One of the most complicated problems in all types of pediatric transplants is that of nonadherence to medical instruction. Although some types of transplant, such as heart transplants, have specific expectations in terms of diet and exercise, consistent use of immunosuppression is the primary behavioral challenge to survival after organ transplantation.
Non-adherence with medications is very common, with studies repeatedly demonstrating that only about half of people prescribed medication take at least 80% of the medications as prescribed (49
). The complexity of the regimen is associated with the likelihood of adherence, such that medications which must be taken several times a day, or in specific relationship to food or milk are less likely to be taken regularly(50
). Medications which have adverse effects are less likely to be taken, but so are medications which are largely preventative, and have no immediate adverse impact when they are not
taken. An example is antihypertensive medications, which can cause sexual side-effects, and often create no immediate perceivable adverse effects when stopped.
It is often surprising to physicians that a transplant recipient would ever stop immunosuppressant medications. After all, they have been saved from death by this transplant. Why would they do anything to risk it? The reasons are multiple.
- As mentioned above, complex regimens are the most likely to lead to poor adherence. Immunosuppressant regimens almost always involve more than one medication, taken more than once a day. Medications which can be paired with a morning or evening regimen are simpler than those which need to be taken at school. Students are almost never allowed to carry medication with them at school, and must go to the nurse’s office to get the medication. This increases the probability that the student will not remember, or will try to avoid the embarrassment of a trip to the nurse’s office.
- Medication which causes adverse effects is less likely to be taken. The weight gain and impact on the face and abdomen associated with steroids makes these quite aversive to children and adolescents. Cyclosporine can lead to increased gum growth, and darker, thicker arm hair, which are of cosmetic concern. Recipients learn that these effects diminish if they reduce or stop their medication.
- Recipients who decrease or stop their medications also find that there are no immediate adverse consequences. Indeed, it turns out that some recipients can successfully stop immunosuppressive medications and not have rejection of the grafted organ. Unfortunately, it is not yet known who those fortunate individuals are, or exactly why it occurs, and so it cannot be predicted. Some other recipients will have a relatively quick response of acute rejection, which can be recognized, but may still result in loss of the graft. However, most recipients will simply intermittently take the immunosupression, resulting in a smoldering chronic rejection. This can also ultimately result in graft failure.
- Adolescents are particularly prone to non-adherence with medical advice. This is partly due to the developmentally appropriate questioning of authority, and desire to make their own decisions. It is also due to what we now know is immaturity of the prefrontal cortex, resulting in poor judgment in emotionally charged situations. The issues of transitions of care, discussed above, contribute to adolescent non-adherence.
Usual interventions, such as education about the consequences of non-adherence, are ineffective at changing behavior in some adolescents. More intensive interventions such as reminder cell calls or texts might be successful, but would be unnecessary and expensive to do with all recipients. However, targeting those for interventions has been difficult. Several studies have demonstrated that clinicians are not effective in predicting or identifying those pediatric recipients who are or will be non-adherent. Studies using self-report, pilling-counting, and computerized pill bottle tops have not been able to predict who will have biopsy proven rejection (51
Studies with tacrolimus levels in pediatric liver transplant recipients have identified one promising possibility. Three programs have found that the standard deviation between at least three routine blood levels can be used to differentiate those who will have biopsy proven rejection from those who will not (52
). This has been replicated demonstrating that intermittent use of immunosuppression is seen in these widely varying levels (53
). Interventions to help decrease nonadherence have been piloted, including one using text-messaging to remind teens to take their medication (54
) and targeted interventions with those who have high fluctuations in tacrolimus levels (55
) or symptoms of posttraumatic stress (56