Imagine To Remember: An Episodic Future Thinking Intervention To Improve Medication Adherence in Patients With Type 2 Diabetes Part 3

EFT Cue Examples

In about 1 week, I am taking a dance lesson. I am enjoying the dance, and I remember to take my medication. I am in the dance lesson with my teacher and other friends and enjoying the learning, and during a break, I take my medication." 2). "In about 1 week, I am sitting in my room taking my medication.

Learning and memory are closely related, and a good learning process can improve memory. The relationship between learning and memory is mutually reinforcing, and we can enjoy the relationship between learning and memory in some positive ways.

First, we need to keep a positive attitude. Learning is a pleasure and we can see it as a challenge rather than a pressure. When we enjoy learning, it is easier for us to get started and retain what we have learned in our long-term memory.

Secondly, we can strengthen our memory in many ways. For example, we can use flashcards to remember information such as facts, words, and definitions. This method can increase our memory capacity and deepen our impressions through constant review and review.

In addition, a healthy lifestyle can also promote the relationship between learning and memory. We need to get enough sleep because sleep is an important period for the brain to consolidate memories. We also need to maintain a healthy body and improve brain efficiency and memory through exercise and diet.

In summary, learning and memory are interconnected. We need to establish an active process for learning and memory and strengthen our memory in a variety of ways. Only in this way can we continue to enjoy the relationship between learning and memory and make continuous progress. It can be seen that we need to improve memory, and Cistanche deserticola can significantly improve memory, because Cistanche deserticola can also regulate the balance of neurotransmitters, such as increasing the levels of acetylcholine and growth factors. These substances are very important for memory and learning. In addition, Cistanche deserticola can also improve blood flow and promote oxygen delivery, which can ensure that the brain receives sufficient nutrients and energy, thereby improving brain vitality and endurance.

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I am getting ready for work and sit on my bed to take my medication. I have a glass of water on the nightstand ready to use. I am alone as my husband has left for work. Next, I test my sugar level, get dressed, and leave for work. I am taking my medications to stay in good health." Participants met weekly with case managers to integrate EFT into their routine to improve medication adherence. Participants were instructed to use their cues right before taking their medications for every medication dosage. 

Case managers would review the participants' medication adherence and cue usage to discuss with challenges in taking their medication and revise cues with further details to strengthen EFT. Participants also practiced and discussed how to use their cues effectively in these sessions. These sessions were recorded and were reviewed for fidelity to the protocol.

Assessment Sessions
Assessments including Backward Corsi, delay discounting, and prospective memory tasks were completed at baseline, and delay discounting and prospective memory tasks were also completed when the intervention was introduced (either at week 7, week 9, or week 11) and after the intervention was complete (week 15).

Analytic Plan

Changes in medication adherence were first analyzed across the four subjects using visual inspection of the multiple baseline graphs to assess whether the baseline was stable and not improving before intervention and whether improvements in medication adherence appeared to be sequentially related to the introduction of EFT. 

Statistical analysis to support visual inspection of each case included analysis of baseline trend, the stability of baseline and EFT data, phase changes from baseline to EFT, percent non-overlapping data from baseline to EFT, and immediacy of change from baseline to EFT.30 

Changes across the three different baseline lengths across the four subjects were accomplished using a mixed model that included fixed effects of level and trend for phases A and B, and random effects level and trend in phase A.53 

The p values for the multiple baseline should be interpreted as evidence for the reliable relationship between treatment and outcome for the participants that were studied, not that the results would generalize beyond the current sample. While the sample size is too small to analyze traditional pre-post changes, effect sizes were calculated for changes from baseline to the end of the study for delay discounting, virtual week, and event-based prospective memory tasks were calculated based on change/SD of change.

Results

Seven participants were recruited, six with a diagnosis of type 2 diabetes, and one with a prediabetes diagnosis. Four participants met the non-adherence criteria during baseline, were entered into the study, and were randomized to one of three staggered baselines in the multiple baseline design. The participants included two females, one male, and one individual identified as non-binary. 

Two of the participants were white, one Asian female, and one American Indian or Alaskan Native. Each participant had a diagnosis of type 2 diabetes, with ages ranging from 43 to 52 years of age, and BMI ranging from 27.2 to 37.2 kg/m2. The number of medications prescribed ranged from 1 to 5. During baseline, MEM caps were provided for multiple medications, with the medication associated with the lowest adherence rates determined as the targeted medication. All participants had backward Corsi scores, a measure of short-term visuospatial memory, within the normal range (mean ± 1 SD).42,43

All participants who began the study completed the study, with 100% attendance at scheduled sessions. The objectively measured MEMs-based adherence is presented in Figure 1, with 80% adherence indicated by a dotted line. Visual inspection of this data shows no upward trends for any participants during baseline and relative improvements for all participants after introducing EFT. 

Analysis of data for each participant, summarized in Table 1, showed significant improvement for three of the four participants, but not for participant 411. This may be because while Participant 411 had overall baseline adherence results of less than 80%, they were at 100% adherence in week 2, and EFT restored them to levels achieved during baseline. The other significant effect was a significant decelerating trend during baseline for Participant 403. Pre to post-effect sizes for delay discounting (0.355 ± 0.295 = ES of 1.20), virtual week (0.083 ± 0.104 = ES of 0.80), and prospective memory task (2.75 ± 3.78 = ES of 0.73) were all in the large effect size range,54 suggesting that EFT training was associated with an improvement in prospective memory and delay discounting. 

The sample size was too small for traditional statistical testing or correlating changes in these variables with a change in medication adherence. Consistent with the inspection and analysis of changes for each participant, mixed model analysis showed a significant overall treatment effect, t = 4.01, p = 0.0002, autocorrelation = −0.095, with a between-case standardized mean difference (BC-SMD) of 1.62.

Discussion

These results show a functional relationship between the introduction of EFT and changes in medication adherence for the participants studied with type 2 diabetes who are taking medication to improve glucose homeostasis, blood pressure, or lipid profiles. In addition to changes in medication adherence, changes in two different measures of prospective memory that may mediate the effects of EFT on medication adherence were observed for the participants studied. 

People who are not adherent to medication often report that they forgot to take their medication,6 and while they may prompt themselves at one time of the day to take their medication, they can easily forget when the time comes to take their medication. Interestingly, participants were not chosen because they uniquely reported forgetting, suggesting the generalizability of effects to a broader range of patients. In addition, EFT was associated with a reduction in delay discounting, which is independently related to poor medication adherence in people with prediabetes and diabetes.12–16 Less discounting of the future and a more prospective mindset may lead people to engage in current behaviors, such as medication taking, for their future benefits. 

Previous research has shown EFT can improve prospective memory using the virtual week task.19 Still, to our knowledge, this is the first time that EFT has been used to improve medication adherence using objectively measured medication adherence. It is possible that for some diseases that can impair working memory, which would include diabetes44 and hypertension,55 EFT may have different effects, as working memory is related to episodic future thinking.28,45 Interestingly, Participant 410 had the lowest Corsi block tapping score of 18, and this person had the lowest baseline medication adherence. A considerable body of research shows that EFT modifies delay discounting.23,26–29,56 

Delay discounting represents a tendency to focus on immediate gratification and discount future events,22 and delay discounting is related to medication adherence in people with prediabetes12 or type 2 diabetes.13 This is generally conceptualized as a failure to engage in positive long-term benefits, but perhaps few immediate benefits. High delay discounting is related to the inability to engage in a wide variety of preventive health behaviors, such as flossing,57 preventive health checkups,58,59 being physically active,12,57 or wearing seatbelts,59 in addition to not taking medication to prevent worsening of prediabetes or type 2 diabetes prediabetes.12,13 Possibly, the effect of EFT on delay discounting may be part of the mechanism for positive changes in adherence observed in participants in this study, in addition to changes in prospective memory. 

This study used a multiple baseline, single-case experimental design to test the effects of EFT on four patients with type 2 diabetes who were nonadherent to their medication. This represents an economical and powerful approach to early-phase translational research that suggests that improvements in medication adherence were a function of the EFT intervention. Single-case experimental designs provide a strong test of the functional relationship between treatments and outcomes and are a first step toward the development of interventions for medication adherence. 

The next step would be to conduct a fully powered randomized controlled study to compare the effects of EFT with other interventions, which could include implementation intentions. This study would also measure potential mediators of treatment effects, which could include both prospective memory and delay discounting. This study would also measure changes in the physiological outcomes of the medication taken, which in this case would be improvements in blood pressure and lipids. 

This would allow generalization of the treatment to people with diabetes and medication nonadherence who met the study entrance criteria. If successful, these methods may be generalizable to a wide variety of diseases where people take the medication in pill or tablet form that can be measured using an objective measure of adherence.

Study Limitations

While the results suggest EFT can be an easy-to-implement, scalable intervention for people with prediabetes or type 2 diabetes who are non-adherent to their medication, the study has several limitations. First, while results showed that all participants exceeded 80% adherence at least for 1 week during treatment, results did not always indicate that EFT enhanced sustained adherence beyond the 80% target used to establish non-adherence. 

Thus, some participants may still have been rated as relatively non-adherent, even though their adherence improved. Second, while 80% adherence is common in diabetes,48,49 greater adherence may involve further improvements in disease management, and based on the relationship between medication use and physiological changes, higher adherence may be indicated to achieve optimal control of risk factors. Third, given that this study was implemented over 15 weeks, the durability of the EFT effects over more extended periods remains unclear. 

Fourth, the repeated measures required for a single subject design raise concerns about improvement due to practical effects, rather than a specific effect of EFT. This concern is less for the Virtual Week task, as there are multiple versions of the task, so the person does not repeat the same task. Likewise, in previous studies with persons with prediabetes, we have not shown significant improvement for control groups who do not receive EFT,24,25,60 making this less of a concern in this study. While no decrement in EFT-influenced medication-taking over time was observed, assessing longer-term changes when participants are not in weekly contact with a case manager would be worthwhile. 

Fifth, replicating these results in a larger number of participants is necessary to increase confidence in the findings and begin to generalize these results to other people who are not adherent to their medication intake and who have type 2 diabetes. Sixth, numerous aspects of the treatment protocol besides or in addition to EFT may have influenced medication adherence. This may be a particular issue since case management itself, without EFT, may result in an improvement in medication taking. Given that corresponding changes in prospective memory and delay discounting were also observed, these effects are unlikely to be attributed to the attentional effects of case management. In the future, utilizing attentional control during the baseline phase may be useful. 

Indeed, if this research moves to the next step of a randomized, controlled study, an attention placebo group would be necessary to control for case management. Finally, the participants were not chosen because they uniquely reported forgetting to take their medication, which may suggest the generalizability of effects to a broader range of patients. Future research could focus on people who report forgetting to take their medication to better understand boundary conditions for this intervention.

Conclusion

This early phase translational study provides experimental evidence that EFT-modified medication adherence for the participants studied with type 2 diabetes. In addition, the study provides suggestive evidence that these effects may be mediated by improvements in prospective memory and delay discounting. Randomized, controlled studies are needed to control for attention effects in case management, and to compare with established treatments for medication adherence on medication adherence and disease-specific outcomes, as well as potential mechanisms for change.

Acknowledgments

Appreciation is expressed to Peter Rendell for sharing and assistance with programming the Virtual Week task.

Funding

This research was funded in part by the National Institutes of Health (NIH) Science of Behavior Change Common Fund Program through an award administered by the National Institute of Diabetes and Digestive and Kidney Diseases (1UH2DK109543), awarded to Drs. Epstein and Bickel.

Disclosure

W. K. Bickel is a principal of HealthSim, LLC; BEAM Diagnostics, Inc.; and Red 5 Group, LLC. The other authors do not declare any conflicts of interest concerning the authorship or publication of this article.

References

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