No drugs are currently approved for the treatment of borderline personality disorder (BPD). These studies (a randomised study and its open-label extension) aimed to evaluate the efficacy, safety and tolerability of brexpiprazole for the treatment of BPD.

The Phase 2, multicentre, randomised, double-blind, placebo-controlled, parallel-group study enrolled adult outpatients with BPD. After a 1-week placebo run-in, patients were randomised 1:1 to brexpiprazole 2–3 mg/day (flexible dose) or placebo for 11 weeks. The primary endpoint was change in Zanarini Rating Scale for BPD total score from randomisation (Week 1) to Week 10 (timing of randomisation and endpoint blinded to investigators and patients). The Phase 2/3, multicentre, open-label extension study enrolled patients who completed the randomised study; all patients received brexpiprazole 2–3 mg/day (flexible dose) for 12 weeks. Safety assessments included treatment-emergent adverse events (TEAEs).

Brexpiprazole was not statistically significantly different from placebo on the primary endpoint of the randomised study (N = 324 randomised; N = 110 analysed per treatment group; least squares mean difference −1.02; 95% confidence limits −2.75, 0.70; p = 0.24). Numerical efficacy advantages for brexpiprazole were observed at other time points. The most common TEAE in the randomised study was akathisia (brexpiprazole, 14.0%; placebo, 1.2%); data from the open-label study (N = 199 analysed) suggested that TEAEs were transient.

The primary endpoint of the randomised study was not met. Further research on brexpiprazole in BPD is warranted based on possible efficacy signals at other time points and its safety profile.

ClinicalTrials.gov identifiers: NCT04100096, NCT04186403. Funding: Otsuka, Lundbeck.

This is a secondary analysis of clinical trial data collected in 12 European countries. We examined changes in weight and weight-related quality of life among community patients with schizophrenia treated with aripiprazole (ARI) versus standard of care (SOC), consisting of other marketed atypical antipsychotics (olanzapine, quetiapine, and risperidone).

Five-hundred and fifty-five patients whose clinical symptoms were not optimally controlled and/or experienced tolerability problems with current medication were randomized to ARI (10–30 mg/day) or SOC. Weight and weight-related quality of life (using the IWQOL-Lite) were assessed at baseline, and weeks 8, 18 and 26. Random regression analysis across all time points using all available data was used to compare groups on changes in weight and IWQOL-Lite. Meaningful change from baseline was also assessed.

Participants were 59.7% male, with a mean age of 38.5 years (SD 10.9) and mean baseline body mass index of 27.2 (SD 5.1). ARI participants lost an average of 1.7% of baseline weight in comparison to a gain of 2.1% by SOC participants (p < 0.0001) at 26 weeks. ARI participants experienced significantly greater increases in physical function, self-esteem, sexual life, and IWQOL-Lite total score. At 26 weeks, 20.7% of ARI participants experienced meaningful improvements in IWQOL-Lite score, versus 13.5% of SOC participants. A clinically meaningful change in weight was also associated with a meaningful change in quality of life (p < 0.001). A potential limitation of this study was its funding by a pharmaceutical company.

Compared to standard of care, patients with schizophrenia treated with aripiprazole experienced decreased weight and improved weight-related quality of life over 26 weeks. These changes were both statistically and clinically significant.

To assess the effects of aripiprazole once-monthly 400 mg (AOM 400) on clinical symptoms and global improvement in schizophrenia after switching from an oral antipsychotic.

In a multicenter, open-label, mirror-image, naturalistic study in patients with schizophrenia (>1 year, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision [DSM-IV-TR] criteria), changes in efficacy measures were assessed during prospective treatment (6 months) with AOM 400 after switching from standard-of-care oral antipsychotics. During prospective treatment, patients were cross-titrated to oral aripiprazole monotherapy (1–4) weeks followed by open-label AOM 400 (24 weeks). Mean change from baseline of the open-label AOM 400 phase in Positive and Negative Syndrome Scale (PANSS) scores (total, positive and negative subscales) and Clinical Global Impression–Severity (CGI-S) scores; mean CGI–Improvement (CGI-I) score; and proportion of responders (≥30% decrease from baseline in PANSS total score or CGI-I score of 1 [very much improved] or 2 [much improved]) were assessed.

PANSS and CGI-S scores improved from baseline (P<0.0001) and CGI-I demonstrated improvement at all time points. By the end of the study, 49.0% of patients were PANSS or CGI-I responders.

In a community setting, patients with schizophrenia who were stabilized at baseline and switched to AOM 400 from oral antipsychotics showed clear improvements in clinical symptoms.

Efficacy and safety of aripiprazole administered at doses lower than those previously studied systematically were investigated in patients with acute exacerbation of schizophrenia.

In this double-blind, multicenter study, 367 patients requiring inpatient hospitalization for acute relapse of schizophrenia were randomized to one of three fixed doses of aripiprazole (2, 5, or 10 mg/day) or placebo for 6 weeks. Efficacy and safety parameters were assessed weekly. Primary outcome measure was mean change from baseline in Positive and Negative Syndrome Scale (PANSS)Total score at endpoint.

Aripiprazole 10 mg/day produced statistically significantly greater improvements from baseline compared with placebo for PANSS Total at endpoint (−11.3 vs −5.3; P=.03) and at weeks 2–5. Aripiprazole 5 mg/day did not produce significantly greater improvement in PANSS Total compared with placebo at endpoint, although significant differences were seen at weeks 3–5. No statistically significant improvements compared with placebo were achieved with aripiprazole 2 mg/day at any time points. All aripiprazole doses were well tolerated. Aripiprazole was not associated with significant extrapyramidal symptoms.

While aripiprazole 5 mg/day warrants further study, the 10 mg/day dose provides effective and well-tolerated therapy for management of acute psychosis in patients with schizophrenia.

Long-acting injectable formulations of antipsychotics are treatment alternatives to oral agents.

To assess the efficacy of aripiprazole once-monthly compared with oral aripiprazole for maintenance treatment of schizophrenia.

A 38-week, double-blind, active-controlled, non-inferiority study; randomisation (2:2:1) to aripiprazole once-monthly 400 mg, oral aripiprazole (10–30 mg/day) or aripiprazole once-monthly 50mg (a dose below the therapeutic threshold for assay sensitivity). (Trial registration: clinicaltrials.gov, NCT00706654.)

A total of 1118 patients were screened, and 662 responders to oral aripiprazole were randomised. Kaplan–Meier estimated impending relapse rates at week 26 were 7.12% for aripiprazole once-monthly 400mg and 7.76% for oral aripiprazole. This difference (−0.64%, 95% CI −5.26 to 3.99) excluded the predefined non-inferiority margin of 11.5%. Treatments were superior to aripiprazole once-monthly 50mg (21.80%, P⩽0.001).

Aripiprazole once-monthly 400mg was non-inferior to oral aripiprazole, and the reduction in Kaplan–Meier estimated impending relapse rate at week 26 was statistically significant v. aripiprazole once-monthly 50 mg.

Efficacy of depression treatments, including adjunctive antipsychotic treatment, has not been explored for patients with worsening symptoms after antidepressant therapy (ADT).

This post-hoc analysis utilized pooled data from 3 similarly designed, randomized, double-blind, placebo-controlled trials that assessed the efficacy, safety, and tolerability of adjunctive aripiprazole in patients with major depressive disorder with inadequate response to ADT. The studies had 2 phases: an 8-week prospective ADT phase and 6-week adjunctive (aripiprazole or placebo) treatment phase. This analysis focused on patients whose symptoms worsened during the prospective 8-week ADT phase (worsening defined as >0% increase in Montgomery–Åsberg Depressive Rating Scale [MADRS] Total score). During the 6-week, double-blind, adjunctive phase, response was defined as ≥50% reduction in MADRS Total score and remission as ≥50% reduction in MADRS Total score and MADRS score ≤10.

Of 1065 patients who failed to achieve a response during the prospective phase, 160 exhibited worsening of symptoms (ADT-Worseners), and 905 exhibited no change/reduction in MADRS scores (ADT-Non-worseners). Response rates for ADT-Worseners at endpoint were 36.6% (adjunctive aripiprazole) and 22.5% (placebo). Similarly, response rates at endpoint for ADT-Non-worseners were 37.5% (adjunctive aripiprazole) and 22.5% (placebo). Remission rates at endpoint for ADT-Worseners were 25.4% (adjunctive aripiprazole) and 12.4% (placebo). For ADT-Non-worseners, remission rates were 29.9% (adjunctive aripiprazole) and 17.4% (placebo).

These results suggest that adjunctive aripiprazole is an effective intervention for patients whose symptoms worsen during antidepressant monotherapy. The results challenge the view that benefits of adjunctive therapy with aripiprazole are limited to partial responders to ADT.

Well-tolerated and effective therapies for bipolar mania are required.

To evaluate the efficacy and tolerability of aripiprazole as acute and maintenance of effect therapy in patients with bipolar I disorder experiencing manic or mixed episodes.

Patients were randomised to double-blind aripiprazole (15 or 30 mg/day; n=167) placebo (n=153) or haloperidol (5–15 mg/day, n=165) for 3 weeks (trial registration NCT00097266). Aripiprazole- and haloperidol-treated patients remained on masked treatment for 9 additional weeks.

Mean change in Young Mania Rating Scale Total score (primary end-point) at week 3 was significantly greater with aripiprazole (–12.0; P<0.05) and haloperidol (–12.8; P<0.01) than with placebo (–9.7). Improvements were maintained to week 12 for aripiprazole (–17.2) and haloperidol (–17.8). Aripiprazole was well tolerated. Extrapyramidal adverse events were more frequent with haloperidol than aripiprazole (53.3% v. 23.5%).

Clinical improvements with aripiprazole were sustained to week 12. Aripiprazole was generally well tolerated.

Los ensayos naturalistas sobre la efectividad de los antipsicóticos atípicos son necesarios para aportar una información más amplia sobre la eficacia, la seguridad y la tolerabilidad en pacientes con esquizofrenia tratados en un centro médico de la comunidad.

En este estudio multicéntrico abierto de 26 semanas, diversos pacientes con esquizofrenia, que necesitaron un cambio en la medicación antipsicótica porque no toleraban bien la medicación actual y/o porque los síntomas clínicos no estaban bien controlados, se aleatorizaron para recibir aripiprazol o un tratamiento estándar (TE) con un antipsicótico atípico (por ejemplo, olanzapina, quetiapina o risperidona en función del juicio del investigador sobre el tratamiento óptimo de cada paciente individual y la respuesta previa del paciente a la medicación antipsicótica). El objetivo principal fue comparar la efectividad de un tratamiento de 26 semanas con aripiprazol con el TE, medido por la puntuación total del Cuestionario de Evaluación del Investigador (IAQ) en la última observación arrastrada (UOA) de la semana 26 (variable primaria), una medida validada que controla el alivio o el empeoramiento de 10 síntomas clave asociados con la psicopatología de la esquizofrenia y los efectos secundarios del tratamiento antipsicótico. Los objetivos secundarios fueron evaluar la efectividad usando las escalas Impresión Clínica Global - Mejoría Global (CGI-I) e Impresión Clínica Global - Gravedad de la Enfermedad, para evaluar el tiempo transcurrido hasta la suspensión del tratamiento, la preferencia del paciente respecto a la medicación, y la calidad de vida y la tolerabilidad de aripiprazol comparado con el TE.

El tratamiento con aripiprazol (n=268) fue significativamente más eficaz que el TE (n = 254; P < 0,001; UOA de la semana 26), evidenciado por la puntuación IAQ total, desde la semana 4 (primera fase de evaluación) y se mantuvo hasta la semana 26. Una relación similar se demostró en los pacientes que terminaron el estudio (análisis de casos observados); aripiprazol se asoció con una efectividad significativamente mayor en todas las fases de evaluación con un mayor efecto diferencial de TE con el tiempo. Los pacientes tratados con aripiprazol también tuvieron mejorías significativamente mayores en la escala CGI-I (tasa de rspuesta, P = 0,009 en la UOA de la semana 26), y en la calidad de vida (puntuación total en la escala de Calidad de Vida; P < 0,001 en la semana 26). Además, una proporción significativamente mayor de pacientes que recibieron aripiprazol calificaron la medicación del estudio como “mucho mejor” en la escala del Cuestionario de Preferencias de Medicación (POM) que la medicación anterior al estudio comparados con los pacientes tratados con TE (P < 0,001; semana 26). El tiempo hasta la suspensión del tratamiento y las tasas de suspensión debidas a episodios adversos fueron similares en los dos grupos de tratamiento. La incidencia de pacientes con uno o varios síntomas extrapiramidales (por ejemplo, acatisia, distonía, episodios parkinsonianos y episodios residuales) fue mayor en los pacientes que recibieron aripiprazol comparados con los pacientes tratados con TE (13,5% frente a 5,6%); sin embargo, una proporción mayor de pacientes del grupo TE tuvo un aumento de peso clínicamente significativo (21,2% frente a 7,3% para aripiprazol) y de las concentraciones séricas (potencialmente importantes desde el punto de vista clínico) de colesterol total, colesterol de lipoproteínas de baja densidad, triglicéridos y prolactina comparados con los pacientes que recibieron aripiprazol.

Aripiprazol es un antipsicótico atípico eficaz para el tratamiento de la esquizofrenia, que ha demostrado más efectividad que los fármacos estándar usados en este estudio en pacientes que necesitaban un cambio en la medicación antipsicótica.

Naturalistic effectiveness trials of atypical antipsychotics are needed to provide broader information on efficacy, safety, and tolerability in patients with schizophrenia treated in a community practice setting.

in this 26-week, open-label, multicentre study, patients with schizophrenia requiring a switch in antipsychotic medication because current medication was not well tolerated and/or clinical symptoms were not well controlled were randomized to receive aripiprazole or an atypical antipsychotic standard of care (SOC) treatment (i.e., olanzapine, quetiapine, or risperidone based on the investigator's judgment of the optimal treatment for the individual patient and the patient's prior response to antipsychotic medication). The primary objective was to compare the effectiveness of a 26-week treatment of aripiprazole versus SOC, as measured by the investigator Assessment Questionnaire (IAQ) total score at Week 26 last observation carried forward (LOCF) (primary endpoint), a validated measure that monitors relief or worsening of 10 key symptoms associated with the psychopathology of schizophrenia and side effects of antipsychotic treatment. Secondary objectives were to further assess effectiveness using the Clinical Global Impression – Global Improvement (CGI-I) and Clinical Global Impression – Severity of Illness scale, to assess time to treatment discontinuation, patient preference of medication, quality of life, and the tolerability of aripiprazole compared with SOC.

Aripiprazole treatment (n = 268) resulted in significantly better effectiveness than SOC treatment (n = 254; P < 0.001; Week 26 LOCF) as evidenced by the IAQ total score beginning at Week 4 (the first assessment point) and sustained through Week 26. A similar relationship was demonstrated among patients who completed the study (observed cases analysis); aripiprazole was associated with significantly better effectiveness at all time points with a greater differential effect from SOC over time. Patients treated with aripiprazole also demonstrated significantly greater improvements on the CGI-I scale (responder rate, P = 0.009 at Week 26 LOCF), as well as on quality of life (Quality of Life scale total score; P < 0.001 at Week 26). Furthermore, a significantly higher proportion of patients receiving aripiprazole rated their study medication as “much better” on the Preference of Medication Questionnaire (POM) scale than their pre-study medication compared with SOC patients (P < 0.001; Week 26). Time to treatment discontinuation and rates of discontinuation due to adverse events were similar in both treatment groups. The incidence of patients with one or more extrapyramidal symptom (e.g., akathisia, dystonia, parkinsonian events, and residual events) was higher in patients receiving aripiprazole compared with patients treated with SOC (13.5% vs. 5.6%); however, a higher proportion of patients in the SOC-treated group had clinically significant weight gain (21.2% vs. 7.3% for aripiprazole) and potentially clinically relevant elevated fasting levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, and serum prolactin compared with patients receiving aripiprazole.

Aripiprazole is an effective atypical antipsychotic for the treatment of schizophrenia, demonstrating better effectiveness than SOC agents used in this study in patients for whom a switch in antipsychotic medication was warranted.