Rates of complete nonadherence among atypical antipsychotic drugs: A study using blood samples from 13,217 outpatients with psychotic disorders

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

doi:10.1016/j.schres.2020.11.025

Cited by 13 publications

(12 citation statements)

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“…Potential nonadherence to treatment is challenging in any chronic illness, including schizophrenia [ 45 ], and may be a non-pharmacokinetic reason for interindividual variability in C/D ratios. The nonadherence rate for clozapine is significantly lower than for other antipsychotics [ 33 ], which may be because of the frequent monitoring of granulocyte counts and serum concentrations during clozapine therapy. Furthermore, in the present study, we excluded patients with clozapine serum concentrations < 150 nmol/L, i.e.…”

Section: Discussionmentioning

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%

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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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Section: Discussionmentioning

confidence: 99%

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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“…Many methods have been proposed, none of which is perfect. Generally, the schizophrenia patient can be considered as adherent, partially adherent or non-adherent ( 13 , 37 ). In the patient's file, upon admission, it is mentioned if the patient is adherent, partially adherent or non-adherent.…”

Section: Methodsmentioning

confidence: 99%

Rating Opportunity for Long-Acting Injectable Antipsychotic Initiation Index (ROLIN)

2021

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Background: Schizophrenia is a severe psychiatric condition with devastating consequences for the individual's functionality and leading to severe disability. Lack of insight and non-adherence to treatment remain the most important factors in the progression of the disease to chronicity. Despite their proven effectiveness in preventing relapses, reducing morbidity and mortality, long-acting injectable antipsychotics (LAIs) are still underused. One of the causes invoked is the lack of guidelines or protocols for initiating LAIs.Objective: The aim of this article is to present Rating Opportunity for Long-Acting Injectable Antipsychotic Initiation Index (ROLIN), a clinician-rated index that rates the important factors of the disorder across seven items: age, duration of illness, relapses, antipsychotic treatment response, family support, antipsychotic existing formulation and adherence.Method: A retrospective study in which all patients with schizophrenia discharged on oral antipsychotics without LAIs treatment lifetime were evaluated with ROLIN for opportunity for LAIs initiation.Results: Of 225 consecutive patients, 126 patients (56%) had a strong indication for initiating LAI (score between 25 and 35). Kolmogorov-Smirnov test was used for checking the normal distribution of values (95% CI for the mean = 9.5781 to 20.4219; 95% CI for the median = 6.5920 to 24.8161; SD = 9.7907; Coefficient of Skewness = 0.0743; Coefficient of Kurtosis = −1.1377).Conclusion: This paper proposed an instrument designed to improve treatment in schizophrenia using a simple conceptual model which integrates important predictors of good or poor outcomes.

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“…Many methods have been proposed, none of which are perfect. In general, the patient with schizophrenia can be considered as adherent, partially adherent or non-adherent [22,23]. In the patient's le, on admission, it is mentioned if the patient is adherent, partially adherent or non-adherent.…”

Section: Treatment Adherencementioning

confidence: 99%

Schizophrenia Long-Acting Injectable Antipsychotic Initiation Index: A Clinician Rated Instrument for Improving Treatment in Schizophrenia

Ifteni

Teodorescu

2021

Preprint

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Background: Schizophrenia is a severe psychiatric condition with devastating consequences for the individual's functionality and leading to severe disability. Lack of insight and non-adherence to treatment remain the most important factors in the progression of the disease to chronicity.Despite their proven effectiveness in preventing relapses, reducing morbidity and mortality, long acting injectable antipsychotics (LAIs) are still underused. One of the causes invoked is the lack of guidelines or protocols for initiating LAIs.Objective: The aim of this article is to present Schizophrenia long-acting injectable antipsychotic initiation index (SLAII), a clinician-rated index that rates the important factors of the disorder across seven items: age, duration of illness, relapses, antipsychotic treatment response, family support, antipsychotic existing formulation and adherence.Method: A retrospective study in which all patients with schizophrenia discharged on oral antipsychotics without LAIs treatment lifetime were evaluated with SLAII for opportunity for LAIs initiation.Results: Of 225 consecutive patients, 144 patients (64%) had a strong indication for initiating LAI and 76 (34%) had moderate indication. 203 patients (90.2 %) had more than 2 relapses. The results of our research showed that 177 patients (78.7%) received at discharge an oral antipsychotic that also had a long-acting formula.Conclusion: This paper proposed an instrument designed to improve treatment in schizophrenia using a simple conceptual model which integrates important predictors of good or poor outcomes.

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Rates of complete nonadherence among atypical antipsychotic drugs: A study using blood samples from 13,217 outpatients with psychotic disorders

Cited by 13 publications

References 29 publications

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

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

Rating Opportunity for Long-Acting Injectable Antipsychotic Initiation Index (ROLIN)

Schizophrenia Long-Acting Injectable Antipsychotic Initiation Index: A Clinician Rated Instrument for Improving Treatment in Schizophrenia

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