Simulated long‐term outcomes of early use of long‐acting injectable antipsychotics in early schizophrenia

Abstract

Aim Duration of untreated psychosis in early schizophrenia impacts long‐term outcomes. Because long‐acting injectable (LAI) antipsychotic drugs improve adherence in early‐stage patients, they could reduce additional time in uncontrolled psychosis (TUP) during the critical period of the illness. However, the long‐term benefit of early LAI use over oral formulations has not been quantified. This study explores the potential magnitude of the benefit with a simulation approach. Methods A microsimulation models the effects of 11 treatment pathways reflecting alternative decisions on whether and when LAI agents are used during a “calibration phase” that starts at treatment entry and lasts until the end of the 3‐year critical period. Treatment failure prolongs time in psychosis. Long‐term outcomes are predicted over the ensuing 7‐year period as a function of TUP. Results An “early LAI” pathway where LAI treatment follows the second oral treatment failure is compared to an oral‐only pathway. Under these pathways, 69% and 46% of patients, respectively, are estimated to exit the calibration phase with adequate symptom control (total positive and negative syndrome scale score below 68). Relative to the oral‐only pathway, the early LAI pathway is predicted to increase competitive employment by 39% (25% vs 18%) and independent or family living by 22% (71% vs 58%), and to decrease receipt of disability benefits by 36% (42% vs 66%) and hospital admissions per 1000 patient‐years by 15% (249% vs 294%). Conclusions While these simulation results need to be confirmed empirically, they suggest that earlier use of LAI antipsychotics can meaningfully improve patient outcomes.

Comparison of Long-Acting Injectable Antipsychotics With Oral Antipsychotics and Suicide and All-Cause Mortality in Patients With Newly Diagnosed Schizophrenia

“…Given that inadequate medication adherence is common among patients with newly diagnosed schizophrenia, more active consideration of LAIs in this stage for better long-term outcomes should be encouraged, particularly for those who have already exhibited poor adherence attitudes. 39 , 37 , 45 , 46 , 47 , 48 Additional studies are also needed to clarify long-term adverse effects specific to LAIs use and identify specific psychotherapeutic and psychosocial interventions that may offer other benefits to patients in the early stage.…”

Controversies Surrounding the Use of Long-Acting Injectable Antipsychotic Medications for the Treatment of Patients with Schizophrenia

“…Also, a 2016 survey of researchers and clinicians with LAI experience reported a strong consensus for prescribing LAIs not only to those who are nonadherent but also to patients with a broader range of conditions, such as certain histories (i.e., multiple hospitalizations/relapses, violence, suicide attempt, substance abuse), poor illness insight, cognitive impairment, and in patients aged 18-25 years [57]. Early introduction of LAIs can provide increased competitive employment/independent living and decreased disability/hospital admissions compared with OA treatment [58], supporting LAI use in a broader range of patients.…”

Aripiprazole Long-Acting Injection During First Episode Schizophrenia—An Exploratory Analysis

“…One of the more frequent causes of relapse in schizophrenia is non-adherence (40). While the use of LAIs is often restricted to chronic patients with frequent relapses and poor adherence, some studies showed that LAIs may be effective also at the outset of schizophrenia (41,42) and there is a strong movement towards implementing LAI treatment early in the course of schizophrenia or other psychoses (43)(44)(45)(46). Furthermore, early treatment of FEP co-occurring with SUD was shown to benefit even patients with poor prognosis (47).…”