A review published in the April 16 Cochrane Database of Systematic Reviews provides various methods of encouraging patients to adhere to their medications, but the reviewers suggest that there are significant limitations and that more research is needed.

“People who are prescribed self-administered medications typically take less than half the prescribed doses,” write R.B. Haynes, and colleagues. “Efforts to assist patients with adherence to medications might improve the benefits of prescribed medications, but also might increase their adverse effects.”

The goal of this updated review was to summarize the results of randomized controlled trials (RCTs) of interventions to help patients follow prescription regimes for medications for medical problems, including mental disorders but not addictions.

In January 2007, the reviewers updated searches of The Cochrane Library, MEDLINE, CINAHL, EMBASE, International Pharmaceutical Abstracts, PsycINFO (all via OVID) and Sociological Abstracts (via CSA), with no language restriction. They also reviewed bibliographies of identified articles on patient adherence and articles in their personal collections, and they contacted the authors of pertinent original and review articles.

Inclusion criteria were reports of an unconfounded RCT of an intervention to improve adherence with prescribed medications, measurement of both medication adherence and treatment outcome, 80% or better follow-up of each group studied, and follow-up of 6 months or more for studies of long-term treatments that initially had positive findings.

One review author extracted study design features, interventions, and controls, and at least 1 other review author confirmed these results. Adherence rates and corresponding measures of variance were extracted for all methods of measuring adherence in each study. All outcome rates and corresponding measures of variance were extracted for each study group, as were levels of statistical significance for differences between study groups. To verify or correct these analyses as needed, the reviewers consulted the study authors.

Because of heterogeneity among studies in medical condition, patient population, intervention, measures of adherence, and clinical outcomes, the reviewers performed a qualitative rather than a quantitative analysis.

For short-term treatments, 4 of 10 interventions studied in 9 RCTs affected both adherence and at least 1 clinical outcome. In contrast, 1 intervention reported in 1 RCT significantly improved patient adherence without improving the clinical outcome.

For long-term treatments, 36 of 81 interventions reported in 69 RCTs were associated with improved adherence. However, only 25 interventions were associated with improvement in at least 1 treatment outcome. Almost all of the interventions that were effective for improving adherence to long-term care were complex, requiring combinations of more convenient care, information, reminders, self-monitoring, reinforcement, counseling, family therapy, psychological therapy, crisis intervention, manual telephone follow-up, and supportive care.

Even the interventions that were most effective in improving adherence were not associated with dramatic improvements in adherence and in treatment outcomes.

“For short-term treatments several quite simple interventions increased adherence and improved patient outcomes, but the effects were inconsistent from study to study with less than half of studies showing benefits,” the review authors write. “Current methods of improving adherence for chronic health problems are mostly complex and not very effective, so that the full benefits of treatment cannot be realized. High priority should be given to fundamental and applied research concerning innovations to assist patients to follow medication prescriptions for long-term medical disorders.”

Limitations of this review include considerations of only published studies, leading to possible overestimation of the benefits of the interventions; use of exceedingly complex and labor-intensive adherence interventions not practical outside of research settings; possible underestimation of intervention effects in some studies; and use of imprecise measures of adherence, often relying on self-report.

In addition, some interventions were not tested well; the review focused on interventions to increase medication adherence, excluding studies that reported only on reducing dropout rates and missed appointments; some authors did not adequately describe all parts of their interventions; most studies paid research staff to administer the interventions, limiting generalizability outside a research setting; many studies had attribution issues; “usual care” possibly included adherence strategies; only studies that measured both adherence and treatment outcome were selected; measures for both outcomes were seldom objective, and evaluators were sometimes unblended; and no studies examined major clinical endpoints.

“For long-term treatments, simplifying the dosage regimen and several complex strategies, including combinations of more thorough patient instructions and counseling, reminders, close follow-up, supervised self-monitoring, rewards for success, family therapy, couple-focused therapy, psychological therapy, crisis intervention, and manual telephone follow-up can improve adherence and treatment outcomes,” the reviewers conclude. “If there is a common thread to these at all, it is more frequent interaction with patients with attention to adherence. However, these complex strategies for improving adherence with long-term medication prescriptions are not very effective despite the amount of effort and resources they can consume.”

The Health Information Research Unit, McMaster University, Hamilton, Ontario, Canada, supported this study. The reviewers have disclosed no relevant financial relationships.

Cochrane Database Syst Rev. Published online April 16, 2008.

Clinical Context
People who are prescribed self-administered medications typically take less than half the prescribed doses. Many reasons exist for nonadherence to medical regimens. They include problems with the regimen (such as adverse effects), poor instructions, poor provider-patient relationship, poor memory, patients’ disagreement with the need for treatment, or patients’ inability to pay. Efforts to assist patients with adherence to medications might improve the benefits of prescribed medications but also might increase their adverse effects. In this current review of trials of ways to help people follow prescriptions, updated from the 2005 version, 21 new studies were reviewed.

The aim of this study was to update a review summarizing the results of RCTs of interventions to help patients follow prescriptions for medications for medical problems, including mental disorders but not addictions.

Study Highlights

In this study, the reviewers performed searches of The Cochrane Library, MEDLINE, CINAHL, EMBASE, the International Pharmaceutical Abstracts, PsycINFO (all via OVID), and Sociological Abstracts (via CSA) in January 2007 with no language restriction.
In addition, bibliographies in articles were reviewed on patient adherence, and authors were contacted of relevant original and review articles.
Articles were selected if they reported an unconfounded RCT of an intervention to improve adherence with prescribed medications, measuring both medication adherence and treatment outcome, with at least 80% of follow-up of each group studied and, for long-term treatments, at least 6 months’ follow-up for studies with positive initial findings.
Study design features, interventions and controls, and results were extracted by 1 review author and confirmed by at least 1 other review author.
The studies differed widely according to medical condition, patient population, intervention, measures of adherence, and clinical outcomes; therefore, a qualitative analysis was performed.
The results of this study demonstrated that for short-term treatments, 4 of 10 interventions reported in 9 RCTs showed an effect on both adherence and at least 1 clinical outcome, whereas 1 intervention reported in 1 RCT significantly improved patient adherence but did not enhance the clinical outcome.
For long-term treatments, 36 of 81 interventions reported in 69 RCTs were associated with improvements in adherence, but only 25 interventions led to improvement in at least 1 treatment outcome.
Almost all of the interventions that were effective for long-term care were complex, including combinations of more convenient care, information, reminders, self-monitoring, reinforcement, counseling, family therapy, psychological therapy, crisis intervention, manual telephone follow-up, and supportive care. This implied that more frequent interaction with patients with attention to adherence may be needed.
Even the most effective interventions did not lead to large improvements in adherence and treatment outcomes.
Of the 21 new RCTs in this update describing 24 interventions to improved adherence, only 5 (21%) studies showed positive outcomes for both adherence and clinical outcomes. All had adequate power to detect a meaningful difference.

Pearls for Practice

Many reasons exist for nonadherence to medical regimens, including problems with the regimen (such as adverse effects), poor instructions, poor provider-patient relationship, poor memory, patients’ disagreement with the need for treatment, or patients’ inability to pay.
For short-term treatments, several quite simple interventions increased adherence and improved patient outcomes, but the effects were inconsistent from study to study, with less than half of studies showing benefits. Current methods of improving adherence for chronic health problems are mostly complex and are not very effective.

Reviewed by Dr. Ramaz Mitaishvili