant difference in favor of LAI for the ‘other reasons’ category; although the number of patients discontinuing medication for this reason over the follow-up period did not differ, patients on LAI continued treatment for a longer time,” the investigators write.
They acknowledge that this finding is “difficult to interpret, given the wide variety of reasons for discontinuation captured in this category,” which prevented an “informative subgroup analysis.”
Nevertheless, since there is “no consistent evidence supporting the use of LAI over oral antipsychotics” in patients with early-phase schizophrenia, their use should be “carefully considered on an individual risk-benefit basis,” they conclude.