To prevent discontinuation of antipsychotic medication in daily clinical practice among patients with early-phase schizophrenia, no difference was found in treatment with long-acting injectable (LAI) antipsychotic vs oral treatment concerning time to discontinuation. These findings were published in The Lancet Psychiatry.
Researchers sought to compare time to all-cause discontinuation of medication in patients with early-phase (less than 7 years since first contact with a health care provider in relation to psychotic symptoms) schizophrenia allocated to LAI vs oral medication. The primary outcome was all-cause medication discontinuation up to 19 months of treatment. Secondary outcomes included changes in global psychosocial functioning, different dimensions of psychopathological symptoms, hospitalizations, and side effects.
This pragmatic trial (EULAST; ClinicalTrials.gov Identifier: NCT02146547) was randomized and open-label conducted at 50 psychiatric specialty clinics and general hospitals in Israel and 15 European countries from February 2015 to December 2018. Inpatients and outpatients (aged at least 18 years) with confirmed DSM-IV schizophrenia (first psychotic episode between 6 months and 7 years prior to screening) were randomly allocated to LAI paliperidone, LAI aripiprazole, oral paliperidone, or oral aripiprazole using block randomization (1:1:1:1), stratified by country and illness duration (6 months to 3 years vs 4 to 7 years). The follow-up period lasted up to 19 months.
Researchers recruited and evaluated 533 individuals of whom 511 were included in the intention-to-treat population (33% women; mean age 30.5±9.6 years; 80% White, 7% Black, 4% Asian). They found in the combined LAI treatment arm (n=264) there were 36% of patients who did not discontinue medication and 64% who met all-cause discontinuation criteria (treatment stopped or dosages outside allowed range, medication switched or augmented with another antipsychotic, patient missed monthly visit, withdrew consent, clinician withdrew patient, loss to follow-up, patient declined treatment for symptoms, or death). In the combined oral antipsychotics treatment arm (n=247) there were 29% of patients who did not discontinue medication and 71% who met all-cause discontinuation criteria.
Treatment discontinuation for any cause did not differ between the 2 combined treatment groups (hazard ratio [HR], 1.16; 95% CI, 0.94-1.43; P =.18) in Cox regression analyses. Researchers found no significant difference in time to all-cause discontinuation between the combined LAI (median 200 days; 95% CI, 131-269) and combined oral (median 175 days; 95% CI, 122-228) treatment groups (log rank test χ²=1.87 [df 1]; P =.17). Discontinuation due to efficacy was 12% in the combined oral group and 17% in the combined LAI group with no significant difference in Cox regression analyses (HR, 0.73; 95% CI, 0.46-1.16; P =.19) and no significant difference between groups in the Kaplan-Meier curve time to discontinuation due to efficacy (log rank test χ²=1.77 [df 1]; P =.18).
There were 103 patients accounting for 121 psychiatric hospitalizations during the study, and 1 patient from each of the LAI groups died (1 death unrelated to medication, 1 cause of death unknown to researchers). They noted at some point during the study, 25% of 350 participants with available data met akathisia criteria and 20% met parkinsonism criteria according to the Mini-International Neuropsychiatric Interview 5 plus.
Study limitations include the open-label study design, the interpretation of side-effects, sample size estimation not based on all-cause discontinuation, and patient sample did not remain representative of the general population of patients with schizophrenia.
Researchers wrote, “We did not find a difference in time to all-cause discontinuation between the combined oral and combined LAI groups.” They concluded their findings “do not support a clear advantage for the use of LAI antipsychotics over oral antipsychotics in a large, representative patient population with early-phase schizophrenia, if the goal is to prevent discontinuation of antipsychotic medication.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Winter-van Rossum I, Weiser M, Galderisi S, et al.; EULAST Study Group. Efficacy of oral versus long-acting antipsychotic treatment in patients with early-phase schizophrenia in Europe and Israel: a large-scale, open-label, randomized trial (EULAST). Lancet Psychiatry. Published online January 27, 2023. doi:10.1016/S2215-0366(23)00005-6