Clozapine has proven to have a unique efficacy on treatment-resistant schizophrenia (TRS). Nevertheless, studies show that 47%-63% of clozapine-treated patients may fail to respond after around 12-years of treatment (CRS). Several augmentation strategies have been proven to be effective in CRS.

Hereby, we present two clinical cases of CRS successfully managed with brexpiprazole augmentation.

A 48-year-old man without comorbid substance use, treated with clozapine-brexpiprazole augmentation, and a 20-year-old man with comorbid substance use, treated with clozapine-brexpiprazole combination and subsequently with twice-injection aripiprazole (TIA). They were administered with the following assessments at t0, t1-3 (first month), t4-8 (monthly until 6-month follow-up): CGI, BPRS, PANSS, CDSS, Craving VAS, BARS, BIS-11, HRS-A, MADRS, YMRS, AIMS.

At 1-month follow-up, both patients showed a considerable improvement (respectively 75% and 55.9% reduction of PANSS total score). At 6-month follow-up, reached only with the first patient, we noticed a further improvement (an overall 37.5% reduction of PANSS total score from the baseline).

The present work is the first report describing combination treatment strategies with clozapine and brexpiprazole which appear to give promising results.

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Brexpiprazole is a novel antipsychotic drug. It exerts antagonistic activity at the serotonin 5HT2A, 5HT2B, 5HT7 and noradrenaline alpha 1b/2c receptors; it also acts as partial agonist of serotonin 5HT1 and dopamine D2, D3 receptors. Brexpiprazole is approved for the treatment of schizophrenia and as an add-on therapy for major depression.

This pilot study aims at exploring efficacy and tolerability of Brexpiprazole in a small sample of patients diagnosed with either a psychotic or a mood disorder.

This observational study was conducted at our Acute Psychiatric Inpatient Unit. We included 7 patients (5 males, 2 females) hospitalized between 2020 and 2021, diagnosed with schizophrenia spectrum disorders or mood disorders with psychotic symptoms confirmed by Mini International Neuropsychiatric Interview. Patients who participated signed an informed consent. Information concerning diagnosis, demographic characteristics (age, sex, education, marital status) and pharmacological therapy were collected examining clinical records. The average lenght of hospitalization was 13.4 days. Psychopathology was assessed by means of the PANSS and the severity of the illness was evaluated with CGI severity scale (CGI-S), both on admission and discharge. We also administered the UKU scale to evaluate the tolerability profile.

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Results can be seen in figures 1, 2, 3

Our study found a significant improvement in both positive and negative symptoms, with good tolerability. Limitations of our study are: small sample size and limited period of observation. These premises suggest that further research is needed in order to elucidate the exact mechanisms underlying Brexpiprazole’s action and the possible implication in mood disorders.

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Antipsychotics are the mainstream treatment of delusional disorder. However, limited therapeutic effect was recognized due to side effect and lack of insight.

This article presents a case with Ekbom’s syndrome, also known as delusional parasitosis, who has significant response with Brexpiprazole.

A 58-year-old female developed her very first episode of psychosis 3 weeks before she visited our emergency department. Delusion of spiders laying eggs and bitsy spiders crawling over her body was claimed, followed by depressed mood and insomnia. The patient denied any substance use in recent months. Examination including biochemical studies, complete blood count, vitamin, and endocrine during admission were all normal. Brain image revealed senile cortical atrophy without apparent acute infarction. Cognitive abilities screening instrument (CASI) revealed total score 75, indicating borderline cognitive function. Ophthalmologist and dermatologist were consulted, and no specific abnormality was found.

Brexpiprazole 2mg was prescribed. After 3 weeks of treatment, the delusion improved with less parasitosis content. We discharged the patient, and kept following her at outpatient department with Brexpiprazole 2mg for 2 months. We tried to taper Brexpiprazole to 1mg at clinic, but her delusional parasitosis relapsed within 1 month. Therefore, we titrated the medication back to 2mg, and kept some dosage for 4 months. No more relapse of psychosis or significant movement dysfunction was observed. The total treatment course was 7 months.

Brexpiprazole, with its D2 partial agonism, shows impressive antipsychotic effect to Ekbom’s syndrome. Little side effect was observed in clinical practice, making Brexpiprazole a worth-trying psychopharmacological management of delusional parasitosis.

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Borderline personality disorder is associated with impaired quality of life and has a number of untoward public health associations. There is no established first-line pharmacological treatment for borderline personality disorder, and available options are not suitable for all individuals.

To evaluate brexpiprazole, which has effects on the dopaminergic and serotonergic systems, for the reduction of borderline personality disorder symptoms.

Eighty adults with borderline personality disorder were recruited for a randomised, double-blind placebo-controlled study. Participants received 12-week treatment with brexpiprazole (1 mg/day for 1 week, then increasing to 2 mg/day) or placebo in a parallel design. The primary efficacy outcome measure was the clinician-rated Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD). Safety data were collected. Effects of active versus placebo treatment were characterised with linear repeated measures models.

There was a significant interaction between treatment and time on the ZAN-BPD scale (P = 0.0031), solely because of differentiation specifically at week 12. Brexpiprazole was generally well tolerated. Secondary measures did not result in statistically significant differences from placebo.

Brexpiprazole appears to have some possible effect on borderline personality disorder symptoms, but further studies are needed because of the significant effects evident, specifically at the final time point. These findings also need to be viewed cautiously, given the small sample size, large drop-out rate and robust placebo response.

To compare the tolerability and efficacy of different antipsychotic cross-titration schedules, using data from a brexpiprazole study (Equator; NCT01668797).

Patients with schizophrenia were cross-titrated from other antipsychotics to brexpiprazole monotherapy in a 1–4 week open-label conversion phase, then entered a single-blind brexpiprazole treatment phase. Patients were stratified into four “conversion groups,” according to the amount of time spent in the conversion phase. Discontinuation rates, treatment-emergent adverse events (TEAEs), and efficacy (Positive and Negative Syndrome Scale [PANSS]) were compared between conversion groups.

Of the 404 patients treated with brexpiprazole, the majority (72.0%) spent 22–33 days in the conversion phase. Discontinuation rates due to lack of efficacy or adverse events were low in all conversion groups. Of the 292 patients who successfully switched and completed 8 weeks of brexpiprazole treatment, most were converted to brexpiprazole over 22–33 days (80.1%), and fewer were converted over 1–7 days (2.4%), 8–14 days (6.5%), or 15–21 days (11.0%). The incidence of TEAEs over 8 weeks was lower among those converted over 22–33 days (44.4%) than in other conversion groups (62.5–84.2%), although low patient numbers with shorter conversion times limit the generalizability of this finding. Each conversion group showed comparable improvement in PANSS total score from baseline.

The majority of patients were cross-titrated to brexpiprazole over a period of 22–33 days, by investigators’ choice. Additional data on shorter conversions may help clinicians to choose a switching paradigm that best meets their patients’ needs.