Effectiveness of 1-year treatment with long-acting formulation of aripiprazole, haloperidol, or paliperidone in patients with schizophrenia: retrospective study in a real-world clinical setting

Abstract

BackgroundSchizophrenia is a chronic mental illness that requires lifelong antipsychotic treatment. Therapy discontinuation, often due to poor adherence, increases the risk of relapses after both first and subsequent psychotic episodes. Long-acting injectable (LAI) antipsychotic drugs (APDs) have been introduced to increase therapeutic adherence, reducing blood-level variability compared to corresponding oral preparations.PurposeTo compare the effectiveness of three LAI-APDs: aripiprazole (Apr) prolonged release once monthly (OM) haloperidol decanoate (Hal-D) and paliperidone palmitate (PP-OM).MethodsWe retrospectively collected data for all patients with schizophrenia or other psychoses (n=217) treated with the three LAI-APDs for the first time from January 1, 2012 to October 31, 2016: n=48 with Apr-OM, n=55 with Hal-D, and n=114 with PP-OM. After 6 and 12 months of LAI treatments, we assessed clinical and functioning improvement, urgent consultations, psychiatric hospitalizations, adverse effects, and dropout. We compared urgent consultations and psychiatric hospitalizations required by the same patient 6 and 12 months before and after LAI implementation. Data were statistically analyzed.ResultsThe three LAI groups differed significantly only for “need for economic support from social service” (more frequent in the Hal-D group) and “schizoaffective disorder” (prevalent in the Apr-OM group). Apr-OM was prescribed at the maximum dose required by the official guidelines, whereas the other two LAIs were prescribed at lower doses. After 6 and 12 months’ treatment with the three LAI-APDs, we registered similar and significant reductions in both urgent consultations and psychiatric hospitalizations (P<0.001) and overlapping clinical and functioning improvement-scale scores (P<0.001), and 14.28% of patients dropped out, with no difference among the three LAI-APDs. Different kinds of adverse effects, though similar for number and severity, were reported in the three LAI groups.ConclusionOur results suggest that both first- and second-generation LAI-APDs represent important therapeutic options, useful for improving schizophrenia’s clinical course and its economic burden. Our study, which offers a wide and comprehensive observation of real-world clinical settings, combined an effectiveness evaluation through mirror analysis performed for each individual patient to a subsequent comparison among the three LAI-APDs, allowing us a more complete evaluation of clinical efficacy.

Improving the “real life” management of schizophrenia spectrum disorders by LAI antipsychotics: A one-year mirror-image retrospective study in community mental health services

“…However, with a specific focus group, we estimated, between 10% and 15%, the number of participants who discontinued LAIs in our department. This data is compatible with what reported in the literature with similar study designs [20,21]. These selection biases represent limitations for nearly all pragmatic studies [11].…”

“…Moreover, RCTs also present selection bias due to the enrolment of patients with different therapy adherence from real-world settings and, furthermore, in such design the trial itself could affect patient outcomes (Hawthorne effect), because of the social treatment and the increased personal attention often associated with participating in trials [1]. Our design choice is supported by several other authors [1,[18][19][20][21] who used studies designed without control groups. A second important limitation is that we took into account only one-way of switching for two reasons.…”

The Current Landscape of Novel Formulations and the Role of Mathematical Modeling in Their Development

“…63,69 Aripiprazole, haloperidol, paliperidone palmitate, risperidone, and olanzapine are LA injectable antipsychotics that have significant advantages over oral formulations for the treatment of schizophrenia. 70,71 Currently, 2 antiretrovirals-cabotegravir and rilpivirine LA IM nanoformulations-are in phase III clinical trials for 4-weekly and 8-weekly administration. 72 LA SDN formulation of atovaquone, an antimalarial, was designed and evaluated in C5BL/6 mice.…”

“…Contraceptives such as medroxyprogesterone acetate and norethisterone enanthate are administered as IM or SC formulations, whereas levonorgestrel and etonorgestrel are administered as implants 63,69 . Aripiprazole, haloperidol, paliperidone palmitate, risperidone, and olanzapine are LA injectable antipsychotics that have significant advantages over oral formulations for the treatment of schizophrenia 70,71 . Currently, 2 antiretrovirals—cabotegravir and rilpivirine LA IM nanoformulations—are in phase III clinical trials for 4‐weekly and 8‐weekly administration 72 .…”

The use of long-acting Aripiprazole in a multi-center, prospective, uncontrolled, open-label, cohort study in Germany: a report on global assessment of functioning and the WHO wellbeing index

“…However, independent of having a first or having had multiple psychotic episodes, nonadherence rates in patients with schizophrenia are high [5], and the reasons for nonadherence are complex [6][7][8]. Adherence to pharmacological treatment may be improved when long-acting injectables (LAIs) are used, which has been mainly demonstrated under real life conditions [9][10][11][12][13][14]. Aripiprazole oncemonthly (AOM) is an atypical LAI that was shown to elicit clinically relevant and lasting improvements in the patientsq uality of life in the QUALIFY study [15,16], accompanied by improvements in functioning and ability to work [17].…”