Frequency and correlates of antipsychotic polypharmacy among patients with schizophrenia in Denmark: A nation-wide pharmacoepidemiological study

Sneider, Benjamin; Pristed, Sofie Gry; Correll, Christoph U.; Nielsen, Jimmi

doi:10.1016/j.euroneuro.2015.04.027

Cited by 28 publications

(39 citation statements)

References 38 publications

(45 reference statements)

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“…Data published subsequent to the years from which the current dataset were attained reflect a pervasive trend of APP despite insufficient evidence supporting its efficacy, effectiveness, or safety (Correll et al 2009). Results of the current investigation suggest that divergence from antipsychotic prescribing guidelines remains common (Nielsen et al 2010; Sneider et al 2015; Thompson et al 2008; Van Duin et al 2013). Geographic, demographic, and diagnostic differences suggest inconsistencies in APP practice that do not appear to be clinically driven or evidence-based.. Education and quality improvement initiatives are needed to reduce multiple antipsychotic prescribing, particularly for patients receiving Medicaid services who may be at increased risk for medical comorbidities.…”

Section: Resultsmentioning

confidence: 82%

Characteristics of Medicaid Recipients Receiving Persistent Antipsychotic Polypharmacy

Cotes

Goldsmith

Kopelovich

et al. 2017

Community Ment Health J

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Antipsychotic polypharmacy (APP) is a common strategy despite guidelines advising against this practice. This article seeks to quantify the prevalence and correlates of APP using Medicaid Analytic eXtract files from 2003 to 2004. Nineteen percent of Medicaid recipients who received an antipsychotic were treated with APP. Individuals who received APP were more likely to be white, male, disabled, between the ages of 18-29, diagnosed with a psychotic disorder, and diagnosed with a higher number of psychiatric conditions. Geographic variation in APP rates was also observed. Quality improvement initiatives may help reduce APP for medically vulnerable patients.

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Section: Resultsmentioning

confidence: 82%

Characteristics of Medicaid Recipients Receiving Persistent Antipsychotic Polypharmacy

Cotes

Goldsmith

Kopelovich

et al. 2017

Community Ment Health J

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“…For example, patients may be taking concomitant medications, including other psychoactive agents, which may affect treatment outcomes. Use of concomitant oral antipsychotics is high in patients receiving LAI therapy -more than 75% in one US analysis of recently hospitalized patients (Doshi et al, 2015) -and patients on LAI antipsychotics tend to be more likely to use concomitant psychotropic agents than those taking oral therapy (Sneider et al, 2015).…”

Section: Methodological Pros and Cons Of Naturalistic Studiesmentioning

confidence: 99%

Clinical trial methodology to assess the efficacy/effectiveness of long-acting antipsychotics: Randomized controlled trials vs naturalistic studies

Fagiolini

Rocca

Giorgi

et al. 2017

Psychiatry Research

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Schizophrenia presents unique difficulties in clinical trial design associated with the condition's variable presentation and clinical course, and multiple features influencing affect, cognition, volition and perception. Randomized controlled trials (RCTs) are explanatory studies using a carefully selected patient population, predefined assessment intervals and, generally, symptom-focused endpoints. Naturalistic studies are pragmatic, with no active intervention, and outcomes that are generally those used in clinical practice (e.g. hospitalization, relapse rate). Both naturalistic studies and RCTs have pros and cons, making it difficult for physicians in clinical practice to apply research findings to their own treatment decisions. The choice of clinical trial design can have a significant impact on the comparative effectiveness or efficacy of drugs. This is particularly true for studies comparing long-acting injectable (LAI) antipsychotics with oral antipsychotics in schizophrenia, in which RCTs generally show no benefit for LAIs over oral drugs, whereas observational studies do. The more pragmatic the study design, the more likely it is to show a benefit for LAIs versus oral therapy. This article reviews the pros and cons of different study types, using published examples. Criteria are outlined to help physicians design appropriate prospective studies in schizophrenia including the relevant pragmatic and/or explanatory features, as required.

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“…Royal Australian and New Zealand College of Psychiatrists guidelines for schizophrenia management 9 cautiously recommend CA for patients who fail clozapine and advise careful monitoring due to high risk for side effects, increased hospitalizations and increased mortality. The rate of CA prescribing in schizophrenia varied from 15% –55% in the US in 2002 1 , to 17–31% in a sample from the Danish health registry 10 , 30.7% in Norway 11 and 19.6% in a review of studies published worldwide between 1970 and 2009 12 . CA use was associated with higher number of patients per psychiatrist, younger age, living alone, treatment with clozapine, long acting injectable antipsychotics, antidepressants and anticholinergic medications, more hospital admissions, and higher Positive and Negative Syndrome Scale and lower Global Assessment of Function scores 10, 11 .…”

Section: Introductionmentioning

confidence: 99%

“…The rate of CA prescribing in schizophrenia varied from 15% –55% in the US in 2002 1 , to 17–31% in a sample from the Danish health registry 10 , 30.7% in Norway 11 and 19.6% in a review of studies published worldwide between 1970 and 2009 12 . CA use was associated with higher number of patients per psychiatrist, younger age, living alone, treatment with clozapine, long acting injectable antipsychotics, antidepressants and anticholinergic medications, more hospital admissions, and higher Positive and Negative Syndrome Scale and lower Global Assessment of Function scores 10, 11 . Antipsychotic combinations are associated with high side effect burden (Parkinsonian side effects, hyperprolactinemia, sexual dysfunction, hyper-salivation, sedation, cognitive impairment and diabetes), but are often prescribed because of possible pharmacodynamic rationale, including optimizing dopamine D2 receptor occupancy, achieving a broad receptor coverage and minimizing side effects from high dose of a single drug 1, 13 .…”

Section: Introductionmentioning

confidence: 99%

“…Antipsychotic combinations are associated with high side effect burden (Parkinsonian side effects, hyperprolactinemia, sexual dysfunction, hyper-salivation, sedation, cognitive impairment and diabetes), but are often prescribed because of possible pharmacodynamic rationale, including optimizing dopamine D2 receptor occupancy, achieving a broad receptor coverage and minimizing side effects from high dose of a single drug 1, 13 . Beyond consistent association with inpatient treatment 10, 11, 12 , longitudinal progression of antipsychotic treatment leading to initiation of CA (rather than switching over to another antipsychotic or clozapine) is poorly understood. A chart-review of 100 antipsychotic-naïve outpatients with schizophrenia in Japan showed that, over two years, 17.8% of patients were placed on CA after a median of 84 days following the initiation of monotherapy and, in many cases (47.4%), before a presumably full effective dose was achieved 14 .…”

Section: Introductionmentioning

confidence: 99%

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Combination Antipsychotic Therapies

Foster¹,

Buckley²,

Looney³

et al. 2017

J Clin Psychopharmacol

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Background Antipsychotic combinations (CA) are prescribed in schizophrenia despite limited evidence of efficacy. To explore the effect of switching from CA to monotherapy, we performed an exploratory analysis of the PROACTIVE study data, in which 305 patients with schizophrenia and schizoaffective disorder were followed for 30-months after randomization to long-acting-injectable (LAI) risperidone or oral 2nd-generation antipsychotic (OA). Methods Patients who entered the PROACTIVE study on CA (n=50), LAI (n=20) or OA (n=206), were compared in terms of time to relapse and clinical measures. Findings The OA group had significantly fewer hospitalizations than the CA group (p=0.009) at baseline. In the CA group, 68% patients relapsed vs. 53% in the LAI, and 52% in the OA groups. While there was no significant difference in the relapse rate among groups on chi-square test (χ2 = 3.85, d.f. = 2, p = 0.146), the log-rank test showed a significant difference among the groups in time to first relapse (χ2 = 6.81, d.f. = 2, p = 0.033), with significantly longer time to relapse in the OA group (mean 562.8 days) than in the CA group (mean 409.5, p = 0.011). The LAI group’s mean time to first relapse (594 days) was not significantly different from the other groups. However, after adjusting for number of hospitalizations, group was no longer significant (hazard ratio = 1.541, p = 0.052). Implications Based on our exploratory analysis, taking antipsychotic combinations predicts earlier relapse and calls for additional treatment guidance in schizophrenia.

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Frequency and correlates of antipsychotic polypharmacy among patients with schizophrenia in Denmark: A nation-wide pharmacoepidemiological study

Cited by 28 publications

References 38 publications

Characteristics of Medicaid Recipients Receiving Persistent Antipsychotic Polypharmacy

Characteristics of Medicaid Recipients Receiving Persistent Antipsychotic Polypharmacy

Clinical trial methodology to assess the efficacy/effectiveness of long-acting antipsychotics: Randomized controlled trials vs naturalistic studies

Combination Antipsychotic Therapies

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