Impact of antipsychotic polypharmacy on nonadherence of oral antipsychotic drugs – A study based on blood sample analyses from 24,239 patients

Smith, Robert L.; Tveito, Marit; Kyllesø, Lennart; Jukić, Marin M.; Ingelman‐Sundberg, Magnus; Andreassen, Ole A.; Molden, Espen

doi:10.1016/j.euroneuro.2020.06.007

Cited by 13 publications

(8 citation statements)

References 22 publications

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“…We deem necessary to remember two important issues. On one hand, as non-adherence phenomenon is strongly associated with polypharmacy ( 29 , 30 ), clinicians should consider to revise AP prescription favoring a monotherapy regimen with the aim to reduce the risk of drug discontinuation and subsequent relapse. On the other hand, the scientific evidence on clozapine efficacy, if compared to FGAs and SGAs, in case of refractory cases is quite massive despite its unfavorable metabolic and hematological profile ( 77 ).…”

Section: Discussionmentioning

confidence: 99%

“…The authors also found that APs were usually combined with other CNS drugs (polypharmacotherapy) in more than half of the cases ( 7 ), confirming that add-on therapies were frequently prescribed in PLWS ( 27 , 28 ). However, oral AP polypharmacy has been extensively associated to non-adherence phenomenon, to reduced tolerability and increased adverse effects and higher costs for MHS ( 29 , 30 ). Coherently, in the U.S. in 2005, it was found that the national rehospitalization costs related to antipsychotic non-adherence were, on average, $1479 million ( 31 ).…”

Section: Introductionmentioning

confidence: 99%

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The patient journey project in Italian mental health services: results from a co-designed survey on clinical interventions and current barriers to improve the care of people living with schizophrenia

Vita,

Barlati,

Porcellana

et al. 2024

Front. Psychiatry

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IntroductionThe Patient Journey Project aimed to analyze the scenario among Italian Mental Health Services (MHS) to understand the clinical interventions that are properly implemented and the ones deserving further implementation to design an effective treatment plan for patients living with schizophrenia (PLWS).MethodsThe 60-items survey was co-designed with all the stakeholders (clinicians, expert patients and caregivers) involved in the Patient Journey and focused on three phases of schizophrenia course: early detection and management, acute phase management, long-term management/continuity of care. Respondents were Heads of the Mental Health Departments and Addiction Services (MHDAS) or facilities directors throughout Italian MHS. For each statement, respondents expressed the consensus on the importance and the degree of implementation in clinical practice.ResultsConsidering the importance of the statement, strong consensus was reached for most of the statements. Good levels of implementation were found on 2/17 statements of early detection and management, on 3/16 statements for acute phase management and on 1/27 statements of long-term management/continuity of care. Poor levels of implementation were found on 1/17 statements of early detection and management, none of acute phase management, and 4/27 statements for long-term management/continuity of care. Moderate levels of implementation were found on 14/17 statements for early detection and management, on 13/16 statements of acute phase management, and on 22/27 statements of long-term management/continuity of care. Thus, among Italian MHDAS, most interventions for PLWS were moderately implemented in clinical practice.DiscussionItalian MHS have to provide new strategies and structural actions to overcome these current limitations and barriers to effectively improve the journey of PLWS. The areas that deserve most implementation include interventions during the early stage (especially the continuity of care between Child and Adolescent Mental Health Services and Adult Mental Health Services), the evidence-based psychosocial interventions during the chronic stages of the disorder, and the continuity of care after acute hospitalization.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The patient journey project in Italian mental health services: results from a co-designed survey on clinical interventions and current barriers to improve the care of people living with schizophrenia

Vita,

Barlati,

Porcellana

et al. 2024

Front. Psychiatry

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“…TDM analyses of clozapine and other psychiatric drugs are ordered by treatment-responsible psychiatrists or general practitioners. Approximately 75% of the samples of antipsychotic drugs submitted for TDM analyses are from outpatient settings [ 32 ], and the remainder represent blood samples drawn from patients during hospitalization.…”

Section: Methodsmentioning

confidence: 99%

“…Monitoring of clozapine levels is also recommended by national guidelines, including those of the UK National Institute for Health and Care Excellence [ 6 , 31 ]. In addition, to titrate dosing and prevent treatment failure, TDM is used as a tool to disclose possible treatment nonadherence, which is a substantial problem in the treatment of schizophrenia [ 19 , 32 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

Absolute and Dose-Adjusted Serum Concentrations of Clozapine in Patients Switching vs. Maintaining Treatment: An Observational Study of 1979 Patients

et al. 2021

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Background Clozapine is an effective drug for the management of schizophrenia that has not responded to other agents, but some patients experience insufficient or adverse effects and discontinue treatment. Objective We investigated a potential association between clozapine serum concentrations and switching to other antipsychotics in a large real-world patient population from a therapeutic drug monitoring service. Methods Absolute and dose-adjusted serum concentrations (concentration-to-dose ratios [C/D ratios]) of clozapine during dosing between 100 and 1000 mg/day were measured in 1979 Norwegian patients during the period 2005-2019. These variables were compared in patients switching to other antipsychotic drugs versus maintaining clozapine treatment using linear mixed models. Smoking habits were known for 49% of the patients. To prevent potential nonadherence affecting clozapine switching, only patients with serum concentrations above 50% of the lower reference range were included. Results In total, 190 patients (9.6%) switched from clozapine to another antipsychotic drug during the study period, whereas the remaining patients were not detected as switchers and were interpreted as maintaining treatment. Patients switching treatment had 23.5% lower absolute concentrations (954 vs. 1245 nmol/L; p < 0.001) and 15.7% lower daily doses (305 vs. 362 mg/day; p < 0.001) of clozapine than did nonswitchers, making the clozapine C/D ratio 9.7% lower in switchers than in nonswitchers after correcting for smoking habits (2.80 vs. 3.10 nmol/L/mg/day; p = 0.032). Conclusions The present study suggests that decreased absolute and dose-adjusted serum concentrations of clozapine were associated with clozapine discontinuation. The significantly reduced clozapine concentrations regardless of prescribed dose in switchers versus nonswitchers may indicate a pharmacokinetic mechanism underlying the risk of clozapine discontinuation.

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“…The use of depot antipsychotics proved more frequent in those patients with a community treatment order ( Callaly and Trauer, 2000 ; Gisev et al, 2014a ). Antipsychotic polypharmacy and high-dose antipsychotics are therapeutic strategies with greater impact, and they are often unaligned to the prescribing clinical guidelines, burdened by greater side effects, possible drug interactions, and the risk for complete non-adherence ( Cullen et al, 2013 ; Papola et al, 2019 ; Smith et al, 2020 ; Aburamadan et al, 2021 ; Lochmann van Bennekom et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Antipsychotic Polypharmacy and High-Dose Antipsychotic Regimens in the Residential Italian Forensic Psychiatric Population (REMS)

et al. 2022

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Few data exist regarding treatment with antipsychotics in forensic psychiatric patient populations with high social dangerousness. We performed a secondary analysis of 681 patients treated with at least one antipsychotic, extracted from a 1-year observational retrospective study, conducted on 730 patients treated in the Italian Residencies for Execution of Security Measures (REMS) (96.4% of the REMS population). We aimed at investigating antipsychotic polypharmacy (prescription of two or more concomitant antipsychotics) and high dose/very high-dose antipsychotics, as well as the possible factors associated with such therapeutic regimens. High dose/very high-dose antipsychotics were defined as a prescribed daily dose to WHO-defined daily dose ratio greater than 1.5 or 3.0, respectively. Binary logistic regression analysis was used in three models to test possible predictors of antipsychotic polypharmacy, high-dose antipsychotics, and very high-dose antipsychotic prescription. Antipsychotic polypharmacy resulted in n = 308 (45.2%) of the patients, n = 346 (50.8%) received high-dose antipsychotics, and n = 96 (14.1%) very high-dose antipsychotics. The multivariate analysis disclosed an association between antipsychotic polypharmacy and male gender (odds ratio (OR): 2.75 and 95% CI: 1.34–5.65), long-acting injectable (LAI) antipsychotic prescription (OR: 2.62 and 95% CI: 1.84–3.74), and aggressive behavior in REMS (OR: 1.63 and 95% CI: 1.13–2.36). High-dose antipsychotics were also associated with male gender (OR: 2.01 and 95% CI: 1.02–3.95), LAI antipsychotic prescription (OR: 2.78 and 95% CI: 1.95–3.97), and aggressive behavior in REMS (OR: 1.63 and 95% CI: 1.12–2.36). The use of antipsychotic polypharmacy and high-dose antipsychotics is frequent in the REMS population. These results might depend on regulatory and organizational aspects of the REMS system, including variability in structures, lack of a common model of care, and lack of stratified therapeutic security.

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Impact of antipsychotic polypharmacy on nonadherence of oral antipsychotic drugs – A study based on blood sample analyses from 24,239 patients

Cited by 13 publications

References 22 publications

The patient journey project in Italian mental health services: results from a co-designed survey on clinical interventions and current barriers to improve the care of people living with schizophrenia

The patient journey project in Italian mental health services: results from a co-designed survey on clinical interventions and current barriers to improve the care of people living with schizophrenia

Absolute and Dose-Adjusted Serum Concentrations of Clozapine in Patients Switching vs. Maintaining Treatment: An Observational Study of 1979 Patients

Antipsychotic Polypharmacy and High-Dose Antipsychotic Regimens in the Residential Italian Forensic Psychiatric Population (REMS)

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