The enduring challenge of antipsychotic non-adherence.

Kane et al provide an excellent review of non-adherence to antipsychotic medication in patients with schizophrenia-spectrum disorders. While stressing the importance of medication adherence, they acknowledge large gaps in what is known, including how best to assess, prevent and manage non-adherence. Nevertheless, they rightly argue for a multi-faceted approach. Medications should be selected as the result of a shared doctor-patient decision in the context of a strong therapeutic alliance and aimed at achieving patient-oriented goals. Simple regimens that are efficacious and have minimal or well-managed side effects are most likely to be taken. The underlying assumption in the review and much of this commentary is that antipsychotics are effective and therefore adherence is obviously desirable. An important alternative perspective is that antipsychotics are variably effective and sometimes harmful. Thus the choice to avoid antipsychotic medications may be rational. Medication adherence is often helpful in achieving patient-centered goals, but an individual's recovery may also take other paths. Kane et al review a long list of methods for monitoring medication adherence and conclude that the methods commonly used in clinical practice are unreliable and underestimate non-adherence. An additional approach deserves mention. The Brief Adherence Rating Scale (BARS) is a validated (1) and clinically useful (2) tool that is administered by clinicians to identify and quantify non-adherence. To make a BARS assessment, a clinician first learns about the patient's knowledge of his/her medication by asking about the prescribed regimen. Then the clinician asks about the number of days in the last month that no doses were taken and the number of days of reduced doses. Based on this information, the clinician makes a global rating using a visual-analog scale to produce a score that is equivalent to the estimated percentage of prescribed pills taken in the last month. The BARS is fast and simple enough to use clinically. It can identify people with significant non-adherence and thus most likely to benefit from available interventions. The 2009 Schizophrenia Patient Outcomes Research Team (PORT) reviewed randomized controlled trials (RCTs) that tested psychosocial approaches to antipsychotic medication non-adherence in people with schizophrenia, and found insufficient evidence to recommend any specific intervention (3). However, the 2009 PORT concluded that behavioral tailoring and environmental supports, such as signs, checklists, and other cues are promising. A 2011 Cochrane review considered a broad range of psychoeducational approaches to schizophrenia, including interventions that did not focus primarily on adherence such as family psychoeducation. These programs were associated with lower levels of treatment non-adherence (4). Long-acting injectable antipsychotics (LAIs) are often proposed as a solution to non-adherence, but the evidence to support this is weak (5). LAI proponents think that a main reason why RCTs fail to find a benefit is that such studies tend not to include individuals who are most likely to be non-adherent. The fundamental problem with studying LAI effectiveness in RCTs is that the people who enroll must consent to take antipsychotic treatment, thus excluding the people who may be most likely to benefit from LAIs (6). Although it is suggested that a large, simple trial to compare oral to LAI treatments would enhance generalizability and help to clarify LAI benefits, it is not clear how the underlying selection bias inherent in RCTs would be addressed by a large, simple trial. Adherence falls along a scale from perfect to none. Improving adherence among people at all levels of non-adherence could lead to better clinical outcomes, with the most benefit likely accruing to those with the lowest levels of adherence. Interventions that improve adherence significantly across the scale could have a huge impact on the global burden of psychotic illness and improve the lives of many affected individuals. Different interventions might be appropriate at different points on the adherence scale and according to the reasons for impaired adherence. For example, people who occasionally and unintentionally miss doses due to cognitive or other barriers may benefit from behavioral tailoring involving reminders and cues. Individuals who are poorly adherent and ambivalent about taking medications might benefit from motivational interviewing, LAIs, or a combination of these. People who intentionally do not take medications due either to poor insight or a personal economy of symptoms vs. side effects favoring symptoms may benefit from comprehensive, multi-faceted approaches that include motivational interviewing techniques which are tailored to individual goals whose attainment might be aided by medications (7). While many interventions to improve antipsychotic adherence are explicitly designed to change the behavior of individuals diagnosed with a psychotic disorder, the need for changes in prescriber behavior is implicit. Doctors should remember that the goal of treatment is recovery, not medication adherence. They should be respectful of patient concerns and preferences, and prescribe according to the best available empirical evidence. In addition, doctors need to accept that some medication non-adherence is rational and have the forbearance to continue to provide support even in the context of non-adherence. In conclusion, doctors and patients overestimate the extent to which patients adhere to medication regimens. A validated clinician-rated instrument such as the BARS may help identify individuals who are non-adherent and suggest appropriate intervention. Systematic assessment of individuals' goals for treatment may complement such ratings. Currently, individually tailored efforts using combinations of psychoeducation, motivational interviewing, simple and effective regimens, family support, behavioral cuing, and long-acting medications represent the best practice for improved medication adherence. However, successful efforts to improve outcomes of individuals diagnosed with schizophrenia require multi-faceted approaches with a broader focus than adherence alone.