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Management Brief No. 109

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Management eBriefs
Issue 109April 2016

The report is a product of the VA/HSR Evidence Synthesis Program.

Systematic Review: Interventions to Improve Medication Adherence for Serious Mental Illness and PTSD

Non-adherence to medication is a serious problem in the United States. It is associated with increased emergency department visits and hospitalizations, higher costs of care, and greater mortality. For patients with serious mental illness, including schizophrenia and other psychotic spectrum disorders, bipolar disorder, and posttraumatic stress disorder (PTSD), adherence to psychopharmacological and/or non-psychopharmacological medications is an important concern. This report synthesized the evidence examining: 1) the effectiveness of interventions to improve medication adherence in patients with psychotic spectrum disorders, bipolar disorder, and PTSD; 2) the effect of these interventions on patient outcomes; and 3) the related costs and any associated intervention-specific harms.

Investigators with VA's Evidence-based Synthesis Program located in Portland, Oregon reviewed the evidence from studies published through January 2015 and identified 25 articles that met inclusion criteria (20 studies in 21 articles on patients with psychotic spectrum disorders, 4 studies examining patients with bipolar disorder, and no studies with patients with PTSD).

Summary of Review

For Patients with Psychotic Spectrum Disorders:

Overall there is insufficient evidence about the effectiveness of interventions to improve medication adherence in patients with psychotic spectrum disorders. Interventions vary widely, including studies evaluating multicomponent behavioral interventions, interventions involving family members, interventions involving technology, pharmacist-led interventions, system-level interventions, and others. Overall, findings are mixed. However, there is low strength of evidence that interventions involving family members, and those involving technology, such as e-monitoring or daily reminder messages, may result in improved psychopharmacological adherence.

There is limited evidence of the effectiveness of depot antipsychotics (injectable medication released into the body over an extended period of time) in combination with a medication adherence intervention. Studies show better adherence associated with a psychosocial intervention in patients prescribed a depot antipsychotic as compared with controls, and improved adherence in a homeless population associated with the prescription of depot and a customized multicomponent behavioral intervention. However, despite evidence suggesting a positive effect, the wide differences in the interventions, small sample sizes, the potential for sampling bias in populations prescribed depot antipsychotics, and lack of methodological rigor preclude drawing firm conclusions.

There is no clear evidence of the effect of medication adherence interventions on patient outcomes. Findings reported for positive, negative, and overall symptom severity are mixed, and there is little support that these interventions improve quality of life. Findings related to functional impairment are also mixed; however, there is limited evidence that interventions involving family members and those including the use of a depot antipsychotic may result in improved functioning. Similarly, while it is unclear whether medication adherence interventions in general are effective in reducing hospitalizations, the time to first hospital readmission, or time spent in the hospital, two studies reported a positive effect of interventions on time to relapse, and limited evidence suggests that interventions involving family members may result in better patient outcomes.

For Patients with Bipolar Disorder:

The four included studies provide limited evidence of the effectiveness of interventions for medication adherence in patients with bipolar disorder. Three of the four studies found a positive effect on psychopharmacological adherence associated with an adherence intervention, with high rates of attrition in the one study reporting no effect. Despite evidence suggesting a generally positive effect, the strength of the evidence is insufficient, and thus precludes drawing conclusions due to the fact that the interventions were heterogeneous, sample sizes were small, and two studies showing a positive effect were conducted in Iran, calling into question applicability.

There is no clear evidence to support conclusions regarding the effect of interventions for improving medication adherence on patient outcomes. Findings related to depression, mania, and functional impairment were mixed. Further, despite limited evidence supporting improvement, the lack of high-quality studies, heterogeneity of the interventions, and setting precluded the ability to draw conclusions.

Future Research

Interventions to improve medication adherence in patients with psychotic-spectrum disorders and bipolar disorder warrant further investigation, particularly in the form of well-designed studies with comparators of adequate sample size and duration. Moreover, few studies examined the same intervention, and replication is needed in order to draw conclusions about the effectiveness of a specific program. Several small studies suggest the effectiveness of some of the interventions (e.g., interventions including family members). However, many of the interventions are multicomponent and complex, and differ widely in their components and implementation, thus research evaluating standardized interventions is needed.

Research evaluating the effectiveness of interventions to improve medication adherence in patients with PTSD is lacking and needed. For all populations examined in this report, future research is required to evaluate the effect of these interventions on non-psychopharmacological interventions. In addition, future studies should examine potential adverse events associated with medication adherence interventions. Objective measures should be used to measure medication adherence, as well as the identification and validation of a gold standard assessment tool for medication adherence. Finally, more research is necessary to determine the cost-effectiveness and feasibility of interventions for medication adherence in the VA healthcare system.

A cyberseminar titled "Interventions to Improve Pharmacological Adherence among Adults with Psychotic Spectrum Disorders, Bipolar Disorder, and Post-traumatic Stress Disorder" will be held on July 18, 2016 from 3:00 to 4:00pm (ET). Register for this cyberseminar session here.

Kondo K, Low A, Jindai K, Mendelson A, Motu'apuaka M, Mansoor D, Judge M, Kansagara D, Freeman M, Hartung D. Interventions to Improve Pharmacological Adherence among Adults with Psychotic Spectrum Disorders, Bipolar Disorder, and Posttraumatic Stress Disorder. VA ESP Project #09-009; 2015.

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ESP is currently soliciting review topics from the broader VA community. Nominations will be accepted electronically using the online Topic Submission Form. If your topic is selected for a synthesis, you will be contacted by an ESP Center to refine the questions and determine a timeline for the report.

This Management e-Brief is provided to inform you about recent HSR&D findings that may be of interest. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. If you have any questions or comments about this Brief, please email CIDER. The Center for Information Dissemination and Education Resources (CIDER) is a VA HSR&D Resource Center charged with disseminating important HSR&D findings and information to policy makers, managers, clinicians, and researchers working to improve the health and care of Veterans.


This report is a product of VA/HSR&D's Quality Enhancement Research Initiative's (QUERI) Evidence-Based Synthesis Program (ESP), which was established to provide timely and accurate synthesis of targeted healthcare topics of particular importance to VA managers and policymakers – and to disseminate these reports throughout VA.

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