Earlier Use of Long-Acting Injectable Paliperidone Palmitate Versus Oral Antipsychotics in Patients With Schizophrenia: An Integrated Patient-Level Post Hoc Analysis.

Objective: To assess the efficacy and safety of paliperidone palmitate (PP) long-acting injectable antipsychotic (LAI) versus oral antipsychotic (OAP) treatment in adult patients diagnosed with schizophrenia (per DSM-IV or DSM-5 criteria) and varying duration of illness (0-3 years and > 3 years).Methods: Patient-level data from the PRIDE, PROSIPAL, and DREaM studies were included in a post hoc analysis. Efficacy and safety outcomes, including relapse assessments, Personal and Social Performance scale scores, Medication Satisfaction Questionnaire total scores, and treatment-emergent adverse events (TEAEs), were measured systematically. Treatment failure (TF) included relapses due to psychiatric hospitalizations, arrest or incarceration, suicidal or homicidal ideation or behavior, discontinuation due to inadequate efficacy and/or safety or tolerability, treatment supplementation due to inadequate efficacy, and significant worsening of symptoms.Results: Fewer TFs were observed with PP versus OAP in both the 0-3 years group (17.7% and 25.3%, respectively) and the > 3 years group (32.3% and 42.4%, respectively). Time to first TF was significantly longer with PP versus OAP treatment in both duration of illness groups. TEAE rates were similar between the PP and OAP groups, with no new safety signals identified.Conclusions: This post hoc analysis suggests that PP provides significant benefit in reducing TF or relapse compared with OAPs regardless of duration of illness and highlights the potential benefit of implementing PP earlier in the course of schizophrenia.Trial Registration: ClinicalTrials.gov identifiers NCT01157351 (PRIDE), NCT01081769 (PROSIPAL), and NCT02431702 (DREaM).

Comparing Relapse Rates in Real-World Patients with Schizophrenia Who Were Adequately versus Not Adequately Treated with Paliperidone Palmitate Once-Monthly Injections Before Transitioning to Once-Every-3-Months Injections.

Purpose: This retrospective cohort study evaluated real-world data on relapses in adult patients with schizophrenia who transitioned to long-acting injectable paliperidone palmitate once-every-3-months (PP3M) following treatment with once-monthly paliperidone palmitate (PP1M). Patients and Methods: Data derived from the IBM® MarketScan® Multi-State Medicaid Database were analyzed. Adults aged ≥18 years with ≥1 schizophrenia diagnosis claim and ≥12 months of continuous medical and prescription enrollment before and/or at index date of PP3M were eligible for inclusion. Patients were matched on propensity score to 2 PP3M cohorts: (1) adequately treated (AT), defined as patients treated with PP1M for ≥4 months, with the last 2 doses the same and a PP3M initiation dose meeting the corresponding PP1M-to-PP3M dose conversion, or (2) not adequately treated (NAT), defined as patients who received ≤2 or no PP1M doses. Relapse rates and time to relapse distributions based on the first occurrence of a qualifying event during the 2-year follow-up period were compared between PP3M cohorts using Kaplan-Meier survival curves and log rank test statistics. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Two sensitivity analyses using different matched populations were performed to assess the robustness of the primary findings. Results: Propensity score matching yielded a sample of 1314 patients (657 per group). Most patients were male (68.9%) and aged 25-64 years (90.1%). The relapse rate was significantly lower in the AT (18.4%) versus NAT cohort (26.8%), P = 0.0002. Risk of relapse decreased by 35% for AT versus NAT (HR: 0.65 [95% CI: 0.51-0.81]). Relapse reductions favored the AT cohort in both sensitivity analyses (HR: 0.67 [95% CI: 0.54-0.83] and HR: 0.74 [95% CI: 0.56-0.97]). Conclusion: In this analysis of Medicaid claims data, patients adequately treated with PP1M before transitioning to PP3M demonstrated significantly lower relapse rates and delayed time to relapse.

Treatment response to esketamine nasal spray in patients with major depressive disorder and acute suicidal ideation or behavior without evidence of early response: a pooled post hoc analysis of ASPIRE.

OBJECTIVE: To assess the likelihood of attaining response/remission of depressive symptoms with esketamine nasal spray (ESK) plus standard of care (SoC) vs placebo nasal spray (PBO) plus SoC at 4 weeks in patients with major depressive disorder and active suicidal ideation with intent (MDSI) without early response. METHODS: A post hoc analysis of pooled data from ASPIRE I and ASPIRE II evaluated ESK plus SoC vs PBO plus SoC in adults with MDSI without response (≥50% improvement from baseline in Montgomery-Åsberg Depression Rating Scale [MADRS] score) at 24 hours after the first dose or at week 1 after the first two doses (ie, 24-hour and week 1 nonresponders). Response and remission (MADRS score ≤ 12) rates were assessed on day 25. RESULTS: The analysis included 362 patients (n = 182, ESK plus SoC; n = 180, PBO plus SoC). Among 24-hour nonresponders, more patients receiving ESK plus SoC vs PBO plus SoC achieved response (63.9% vs 48.0%, P = .010) and remission (35.1% vs 24.4%, P = .074) at day 25. Odds of response/remission were higher with ESK plus SoC vs PBO plus SoC (response: 1.89, 95% CI, 1.17-3.05; remission: 1.48, 95% CI, 0.93-2.35). Similar findings were observed among week 1 nonresponders for response (48.4% vs 34.5%, P = .075), remission (25.0% vs 13.1%, P = .060), and odds of response/remission (response: 2.03, 95% CI, 1.22-3.40; remission: 1.63, 95% CI, 1.01-2.62). CONCLUSIONS: Patients with MDSI not responding within the first week of treatment with ESK plus SoC may still benefit from a full 4-week treatment course.

Health care resource use, short-term disability days, and costs associated with states of persistence on antidepressant lines of therapy.

AIMS: To compare health care resource utilization (HCRU), short-term disability days, and costs between states of persistence on antidepressant lines of therapy after evidence of treatment-resistant depression (TRD). METHODS: Patients with major depressive disorder (MDD) were identified in the IBM MarketScan Commercial and Medicare Supplemental Databases (01/01/2013-03/04/2019), Multi-State Medicaid Database (01/01/2013-12/31/2018), and Health Productivity Management Database (01/01/2015-12/31/2018). The index date was the date of the first evidence of TRD during the first observed major depressive episode. The follow-up period was divided into 45-day increments and categorized into persistence states: (1) evaluation (first 45 days after evidence of TRD); (2) persistence on the early line after evidence of TRD; (3) persistence on a late line; and (4) non-persistence. HCRU, short-term disability days, and costs were compared between persistence states using multivariate generalized estimating equations. RESULTS: Among 10,053 patients with TRD, the evaluation state was associated with higher likelihood of all-cause inpatient admissions (odds ratio [OR; 95% confidence interval (CI)] = 1.79 [1.49, 2.14]), emergency department visits (OR [95% CI] = 1.23 [1.12, 1.34]), and outpatient visits (OR [95% CI] = 3.83 [3.51, 4.18]; all p < .001) versus persistence on the early-line therapy. This resulted in $374 higher mean PPPM all-cause health care costs (95% CI = 265, 470; p < .001) during evaluation versus persistence on the early line therapy. The evaluation state was associated with 89% more short-term disability days (OR [95% CI] = 1.89 [1.49, 2.57] and $212 higher mean PPPM short-term disability costs (95% CI = 64, 259) relative to persistence on the early line (both p < .001). Moreover, during persistence on a later line, mean PPPM all-cause health care costs were $141 higher (95% CI = 13, 242; p = .028) relative to the early line. LIMITATIONS: Medication may have been dispensed but not actually taken. CONCLUSIONS: Higher costs during the first 45 days after evidence of the presence of TRD and during persistence on a late line relative to persistence on the early-line therapy suggest there are benefits to using more effective treatments earlier.

Prevalence of Pre-existing Conditions Relevant for Adverse Events and Potential Drug-Drug Interactions Associated with Augmentation Therapies Among Patients with Treatment-Resistant Depression.

INTRODUCTION: Pre-existing conditions relevant for adverse events (AE) and the potential for drug-drug interactions (DDIs) may limit safe pharmacotherapeutic augmentation options for patients with major depressive disorder (MDD). This concern may be heightened among patients with treatment-resistant depression (TRD), who often have comorbid medical disorders. METHODS: Adults with MDD and ≥ 1 antidepressant claim within the first observed major depressive episode were identified in the MarketScan® Databases. Those initiating a new regimen after two regimens at adequate dose and duration were considered to have TRD. The index date was defined at TRD onset or on a random antidepressant claim among patients with non-TRD MDD. Pre-existing conditions 12 months pre-index and potential DDIs 3 months pre/post-index associated with specific non-antidepressant augmentation therapies, including atypical antipsychotics (APs), buspirone, psychostimulants, anticonvulsants, thyroid hormone, and lithium were compared between 1:1 matched TRD and non-TRD MDD cohorts. RESULTS: Overall, 3414 patients with TRD and non-TRD MDD (mean age 39.7 years, 69% female) were matched. Relative to non-TRD MDD, patients with TRD had 33% higher likelihood of ≥ 1 pre-existing condition relevant for AEs listed in product labels of non-antidepressant augmentation therapies (p < 0.001). Patients with TRD vs. non-TRD MDD had 12.9 and 6.4 times higher likelihood of ≥ 2 and ≥ 3 DDIs, respectively, based on their medication regimen (all p < 0.001). CONCLUSION: Pre-existing conditions relevant for listed AEs and potential DDIs limit safe augmentation options in MDD, particularly among patients with TRD. Payer prior authorization policies requiring several augmentation therapy trials to access novel treatments may complicate clinical management of this population.