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.

Quality of life is decreased in bipolar disorders (BD) and contributes to poor prognosis. However, little is known about the causal pathways that may affect it. This study aimed to explore health-related QoL (HRQoL) in BD and investigate its relationship with cognition and psychosocial functioning.

This multicenter cross-sectional study used a neuropsychological battery to assess five cognition domains. Functioning was evaluated using global and domain-based tools, and health-related HRQoL was assessed using the EQ-5D-3L. Structural equation modeling was used to test whether the association between cognition and HRQoL would be mediated by functioning in BD while controlling for covariates such as residual depression, anxiety, antipsychotic medication, and psychotic features.

We included 1 190 adults with euthymic BD. The model provided a good fit for the data. In this model, the direct effect of cognition on HRQoL was not significant (β = − 0.03, z = −0.78, p = 0.433). The total effect of cognition on HRQoL was weak, albeit significant (β = 0.05, z = 3.6, p < 0.001), thus suggesting that cognition affected HRQoL only indirectly through functioning. Anxiety was associated with decreased functioning (β = −0.27, z = −7.4, p < 0.001) and QoL (β = −0.39, z = −11.8, p < 0.001).

These findings suggest that improving cognition may not directly lead to a higher HRQoL. Cognitive remediation is expected to improve HRQoL only through functioning enhancement. They also reveal the potential importance of functional remediation and reduction of comorbid anxiety symptoms in improving HRQoL in BD.

To compare time to relapse in patients with major depressive disorder (MDD) stabilised on antidepressant treatment (ADT) + brexpiprazole who were randomised to continued adjunctive brexpiprazole or brexpiprazole withdrawal (switch to placebo).

This Phase 3, multicentre, double-blind, placebo-controlled, parallel-arm, randomised withdrawal study enrolled adults with MDD and inadequate response to 2–3 ADTs. All patients started on adjunctive brexpiprazole 2–3 mg/day (Phase A, 6–8 weeks). Patients whose symptoms stabilised (Phase B, 12 weeks) were randomised 1:1 to adjunctive brexpiprazole or adjunctive placebo (Phase C, 26 weeks). The primary endpoint was time to relapse in Phase C. Depression rating scale score changes were secondary endpoints.

1149 patients were enrolled and 489 patients were randomised (ADT + brexpiprazole n = 240; ADT + placebo n = 249). Median time to relapse was 63 days from randomisation in both treatment groups for patients who received ≥1 dose. Relapse criteria were met by 22.5% of patients (54/240) on ADT + brexpiprazole and 20.6% (51/248) on ADT + placebo (hazard ratio, 1.14; 95% confidence interval, 0.78–1.67; p = 0.51, log-rank test). Depression scale scores improved during Phases A–B and were maintained in Phase C. Mean weight increased by 2.2 kg in Phases A–B and stabilised in Phase C.

Time to relapse was similar between continued adjunctive brexpiprazole and brexpiprazole withdrawal; in both groups, ∼80% of stabilised patients remained relapse free at their last visit. Adjunctive brexpiprazole therapy was generally well tolerated over up to 46 weeks, with minimal adverse effects following brexpiprazole withdrawal.

ClinicalTrials.gov identifier: NCT03538691. Funding: Otsuka, Lundbeck.

There is growing concern regarding teratogenic effect of antipsychotics. Previous research assessing association between antipsychotics and congenital malformations (CMs) yielded mixed results and were all derived from Western countries. We aimed to examine risk of major and organ/system-specific CMs associated with prenatal antipsychotic exposure in Hong Kong.

This population-based study identified women aged 15–50 years who delivered their first/singleton child between 2003–2018 from public healthcare service database. Propensity score (PS)-weighted logistic-regression analyses were performed to examine risk of CMs following first-trimester exposure to antipsychotic classes (second- and first-generation antipsychotic; SGA and FGA) and six most frequently-prescribed individual antipsychotics.

Of 465,069 women, 419 and 420 redeemed ≥1 prescription of SGA and FGA during first-trimester, respectively. Prevalence of any CMs was 4.9% (95%CI:4.9–5.0%) in unexposed-infants, 9.1% (6.7–12.3%) in SGA-exposed infants, and 6.2% (4.3–9.0%) in FGA-exposed infants. SGA exposure (adjusted-odds-ratio: 2.11 [95%CI:1.19–3.86]) was associated with increased risk of CMs. This finding was consistent with sensitivity analyses addressing exposure misclassification and confounding by treatment indication, but not with PS-matched sensitivity analysis. Elevated risk of CMs was observed in infants exposed to high-dose olanzapine (7.50 [1.65–36.13]) and high-dose quetiapine (15.03 [4.86–56.72]), but with wide-CIs. Organ/system-specific malformations were not associated with SGA, FGA or individual antipsychotics.

We observed a small increased risk of major malformations associated with SGA, but was not consistently affirmed in sensitivity analyses, precluding firm conclusions. Research with large sample size clarifying comparative safety of individual antipsychotics on specific malformations is warranted.

The optimal duration of antipsychotic treatment following remission of first-episode psychosis (FEP) is uncertain, considering potential adverse effects and individual variability in relapse rates. This study aimed to investigate the effect of antipsychotic discontinuation compared to continuation on recovery in remitted FEP patients.

CENTRAL, MEDLINE (Ovid), Embase, and PsycINFO databases were searched on November 2, 2023, with no language restrictions. RCTs evaluating antipsychotic discontinuation in remitted FEP patients were selected. The primary outcome was personal recovery, and secondary outcomes included functional recovery, global functioning, hospital admission, symptom severity, quality of life, side effects, and employment. Risk of bias was assessed using the Cochrane risk-of-bias tool 2, and the certainty of evidence was evaluated with GRADE. Meta-analysis used a random-effect model with an inverse-variance approach.

Among 2185 screened studies, 8 RCTs (560 participants) were included. No RCTs reported personal recovery as an outcome. Two studies measured functional recovery, and discontinuation group patients were more likely to achieve functional recovery (RR 2.19; 95% CIs: 1.13, 4.22; I2 = 0%; n = 128), although evidence certainty was very low. No significant differences were found in hospital admission, symptom severity, quality of life, global functioning, or employment between the discontinuation and continuation groups.

Personal recovery was not reported in any antipsychotic discontinuation trial in remitted FEP. The observed positive effect of discontinuation on functional recovery came from an early terminated trial and an RCT followed by an uncontrolled period. These findings should be interpreted cautiously due to very low certainty of evidence.

Individuals with schizophrenia exposed to second-generation antipsychotics (SGA) have an increased risk for diabetes, with aripiprazole purportedly a safer drug. Less is known about the drugs' mortality risk or whether serious mental illness (SMI) diagnosis or race/ethnicity modify these effects.

Authors created a retrospective cohort of non-elderly adults with SMI initiating monotherapy with an SGA (olanzapine, quetiapine, risperidone, and ziprasidone, aripiprazole) or haloperidol during 2008–2013. Three-year diabetes incidence or all-cause death risk differences were estimated between each drug and aripiprazole, the comparator, as well as effects within SMI diagnosis and race/ethnicity. Sensitivity analyses evaluated potential confounding by indication.

38 762 adults, 65% White and 55% with schizophrenia, initiated monotherapy, with haloperidol least (6%) and quetiapine most (26·5%) frequent. Three-year mortality was 5% and diabetes incidence 9.3%. Compared with aripiprazole, haloperidol and olanzapine reduced diabetes risk by 1.9 (95% CI 1.2–2.6) percentage points, or a 18.6 percentage point reduction relative to aripiprazole users' unadjusted risk (10.2%), with risperidone having a smaller advantage. Relative to aripiprazole users' unadjusted risk (3.4%), all antipsychotics increased mortality risk by 1.1–2.2 percentage points, representing 32.4–64.7 percentage point increases. Findings within diagnosis and race/ethnicity were generally consistent with overall findings. Only quetiapine's higher mortality risk held in sensitivity analyses.

Haloperidol's, olanzapine's, and risperidone's lower diabetes risks relative to aripiprazole were not robust in sensitivity analyses but quetiapine's higher mortality risk proved robust. Findings expand the evidence on antipsychotics' risks, suggesting a need for caution in the use of quetiapine among individuals with SMI.

Subjective response (SR) to antipsychotic medication is relevant for quality of life, adherence and recovery. Here, we evaluate (1) the extent of variation in SR in patients using a single antipsychotic; (2) the association between subjective and symptomatic response; and (3) predictors of SR.

Open-label, single treatment condition with amisulpride in 339 patients with a first episode of a schizophrenia spectrum disorder, at most minimally treated before inclusion. Patients were evaluated at baseline, before start with amisulpride and after four weeks of treatment with the Subjective Wellbeing under Neuroleptic scale, the Positive and Negative Syndrome Scale, and the Calgary Depression Scale for Schizophrenia.

(1) 26.8% of the patients had a substantial favorable SR, and 12.4% of the patients experienced a substantial dysphoric SR during treatment with amisulpride. (2) Modest positive associations were found between SR and 4 weeks change on symptom subscales (r = 0.268–0.390, p values < 0.001). (3) Baseline affective symptoms contributed to the prediction of subjective remission, demographic characteristics did not. Lower start dosage of amisulpride was associated with a more favorable SR (r = −0.215, p < 0.001).

We conclude that variation in individual proneness for an unfavorable SR is substantial and only modestly associated with symptomatic response. We need earlier identification of those most at risk for unfavorable SR and research into interventions to improve SR to antipsychotic medication in those at risk.

A combination of olanzapine and the opioid receptor antagonist samidorphan (OLZ/SAM) has been approved in the United States for the treatment of adults with schizophrenia or adults with bipolar I disorder. In a phase 3 study in adults with schizophrenia (ENLIGHTEN-2), OLZ/SAM treatment was associated with significantly less weight gain compared with olanzapine. Prespecified subgroup analyses explored the consistency of the weight mitigation effect of OLZ/SAM vs olanzapine across demographic subgroups in ENLIGHTEN-2.

The multicenter, randomized, double-blind ENLIGHTEN-2 study (NCT02694328) included outpatients aged 18–55 years with a diagnosis of schizophrenia based on DSM-5 criteria, a body mass index (BMI) of 18 to 30 kg/m2, and stable body weight (self-reported change ≤5% for ≥3 months before study entry). Patients were randomized 1:1 to receive OLZ/SAM or olanzapine for 24 weeks. Co-primary endpoints (previously reported) were percent change in body weight and proportion of patients with at least 10% weight gain from baseline at week 24. Prespecified exploratory subgroup analyses by sex, age, self-reported race, and baseline BMI were conducted.

At week 24, treatment with OLZ/SAM resulted in numerically less percent weight gain than with olanzapine across all subgroups evaluated. The proportion of patients with at least 10% weight gain was smaller in each subgroup treated with OLZ/SAM vs olanzapine.

In these exploratory subgroup analyses from the ENLIGHTEN-2 study, weight-mitigating effects of OLZ/SAM vs olanzapine were observed consistently across patient subgroups and were in line with results from the overall study population.

Relatively few studies have explored the differential contributions of the accumulative dosage of psychotropic medications on mortality in patients with schizophrenia.

We aimed to explore the effects of the exposure dosage of psychotropic medications on mortality during a follow-up period of 5 years with a national cohort of individuals with schizophrenia in 2010. Causes of death were linked through Taiwan's National Mortality Registry. The mean defined daily dose of antipsychotics, antidepressants, mood stabilizers, and sedative-hypnotics, were calculated and survival analyses were conducted.

A total of 102 964 individuals (54 151 men, 52.59%) with schizophrenia were included. Compared to patients with no exposure to antipsychotics, those with antipsychotic exposure had better survival outcomes, regardless of antipsychotic dosage. Antidepressant exposure, in low and moderate dosage, was associated with decreased all-cause mortality; exposure to mood stabilizers appeared to be associated with an increase in all-cause mortality. Although 89.7% of the patients had been prescribed sedative-hypnotics, exposure to sedative-hypnotics was associated with dose-related increased mortality risk [hazard ratio (HR) in low dose group: 1.16, 95% confidence interval (CI) 1.07–1.27; HR in moderate dose: 1.32, 95% CI 1.21–1.44; HR in high dose: 1.83, 95% CI 1.67–2.01)].

The results indicate that in the treatment of schizophrenia, antipsychotics and antidepressants are associated with lower mortality when using adequate dosages and mood stabilizers and sedative-hypnotics with higher mortality compared with no use. Furthermore, exposure to sedative-hypnotics is associated with a dose-related increased mortality risk which warrants clinical attention and further study.

Sexual dysfunction (SD) can often be a side-effect of treatment with antipsychotics (APS). It often jeopardizes long-term adherence to treatment, while deeply affecting the patient’s quality of life. The pathogenic mechanisms may be associated with postsynaptic dopamine antagonism, a1-antagonism and prolactin elevation. APS-induced hyperprolactinemia has been linked to the occurrence of galactorrhea, gynecomastia, amenorrhea and SD.

To synthesize the available evidence on the management of APS-related sexual dysfunction, with a main focus on the second-generation antipsychotics.

A search for randomized controlled trials (RCT) published between 2021 and 2011 on PubMed was made using the keywords “sexual”; “dysfunction”; “antipsychotic” and “treatment”, from which resulted sixteen articles. Only six of those were considered relevant for the study’s objectives.

Three studies focused on the comparison between different APS and prolactin levels and SD occurrence, showing that treatment with aripiprazole is mostly related to prolactin levels with the normal range and a lower incidence of sexual dysfunction. Addition of aripiprazole to previous APS may be associated with normalization of sexual function and pose as a possible management option. Adjunctive treatment with tadalafil showed no significant effect on its primary outcome.

There seems to be a general consensus that patients treated with first-generation antipsychotics (FGA), along with risperidone, paliperidone and amissulpride show higher prolactin levels and incidence of SD. Whether there is a causal relationship between these two variables still remains a question. Larger and more prolonged trials are still needed to evaluate APS-related sexual dysfunction and its management.

No significant relationships.

Priapism is an abnormally prolonged erection, painful and irreducible, unrelated to sexual stimulation. Around 25-40% of cases are iatrogenic, especially associated with pharmacological treatments, of which antipsychotics (first and second generation) account for 50%.

The aim is to discuss a clinical case to provide further evidence.

The patient was a 37-year-old man with a diagnosis of schizophrenia who was admitted for clinical decompensation. He had stopped antipsychotic treatment three months earlier due to side effects. He reported previous episodes of priapism associated with Risperidone, Aripiprazole, Olanzapine, and Paliperidone. At admission, he was administered Asenapine 20mg with development of priapism. Treatment was stopped. The urologists performed a lavage of the corpora cavernosa and administered adrenaline. In the absence of effectiveness, surgical intervention was successfully performed. Given the psychopathological improvement, he was discharged without antipsychotic treatment and close follow-up.

He presented a new admission one month later. Amisulpride was prescribed up to 800mg/day with good evolution and no adverse effects.

Antipsychotic-induced priapism appears to be related to the blockade of alpha-1 adrenergic receptors in the corpora cavernosa. There is a positive correlation between the affinity for the receptor and the propensity to cause priapism. The dose and duration of the medication do not appear to be correlated. Other risk factors are a history of previous episodes, restarting medication after noncompliance, use of concomitant substances or medications that cause priapism. Our choice of amisulpride was based on the fact that it has no affinity for alpha-1 adrenergic receptors.

No significant relationships.

At present, there is no universally approach to treating patients at clinical high-risk for psychosis (CHR) without comorbid mental disorders. However, if there are revealed depressive symptoms, proper treatment becomes necessary.

Establish pharmacological classes and doses of drugs that have proved effective in treating depressive patients at CHR.

A comparative study of pharmacological classes and doses of drugs was carried out, showing the effectiveness in treatment of 219 depressive patients at CHR and 52 depressive patients without CHR. The treatment effectiveness was carried out on the reduction of depression symptoms on the HDRS scale, and the CHR symptoms on the SOPS scale.

A significant reduction of depression symptoms was achieved in the group of depressive patients with and without CHR on the HDRS scale (67.9% and 76.6% respectively). The reductions of the CHR symptoms were 46.1% and 53.3% respectively. There were differences between the severity of depression symptoms and CHR symptoms before and after the treatment. Both groups used antidepressants followed by the prescription of antipsychotics to increase the effectiveness of the therapy. No difference was found in the doses of antidepressants for the fluoxetine equivalent (46.0 vs 42.6 mg per day, p 0.05) and some differences were found for the average effective doses of antipsychotics for the chlorpromazine equivalent (385.4 vs 230.8 mg per day, p 0.05).

The same pharmacological classes are used for the treatment of young depressive patients with and without CHR, but the former have significantly higher doses of antipsychotics.

No significant relationships.

Delusional disorder (DD) is defined by the presence of one or more delusions, of at least one month’s duration, in the absence of prominent hallucinations or other symptoms of schizophrenia. Although functioning may not be markedly impaired, the delusion(s) or its ramifications may have a significant impact in the patient’s life. With a life-time prevalence of 0.18%, DD is still neglected in terms of approved treatment recommendations.

We present the case of a patient diagnosed with DD and discuss the treatment of DD according to current evidence.

Relevant clinical information was extracted from the patient’s clinical process. A non-systematic review was made in Pubmed database with the terms “Delusional Disorder” and “Treatment”.

Male, 76 years old, divorced, living alone, autonomous. First admitted at age 62 in our inpatient psychiatry ward for a persecutory delusion regarding his neighbors. He was discharged with the diagnosis of DD and started a follow-up in a mental health community team. He abandoned treatment and psychiatric consultation after 9 years. During 17 years he moved home more than 10 times due to a progressive dynamism of the delusion, leading to recent marked behavior changes towards his neighbors. He is again admitted in our inpatient psychiatry ward.

This case illustrates the impact that untreated DD can have on its patients. Although consensus using antipsychotics, there are still insufficient studies to make evidence-based recommendations to treat people with DD. Further research is needed in this sense.

No significant relationships.

Long-acting injectable antipsychotics (LAIs) hold an important place in the treatment of psychosis. Knowledge of the best way to administer LAIs is important to maximize the efficacy and minimize the side-effects

To assess the effectiveness of flexible doses of palmitate paliperidone long-acting injectable (PPLAI) against standard doses in initiation regimen in the subset of acutely hospitalized patients with schizophrenia and other psychosis

Retrospective, noninterventional study. Group of initiation regimen: A)“Standard-doses” (recommended PPLAI initiation regimen: 150mg-Day-1 and 100mg-Day-8±4days), B)“Low-doses” (any dosage lower than the Standard-dose) C)“High-doses” (150mg-Day-1 and 150mg-Day-8±4days) Effectiveness was measured with the number of psychiatric hospital admission and psychiatric emergency visit 6-months post-discharge. Length of stay of the index hospitalization, adherence to treatment and adverse events was confirmed in the medical record. Concomitant use of biperiden was recorded.

51 patients were included. We found no statistically differences in study variables between groups (Table-1). Table-1.

No differences were found in the effectiveness of flexible-doses in PPLAI initiation regimen. The use of low doses of PPLAI could keep the efficacy of the standard dose with a better side effect profile and treatment adherence. The strength of the conclusion is limited by the design and the number of patients.

No significant relationships.

Autism is a neurodevelopmental disorder characterized by qualitative impairments in social interaction, communication, and restricted and repetitive behaviors [1]. Despite of these symptoms, some patients present different manifestations of irritability. These can be expressed in different kinds of disruptive behaviors. Recent studies shown that, at least 20% of children with autism present irritability symptoms, which cause severe social and familiar disturbances [2].

The aim of this study was to evaluate short-term efficacy of aripiprazole in children in comparison with other antipsychotic. We include behaviors related to irritability as all kinds of aggressions, tantrums and self-injuries.

90 patients were recruited. 45 of the patients received aripiprazole and 45 received other antipsychotic. The initial doses of aripiprazole was 2,5 mg/day. Doses were increase related to symptoms. The range of the doses were from 2,5 to 15 mg/day.

From these 45 patients 12 had a relapse (26,6%) during the next two years. From the second group, 20 (44.4%) of the patients had a relapse during the next two years. Five of the aripiprazole group (11,1%) abandon treatment. From the second group twelve patients (26.6%) also abandon treatment. Prolactin rates with aripiprazole were 28.2 ng/ml for males and 14.1 ng/ml for women.

In general, the result of our research indicated that Aripiprazole was effective and generally safe and well tolerated in the treatment of irritability associated with ASD. One of the limitations was that we do not use scales in order to measure the changes.

No significant relationships.

Tobacco-use is currently one of the major public health problems and is more common among patients with schizophrenia.

We aimed in this study to estimate the prevalence of smoking in a population of patients with schizophrenia, to assess tobacco dependence and to identify its correlated factors.

This is a descriptive and analytical cross-sectional study carried out on 50 outpatients at the Department of Psychiatry (Tunisia) over a period of two months. For the data collection, we used: a general questionnaire on sociodemographic characteristics and tobacco consumption and the Fagerström test for nicotine dependence.

All the patients were male with a mean age of 32.7±7.02 years and 84% of them were tobacco consumers. More than half of the sample were single (68%) and had a primary school level (52%). A professional irregularity and low socio-economic level were found successively in 84% and 78% of cases. Half of the patients (52%) were diagnosed with paranoid schizophrenia and 46% of them were treated by atypical antipsychotics. Cigarette dependence was strong or very strong in 82% according to the Fagerstrom test. A positive correlation was found between strong tobacco dependence on the one hand and low socio-economic level, professional irregularity, smoking in a first-degree relative and treatment with a typical neuroleptic on the other hand.

Our study and data from the literature show that subjects with schizophrenia constitute a population of highly dependent smokers. A smoking cessation assistance program for this vulnerable population is a priority to improve their quality of life.

No significant relationships.

The use of antipsychotics (APS) is essential. Despite their great efficacy, some of them are associated with an increase in prolactin levels that can lead to hormonal changes needing to be identified and managed [1,2,3]. Hormonal changes use to have clinical implications including hypogonadism, infertility and sexual dysfunction

To evaluate possible hormonal alterations and some clinical implications produced by hyperprolactinemia (HPRL) derived from the use of some antipsychotic compounds.

A complete fasting blood test was performed on a sample of 113 subjects (69 men and 44 women). 54% (n = 61) showed a normal prolactin level and 46% (n = 52) showed hyperprolactinaemia ( >50ng / ml). On the global sample, 39.8% (n = 45) was treated with some hyperprolactinemic drug , mostly risperidone and paliperidone.

Some differences were found depending on the gender of the subjects. A highly significant inverse relationship between the values of prolactin and testosterone was found in males (p=0.020, r=-0.285). In females, increased prolactin level was significantly related to decreased cortisol values.

Antipsychotic-related Hyperprolactinaemia ( mainly risperidone and paliperidone) is related with a decrease in testosterone levels in males and with an increase in cortisol levels in females.

No significant relationships.