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.

Patients with schizophrenia who initiated LAI vs oral antipsychotics experienced reductions in hospitalizations and schizophrenia relapses after drug initiation, which may be indicative of improved disease management.

Norepinephrine (NE) is recognized as having a key role in the pathophysiology of major depressive disorder (MDD) and schizophrenia, although its distinct actions via α-adrenergic receptors (α-ARs) are not well defined. We performed a systematic review examining the roles of NE and α-ARs in MDD and schizophrenia. PubMed and ProQuest database searches were performed to identify English language papers published between 2008 and 2015. In total, 2,427 publications (PubMed, n = 669; ProQuest, n = 1,758) were identified. Duplicates, articles deemed not relevant, case studies, reviews, meta-analyses, preclinical reports, or articles on non-target indications were excluded. To limit the review to the most recent data representative of the literature, the review further focused on publications from 2010 to 2015, which were screened independently by all authors. A total of 16 research reports were identified: six clinical trial reports, six genetic studies, two biomarker studies, and two receptor studies. Overall, the studies provided indirect evidence that α-AR activity may play an important role in aberrant regulation of cognition, arousal, and valence systems associated with MDD and schizophrenia. Characterization of the NE pathway in patients may provide clinicians with information for more personalized therapy of these heterogeneous diseases. Current clinical studies do not provide direct evidence to support the role of NE α-ARs in the pathophysiology of MDD and schizophrenia and in the treatment response of patients with these diseases, in particular with relation to specific valence systems. Clinical studies that attempt to define associations between specific receptor binding profiles of psychotropics and particular clinical outcomes are needed.

Approximately 60% of patients with schizophrenia are nonadherent to antipsychotic medication early in treatment and are less likely to be adherent later. Early nonadherence resulted in more all-cause and schizophrenia-related hospitalizations with a greater LOS and cost of care.

Real-world medication adherence and healthcare costs of patients with schizophrenia initiating long-acting injectable (LAI) vs. oral antipsychotics were compared. Patients with schizophrenia initiating LAI or oral antipsychotics (index event) were identified from MarketScan Commercial and Medicare claims databases and their medication possession ratios (MPR), pre- and post-index costs for inpatient/outpatient care were compared. Of 3,004 patients, 394 initiated LAI antipsychotics and 2,610 oral antipsychotics. Post-index, the mean MPR was greater for the LAI cohort (0.67 ± 0.34 vs. 0.56 ± 0.35; p < 0.001). Schizophrenia-related hospital costs for LAI users were reduced during the follow-up period in comparison to the pre-index period, but were increased for patients using oral antipsychotics (-$5,981 ± $16,554 vs. 758 ± 14,328, p < 0.001). The change in costs of outpatient care also favored LAI medications ($134 ± 8,280 vs. 658 ± 3,260, p = 0.023). Drug costs of LAI antipsychotics were higher ($4,132 ± 4,533 vs. 2,562 ± 2,714, p < 0.001). Schizophrenia patients initiating LAI antipsychotics incur less healthcare costs in comparison to patients initiating oral antipsychotics.