Antipsychotic combinations for schizophrenia

Ortiz-Orendain, Javier; Castiello, Santiago; Colunga‐Lozano, Luis Enrique; Hu, Yue; Maayan, Nicola; Adams, Clive E

doi:10.1002/14651858.cd009005.pub2

Cited by 42 publications

(36 citation statements)

References 140 publications

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“…There is no strong, consistent evidence for combining antipsychotic medications, for example, for refractory illness (e.g. Correl et al, 2009Correl et al, , 2017aHaddad and Correll, 2018;Ortiz-Orendain et al, 2017; see also the section below on Combined non-clozapine antipsychotic medications (antipsychotic polypharmacy) for treatment-resistant schizophrenia) and a clear risk of toxicity from the combined dose (Barnes and Paton, 2011;Girardin et al, 2013). Existing guidelines such as NICE CG178 (NICE, 2014a) are clear on the need for psychosocial treatment such as CBT for psychosis and family intervention whenever possible.…”

Section: Acute Psychotic Episodementioning

confidence: 99%

Evidence-based guidelines for the pharmacological treatment of schizophrenia: Updated recommendations from the British Association for Psychopharmacology

2019

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These updated guidelines from the British Association for Psychopharmacology replace the original version published in 2011. They address the scope and targets of pharmacological treatment for schizophrenia. A consensus meeting was held in 2017, involving experts in schizophrenia and its treatment.They were asked to review key areas and consider the strength of the evidence on the risk-benefit balance of pharmacological interventions and the clinical implications, with an emphasis on meta-analyses, systematic reviews and randomised controlled trials where available, plus updates on current clinical practice. The guidelines cover the pharmacological management and treatment of schizophrenia across the various stages of the illness, including first-episode, relapse prevention, and illness that has proved refractory to standard treatment. It is hoped that the practice recommendations presented will support clinical decision making for practitioners, serve as a source of information for patients and carers, and inform quality improvement.

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Section: Acute Psychotic Episodementioning

confidence: 99%

Evidence-based guidelines for the pharmacological treatment of schizophrenia: Updated recommendations from the British Association for Psychopharmacology

2019

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“…The meta-analyses published after 2009 have generally not been able to replicate the positive findings for augmenting clozapine treatment with an additional antipsychotic compound, [31][32][33][34] but results are mixed. 35 The most recent meta-analysis indicates a potential therapeutic effect on negative symptoms only when augmenting with aripiprazole (a partial dopamine D2 agonist) compared with antipsychotic monotherapy (standardized mean difference [SMD] −0.41; 95% confidence interval [CI] −0.79 to −0.03; N = 532). 36 If choosing to combine two antipsychotic compounds with the aim of obtaining supplementary efficacy, the rational choice will be to combine two compounds with different receptor profiles (cf.…”

Section: Antipsychotic Polypharmacymentioning

confidence: 99%

Polypharmacy in schizophrenia

Baandrup

2020

Basic Clin Pharma Tox

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Schizophrenia is a severe mental disorder characterized by a heterogeneous symptom profile which comprises a clinical platform for widespread use of polypharmacy even though antipsychotic monotherapy is the recommended treatment regimen. This narrative review provides a summary of the current gap between evidence and practice for use of antipsychotic combination therapy in patients with schizophrenia. Antipsychotic polypharmacy is frequently prescribed instead of following international consensus of clozapine monotherapy in treatment‐resistant patients. Antipsychotic‐benzodiazepine combination therapy clearly has a role in the treatment of acute agitation whereas there is no evidence to support an effect on core schizophrenia symptoms when chronically prescribed. Antidepressants are typically added to antipsychotic treatment in case of persistent negative symptoms. Available evidence suggests that antidepressants may improve negative symptom control in schizophrenia. Combining an antipsychotic with an antiepileptic is not supported by any firm evidence, but individual mood stabilizers have come out positively in single trials. Generally, the evidence base for polypharmacy in schizophrenia maintenance treatment is sparse but may be warranted in certain clinical situations. Therapeutic benefits and side effects should be carefully monitored and considered to ensure a beneficial risk‐benefit ratio if prescribing polypharmacy for specific clinical indications.

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“…Several researchers have recommended that it is essential to check liver function tests before starting therapy with clozapine and re-examination every 6 months has been advised. 47 Although the effective clozapine plasma levels remain debated, most researchers find that a therapeutic window of 350-600 ng/mL for clozapine plasma concentrations is associated with an increased probability of a good clinical response to the drug. Concentrations higher than 1000 ng/mL could increase the risk of seizures.…”

Section: Discussionmentioning

confidence: 99%

<p>The Effect of Liver and Kidney Disease on the Pharmacokinetics of Clozapine and Sildenafil: A Physiologically Based Pharmacokinetic Modeling</p>

Ghoneim¹,

Mansour²

2020

DDDT

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Background and Objectives: Physiologically based pharmacokinetic (PBPK) modeling permits clinical scientists to reduce practical constraints for clinical trials on patients with special diseases. In this study, simulations were carried out to validate the pharmacokinetic parameters of clozapine and sildenafil using Simcyp ® simulator in young male adults and compare the effect of renal or hepatic impairment on the pharmacokinetic parameters of clozapine and sildenafil. Also, the effect of age on pharmacokinetic parameters of both drugs was investigated in healthy population and in patients with renal and hepatic impairment. Methods: A full PBPK model was built in the simulator for clozapine and sildenafil based on physicochemical properties and observed clinical results. The model used was Advanced, Dissolution, Absorption and Metabolism (ADAM) for both drugs. Results: The PBPK model adequately predicted the pharmacokinetic parameters of clozapine and sildenafil for the healthy adult population. In the simulation results, the bioavailability of both drugs was remarkably raised in both renal and hepatic impairment in young and elderly populations. Conclusion: PBPK modeling could be helpful in the investigation and comparison of the pharmacokinetics in populations with specific disease conditions.

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Antipsychotic combinations for schizophrenia

Cited by 42 publications

References 140 publications

Evidence-based guidelines for the pharmacological treatment of schizophrenia: Updated recommendations from the British Association for Psychopharmacology

Evidence-based guidelines for the pharmacological treatment of schizophrenia: Updated recommendations from the British Association for Psychopharmacology

Polypharmacy in schizophrenia

<p>The Effect of Liver and Kidney Disease on the Pharmacokinetics of Clozapine and Sildenafil: A Physiologically Based Pharmacokinetic Modeling</p>

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