When Clozapine Fails: Augmentation Strategies in the Management of Clozapine-Resistant Schizophrenia

Berardis, Domenico De; Fornaro, Michele; Anastasia, Annalisa; Vellante, Federica; Valchera, Alessandro; Cavuto, Marilde; Perna, Giampaolo; Nicola, Marco Di; Serafini, Gianluca; Carano, Alessandro; Pompili, Maurizio; Orsolini, L.; Tomasetti, Carmine; Emidio, Gabriella Di; Martinotti, Giovanni; Giannantonio, Massimo Di

doi:10.1007/978-981-10-4358-1_23

Cited by 6 publications

(4 citation statements)

References 164 publications

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“…The gold standard in the case of resistant schizophrenia is the clozapine treatment [ 3 ]. However, despite the greater efficacy of clozapine over other antipsychotics in the management of resistant schizophrenia, a signifi-cant number of patients fail to attain adequate response or develop clozapine-related adverse effects, and clozapine-resistant schizophrenia represents a challenge for the clinician and a calamity for the patients [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Cariprazine Add-on in Inadequate Clozapine Response: A Report on Two Cases

Berardis

Rapini²,

Olivieri³

et al. 2021

Clin Psychopharmacol Neurosci

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Cariprazine is a novel antipsychotic drug that exerts partial agonism of dopamine D 2 /D 3 receptors with preferential binding to the D 3 receptor, antagonism of 5HT 2B receptors, and partial agonism of 5HT 1A . Currently, cariprazine has shown clinical efficacy in patients with schizophrenia and with bipolar disorder, as well as adjunctive treatment in patients with Major Depressive Disorder (MDD) and drug-resistant MDD. In the present case series, we report on two patients with treatment-resistant schizophrenia and partial response to clozapine who benefit from combination with cariprazine. The effects of cariprazine combination were remarkable also concerning the adverse metabolic effects of clozapine.

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Section: Introductionmentioning

confidence: 99%

Cariprazine Add-on in Inadequate Clozapine Response: A Report on Two Cases

Berardis

Rapini²,

Olivieri³

et al. 2021

Clin Psychopharmacol Neurosci

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“…Typically, the primary approach entails enhancing treatment plans by incorporating different medications such as additional antipsychotics. However, despite these endeavours, there exists limited evidence supporting the efficacy of these augmentation strategies [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Impact of Pharmacogenetic Testing on Clozapine Treatment Efficacy in Patients with Treatment-Resistant Schizophrenia

Sangüesa,

Fernández-Egea,

Concha

et al. 2024

Biomedicines

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Managing schizophrenia with clozapine poses a significant challenge due to prevalent therapeutic failures. The increasing interest in personalized medicine underscores the importance of integrating pharmacogenetic information for effective pharmacotherapeutic monitoring in patients. The objective of this study was to explore the correlation between DRD2, HTR2A, SLC6A4, CYP1A2, and ABCB1 polymorphisms and clozapine response in 100 patients with Treatment-Resistant Schizophrenia. Different scales such as the Positive and Negative Syndrome Scale (PANSS), the Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS), the Global Assessment of Functioning Scale (GAF), the Brief Negative Symptom Scale (BNSS), and pharmacokinetic parameters were used to analyse the efficacy of the treatment. Patients who exclusively responded to clozapine compared to the patients with augmentation strategies exhibited distinctive features, such as lower doses, plasma levels, and presented less-pronounced symptomatology. Genetic associations were explored, highlighting SLC6A4, HTR2A, and the *1F/*1F polymorphism for the CYP1A2 gene.

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“…Currently, it is the only FDA-approved antipsychotic for patients with TRS who have previously taken adequate doses of other antipsychotics, with a minimum requirement of a trial of two or more, with at least one being an atypical antipsychotic. However, even with optimal treatment, a significant proportion of patients with TRS, ranging from 40% to 70%, fail to respond to clozapine [ 12 , 13 , 14 ]. They form a distinct subgroup of TRS, referred to as clozapine-resistant schizophrenia (CRS).…”

Section: Introductionmentioning

confidence: 99%

“…The most common approach to address this condition is through augmentation with other medications, such as additional antipsychotics, anxiolytics, mood stabilizers, and antidepressants. However, despite these efforts, there is limited evidence to support the efficacy of augmentation with other medications [ 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. Non-pharmacological interventions, including electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), and cognitive behavioral therapy (CBT), have emerged as alternative strategies to manage UTRS.…”

Section: Introductionmentioning

confidence: 99%

Clozapine in Treatment-Resistant Schizophrenia and Its Augmentation with Electroconvulsive Therapy in Ultra-Treatment-Resistant Schizophrenia

et al. 2023

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Clozapine is considered the gold standard for patients with treatment-resistant schizophrenia (TRS) who have previously tried other antipsychotics at adequate doses (two or more, with at least one being atypical). However, despite optimal treatment, a subgroup of TRS patients with what is known as ultra-treatment-resistant schizophrenia (UTRS) fails to respond to clozapine, which occurs in 40–70% of cases. The most common approach to manage UTRS involves augmenting clozapine with pharmacological or non-pharmacological interventions, with a growing body of evidence that supports the use of electroconvulsive therapy (ECT) as an augmenter. This prospective non-randomized 8-week study, which followed the TRIPP Working Group guidelines and is one of few that separate TRS from UTRS, aimed to evaluate the effectiveness of clozapine in TRS patients and the efficacy of ECT augmentation of clozapine in UTRS patients. Patients with TRS were assigned to receive clozapine alone (clozapine group), whereas UTRS patients received bilateral ECT in addition to their current medication regimen (ECT plus clozapine group). The severity of symptoms was evaluated using the Clinical Global Impression Scale (CGI) and Positive and Negative Syndrome Scale (PANSS) at baseline and at the end of the 8-week trial. Both treatment approaches resulted in improved CGI and PANSS scores. The results suggest that both clozapine and ECT are effective treatment options for patients with TRS and UTRS, respectively, and that adherence to guidelines should provide a better frame for future clinical studies.

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When Clozapine Fails: Augmentation Strategies in the Management of Clozapine-Resistant Schizophrenia

Cited by 6 publications

References 164 publications

Cariprazine Add-on in Inadequate Clozapine Response: A Report on Two Cases

Cariprazine Add-on in Inadequate Clozapine Response: A Report on Two Cases

Impact of Pharmacogenetic Testing on Clozapine Treatment Efficacy in Patients with Treatment-Resistant Schizophrenia

Clozapine in Treatment-Resistant Schizophrenia and Its Augmentation with Electroconvulsive Therapy in Ultra-Treatment-Resistant Schizophrenia

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