Why do psychiatric patients stop antipsychotic medication? A systematic review of reasons for nonadherence to medication in patients with serious mental illness

Dawn I Velligan,1 Martha Sajatovic,2 Ainslie Hatch,3 Pavel Kramata,4 John P Docherty3 1Department of Psychiatry, The University of Texas Health Science Center, San Antonio, TX, 2Departments of Psychiatry and Neurology, Case Western Reserve University School of Medicine, Cleveland, OH, 3Medical Affairs, ODH, Inc., Princeton, NJ, 4C4 MedSolutions LLC, Yardley, PA, USA Background: Antipsychotic 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. Methods: Articles 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. Results: A 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. Discussion: Although 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. Conclusion: This 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. Keywords: adherence, antipsychotics, attitude toward medication, bipolar disorder, schizophrenia, substance abus

Medicinal Chemistry of Nucleoside Phosphonate Prodrugs for Antiviral Therapy

Considerable attention has been focused on the development of phosphonate-containing drugs for application in many therapeutic areas. However, phosphonate diacids are deprotonated at physiological pH and thus phosphonate-containing drugs are not ideal for oral administration, an extremely desirable requisite for the treatment of chronic diseases. To overcome this limitation several prodrug structures of biologically active phosphonate analogues have been developed. The rationale behind the design of such agents is to achieve temporary blockade of the free phosphonic functional group until their systemic absorption and delivery, allowing the release of the active drug only once at the target. In this paper, an overview of acyclic and cyclic nucleoside phosphonate prodrugs, designed as antiviral agents, is presented