Background: Despite research comparing adherence/persistence among long-acting injectables (LAIs) and oral antipsychotics (OAPs), a systematic synthesis of the available evidence is lacking. This study systematically reviewed real world evidence comparing LAIs and OAPs adherence/persistence among patients with schizophrenia.

Methods: In addition to examining grey literature, a systematic review was conducted in PubMed, Cochrane, CINAHL, and PsychInfo. Three independent researchers conducted screening and PRISMA guidelines and PICO criteria were employed. Only observational studies directly comparing adherence/persistence between LAIs and OAPs in adults were included.

Results: Of the 1,118 studies identified, N=36 were included with N=24 conducted in the US and N=14 using Medicaid databases. A total of 172,916 OAPs and 11,547 LAIs users were analyzed. Sixteen studies reported adherence and persistence, while 13 studies reported adherence only and 7 studies reported persistence only. Most of the studies used proportion of days covered (PDC; N=16) vs. medication possession ratio (MPR; N=9); 20 studies (55.6%) reported proportion of adherence using ≥80% threshold. Among 29 studies, 21 (72.4%) indicated that LAIs users had significantly higher adherence (MPR/PDC≥80%) vs. OAP (range: 26.7-74.0 vs 9.0-61.6%, respectively). One study found no difference and 4 studies revealed inconsistent results when different measurements or subgroups were employed. Descriptive analyses showed that proportion of adherent patients was higher among LAIs than OAPs. Additionally, 17 studies involving persistence (out of N=23 total) reported LAI users were less likely to discontinue or had significantly longer time to discontinue compared to OAPs. Only 1 study found no difference in persistence between LAIs and OAPs.

Conclusion: This review highlighted the advantage of LAIs over OAPs in improving adherence and persistence in heterogeneous patient populations. Given that LAIs are underutilized and frequently reserved as the “last resort” for patients with more severe schizophrenia, LAIs should be considered earlier as an option for patients with schizophrenia.