Conceptualization and Study of Antipsychotic Medication Use: From Adherence to Patterns of Use

In recent years, controversy has increased about APM use, with responses ranging from moderate reservations (e.g., questions about whether a subgroup of youths diagnosed as having first-episode psychosis [FEP] might do well without APM) (7) to strong opposition, particularly regarding the unknown neurological consequences of long-term use (8). Along this spectrum, critics have emphasized the risk in prescribing APM too fast, sometimes because of misdiagnosis or overdiagnosis (9). Emerging evidence has also challenged common assumptions that the use of APM is universally beneficial over the long term and that discontinuation necessarily leads to adverse outcomes (9, 10). For example, several naturalistic follow-up studies have found that, over time, individuals discontinue APMs at relatively high rates and many of those who discontinue nevertheless report high quality of life (10). More recent evidence from a randomized controlled trial (RCT) on APM discontinuation suggests that a subgroup of individuals with FEP may function well without medications and supports the implementation of structured discontinuation strategies (11). Additionally, two recent feasibility trials, both of which were designed to inform fully powered RCTs, have examined the use of medication-free FEP treatment (12, 13). Other service users may follow nonstandard APM dosing regimens or augment or substitute treatment with nontraditional drugs or medications, such as cannabis. At the individual level, these heterogeneities are reflected in the different ways people understand and experience psychosis and APM use, in their motivation to alleviate symptoms, and in their preference for managing tradeoffs. For example, some people prefer symptoms over side effects, and others have reported missing certain symptoms once they have been eliminated or suppressed (14).

These developments in the spheres of both research and advocacy arguably push for a shift in focus of adherence research, from a narrow, dichotomous perspective (taking medications as prescribed versus not) to exploration of the range of ways people with psychosis choose to use medication. With this context in the foreground, we argue that it is incumbent upon the field, particularly among researchers actively focused on the study of medication use, adherence, and effectiveness, to fundamentally rethink the concept of adherence and its measurement.

Most existing adherence measures and metrics have been developed from the perspective of clinical researchers. Within this paradigm, adherence is typically considered a categorical concept, with little attention to the many alternative ways in which service users may utilize medications to support recovery goals without “adhering” as prescribed. Core adherence measures in psychiatry do not aim to capture personal medicine behaviors that support alternative approaches to mental health and recovery, such as tapering or discontinuation of APM, extended or sporadic dosing, person-developed augmentation strategies, or other forms of “mindful” nonadherence. Even where implemented, extant shared decision making (SDM) tools and approaches often fail to include the option to taper or discontinue APM or to neutrally present both the short- and long-term risks, as well as benefits, of APM. Furthermore, many of the samples included in adherence research are recruited from inpatient and outpatient settings and are unlikely to represent the broader population of individuals with a current or prior diagnosis of psychosis who use community services or choose not to use services at all. Sample selection bias, especially in clinical trials, is often compounded by narrow eligibility criteria that exclude the profiles of many clients.

To better capture different patterns of APM use in research, we propose a set of specific, actionable changes. These recommendations are described below.

Individuals with long-term psychosis often do not share whether or how they are using APM nor the strategies they may utilize as alternatives to APM. In combination with overly simplistic, dichotomized measures of adherence, this tendency has arguably led to the impoverishment of research on APM use. Simultaneously, in spite of current tensions and controversies, it seems likely that stakeholders with various viewpoints would agree that a deeper understanding of the use and discontinuation of APM and associated consequences is of great importance to the field.

In this Open Forum, we have described a series of challenges pertaining to the conceptualization and operationalization of adherence in APM research, offering concrete ways to advance the field. We hope that these ideas can help energize and diversify current research efforts. Ultimately, we hope that these efforts will contribute to a transformed culture of care in which service users have meaningful opportunities to explore their options and to choose whether to take medication as well as the kinds of medications, doses, and patterns of use that best support their recovery processes. A reorientation is needed away from the current dichotomous viewpoints and toward a diversity of views and experiences. We believe a shift from studying adherence to a prescribed regimen to studying user-directed patterns of use will help move research past often-polarized positions and insufficient attention to service user perspectives and concerns. This shift may help empower those with the most at stake—those prescribed APM—to make truly informed personalized choices among a range of evidence-based options emerging from APM users’ real-world patterns of use.