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Psychiatric Times. Vol. 25 No. 2
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Reducing Nonadherence: New Formulations of Antipsychotic Medications

By John M. Kane, MD
| February 1, 2006
Dr. Kane is chair of the department of psychiatry at Zucker Hillside Hospital, a division of Long Island Jewish Medical Center in Glen Oaks, N.Y. Dr. Kane is a consultant to Abbott Laboratories, BMS, Eli Lilly and Company, Janssen and Pfizer.

In the treatment of schizophrenia, as in any chronic medical illness, adherence with treatment remains a major obstacle. In a disease like schizophrenia, there is an even broader array of factors which can contribute to problems in adherence, as shown in the Table. At the same time, there are a number of important approaches to facilitating adherence, including: good therapeutic alliance; psychoeducation; minimization of adverse effects; convenient regimen; minimum number of appropriate/effective medications; psychosocial treatment; compliance therapy; and medication formulations tailored to specific patient needs.

Adherence is often a difficult problem with which clinicians have to deal, because on some level, it is narcissistic injury. After all of the effort and care that goes into making an appropriate diagnosis and developing the indicated treatment plan, it is difficult to fully and appropriately acknowledge the very real possibility that the patient will not follow through with the prescribed treatment. The same also applies equally to proscribed behaviors (e.g., drugs of abuse, unhealthy diet).

As a result of what may be cognitive dissonance on the part of clinicians, the consideration and ascertainment of nonadherence is given inadequate attention. In addition, it can be very difficult to accurately determine adherence levels. There are no ideal measures. Asking the patient is a first step, but the results can often be misleading. Patients might not be prepared to acknowledge or may not even realize the full extent of nonadherence. They could be concerned about hurting the doctors' feelings or angering the clinician. Given the extent of cognitive difficulties that many patients experience, remembering if and when medication was taken is not straightforward. Pill counts can be helpful, but are by no means consistently accurate. Blood levels can provide a qualitative assessment, but are impractical to do on a regular basis. An antipsychotic blood level could be informative when patients present to a hospital or emergency room in a state of psychotic relapse, yet this is rarely obtained.

Microelectronic monitoring devices have also been used. This technology involves a microchip placed in the cap of the medication bottle that records the exact date and time at which the bottle is opened. This may come closest to an accurate objective measure, but opening the bottle does not necessarily mean taking (or taking the correct amount of) medication. In addition, these devices are costly and can be easily lost or misplaced.

Although the methods to assess adherence are neither foolproof nor easy to apply routinely, their use has provided a wealth of data on the scope of the problem. It is clear that nonadherence or partial adherence is a major problem in schizophrenia. This is not confined to the minority of patients, but is something that affects the average patient.

In addition, numerous studies have shown a dramatic relationship between degrees of nonadherence and increasing levels of psychopathology or rates of rehospitalization (Valenstein et al., 2002). This underscores the fact that adherence is not an all-or-none phenomenon and that even partial adherence can have a clinically significant impact on outcome.

This is critical in highlighting one of the major problems in clinician's attitudes towards nonadherence. First, there is often an unrealistic sense that the clinician will be able to find out from the patient, or readily determine in some other way, if and when nonadherence is occurring. Second, physicians also believe they will be particularly able to tell when nonadherence is occurring to a point that would be cause for concern. There are two critical problems with these assumptions. Study after study has shown that clinicians grossly underestimate the degree of nonadherence found when it is measured concurrently by other strategies (Byerly et al., 2005). Second, there is no readily detectable or identifiable threshold when the degree of nonadherence becomes a risk for clinically significant consequences.

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