Efficacy and Effectiveness of Depot Versus Oral Antipsychotics in Schizophrenia

Abstract

Objective: Nonadherence is a major challenge in schizophrenia treatment. While long-acting (depot) antipsychotic medications are often recommended to address adherence problems, evidence on the comparative effectiveness of depot versus oral antipsychotics is inconsistent. We hypothesize that this inconsistency could be due to systematic differences in study design. This review evaluates the effect of study design on the comparative effectiveness of antipsychotic formulations. The optimal use of different antipsychotic formulations in a general clinical setting depends on better understanding of the underlying reasons for differences in effectiveness across research designs.Data Sources: A PubMed literature review targeted English-language studies (2000-2011) with information on relapse, hospitalization, or allcause discontinuation for depot and oral antipsychotic treatment arms in schizophrenia. The time frame was chosen to reflect research focused on the newer generation of antipsychotic agents. The search required at least 1 term from each of the following categories: (1) schizophrenia; (2) inject, injection, injectable, injectables, injected, depot, long-acting; and (3) iloperidone, fluphenazine, haloperidol, paliperidone, risperidone, olanzapine, asenapine, flupentixol, flupenthixol, lurasidone, clopenthixol, fluspirilene, zuclopentixol, zuclopenthixol. Study Selection: Thirteen relevant studies were identified by 2 independent reviewers; these studies included information on 19 depot-oral comparisons.Data Extraction: Age-and gender-adjusted risk ratios (RRs) (depot/ oral) were calculated for the identified endpoints and pooled by study design (randomized controlled trial [RCT], prospective observational, and retrospective observational). Meta-analysis with random effects was used to estimate the pooled RRs, by study design. Average conversion factors between study designs were calculated as the ratios of pooled RRs.Results: Meta-analysis of adjusted endpoints showed no apparent benefit of depot over oral formulations in RCTs, with an RR of 0.89 (P = .416). In contrast, there was a significant advantage for depot formulations in other study designs (prospective RR = 0.62 [P < .001]; retrospective RR = 0.56 [P < .001]). These imply conversion factors of 1.43 and 1.59 between RCTs and prospective and retrospective designs, respectively. Conclusions:The comparative effectiveness of antipsychotic formulations is sensitive to research design. Depot formulations displayed significant advantages in nonrandomized observational studies, whereas in RCTs no difference was observed. The estimated conversion factors may facilitate comparison across studies.

Treatment response and tolerability with once-monthly paliperidone palmitate initiated shortly after hospital admission in patients with schizophrenia

“…Although there has been conflicting evidence regarding the superiority of LATs over oral antipsychotics (Leucht et al 2011;Kishimoto et al 2013Kishimoto et al , 2014, the outcomes of these studies are highly related to the trial design (Kirson et al 2013). Naturalistic and pragmatic studies, such as the current and other recent studies in acute and nonacute patients with schizophrenia (Schreiner et al 2014, provide valuable information in populations more akin to those encountered in routine clinical practice , by allowing patients with relevant comorbidities, co-medications and substance abuse to be included.…”

The influence of application of neuroleptics orally or parenterally on body mass index in patients with schizophrenia

“…DISKUSIJA Porast tjelesne težine češće se uočava pri tretmanu neurolepticima druge i treće generacije (klozapin, olanzapin, sertindol, risperidon i kvetiapin) u odnosu na neuroleptike prve generacije, što se objašnjava afinitetom neuroleptika druge i treće generacije prema histaminskim H1 receptorima [23][24][25][26][27]. Studija u trajanju 12 sedmica bolničkog liječenja, na uzorku od 33 bolesnika tretirana haloperidolom i 23 pacijenta tretirana olanzapinom, pokazala je da se BMI povećao u obe skupine, kao i obim struka, kukova, potkožnog masnog tkiva, holesterola, triglicerida i prolaktina, što naglašava značaj redovnog praćenja metaboličkih parametara u bolesnika sa shizofrenijom koji se liječe tipičnim i atipičnim neurolpeticima [28].…”

Design and Rationale of the Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) Study

“…Studies comparing long-acting injectable versus oral antipsychotic treatment have provided inconsistent results, [6][7][8][9][10][11][12][13][14][15] with some indication that demonstrating a differential effectiveness among these formulations is better established with a more pragmatic clinical trial design than with one that is more explanatory. [16][17][18][19] With this in mind, we designed the Paliperidone Palmitate Research in Demonstrating Effectiveness (PRIDE) study (ClinicalTrials.gov identifier: NCT01157351) to compare once-monthly paliperidone palmitate and daily oral antipsychotics in real-world schizophrenia, as defined by subject inclusion criteria, treatment, and outcomes. It was hypothesized that paliperidone palmitate would be more effective than oral antipsychotics.…”