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BackgroundAntipsychotic medication reduces the severity of serious mental illness (SMI) and improves patient outcomes only when medicines were taken as prescribed. Nonadherence to the treatment of SMI increases the risk of relapse and hospitalization and reduces the quality of life. It is necessary to understand the factors influencing nonadherence to medication in order to identify appropriate interventions. This systematic review assessed the published evidence on modifiable reasons for nonadherence to antipsychotic medication in patients with SMI.MethodsArticles published between January 1, 2005, and September 10, 2015, were searched on MEDLINE through PubMed. Abstracts were independently screened by 2 randomly assigned authors for inclusion, and disagreement was resolved by another author. Selected full-text articles were divided among all authors for review.ResultsA qualitative analysis of data from 36 articles identified 11 categories of reasons for nonadherence. Poor insight was identified as a reason for nonadherence in 55.6% (20/36) of studies, followed by substance abuse (36.1%, 13/36), a negative attitude toward medication (30.5%, 11/36), medication side effects (27.8%, 10/36), and cognitive impairments (13.4%, 7/36). A key reason directly associated with intentional nonadherence was a negative attitude toward medication, a mediator of effects of insight and therapeutic alliance. Substance abuse was the only reason consistently associated with unintentional nonadherence, regardless of type and stage of SMI.DiscussionAlthough adherence research is inherently biased because of numerous methodological limitations and specific reasons under investigation, reasons for nonadherence consistently identified as significant across studies likely reflect valid existing associations with important clinical implications.ConclusionThis systematic review suggests that a negative attitude toward medication and substance abuse are consistent reasons for nonadherence to antipsychotic medication among people with SMI. Adherence enhancement approaches that specifically target these reasons may improve adherence in a high-risk group. However, it is also important to identify drivers of poor adherence specific to each patient in selecting and implementing intervention strategies.

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Poor adherence to medication treatment can have devastating consequences for patients with serious mental illness. The literature review and recommendations in this article concerning assessment of adherence are reprinted from The Expert Consensus Guideline Series: Adherence Problems in Patients with Serious and Persistent Mental Illness, published in 2009. The expert consensus survey contained 39 questions (521 options) that asked 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. When evaluating adherence, the experts considered it important to assess both behavior and attitude, although they considered actual behavior most important. They also noted the importance of distinguishing patients who are not willing to take medication from those who are willing but not able to take their medication as prescribed due to forgetfulness, misunderstanding of instructions, or financial or environmental problems, since this will affect the type of intervention needed. Although self- and physician report are most commonly used to clinically assess adherence, they are often inaccurate and may underestimate nonadherence. The experts believe that more accurate information will be obtained by asking about any problems patients are having or anticipate having taking medication rather than if they have been taking their medication; They also recommended speaking with family or caregivers, if the patient gives permission, as well as using more objective measures (e.g., pill counts, pharmacy records, smart pill containers if available, and, when appropriate, medication plasma levels). Use of a validated self-report scale may also help improve accuracy. For patients who appear adherent to medication, the experts recommended monthly assessments for adherence, with additional assessments if there is a noticeable symptomatic change. If there is concern about adherence, they recommended more frequent (e.g., weekly) assessments. The article concludes with suggestions for clinical interview techniques for assessing adherence.

ObjectiveDigital medicine system (DMS) is a novel drug–device combination that objectively measures and reports medication ingestion. The DMS consists of medication embedded with an ingestible sensor (digital medicine), a wearable sensor, and software applications. This study evaluated usability of the DMS in adults with schizophrenia rated by both patients and their health care providers (HCPs) during 8-week treatment with prescribed doses of digital aripiprazole.MethodsSix US sites enrolled outpatients into this Phase IIa, open-label study (NCT02219009). The study comprised a screening phase, a training phase (three weekly site visits), and a 5-week independent phase. Patients and HCPs independently rated usability of and satisfaction with the DMS.ResultsSixty-seven patients were enrolled, and 49 (73.1%) patients completed the study. The mean age (SD) of the patients was 46.6 years (9.7 years); the majority of them were male (74.6%), black (76.1%), and rated mildly ill on the Clinical Global Impression – Severity scale (70.1%). By the end of week 8 or early termination, 82.1% (55/67) of patients had replaced the wearable sensor independently or with minimal assistance, based on HCP rating. The patients used the wearable sensor for a mean (SD) of 70.7% (24.7%) and a median of 77.8% of their time in the trial. The patients contacted a call center most frequently at week 1. At the last visit, 78% (47/60) of patients were somewhat satisfied/satisfied/extremely satisfied with the DMS.ConclusionA high proportion of patients with schizophrenia were able to use the DMS and reported satisfaction with the DMS. These data support the potential utility of the DMS in clinical practice.