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Journal ArticleDOI

Medication adherence in schizophrenia: factors influencing adherence and consequences of nonadherence, a systematic literature review

01 Aug 2013-Therapeutic Advances in Psychopharmacology (SAGE Publications)-Vol. 3, Iss: 4, pp 200-218
TL;DR: Improving adherence in schizophrenia may have a considerable positive impact on patients and society by focusing on the identified multitude of factors driving nonadherence, including lack of insight, medication beliefs and substance abuse.
Abstract: Background:Nonadherence to medication is a recognized problem and may be the most challenging aspect of treatment.Methods:We performed a systematic review of factors that influence adherence and the consequences of nonadherence to the patient, healthcare system and society, in patients with schizophrenia. Particular attention was given to the effect of nonadherence on hospitalization rates, as a key driver of increased costs of care. A qualitative systematic literature review was conducted using a broad search strategy using disease and adherence terms. Due to the large number of abstracts identified, article selection was based on studies with larger sample sizes published after 2001. Thirty-seven full papers were included: 15 studies on drivers and 22 on consequences, of which 12 assessed the link between nonadherence and hospitalization.Results:Key drivers of nonadherence included lack of insight, medication beliefs and substance abuse. Key consequences of nonadherence included greater risk of relapse,...
Citations
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Journal ArticleDOI
TL;DR: Individual patient’s behaviors, lack of social support, clinical or treatment and illness-related, and health system factors influenced psychotropic medication non-adherence, which was influenced by various factors operating at different levels.
Abstract: Major psychiatric disorders are growing public health concern that attributed 14% of the global burden of diseases. The management of major psychiatric disorders is challenging mainly due to medication non-adherence. However, there is a paucity of summarized evidence on the prevalence of psychotropic medication non-adherence and associated factors. Therefore, we aimed to summarize existing primary studies’ finding to determine the pooled prevalence and factors associated with psychotropic medication non-adherence. A total of 4504 studies written in English until December 31, 2017, were searched from the main databases (n = 3125) (PubMed (MEDLINE), Embase, CINAHL, PsycINFO, and Web of Science) and other relevant sources (mainly from Google Scholar, n = 1379). Study selection, screening, and data extraction were carried out independently by two authors. Observational studies that had been conducted among adult patients (18 years and older) with major psychiatric disorders were eligible for the selection process. Critical appraisal of the included studies was carried out using the Newcastle Ottawa Scale. Systematic synthesis of the studies was carried out to summarize factors associated with psychotropic medication non-adherence. Meta-analysis was carried using Stata 14. Random effects model was used to compute the pooled prevalence, and sub-group analysis at 95% confidence interval. Forty-six studies were included in the systematic review. Of these, 35 studies (schizophrenia (n = 9), depressive (n = 16), and bipolar (n = 10) disorders) were included in the meta-analysis. Overall, 49% of major psychiatric disorder patients were non-adherent to their psychotropic medication. Of these, psychotropic medication non-adherence for schizophrenia, major depressive disorders, and bipolar disorders were 56%, 50%, and 44%, respectively. Individual patient’s behaviors, lack of social support, clinical or treatment and illness-related, and health system factors influenced psychotropic medication non-adherence. Psychotropic medication non-adherence was high. It was influenced by various factors operating at different levels. Therefore, comprehensive intervention strategies should be designed to address factors associated with psychotropic medication non-adherence. PROSPERO CRD42017067436

140 citations


Cites background from "Medication adherence in schizophren..."

  • ...Non-adherence issues need to be looked at from many angles and taking a multifaceted approaches with patients and healthcare providers to address identified challenges [81]....

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  • ...The heterogeneity of factors related to non-adherence calls for individually tailored approaches to promote adherence [80, 81]....

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Journal ArticleDOI
TL;DR: PP3M was noninferior to PP1M: relapse rates were similar in both groups and increased weight was the most common treatment-emergent adverse event (double-blind phase; 21% each).
Abstract: Background: This double-blind, parallel-group, multicenter, phase-3 study was designed to test the noninferiority of paliperidone palmitate 3-month formulation (PP3M) to the currently marketed 1-month formulation (PP1M) in patients (age 18–70 years) with schizophrenia, previously stabilized on PP1M. Methods: After screening (≤3 weeks) and a 17-week, flexible-dosed, open-label phase (PP1M: day 1 [150mg eq. deltoid], day 8 [100mg eq. deltoid.], weeks 5, 9, and 13 [50, 75, 100, or 150mg eq., deltoid/gluteal]), clinically stable patients were randomized (1:1) to PP3M (fixed-dose, 175, 263, 350, or 525mg eq. deltoid/gluteal) or PP1M (fixed-dose, 50, 75, 100, or 150mg eq. deltoid/gluteal) for a 48-week double-blind phase. Results: Overall, 1016/1429 open-label patients entered the double-blind phase (PP3M: n=504; PP1M: n=512) and 842 completed it (including patients with relapse). PP3M was noninferior to PP1M: relapse rates were similar in both groups (PP3M: n=37, 8%; PP1M: n=45, 9%; difference in relapse-free rate: 1.2% [95% CI:-2.7%; 5.1%]) based on Kaplan-Meier estimates (primary efficacy). Secondary endpoint results (changes from double-blind baseline in positive and negative symptom score total and subscale scores, Clinical Global Impression-Severity, and Personal and Social Performance scores) were consistent with primary endpoint results. No clinically relevant differences were observed in pharmacokinetic exposures between PP3M and PP1M. Both groups had similar tolerability profiles; increased weight was the most common treatment-emergent adverse event (double-blind phase; 21% each). No new safety signals were detected. Conclusion: Taken together, PP3M with its 3-month dosing interval is a unique option for relapse prevention in schizophrenia.

121 citations


Cites background from "Medication adherence in schizophren..."

  • ...The partial- and total nonadherence to oral antipsychotic therapy that is common among patients with schizophrenia has significant impacts on treatment outcomes and healthcare resources (Higashi et al., 2013; Fleischhacker et al., 2014)....

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Journal ArticleDOI
TL;DR: There is a strong association between non-adherence to antidepressants and a worsening of patients' clinical and economic outcomes and cost-effective interventions should be directed to this group of patients to improve medication adherence.

116 citations


Cites result from "Medication adherence in schizophren..."

  • ...These findings were similar to that seen in recent systematic reviews conducted in schizophrenia, where most of the studies included found an increase in overall direct medical and healthcare costs in patients who were non-adherent (Dilla et al., 2013; Higashi et al., 2013)....

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  • ...structive pulmonary disease (COPD) (Bitton et al., 2013; Dilla et al., 2013; Higashi et al., 2013; van Boven et al., 2014)....

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Journal ArticleDOI
TL;DR: The results support genetic overlap between schizophrenia pathogenesis and antipsychotic mechanism of action and provide evidence of a role for rare functional variants in antipsychotics treatment response, pointing to a subset of patients where their genetic information could inform treatment.

108 citations

Journal ArticleDOI
TL;DR: It is suggested that antipsychotic treatment response is reduced or delayed in the face of relapse following effective treatment of the first episode of schizophrenia.

101 citations

References
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Journal ArticleDOI
TL;DR: An Explanation and Elaboration of the PRISMA Statement is presented and updated guidelines for the reporting of systematic reviews and meta-analyses are presented.
Abstract: Systematic reviews and meta-analyses are essential to summarize evidence relating to efficacy and safety of health care interventions accurately and reliably. The clarity and transparency of these reports, however, is not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (QUality Of Reporting Of Meta-analysis) Statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realizing these issues, an international group that included experienced authors and methodologists developed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA Statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this Explanation and Elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA Statement, this document, and the associated Web site (http://www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.

25,711 citations

Journal ArticleDOI
TL;DR: This Explanation and Elaboration document explains the meaning and rationale for each checklist item and includes an example of good reporting and, where possible, references to relevant empirical studies and methodological literature.

8,021 citations


"Medication adherence in schizophren..." refers background or methods in this paper

  • ...nonadherence drivers or consequences) based on abstract screening [Liberati et al. 2009]....

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  • ...Thus a very broad search strategy was adopted in order to avoid missing potentially relevant information, with the identification of relevant studies per outcome (i.e. nonadherence drivers or consequences) based on abstract screening [Liberati et al. 2009]....

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Journal ArticleDOI
TL;DR: Olanzapine was the most effective in terms of the rates of discontinuation, and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone.
Abstract: background The relative effectiveness of second-generation (atypical) antipsychotic drugs as compared with that of older agents has been incompletely addressed, though newer agents are currently used far more commonly. We compared a first-generation antipsychotic, perphenazine, with several newer drugs in a double-blind study. methods A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and randomly assigned to receive olanzapine (7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day) for up to 18 months. Ziprasidone (40 to 160 mg per day) was included after its approval by the Food and Drug Administration. The primary aim was to delineate differences in the overall effectiveness of these five treatments. results Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone. The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine (P<0.001) or risperidone (P=0.002) group, but not in the perphenazine (P=0.021) or ziprasidone (P=0.028) group. The times to discontinuation because of intolerable side effects were similar among the groups, but the rates differed (P=0.04); olanzapine was associated with more discontinuation for weight gain or metabolic effects, and perphenazine was associated with more discontinuation for extrapyramidal effects. conclusions The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons. Olanzapine was the most effective in terms of the rates of discontinuation, and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone. Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism.

5,437 citations


"Medication adherence in schizophren..." refers methods in this paper

  • ...Data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study showed that 74% of patients had discontinued medication within 18 months due to insufficient efficacy, intolerable side effects or for other reasons [Lieberman, 2005]....

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Journal ArticleDOI
TL;DR: Recommendations for addressing adherence problems to improve patient outcomes are developed, noting that multiple problems may be involved, requiring a combination of interventions.
Abstract: Objectives Poor adherence to medication treatment can have devastating consequences for patients with mental illness. The goal of this project was to develop recommendations for addressing adherence problems to improve patient outcomes. Methods The editors identified important topics and questions concerning medication adherence problems in serious mental illness that are not fully addressed in the literature. A survey was developed containing 39 questions (521 options) asking about defining nonadherence, extent of adherence problems in schizophrenia and bipolar disorder, risk factors for nonadherence, assessment methods, and interventions for specific types of adherence problems. The survey was completed by 41 (85%) of the 48 experts to whom it was sent. Results of the literature review and survey were used to develop recommendations for assessing and improving adherence in patients with serious mental illness. Results ASSESSING ADHERENCE: The experts endorsed percentage of medication not taken as the preferred method of defining adherence, with 80% or more of medication taken endorsed as an appropriate cut-off for adherence in bipolar disorder and schizophrenia. Although self- and physician report are the most common methods used to assess adherence in clinical settings, they are often inaccurate and may underestimate nonadherence. The experts recommend that, if possible, clinicians also use more objective measures (e.g., pill counts, pharmacy records, and, when appropriate, serum levels such as are used for lithium). Use of a validated self-report scale may help improve accuracy. Scope of the problem The majority of the experts believed the average patient with schizophrenia or bipolar disorder in their practices takes only 51%-70% of prescribed medication. FACTORS ASSOCIATED WITH NONADHERENCE: The experts endorsed poor insight and lack of illness awareness, distress associated with specific side effects or a general fear of side effects, inadequate efficacy with persistent symptoms, and believing medications are no longer needed as the most important factors leading to adherence problems in schizophrenia and bipolar disorder. The experts considered weight gain a side effect that is very likely to lead to adherence problems in patients with schizophrenia and bipolar disorder; sedation was considered a more important contributor to adherence problems in bipolar disorder than schizophrenia. The experts rated persistent positive or negative symptoms in schizophrenia and persistent grandiosity and manic symptoms in bipolar disorder as the most important symptomatic contributors to adherence problems in these illnesses. Interventions It is important to identify the specific factors that may be contributing to a patient's adherence problems in order to customize interventions to target those problems. Multiple problems may be involved, requiring a combination of interventions. Conclusions Adherence problems are complex and multidetermined. The experts recommended customized interventions focused on the underlying causes.

619 citations


"Medication adherence in schizophren..." refers background or methods or result in this paper

  • ...In addition, there was one retrospective database study [Valenstein et al. 2004] and one review/survey of experts [Velligan et al. 2009]....

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  • ...The expert survey [Velligan et al. 2009] rated distress associated with persistent side effects (especially weight gain in women and excessive sedation) to be important contributors to adherence problems....

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  • ...Physician perception on important factors of nonadherence In the expert survey [Velligan et al. 2009] on potential contributors to adherence problems in schizophrenia, experts were asked to rate factors as very important, somewhat important and not important for medication adherence....

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  • ...…and Weiden, 2009; Laan et al. 2010; Law et al. 2008; Leucht and Heres, 2006; Llorca, 2008; Marcus and Olfson, 2008; Morken et al. 2008; Rittmannsberger et al. 2004; Rzewuska, 2002; Svarstad et al. 2001; Svestka and Bitter, 2007; Valenstein et al. 2002; Velligan et al. 2009; Weiden et al. 2004a]....

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  • ...Furthermore, a review [Velligan et al. 2009] reported that the ‘positive relationship with clinical staff ’ was a significant predictor of good adherence....

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Journal ArticleDOI
TL;DR: This study showed a direct correlation between estimated partial compliance and hospitalization risk among patients with schizophrenia across a continuum of compliance behavior.
Abstract: OBJECTIVE: The objective of this study was to evaluate the relationship between compliance with an antipsychotic medication regimen and risk of hospitalization in a cohort of California Medicaid patients with schizophrenia. METHODS: Compliance behavior was estimated by using a retrospective review of California Medicaid pharmacy refill and medical claims for 4,325 outpatients for whom antipsychotics were prescribed for treatment of schizophrenia from 1999 to 2001. Compliance behavior was estimated by using four different definitions: gaps in medication therapy, medication consistency and persistence, and a medication possession ratio. Patients were followed for one year and had an average of 19.1 dispensing events. Logistic regression models using each compliance estimate were used to determine the odds of hospitalization. RESULTS: Risk of hospitalization was significantly correlated with compliance. With all definitions, lower compliance was associated with a greater risk of hospitalization over and abov...

615 citations


"Medication adherence in schizophren..." refers background or methods or result in this paper

  • ...…and Weiden, 2009; Laan et al. 2010; Law et al. 2008; Leucht and Heres, 2006; Llorca, 2008; Marcus and Olfson, 2008; Morken et al. 2008; Rittmannsberger et al. 2004; Rzewuska, 2002; Svarstad et al. 2001; Svestka and Bitter, 2007; Valenstein et al. 2002; Velligan et al. 2009; Weiden et al. 2004a]....

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  • ...…Karve et al. 2009; Kozma and Weiden, 2009; Laan et al. 2010; Law et al. 2008; Marcus and Olfson, 2008; Svarstad et al. 2001; Valenstein et al. 2002; Weiden et al. 2004a] and five reviews [Byerly et al. 2007; Leucht and Heres, 2006; Llorca, 2008; Svestka and Bitter, 2007; Velligan et al. 2009]....

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  • ...…studies [Ahn et al. 2008; Ascher-Svanum et al. 2006; Eaddy et al. 2005; Gilmer et al. 2004; Karve et al. 2009; Knapp et al. 2004; Kozma and Weiden, 2009; Law et al. 2008; Marcus and Olfson, 2008; Svarstad et al. 2001; Valenstein et al. 2002; Weiden et al. 2004a] included more than 500 subjects....

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  • ...…et al. 2003; McCann et al. 2009; Novick et al. 2010; Olfson et al. 2006; Rettenbacher et al. 2004; Valenstein et al. 2004; Velligan et al. 2009; Weiden et al. 2004b] assessed drivers of nonadherence in schizophrenia; seven were prospective longitudinal studies [Acosta et al. 2009;…...

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  • ...…Hudson et al. 2004; Janssen et al. 2006; Linden et al. 2001; Loffler et al. 2003; Novick et al. 2010; Olfson et al. 2006; Valenstein et al. 2004; Weiden et al. 2004b] included more than 100 subjects (i.e. patients or psychiatrists), and five of these studies [AscherSvanum 2006; Janssen et al.…...

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