Therapeutic Delivery

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Enhancing patient adherence: introducing smart pill devices “

The promise is that better adherence, as well as better information about the adherence, of a particular patient will ultimately improve outcomes for multiple long-standing medical and psychiatric conditions.

Keywords: medication adherence • medication compliance • schizophrenia • serious mental illness • smart pill containers

“Medicine is a science of uncertainty and an art of probability.” – William Osler Medication adherence refers to whether patients take their prescribed medications in the right quantity and dose, as well as whether they continue to follow the regimen for their prescribed medications that have been agreed upon within the context of shared decision making. Only half of patients with serious mental illness take medication as prescribed [1] . Poor adherence is due to multiple reasons. Patient-related factors that impact adherence include simple forgetfulness, disorganized behavior, cognitive impairments, and having a poor understanding of the reasons for taking a certain medication. Medicationrelated factors including side effect burden and poor efficacy are also important factors to be considered. Other factors that contribute to poor adherence include, problems with the therapeutic alliance, and problems with the healthcare delivery system [1] . Poor adherence has been found to lead to higher rates of relapse and re-hospitalization. A recent study by Valenstein et al. [2] found that a gap of only 1–10 days in antipsychotic therapy over the course of a year is associated with a twofold risk of hospitalization. Even missing just a few days of medication can set the stage for relapse. Costs associated with nonadherence in schizophrenia are estimated to be over US$1.48 billion per year for hospitalizations alone. This estimate does not include extra psychiatry visits, emergency and crisis ser-

10.4155/TDE.14.33 © 2014 Future Science Ltd

vices, and unused medication. The estimated total economic cost of serious mental illness in the USA is approximately $317 billion annually [3] . In order for a medication to work or to be identified as ineffective for a particular patient, it has to get into the patient. Poor adherence makes it difficult for prescribers to engage in effective clinical management, as they are unable to distinguish between poor adherence and poor response to a certain medication. Prescribers may increase the dose, switch the person to a different medication, or add concomitant medications unnecessarily, as a result of poor adherence. Identifying and improving adherence is therefore a significant mental health priority. Our research group has, in the past, developed treatments that make use of environmental supports such as alarms, calendars, checklists, signs, pill containers, and reorganization of belongings established and maintained on weekly home visits to help individuals with schizophrenia to take medication and make it to clinic appointments [4] . However, these measures may be less necessary since technology has progressed to such an extent that patients’ medication adherence can be prompted and monitored without the need for weekly home visits. In a recent study, we compared in person supports in a treatment known as PharmCAT to treatment using a smart pill device, and to treatment as usual (TAU), which consisted of case management and medication follow up. We randomized 142 patients to one of the three groups for a period of 9 months [5] .

Therapeutic Delivery (2014) 5(6), 611–613

Dawn I Velligan*,1 1 The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA *Author for correspondence: Tel.: +1 210 567 5508 Fax: +1 210 567 1291 [email protected] uthscsa.edu

Saher Hoda Kamil1 1 The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

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Editorial  Velligan & Kamil The smart pill container used in the study was the Med-eMonitor. This device stores up to a month’s worth of five different medications, contains virtual drawers for medications that are not in tablet form (e.g., inhalers), reminds patients to take their prescribed medications at the correct time, and is capable of tracking the intake of medication by asking the patient, when the drawer is opened, whether or not the patient took the medication, and if not, the reason for failure to do so. In addition, Med-eMonitor warns patients if they are taking the wrong medication, records adverse side effects of prescribed medications, and informs the case manager (via connection to a secure website) if the patients have missed a specified number of doses. This information can be emailed automatically to the case manager who can then contact the patient via telephone to determine the reason the patient is noncompliant with his/her prescribed medication. Smart pill containers can be set up by the patient or a case manager can visit the home to ensure that the patient understands how to work the device. The case manager can find a location for the device that assures it will be easily accessible to the patient, and where he/ she can hear the alarm [5] . The Med-eMonitor device has been tested for use in patients with congestive heart failure [6] and has wide applicability to a broad range of individuals with complicated medication regimens and/or who stand to experience severe consequences from poor adherence. Similar smart pill devices have been found to improve adherence and illness markers in multiple long-standing conditions including HIV/AIDS, depression, and cardiovascular diseases [7] . Devices such as this are an advance over electronic caps which monitor the opening of the pill bottle, but do not remind the patient to take medication, store only one type of medication, and do not indicate if the pill is actually ingested by the patient. Results of our study demonstrated that the Med-eMonitor with follow-up telephone contact was as effective as weekly in home visits to establish prompts. Medication adherence averaged 91% for Med-e­ Monitor, 90% for PharmCAT, and 72% for TAU. Unfortunately, in this trial, which was conducted with relatively stable outpatients, the significant improvement in adherence to oral antipsychotic medications in the treatment groups did not lead to significant improvement in hospital or emergency room visits. A previous study of inpatients has demonstrated that Pharm-CAT improved rates of relapse and re-hospitalization in patients who were recently discharged from the hospital. In addition to smart pill containers, other technologies are being increasingly used to assist individuals in maintaining adherence to medication in the long term


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Granholm and colleagues [8] found that it was feasible to deliver simple reminders to take medication via cell phone to patients with schizophrenia. SMS text messages have also been used to improve adherence to medications for chronic medical conditions such as tuberculosis [9] . In 2010 the US FDA approved a tiny digestible microchip that is placed on medication tablets and can identify when medication has or has not been taken. Noningestion of medication can prompt specific interventions by care workers or family.

Smart pill devices have been found to improve adherence and illness markers in multiple long-standing conditions including HIV/AIDS, depression, and cardiovascular diseases.

In addition, instead of putting a lot of resources into adherence interventions in schizophrenia, freeing up case managers to work on social and role functioning by using long acting injectable medications is an important option to consider. Depot or long-acting antipsychotic medication is administered every 2–4 weeks and can be given by visiting nurses or in a clinical setting. Benefits of long-acting antipsychotic medications include the ability to determine when non-adherence starts and to be able to intervene. From the prescriber’s perspective, long-acting injection can be used to determine whether poor efficacy is due to poor adherence or is due to the medication not working well for that particular patient. Separating lack of efficacy from poor adherence is an important key to good clinical decision making. It can be concluded that technology may have surpassed human resources for dealing with the patient adherence issue. Given the benefits that smart pill devices, web based adherence applications and cell phone reminders have to offer, these techniques should be increasingly used to deal with what has been called ‘American’s other drug problem’ [3] . Within the next 5 years, it is likely that these devices and smart pills will be increasingly adopted in an effort to provide care that is outcome based in the context of a service delivery system that is moving toward a ‘pay for performance’ system. These technological advances could improve clinical management by taking the mystery out of how much medication is making it into the patient, giving prescribers better information in terms of making treatment recommendations. The promise is that better adherence, as well as better information about the adherence, of a particular patient will ultimately improve outcomes for multiple long-standing medical and psychiatric conditions.

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Enhancing patient adherence: introducing smart pill devices 

Financial & competing interests disclosure D Velligan is a Consultant at University of Tennessee (TN, USA), ProPhase, LLC (NY, USA) and is an Editorial Board Member and Consultant at Forum Pharmaceuticals, Inc. (MA, USA). D Velligan would like to acknowledge honoraria from Janssen Pharmaceutica (NJ, USA), Adelphi Values (MA, USA), Genentech (CA, USA), Otsuka America Pharmaceuticals, Inc

(MD, USA). D Velligan has also received a grant from Amgen (Cambridge, UK) for her research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.



Velligan DI, Weiden PJ, Sajatovic M et al. The expert consensus guideline series: adherence problems in patients with serious and persistent mental illness. J. Clin. Psychiatry 70(Suppl. 4), 1–46, quiz 47–48 (2009). 

Artinian NT, Harden JK, Kronenberg MW et al. Pilot study of a Web-based compliance monitoring device for patients with congestive heart failure. Heart Lung 32(4), 226–233 (2003). 


Valenstein M, Copeland LA, Blow FC et al. Pharmacy data identify poorly adherent patients with schizophrenia at increased risk for admission. Med. Care 40(8), 630–639 (2002). 

Simoni MM, Wiebe JS, Sauceda JA et al. A preliminary RCT of CBT-AD for adherence and depression among HIVpositive Latinos on the U.S.-Mexico border: the Nuevo Día study. AIDS Beh. 17(8), 2816–2829 (2013). 


Granholm E, Ben-Zeev D, Link PC, Bradshaw KR, Holden JL. Mobile assessment and treatment for schizophrenia (MATS): a Pilot Trial of an interactive text-messaging intervention for medication adherence, socialization, and auditory hallucinations Schizophr. Bull. 38(3), 414–425 (2012). 


Iribarren S, Beck S, Pearce PF et al. TextTB: A mixed method pilot study evaluating acceptance, feasibility, and exploring initial efficacy of a text messaging intervention to support TB treatment adherence. Tuberc. Res. Treat. 2013(349394), 12 (2013). 




Insel T. Assessing the economic costs of serious mental illness. Am. J. Psychiatry 165(6), 663–665 (2008). 


Velligan DI, Diamond PM, Mintz J et al. The use of individually tailored environmental supports to improve medication adherence and outcomes in schizophrenia. Schizophr. Bull. 34(3), 483–493 (2008). 


Velligan DI, Mintz J, Maples N et al. A randomized trial comparing in person and electronic interventions for improving adherence to oral medication in schizophernia. Schizophr. Bull. 39(5), 999–1007 (2013). 

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