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Background: TV46000 is a long-acting subcutaneous antipsychotic (LASCA) formulation of risperidone approved for the treatment of schizophrenia in adults. Methods: The RISE study (NCT03503318) compared TV-46000 once monthly (q1m) and once every 2 months (q2m) with placebo (1:1:1) in patients with schizophrenia who underwent stabilization on oral risperidone. The SHINE study (NCT03893825) evaluated the long-term safety, tolerability, and effectiveness of TV-46000 in patients who completed RISE without relapse (rollover; placebo rollover randomized [1:1] to q1m or q2m; TV-46000 rollover continued assigned treatment) or who were newly recruited (de novo; randomized [1:1] to q1m or q2m after oral stabilization). Patient-centered outcomes included the Schizophrenia Quality of Life Scale (SQLS), the 5-Level EuroQoL 5-Dimensions Questionnaire (EQ-5D-5L), the Personal and Social Performance Scale (PSP), and the Drug Attitudes Inventory 10-item version (DAI-10). Results: In RISE, SQLS least-squares mean changes (SE) improved to last assessment (LA) for TV-46000 q1m (– 4.15 [1.03]) and q2m (– 3.28 [1.06]) but worsened for placebo (1.75 [1.07]; P< 0.001 for both). PSP, EQ5D-5L, and DAI-10 showed similar trends. In SHINE, SQLS decreased (improved) at LA for both TV-46000 q1m (− 0.43 [0.98]) and q2m (− 2.16 [0.98]); reductions were observed in the de novo (q2m only) and placebo rollover (q1m and q2m) cohorts, but not for the TV46000 rollover cohort. Results for PSP, EQ5D-5L, and DAI-10 were consistent with those reported in the RISE study. Conclusion: Improvements in patient-centered outcomes were observed across cohorts, with the largest improvements observed for patients who began TV-46000 during SHINE (ie, de novo and placebo rollover cohorts), while gains made during RISE were minimally improved or maintained in the TV-46000 rollover cohort, indicating the benefit of uninterrupted TV-46000 treatment. These data support the effectiveness of TV-46000 to improve patient-centered outcomes in patients with schizophrenia. Plain Language Summary: RISE and SHINE were clinical studies where patients with schizophrenia received TV-46000. TV-46000 is injected under the skin once monthly or once every 2 months to treat schizophrenia in adults. In RISE, patients took pills for the first 3 months, and then received injections under the skin. Some patients received inactive (placebo) injections. Comparing results among groups showed the effectiveness and side effects of TV-46000. Patients who completed RISE could continue into SHINE. SHINE included patients who had not been part of RISE as well. All patients received TV-46000 in SHINE to see if results were the same long term. This report summarizes the results of patient-centered outcomes. These included measures of quality of life and attitudes toward the medicine. In RISE, quality of life and attitudes toward the medicine improved with TV-46000, but worsened with placebo. In SHINE, the patient-centered outcomes also improved. The largest improvements were for patients who began taking TV-46000 during SHINE. This analysis showed that there is a benefit in taking TV-46000 for longer times without breaks. It also showed that TV-46000 improves quality of life and attitudes toward the medicine. [ABSTRACT FROM AUTHOR]

Aripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU 960) is a novel long-acting injectable (LAI) formulation of aripiprazole monohydrate for administration once every 2 months, developed for the treatment of schizophrenia or maintenance monotherapy treatment of bipolar I disorder in adults (indication will vary by country). Aripiprazole lauroxil 1064 mg (AL 1064) is an LAI formulation of aripiprazole lauroxil, an aripiprazole prodrug, for administration once every 2 months, indicated for the treatment of schizophrenia in adults. This analysis provides an indirect comparison of aripiprazole plasma concentrations following multiple doses of either formulation. Clinical trial data were used to determine average steady-state aripiprazole plasma concentration (Cavg,ss), maximum aripiprazole plasma concentration (Cmax), and other pharmacokinetic parameters of either formulation following four administrations (96 patients received Ari 2MRTU 960; 28 patients received AL 1064). All pharmacokinetic parameters were considered in the context of a minimum aripiprazole therapeutic concentration (Cmin) of ≥ 95 ng/mL. An exposure–response analysis using data from two Phase III trials of aripiprazole once-monthly (an aripiprazole monohydrate LAI, administered monthly), showed that patients with a Cmin ≥ 95 ng/mL are 4.41 times less likely to relapse than patients with a Cmin < 95 ng/mL. A similar analysis has not been performed for AL 1064. However, consensus guidelines for therapeutic drug monitoring recommend a range of 100– 350 ng/mL for aripiprazole. Following four administrations, mean (standard deviation [SD]) Cavg,ss over the 2-month dosing interval was 263 (133) ng/mL for Ari 2MRTU 960 and 140.7 (57.3) ng/mL for AL 1064. Mean (SD) Cmax during the fourth dosing interval was 342 (157) ng/mL for Ari 2MRTU 960 and 188.8 (79.8) ng/mL for AL 1064. This indirect comparison showed that, following four administrations, Ari 2MRTU 960 and AL 1064 delivered mean aripiprazole plasma concentrations that remained above the minimum therapeutic concentration of aripiprazole over the 2-month dosing interval. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to assess the efficacy and safety of paliperidone palmitate (PP) treatment compared with risperidone long-acting injectable (LAI) treatments for patients with schizophrenia. Patients and Methods: Data mining was conducted in April 2022 across PubMed, Web of Science, Embase, the Cochrane Library, ClinicalTrials.gov, and PsycINFO. All published randomized controlled trials (RCTs) that assessed the effect of PP treatment for patients with schizophrenia when compared with the risperidone-LAIAs group were included. Relevant data were extracted and synthesized narratively. Results were expressed as standardized mean differences (SMDs) or risk ratios (RRs), with 95% confidence intervals (CIs). Results: Four RCTs with 2451 patients met all the inclusion and exclusion criteria. Efficacy analyses showed no significant statistical differences in Positive and Negative Syndrome Scale (PANSS) total score changes at the endpoint (SMD = 0.10, P = 0.19), or in response rates (RR = 0.93; P = 0.40). Regarding the safety outcomes, PP treatment showed significantly increased risks of discontinuation rates for any reason (35.7% vs 30.4%; RR = 1.19; 95% CI, 1.03 to 1.39; P = 0.02) and nonsignificantly increased risks of total treatment emergent adverse events (TEAEs) (66.6% vs.64.8%; RR = 1.01; 95% CI, 0.94 to 1.09; P = 0.78) compared with the risperidone-LAIAs-treated group. Furthermore, PP may significantly increase total discontinuation rates compared with risperidone-LAIAs. Conclusion: Our meta-analysis did not find a more beneficial effect of PP compared to risperidone-LAIAs treatments for schizophrenia. Clinicians should interpret and translate our data with caution, as the meta-analysis was based on a limited number of randomized controlled trials and patients. [ABSTRACT FROM AUTHOR]

Purpose: To examine efficacy and safety of paliperidone palmitate (PP) 6-month (PP6M) vs PP3-month (PP3M) long acting injectable (LAI) in patients with schizophrenia from European sites previously stabilized on PP3M or PP1-month (PP1M). Methods: This post-hoc subgroup analysis used data from a global phase-3 double-blind (DB) randomized non-inferiority study (NCT03345342). Patients were randomized (2:1, respectively) to receive dorsogluteal injections of PP6M (700 mg eq. or 1000 mg eq.) or PP3M (350 mg eq. or 525 mg eq.) in the 12-month DB phase. Primary endpoint was time-to-relapse during the DB phase, using a Kaplan–Meier cumulative survival estimate (non-inferiority margin 95% CI lower bound larger than prespecified as − 10%). Treatment emergent adverse events (TEAEs), physical examinations, and laboratory tests were also evaluated. Results: A total of 384 patients who entered the DB phase were included in European sites (PP6M, n = 260; PP3M, n = 124) with a mean age similar in both groups (mean age [SD] years: PP6M, 40.0 [11.39]; PP3M, 38.8 [10.41]). Baseline characteristics were similar across both groups. The number of patients who experienced a relapse during DB phase were PP6M: 18 (6.9%) vs PP3M: 3 (2.4%) with percentage relapse-free difference of − 4.9% (95% CI: − 9.2%, − 0.5%), thus achieving non-inferiority criteria. Secondary efficacy endpoints indicated comparable improvements. Incidence of TEAEs was similar between PP6M (58.8%) and PP3M (54.8%) groups. Nasopharyngitis, headache, increased weight, and injection-site pain were the most common TEAEs. Conclusion: The efficacy of PP6M was non-inferior to that of PP3M in preventing relapse in the European subgroup previously treated with PP1M or PP3M, which was consistent with the global study. No new safety signals were identified. [ABSTRACT FROM AUTHOR]

Medication nonadherence in schizophrenia can have serious implications including relapses and hospitalization. Long-acting injectable (LAI) antipsychotics require fewer administrations, while ensuring sustained medication coverage. In this review, we summarize the expected real-world benefits of longer dosing intervals in the management of schizophrenia. LAIs are associated with improved clinical outcomes of less frequent relapses and reduced functional impairment, encouraging patients to regain control of their lives. Aripiprazole lauroxil and paliperidone palmitate three-monthly (PP3M) LAIs have longer dosing intervals of 2– 3 months and provide improved outcomes in patients with schizophrenia. Paliperidone palmitate six-monthly (PP6M) LAI provides the longest dosing interval, twice-yearly dosing, among existing LAIs. Decreasing the frequency of LAI administrations has the potential to reduce occurrence of serious outcomes associated with poor medication adherence. By eliminating the need for daily oral antipsychotic dosing, LAIs could increase the likelihood of patient acceptance, decrease stigma, and promote self-esteem. Longer intervals of medication coverage may be desirable for patients with higher risk of relapse including adults with recent-onset schizophrenia, those living in circumstances that may deprive them of regular access (eg, homeless), those that are in transitions between care settings or to reduce interpersonal contact during public health emergencies (eg, COVID-19 pandemic). [ABSTRACT FROM AUTHOR]

Those patients who completed the DB phase according to the protocol were invited to enter an OLE phase along with other newly enrolled patients (de novo) to determine the efficacy, safety and tolerability of the long-term use of Risperidone ISM. Finally, the inclusion of de novo patients in the OLE phase allowed us to study the impact of Risperidone ISM on schizophrenia in patients who were clinically stable with oral risperidone at the time of entering the study. [Extracted from the article]

Background: To obtain real-world evidence of functional improvements during atypical long-acting injectable (aLAI) therapy in recent-onset schizophrenia, an online survey was conducted to assess the impact of aripiprazole once-monthly injectable 400 mg (AOM 400; partial D2 receptor agonist) and paliperidone palmitate once-monthly (PP1M; injectable, full D2 receptor antagonist). Methods: Psychiatrists provided data for their 2 most recent AOM 400 patients, 2 most recent PP1M patients. Survey included 2000 patient cases (1000 AOM 400; 1000 PP1M). Eligible patients were aged 18– 35 years, had been diagnosed with schizophrenia within 5 years, received AOM 400 or PP1M continuously for ≥ 6 months according to approved labels (mean durations: 1.6 and 1.7 years with AOM 400 and PP1M, respectively). Assessments included Global Assessment of Functioning (GAF) Scale, Personal and Social Performance Scale, Positive and Negative Syndrome Scale, and Quality of Life Scale. GAF assessments were done retrospectively and also at the time of survey. Results: Baseline mean GAF scores were 43.3 and 43.8 for AOM 400 and PP1M, respectively, indicating serious symptoms/functional impairment in both groups. Mean improvements following AOM 400 and PP1M therapy were 19.7 and 16.3 points, respectively (final scores in mild functional impairment category). Other measures assessing symptoms/functionality/quality of life demonstrated the benefits of long-term aLAI therapy. Conclusion: Schizophrenia patients with serious functional impairment prior to current aLAI treatment showed improvements in functional outcome after AOM 400 or PP1M therapy. These results suggest functional improvements with aLAIs are apparent not only in research but also real-world settings. [ABSTRACT FROM AUTHOR]

Figure1 PANSS responders (defined by PANSS total score reduction thresholds of 20-50%) with AL 441 mg, 882 mg, or AL doses pooled: NNTand 95% CI vs placebo, at Placebo (n=196) AL 441 mg q4wk (n=196) AL 882 mg q4wk (n=204) AL Pooled (n=400) Placebo (n=207) AL 441 mg q4wk (n=207) AL 882 mg q4wk (n=208) AL Pooled (n=415) Placebo (n=207) AL 441 mg q4wk (n=207) AL 882 mg q4wk (n=208) AL Pooled (n=415). [Extracted from the article]

Purpose: There is growing agreement that definitions of "recovery" in bipolar-I disorder (BP-I) should include functional outcomes beyond sustained symptomatic remission. In this post-hoc analysis, we assessed functional recovery rates according to the validated Functioning Assessment Short Test (FAST) in participants with BP-I after 52 weeks of maintenance treatment with aripiprazole once monthly (AOM). Patients and methods: Rates of functional recovery with AOM 400 were investigated in two 52-week studies. NCT01567527 was a placebo-controlled, double-blind, randomized-withdrawal study and NCT01710709 was an open-label study. Functional recovery, assessed at the end of the respective maintenance phases, was defined as a total FAST score of ≤11 for 8 consecutive weeks. Results: Post-hoc analyses included 229 patients from the randomized-withdrawal study (AOM 400 n=116; placebo n=113). The open-label study included 402 patients (including 321 de novo patients and 81 rollover patients who had completed the randomized-withdrawal study). In the randomized-withdrawal study, functional recovery was achieved by 30.2% (n=35) of the AOM 400 group compared with 24.8% (n=28) in the placebo group. The difference was not statistically significant (p=0.39). In the open-label study, 36% (n=116) of de novo patients and 43% (n=35) of rollover patients had functionally recovered after 52 weeks of AOM 400 treatment. Conclusion: These data highlight the utility of a sustained FAST total score of ≤11 as a definition of recovery and emphasize the possibility of achieving this ambitious treatment goal with effective long-term treatment. [ABSTRACT FROM AUTHOR]

Background: In this study, we applied a qualitative approach to explore patients' subjective experiences of long-acting injectable antipsychotics (LAIs). Methods: Patients undergoing psychiatric treatment from the chronic ward or outpatient department of a medical center in northern Taiwan who had experience with LAI treatment were enrolled. Information was obtained through semi-structured in-depth interviews. The interviews were audio-recorded and then translated verbatim, and the data were collected and analyzed concurrently to develop major themes and categories. Result: In total, 14 participants (8 female) were interviewed. In a bio-psycho-social model, the participants used LAIs as a method to become "normal," in order to achieve a balance between the "effects" and "side effects" that may influence their daily lives. Their past experiences constructed their concepts about and expectations regarding LAIs, and their relationships with their family members and co-workers also modeled their experiences. Conclusion: In our study, we sought to understand the experience of LAI in the daily life context of the patients. We attempted to use a bio-psycho-social model to evaluate the subjective experience of the patients; an improved understanding can help mental health specialists gain a closer insight into patient experience. [ABSTRACT FROM AUTHOR]

Highlights from the article: Maintenance treatment in stable patients with schizophrenia Patients were aged <=35 years and 118 patients were aged Table 1 Baseline demographics and patient disposition in subgroups of randomized patients stratified by age from a 12-week Patients included schizophrenia (1.8%, AOM 400; 1.7%, Patients, n (%) Acute Treatment (Study 291) Maintenance Treatment.

Highlights from the article: Conclusion: In acute treatment and maintenance therapy settings, AOM 400 was effective Abbreviations:AOM,aripiprazoleonce-monthly;CGI-S,ClinicalGlobalImpressionSeverity;OA,oralaripiprazole;Pts,patients;PANSS,PositiveandNegativeSyndromeScale; 246 patients, Study 247 patients, and de novo patients. Numerically larger treatment effects seen among patients Adherence and treatment outcome in patients with schizophrenia or.

Background: The subgroup analysis of a primary study (NCT01051531) evaluated the effect of long-term paliperidone palmitate once-monthly (PP1M) therapy in Chinese patients with recent-onset schizophrenia responding unsatisfactorily to previous oral antipsychotics. Patients and methods: This 18-month, open-label study consisted of 3 phases – screening (7 days), treatment (18 months) and end-of-study/withdrawal visit. All enrolled patients (18–50 years) received PP1M: 150 mg eq. (day 1), 100 mg eq. (day 8) followed by a once-monthly flexible dose (50, 75, 100 or 150 mg eq.). Efficacy and safety were assessed. Results: Among the 118 enrolled Chinese patients, 68 completed the treatment (mean age: 25.6 years; male: 54.7%). A clinically meaningful change from baseline to day 548 was observed in Positive and Negative Syndrome scale (primary endpoint, mean [SD]: −15.3 [20.76]), Personal and Social Performance scale (15.9 [19.65]), Clinician Global Impression-schizophrenia score (−1.2 [1.54]) and Medication Satisfaction Questionnaire score (0.9 [1.73]). Commonly reported treatment-emergent adverse events (TEAEs) included insomnia (13.9%), injection-site pain (13.9%), upper respiratory tract infection (13.0%), restlessness (13.0%) and akathisia (13.0%). Serious TEAEs were reported in 9.3% patients with schizophrenia being most common (6.5%) and one death (suicide) was observed. Conclusion: Efficacy of PP1M corroborate findings from earlier studies and no new safety concerns emerged in this Chinese subgroup of patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Purpose: Long-acting injectable (LAI) antipsychotic paliperidone palmitate 3-month formulation (PP3M) is indicated in the United States for the treatment of schizophrenia only after adequate treatment with paliperidone palmitate 1-month formulation (PP1M) for ≥4 months. This analysis aimed to identify patient and disease characteristics during PP1M treatment associated with greater likelihood of achieving remission after transition to PP3M. Methods: A post hoc analysis of a randomized, Phase III, double-blind, noninferiority trial of PP3M vs PP1M (ClinicalTrials.gov identifier: NCT01515423) was conducted in adult patients with schizophrenia. Patients achieving clinical stability after 17 weeks of open-label PP1M were randomized to 48 weeks of double-blind treatment with PP3M or PP1M. The primary objective of this exploratory post hoc analysis was to identify demographic and/or clinical variables associated with persistent remission after treatment with PP3M. Multiple logistic regression analysis identified the following significant predictors of remission: Positive and Negative Syndrome Scale (PANSS) Marder negative symptom factor score, Clinical Global Impression-Severity (CGI-S) total score, and Personal and Social Performance (PSP) total score. Results: At double-blind baseline, a 1-point reduction in Marder negative symptom factor score was associated with a 20% increase in the odds of achieving remission after PP3M treatment; 1-point reduction in CGI-S was associated with a doubling in remission odds; and 7- and 10-point improvements in PSP scores, respectively, were associated with 42% and 65% increases in remission odds. Conclusion: Patients with early clinically meaningful improvements in disease symptoms and severity while establishing stable PP1M dosage are more likely to achieve remission after transition to PP3M. [ABSTRACT FROM AUTHOR]

Purpose: This randomized, double-blind (DB), non-inferiority phase 3 study was conducted to assess the efficacy and safety of paliperidone palmitate 3-month (PP3M) vs 1-month formulation (PP1M) in European and non-European patients with schizophrenia. Patients and methods: In this randomized, DB, parallel-group study, adult patients (18–70 years) with schizophrenia (per DSM-IV-TR) having Positive and Negative Syndrome Scale (PANSS) total score between 70 and 120; previously stabilized on PP1M were enrolled. The study had 4 phases: screening (3 weeks), open-label (OL) stabilization (17 weeks), DB (48 weeks) and follow-up (4–12 weeks) phase. Patients were treated with fixed-dose PP3M (175–525 mg eq deltoid/gluteal) or PP1M (50–150 mg eq deltoid/gluteal) for 48 weeks in DB phase. Results: In total, 487 European (PP3M, n=242; PP1M, n=245) and 508 non-European patients (PP3M, n=241; PP1M, n=267) entered DB phase (modified intent-to-treat (mITT) [DB] analysis set). Among the 508 non-European patients in mITT set, 67.7% were from Asia (n=344) and 32.3% were from rest of world (ROW, n=164). During the DB phase, similar percentage of Europeans (PP3M: 7%; PP1M: 8%) and non-Europeans (PP3M: 9%; PP1M: 10%) experienced relapse (Kaplan–Meier estimate PP3M–PP1M [95% CI] of percentage of relapse-free patients at the end of DB phase [primary endpoint]: European: 1.0% [-4.3%; 6.2%]; non-European: 1.4% [-4.4%; 7.1%]; Asian: 1.6% [-5.7%; 9.0%]; and ROW: 1.4% [-7.0%, 9.8%], per-protocol analysis set). Incidence of treatment-emergent adverse events (TEAEs) was lower in Europeans (PP3M: 56%, PP1M: 59%) than non-Europeans (PP3M: 80%, PP1M: 73%). The most commonly reported TEAE was weight gain. Conclusion: PP3M showed similar efficacy to PP1M in Europeans and non-Europeans, consistent with non-inferiority of PP3M to PP1M observed in overall population. Rates of AEs were higher in non-Europeans. However, weight gain was greater in non-Europeans, especially the Asian population. [ABSTRACT FROM AUTHOR]

Maintaining therapeutic plasma concentrations of an antipsychotic agent is essential in preventing relapse of symptoms in schizophrenia. Long-acting injectable (LAI) formulations provide extended exposure to antipsychotic therapy and have been useful in addressing treatment nonadherence. Aripiprazole is an atypical antipsychotic used in the treatment of schizophrenia and is available in 2 chemically different (aripiprazole monohydrate and aripiprazole lauroxil [AL]) and pharmaceutically different LAI formulations (aripiprazole once-monthly 400 mg [AOM 400] and AL). The pharmaceutical difference is that AL, unlike AOM 400, is a prodrug that requires additional metabolic steps to form the active drug aripiprazole. We present data demonstrating that aripiprazole plasma concentrations are similar for AOM 400 and the 882 mg dose of AL when administered once every 4 weeks and that both provide similar therapeutic plasma concentrations of aripiprazole when compared with therapeutic oral doses. [ABSTRACT FROM AUTHOR]

This open-label, single-arm, multicenter, 13-week, prospective study explored the efficacy, safety, and tolerability of paliperidone palmitate (150 milligram equivalents [mg eq] [day 1], 100 mg eq [day 8], both deltoid injections; 75-150 mg eq, deltoid/gluteal injection) in Chinese patients with acute schizophrenia (Positive and Negative Syndrome Scale [PANSS] total score ≥70), who previously had unsatisfactory therapeutic effect following oral antipsychotic treatment (without washout period). Primary efficacy endpoint was percentage of patients with ≥30% improvement in the PANSS total score at the end of 13 weeks. Secondary efficacy endpoints included change from baseline to end of week 13 in PANSS total score, PANSS subscale scores, Marder factor scores, Clinical Global Impressions-Severity score, and Personal and Social Performance Scale scores. Overall, 477/610 enrolled patients (full analysis set, 78.2%) completed the study (men: 55.1%; women: 44.9%; mean age: 31.5 years). Total, 443/610 (72.6%, full analysis set) patients achieved primary endpoint (mean [standard deviation] change from baseline: -30.9 [19.51]). All secondary endpoints demonstrated significant improvement at the end of 13 weeks. One death occurred during this acute phase. The most common (>5%) treatment-emergent adverse events were extrapyramidal disorders (8.4%). The efficacy and safety data are consistent with other short-term, placebo-controlled studies of paliperidone palmitate conducted in similar populations. [ABSTRACT FROM AUTHOR]

Purpose: To assess the efficacy and safety of aripiprazole once-monthly 400 mg (AOM 400), an extended-release injectable suspension of aripiprazole, in obese and nonobese patients. Patients and methods: This post hoc analysis of a 38-week randomized, double-blind, active-controlled, noninferiority study (NCT00706654) compared the clinical profile of AOM 400 in obese (body mass index [BMI] ≥30 kg/m2) and nonobese (BMI <30 kg/m2) patients with schizophrenia for ≥3 years. Patients were randomized 2:2:1 to AOM 400, oral aripiprazole 10-30 mg/d, or aripiprazole once-monthly 50 mg (AOM 50 mg) (subtherapeutic dose). Within obese and nonobese patient subgroups, treatment-group differences in Kaplan-Meier estimated relapse rates at week 26 (z-test) and in observed rates of impending relapse through week 38 (chi-square test) were analyzed. Treatment-emergent adverse events (TEAEs) (>10% in any treatment group) were summarized. Results: At baseline of the randomized phase, obesity rates were similar among patients randomized to AOM 400 (n=95/265, 36%), oral aripiprazole (n=95/266, 36%), and AOM 50 mg (n=43/131, 33%). In both obese and nonobese patients, relapse rates through week 38 for patients randomized to AOM 400 (obese, 7.4%; nonobese, 8.8%) were similar to those in patients on oral aripiprazole (obese, 8.4%; nonobese, 7.6%), whereas relapse rates were significantly lower with AOM 400 versus AOM 50 mg (obese, 27.9% [P=0.0012]; nonobese, 19.3% [P=0.0153]). The most common TEAEs with AOM 400 in obese and nonobese patients were insomnia (12.6% and 11.2%), headache (12.6% and 8.2%), injection site pain (11.6% and 5.3%), akathisia (10.5% and 10.6%), upper respiratory tract infection (10.5% and 4.7%), weight increase (10.5% and 8.2%), and weight decrease (6.3% and 11.8%). Within the AOM 400 group, 7.6% of patients who were nonobese at baseline became obese, and 17.9% of obese patients became nonobese during randomized treatment. Conclusion: The clinical profile of AOM 400 was similar in obese and nonobese patients. [ABSTRACT FROM AUTHOR]

Improving medication adherence is critical to improving outcomes in patients with schizophrenia. A long-acting injectable (depot) antipsychotic is one of the most effective methods for improving treatment adherence and decreasing rehospitalization rates in patients with schizophrenia. Until recently, only three second-generation antipsychotics were available in a long-acting injectable formulation (risperidone, paliperidone, and olanzapine). In this respect, the emergence of long-acting aripiprazole injection (ALAI), approved by the US Food and Drug Administration for the treatment of schizophrenia in 2013, is timely. ALAI is a lyophilized powder of aripiprazole, and the aripiprazole molecule is unmodified. The initial and target dosage of ALAI is 400 mg once monthly, but it could be reduced to 300 mg if adverse reactions occur with 400 mg. When first administering ALAI, it is recommended to continue treatment with oral aripiprazole (10-20 mg/day) or another oral antipsychotic for 2 weeks in order to maintain therapeutic antipsychotic concentrations. The primary clearance route for ALAI is hepatic, ie, cytochrome P450 (CYP)2D6 and CYP3A4, so dose adjustment is required in poor CYP2D6 metabolizers. The efficacy of ALAI was demonstrated in three studies. A randomized controlled trial that formed the basis for approval of ALAI in the treatment of schizophrenia showed that ALAI significantly delayed time to impending relapse when compared with placebo (P<0.0001, log-rank test). An open-label, mirror study demonstrated that total psychiatric hospitalization rates were significantly lower after switching from oral antipsychotics to ALAI. Another randomized controlled trial presented in poster form suggested that ALAI 400 mg was comparable with oral aripiprazole 10-30 mg in preventing relapse. ALAI was generally well tolerated during both short-term and long-term studies. Its tolerability profile, including extrapyramidal symptoms and clinically relevant metabolic parameters, was similar to placebo. However, insomnia, headache, anxiety, akathisia, weight gain, injection site pain, and tremor need clinical attention. These studies suggest that ALAI is a viable treatment option for patients with schizophrenia, but direct head-to-head comparisons between ALAI and other long-acting injectable antipsychotics are needed to elucidate its risk-benefit profile. [ABSTRACT FROM AUTHOR]