Add-on of aripiprazole improves outcome in clozapine-resistant schizophrenia

Risio, Alessandro De; Pancheri, Angelo; Simonetti, Giovanna; Giannarelli, Diana; Stefanutto, Luciana; Gentile, Bruno

doi:10.1016/j.pnpbp.2011.03.011

Cited by 11 publications

(11 citation statements)

References 34 publications

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“…Although these reviews only indicate modest gains at best as a result of combination antipsychotic therapy, a recent retrospective study conducted by DeRisio and colleagues (21) indicated favourable results. Namely, they found an improved functional outcome in a small sample of patients; they postulated that such an outcome may assist with this population being more amenable to change through non‐pharmaceutical interventions.…”

Section: Discussionmentioning

confidence: 99%

“…Previous augmentation strategies reported in the literature are not limited to the adjunctive treatment with an additional antipsychotic. Rather antidepressants, benzodiazepines, mood stabilisers and anticholinergics have also been reported in the literature although contradictory results are evident (5, 14, 16, 18, 21). The results of the present study indicated that 30% of the patients in the sample were taking antidepressants, 7% on benzodiazepines, 17% on mood stabilisers and lastly 4% on anticholinergics.…”

Section: Discussionmentioning

confidence: 99%

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Augmentation of clozapine with another pharmacological agent: treatment for refractory schizophrenia in the ‘real world’

Pai

Laidlaw²,

Vella

2012

Acta Psychiatr Scand

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Pai NB, Laidlaw M, Vella S‐C. Augmentation of clozapine with another pharmacological agent: treatment for refractory schizophrenia (SZ) in the ‘real world’. Objective: Refractory schizophrenia (SZ) affects approximately 30% of people with SZ. Clozapine (CLZ) is the gold standard treatment; however, there are still patients who are non‐responsive or partially responsive to treatment. Although a lack of evidence exists in reality, these patients are treated with a combination of agents in addition to CLZ. Therefore, this article reviews the prevalence of the augmentation of CLZ with additional agents. Method: This study was cross‐sectional; physicians in a region of Australia in May 2011 were contacted to provide details of their patients on CLZ and any additional agents. The data set consists of 84 patients. Results: The majority of the patients 84.5% were taking at least one additional agent. Of those taking additional agents, they derived from the following classes’ antipsychotics (72%), antidepressants (30%), mood stabilisers (17%), antimetabolic agents (13%), benzodiazepines (7%), anticholinergics (4%) and miscellaneous agents (12.5%). Conclusion: It is apparent that CLZ is routinely augmented with other agents despite the lack of an evidence base. However, concerning was the lack of augmentation with antimetabolic agents despite the paucity of literature reporting the detrimental impact of antipsychotic treatment upon patients metabolic indices. The findings are discussed in the context of the current recommendations and empirical literature.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Augmentation of clozapine with another pharmacological agent: treatment for refractory schizophrenia in the ‘real world’

Pai

Laidlaw²,

Vella

2012

Acta Psychiatr Scand

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“…Given that a relevant proportion of patients with a psychotic disorder do not respond adequately to monotherapy with clozapine, there is a need to know which coadjuvant treatments can be more effective and safer [4,7,8,[43][44][45][46]. The combination of clozapine with LAI antipsychotics could be one of the strategies with more potential [3,47], especially with the appearance of monthly or quarterly second-generation antipsychotics.…”

Section: Discussionmentioning

confidence: 99%

Clozapine and paliperidone palmitate antipsychotic combination in treatment-resistant schizophrenia and other psychotic disorders: A retrospective 6-month mirror-image study

et al. 2020

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Background: Around 30% of patients with schizophrenia are considered treatment resistant (TRS). Only around 40% of TRS patients respond to clozapine. Long acting injectable antipsychotics could be a useful augmentation strategy for nonresponders. Methods: We conducted a multicenter, observational, naturalistic, retrospective, 6-month mirror-image study to evaluate the efficacy and tolerability of clozapine and paliperidone palmitate association in 50 patients with TRS and other psychotic disorders. Clinical outcomes and side effects were systematically assessed. Results: Six months after starting the combined treatment, participants showed a significant relief of symptoms, decreasing the Brief Psychiatric Rating Scale total score from 18.32 ± 7.71 to 7.84 ± 5.16 (p < 0.001). The number of hospitalizations, the length of hospital stays and the number of visits to emergency services also decreased, while an increase of the functionality was observed (Personal and Social Performance total score increased from 46.06 ± 118.7 to 60.86 ± 18.68, p < 0.001). There was also a significant decrease in the number and severity of side effects with the combination therapy, decreasing the Udvalg for Kliniske Undersogelser total score from 10.76 ± 8.04 to 8.82 ± 6.63 (p = 0.004). Conclusions: This study provides the first evidence that combining clozapine with paliperidone palmitate in patients with TRS and other psychotic disorders could be effective and safe, suggesting further research with randomized controlled trials of augmentation strategies for clozapine nonresponder patients. Policy Significance Statement: Patients with psychotic disorders such as schizophrenia show a variable response to antipsychotic treatments. Around 30% of patients are considered treatment resistant, indicated by insufficient symptom control to at least two different drugs. In these resistant cases, clozapine should be indicated, as it has shown to be superior to other options. However, only 40% of patients respond to clozapine, being necessary to establish which treatments could best potentiate clozapine action. Combining clozapine with long acting injectable antipsychotics, and particularly paliperidone palmitate, could be a useful strategy. We conducted a multicenter study of 50 patients with treatment-resistant schizophrenia and other psychotic disorders comparing the efficacy and tolerability in the 6 month-period prior and after starting the clozapine and paliperidone palmitate association. Our study suggests that this combination could be effective and safer, laying the groundwork for future clinical trials with this combination.

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“…Starting off with promising case reports53,93–99 and prospective or retrospective clinical observations,100–104 a small number of RCT were initiated to analyze the combination of clozapine and aripiprazole in treatment-resistant schizophrenia 105–108. Most of the open-label and case studies as well as case reports show positive effects of this combination on overall psychopathology53,93–95,99,101–104,109 and on negative symptoms 96,97,99,102,103.…”

Section: Aripiprazole and Clozapinementioning

confidence: 99%

“…Most of the open-label and case studies as well as case reports show positive effects of this combination on overall psychopathology53,93–95,99,101–104,109 and on negative symptoms 96,97,99,102,103. Several reports describe the possibility of dose reduction for clozapine in combination with aripiprazole, a strategy that might help so-called treatment-intolerant patients 93,98,101,102.…”

Section: Aripiprazole and Clozapinementioning

confidence: 99%

Role of aripiprazole in treatment-resistant schizophrenia

Mossaheb¹

2012

NDT

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About one third of patients with schizophrenia respond unsatisfactorily to antipsychotic treatment and are termed “treatment-resistant”. Clozapine is still the gold standard in these cases. However, 40%–70% of patients do not improve sufficiently on clozapine either. In the search for more efficacious strategies for treatment-resistant schizophrenia, drugs with different pharmacological profiles seem to raise new hopes, but are they valid? The aim of this review was to evaluate the evidence for aripiprazole as a potential strategy in monotherapy or combination therapy for patients with treatment-resistant schizophrenia. The evidence for aripiprazole monotherapy and for the combination of aripiprazole with psychotropics other than clozapine is scant, and no recommendation can be made on the basis of the currently available data. More effort has been made in describing combinations of aripiprazole and clozapine. Most of the open-label and case studies as well as case reports have shown positive effects of this combination on overall psychopathology and to some extent on negative symptoms. Several reports describe the possibility of dose reduction for clozapine in combination with aripiprazole, a strategy that might help so-called “treatment-intolerant” patients. The findings of four randomized controlled trials with respect to changes in psychopathology seem less conclusive. The most commonly found beneficial effects are better metabolic outcomes and indicators of the possibility of reducing the clozapine dose. However, other side effects, such as akathisia, are repeatedly reported. Further, none of the studies report longer-term outcomes. In the absence of alternatives, polypharmacy is a common strategy in clinical practice. Combining aripiprazole with clozapine in clozapine-resistant or clozapine-intolerant patients seems to be worthy of further investigation from the pharmacological and clinical points of view.

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Add-on of aripiprazole improves outcome in clozapine-resistant schizophrenia

Cited by 11 publications

References 34 publications

Augmentation of clozapine with another pharmacological agent: treatment for refractory schizophrenia in the ‘real world’

Augmentation of clozapine with another pharmacological agent: treatment for refractory schizophrenia in the ‘real world’

Clozapine and paliperidone palmitate antipsychotic combination in treatment-resistant schizophrenia and other psychotic disorders: A retrospective 6-month mirror-image study

Role of aripiprazole in treatment-resistant schizophrenia

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