Clozapine-Treatment-Resistant Schizophrenia Successfully Managed with Brexpiprazole Combination Therapy: Two Case Reports

Orsolini, Laura; Valenta, S. Tempia; Bellagamba, S.; Salvi, V.; Volpe, U.

doi:10.1192/j.eurpsy.2022.903

Cited by 2 publications

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“…The same team reported in a short communication on two cases of brexpiprazole and clozapine association in two patients with URS, both patients being subsequently switched on clozapine plus aripiprazole LAI ( 53 ). After 1 month of treatment, the clinical evolution was favorable, reflected in the PANSS scores’ improvement (over 55% total score decrease) ( 53 ). Only one patient presented at the 6 months follow-up, and his clinical status continued to improve ( 53 ).…”

Section: Resultsmentioning

confidence: 98%

“…After 1 month of treatment, the clinical evolution was favorable, reflected in the PANSS scores’ improvement (over 55% total score decrease) ( 53 ). Only one patient presented at the 6 months follow-up, and his clinical status continued to improve ( 53 ).…”

Section: Resultsmentioning

confidence: 99%

“…It is metabolized by CYP3A4 and 2D6, thus leaving unoccupied the CYP1A2 isoform. Based on the reviewed data, which are very limited ( n = 3 case reports), this augmentative strategy could be efficient, but treatment adherence is challenging ( 52 , 53 , 61 ).…”

Section: Discussionmentioning

confidence: 99%

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Third-generation antipsychotics in patients with schizophrenia and non-responsivity or intolerance to clozapine regimen: What is the evidence?

Vasiliu¹

2022

Front. Psychiatry

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Clozapine is considered « the golden standard » for the management of treatment-resistant schizophrenia, but many patients do not present adequate responsivity even to this antipsychotic. If we add the need to strictly monitor the hematologic and cardiometabolic adverse events during each clozapine trial and the difficulty of preserving therapeutic adherence in patients with low insight, residual negative/positive symptoms, or economic challenges, then the necessity of exploring alternative interventions for these patients becomes obvious. Also, in case of intolerance to clozapine or where clozapine did not induce remission, clinicians have to find new ways to help their patients. Switching to other antipsychotics or using these agents as add-ons to clozapine are the main interventions explored in this review, for patients with schizophrenia resistant to clozapine (ultra-resistant schizophrenia, URS). When clozapine intolerance is detected, conversion to another antipsychotic with distinct pharmacologic properties or formulation (e.g., long-acting intramuscular injectable agents, LAI) may be a useful option. Third-generation antipsychotics (TGA) have been selected for their distinct pharmacodynamically profile, which allows, at a theoretical level, their use in combination with clozapine. This narrative review is based on searching four electronic databases, that retrieved 19 primary and secondary reports on aripiprazole (seven case reports or case series presenting 24 patients; nine clinical trials, and three systematic reviews/meta-analyses), two primary reports on brexpiprazole (case report and case series, N = 3 patients), and six primary reports on cariprazine (case reports and case series, N = 14 patients). Based on the information collected from these reports, which included oral and LAI formulations, the TGA most supported by evidence for the augmentation of clozapine is aripiprazole (high-and medium-quality data), followed by cariprazine (low-quality data). Brexpiprazole has not yet been systematically explored for this indication, and in the case of lumateperone, no report could be found. The efficacy of aripiprazole and cariprazine was supported in the domains of positive, negative, and general symptoms, and aripiprazole may positively impact the metabolic profile in patients with URS. Also, adding TGA may lead to a decrease in the dose of clozapine concomitantly administered. More data derived from good quality research are needed in order to confirm the circumstances of TGAs recommendation in patients with URS, either as monotherapy, or added to clozapine.

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Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

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Third-generation antipsychotics in patients with schizophrenia and non-responsivity or intolerance to clozapine regimen: What is the evidence?

Vasiliu¹

2022

Front. Psychiatry

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“…Несмотря на ограниченные исследования применения комбинированной терапии клозапина с брексипразолом, результаты оказались небезынтересными. Так, в отдельном клиническом случае сообщалось и об эффективности данной терапии (улучшение настроения, уменьшение выраженности нарушений мышления, враждебности, продуктивных и негативных симптомов, влечения к ПАВ), и об ее безопасности [67].…”

Section: Guidelines For the Practitioner в помощь практикующему врачуunclassified

The phenomenon of therapeutic resistance in the treatment of schizophrenia: the possibilities of modern diagnostics and methods of anti-resistant effects

Stanovaya,

Guseynova,

Ivanov

et al. 2023

V.M. BEKHTEREV REVIEW OF PSYCHIATRY AND MEDICAL PSYCHOLOGY

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The formation of resistance is a key factor in curbing progress in the treatment of schizophrenia. In modern psychiatric practice, despite the emergence of new medical technologies, including the use of a wide arsenal of psychotropic medicinal effects, the frequency of manifestations of therapeutic resistance in the cohort of mentally ill is on average about 30%. The reasons for the formation of resistance identified to date are diverse and can be associated with both biological changes due to violations of the functioning of various neurotransmitter systems. so it is with non-compliance with the regimen of taking medications (drug noncompliance). Therapy-resistant schizophrenia is a serious clinical problem, since patients with such manifestations often feel the need for repeated hospitalizations, have more pronounced violations of social and professional functioning. It has been established that the formation of therapeutic resistance can occur both at the beginning of active treatment and in the process of psychopharmacotherapy. Therefore, it is important to identify predictors of therapeutic resistance, which will allow using methods to overcome it as soon as possible. This literature review examines both the main forms of therapeutic resistance and the features of its formation, as well as the possibilities of drug and non-drug therapy of resistant schizophrenia.Materials and methods. A literature review was performed in the PubMed database. The keywords types of therapeutic resistance, therapeutically resistant schizophrenia, antipsychotics, methods of anti-resistant effects. Inclusion criteria: randomized and non-randomized clinical trials, meta-analyses and systematic reviews, fulltext articles on therapeutic resistance in mentally ill patients and coping methods. Exclusion criteria: articles of poor quality. Results. The analysis of the literature data has shown the expediency of using not only clozapine, a first-line drug, for therapeutic resistance, but also modern drugs, primarily cariprazine, which, despite limited studies, have shown high efficacy both in combination therapy with clozapine and in monotherapy, in correcting stable productive, negative and cognitive symptoms. The use of augmentation with antidepressants, normotimic and glutamatergic drugs can be used to overcome resistance, but data on the effectiveness of this strategy are ambiguous. Of the non-medicinal methods of treating therapeutically resistant schizophrenia, the use of electroconvulsive therapy is recommended as the only method of biological effects that currently has an evidence base. Conclusions. According to the results of the literature review, the most studied, proven methods of overcoming therapeutically resistant schizophrenia are clozapine and electroconvulsive therapy. At the same time, taking into account the preliminary positive results of the use of third-generation antipsychotics, it can be considered appropriate to use them both in combination therapy and in monotherapy, with insufficient effectiveness of clozapine.

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Clozapine-Treatment-Resistant Schizophrenia Successfully Managed with Brexpiprazole Combination Therapy: Two Case Reports

Cited by 2 publications

References 0 publications

Third-generation antipsychotics in patients with schizophrenia and non-responsivity or intolerance to clozapine regimen: What is the evidence?

Third-generation antipsychotics in patients with schizophrenia and non-responsivity or intolerance to clozapine regimen: What is the evidence?

The phenomenon of therapeutic resistance in the treatment of schizophrenia: the possibilities of modern diagnostics and methods of anti-resistant effects

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