Monday, May 7, 2018

The stability and influence of barriers to medication adherence on seizure outcomes and adherence in children with epilepsy

Rachelle R. Ramsey, Nanhua Zhang, Avani C. Modi.  The Stability and Influence of Barriers to Medication Adherence on Seizure Outcomes and Adherence in Children With Epilepsy Over 2 Years.  J Pediatr Psychol. 2018;43(2):122-132.


Objective To determine the stability and influence of adherence barriers on medication adherence and seizure control in pediatric epilepsy.

Methods Caregivers of 118 children aged 2–12 years old with epilepsy completed the Pediatric Epilepsy Medication Self-Management Questionnaire at nine time points over 2 years post diagnosis. Electronically monitored antiepileptic drug adherence and seizure outcome data were collected. 

Results Hierarchical linear modeling results for overall barriers remained stable over 2 years. Specific item-level barriers were also generally stable over time, with the exception of running out of medication becoming more of a barrier over time. No specific barriers were related to seizure control; however, difficulties swallowing medication, forgetting, and medication refusal were related to electronically monitored adherence over time.

Conclusions Assessing for specific adherence barriers over time may lead to identification of interventions that result in improved adherence and care.

From the article

The current study highlights the importance of assessing treatment adherence barriers in children with epilepsy to promote AED adherence and optimal seizure treatment. For families of children with epilepsy, the overall number of barriers and nearly all of the specific barriers (e.g., forgetting, disliking taste) remain stable during the initial 2 years of a child's epilepsy diagnosis. One barrier, running out of medication, became more of a barrier to AED adherence over time. From a clinical standpoint, this suggests that barriers experienced by patients and caregivers following diagnosis are likely to persist or worsen over the initial 24 month period following diagnosis. It seems reasonable to believe that these barriers would remain stable or worsen without appropriate identification of these barriers and interventions to mitigate these barriers. If barriers remain consistent, AED adherence will likely not improve. These findings are similar to studies of adherence barriers in children taking immunosuppressant drugs following transplant. Obtaining information about the specific barriers that are present for children with epilepsy and their families will help clinicians to identify children in need of interventions aimed at improving adherence select appropriate interventions, and provide resources that will be helpful to the family. Similar to studies of adherence barriers in other illness groups, forgetting to give medication and disliking the taste of the medication were the most common adherence barriers reported during the initial 25 months following an epilepsy diagnosis.

One major strength of the current study is that we were able to examine the interaction between time and adherence barriers on two different outcome variables: electronically monitored adherence and seizure control. Although none of the time-by-barrier interactions predicted seizure control, several of the time-by-barrier interactions were related to electronically monitored adherence over time: child difficulty swallowing medication, forgetting to give medications, and child refusing to take the medication.  These barriers appear to be critical agents for change in adherence promotion efforts in the future. It should be noted that although barriers remained stable over time, adherence decreased substantially over time. Declining adherence over time is consistent with the larger adherence literature; however, our study findings suggest that other factors, such as SES, family involvement, and child behavioral/emotional disorders, may contribute to nonadherence above and beyond adherence barriers measured in this study. The lack of seizure control findings may also be because of other salient factors that contribute to seizure control beyond adherence and adherence barriers, including biology (e.g., type of seizure, medication, and seizure combination), SES, or a host of other factors .

Results demonstrate that shortly following diagnosis, adherence did not vary based on the reported level of difficulty swallowing medication; however, increased difficulty swallowing the medication and adherence were related at 25 months post diagnosis, such that more difficulty swallowing the medication was related to lower adherence. It should be noted that at 1 month post diagnosis adherence was high across all levels of reported barriers with regard to difficulty swallowing. In other words, although some children with epilepsy reported having difficulty swallowing their AED medication, children with all levels of swallowing difficulty maintained, on average, a high level of adherence (>84.17%) during the first month of a child's epilepsy. The relationship between higher levels of difficulty swallowing and poorer adherence, however, becomes more exaggerated over time such that by the end of 25 months, children who report the more difficulty swallowing had, on average, 38.81% adherence, while children with no difficulty swallowing difficulties had 60.36% adherence. Although speculative, perhaps early in the child's diagnosis, parents are more vigilant about ensuring that the child is adherent to the AED despite swallowing barriers or they quickly identify and implement solutions that are beneficial (e.g., pill glide or coating the capsules or switching to liquid AEDs). With time, however, this vigilance may decrease, previously used solutions may be less effective or less frequently used, and simultaneously a new normal related to seizure activity (seizure free vs. continued seizures) is developing. The combination of these factors, along with the frustration and conflict that may arise from swallowing problems and medication refusal, may lead to AED nonadherence as an avoidance coping strategy. Alternatively, parents may attempt to give AEDs (despite swallowing difficulties) more consistently following diagnosis and may open the bottle less often months into the diagnosis because of frustration of trying to make the child swallow their AEDs. In this case, the barrier of swallowing is still present; however, attempting to overcome the barrier may be absent. Given the relationship between difficulty swallowing medication and rates of adherence over time, providers should assess and provide interventions for this particular barrier at diagnosis and throughout treatment. In fact, pill swallowing can be effectively taught to even young children.

The adherence barrier "child refusal to take AEDs" by time interaction was significant in predicting adherence resulting in a positive relationship at 1 month post diagnosis and a negative relationship at 25 months post diagnosis. The relationship between increased refusal of taking AEDs and poorer adherence at 25 months was expected; however, the relationship between increased refusal and increased adherence at 1 month post diagnosis was surprising. Both difficulty swallowing and child refusing medication are ingestion barriers that fall under the broad category of Health and Illness barriers.  As such, they are categorically different from the typical barriers of forgetting, organizational, or financial cost types of adherence barriers. In the case of ingestion-related barriers, families are often hyperaware of the barriers, eager to discuss these difficulties, and actively working to fix these barriers to improve adherence. For example, it may be that early in treatment, parents are acknowledging barriers, such as medication refusal and difficulty swallowing, even if the child eventually winds up taking the AED, and therefore AED adherence is high. This may be in direct contrast to other barriers such as forgetting or financial barriers, which often results in a missed AED dose. As mentioned, the identification of ingestion-related barriers are amenable to intervention with the use of pill swallowing (Patel et al., 2015) or behavior management techniques. Given our results, it is important that providers continue to assess barriers over time and understand that barriers may impact adherence differentially over the disease course.

Finally, regarding the barrier of forgetting to give medication, the main effect of time indicated that overall adherence is higher at 1 month post diagnosis compared with 25 months post diagnosis across the range of forgetting difficulties. For the interaction of time and forgetting, increased AED forgetting was related to poorer adherence 1 month following diagnosis and improved adherence 25 months later. This time by barrier interaction was in the expected direction at 1 month post diagnosis as increased forgetting to give/take AEDs resulted in poorer electronically monitored adherence. However, the finding at 25 months post diagnosis is unexpected. Specifically, results revealed higher adherence for those individuals endorsing forgetting as a barrier. There are several plausible explanations. First, social desirability may play a large role in whether parents endorse forgetting as an adherence barrier. Acknowledging that you sometimes or often forget to give your child his/her AED for epilepsy places the responsibility for the child's adherence and condition status on the parent. Perhaps when adherence is high across the board (shortly following AED initiation and early in treatment), the influence of social desirability reporting is less evident, but as adherence decreases, it becomes clearer. Alternatively, it may be that parents become less aware of how often they forget to give AEDs because forgetting has become more routinized. It is also important for clinicians to consider whether it is likely that any child "never" forgets to take their AEDs. One additional consideration regarding forgetting, which was not assessed in this study, is purposeful forgetting or volitional nonadherence. It is possible that "purposefully forgetting" is because of side effects or beliefs regarding the efficacy of the medication. Barriers such as forgetting are amenable to organization-focused strategies, including reminders via technology (e.g., cell phone reminders and text messaging services) or incorporating AEDs into daily routines (e.g., pairing with brushing teeth and use of pillbox.

The findings from the current study should be considered in the context of several limitations. First, children age 2–12 years participated in this study, and results are not generalizable to adolescents with epilepsy. In addition, parents provided information regarding adherence barriers because of the young age of the participants. A larger developmental range and child assessment of adherence barriers should be included in future studies given that adolescents with epilepsy may have their own unique perspective on how adherence barriers interfere with their treatment regimen. Second, there was attrition across the course of this 2-year longitudinal study, which further limits the generalizability of the results. Third, adherence was assessed by MEMS Caps and nonmonitored periods, as reported by families, were not included in the adherence calculation. Although use of the MEMS TrackCaps can only confirm when the bottle was opened and not actual ingestion, this method is still considered the gold standard of adherence assessment. Also, it is possible that medication refills were not always placed in the MEMS bottle and that nonmonitored periods occurred during times of nonadherence, artificially inflating the adherence rate. It should be noted, however, the exact dates of the nonmonitored periods were reported to study staff during the study visit, with no information regarding their actual adherence data. Finally, data collection occurred at one site, and future studies should include a larger sample size across multiple sites to further examine the stability of overall barriers over time.

Overall, this study contributes to the literature by addressing the important question of the stability and influence of adherence barriers on AED medication adherence and seizure control for children with epilepsy over the 25-month disease course. The overall barriers experienced by families of children with epilepsy were stable, while the specific barriers were stable or worsened over time. The specific barriers including difficulties swallowing medication, medication refusal, and forgetting, were related to adherence over time; however, the relationship between these barriers and AED adherence changed over time. Assessing patients' specific barriers at diagnosis and throughout epilepsy treatment will allow for the selection of the most appropriate interventions to improve clinical care and outcomes.

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