Potential Benefits to Patients and Payers From Increased Measurement of Antipsychotic Plasma Levels in the Management of Schizophrenia

Relative to its prevalence, schizophrenia has an outsized impact because of its early onset, chronicity, and highly disabling course. In the United States, annual direct health care costs for schizophrenia have been estimated at over $40 billion in 2017 dollars, as high as they had been more than a decade earlier (1). Although timely and high-quality treatment has been shown to improve the cost-effectiveness of schizophrenia care (2), evidence-based treatments have not been fully adopted by providers of routine care (3). As a result, payers have not seen significant improvements in the value of health care for people with schizophrenia (4).

In this column, we discuss the measurement of antipsychotic plasma levels as a tool to improve pharmacological management of schizophrenia and its potential effects on patient outcomes and the value of care, especially under emerging payment models and delivery system reform efforts.

Plasma Level–Guided Decision Making

Given the central role of antipsychotics in schizophrenia care, efforts to improve their management are a logical approach to improving quality and outcomes of care and avoiding unnecessary health care utilization. For many patients, antipsychotic management is straightforward. Such is the case for patients who are responding to treatment and experiencing tolerable side effects, who should remain on the antipsychotic drug, and also for those who are not responding to treatment and experiencing intolerable side effects, who should be switched to a different antipsychotic drug. However, antipsychotic management can be challenging for patients who do not fall into either of these categories, and prescribers lack tools to determine the causes of complications in the course of antipsychotic treatment. Such complications include inadequate treatment response, seen in approximately 25% of patients prescribed nonclozapine antipsychotics (5), and intolerable side effects, seen in approximately 15% of patients prescribed antipsychotics (5).

Clinical guidelines have recognized the value of measuring antipsychotic plasma levels (6), particularly in the treatment management of the approximately 40% of patients who have complicated courses of treatment (5). Although the evidence base for the measurement of plasma levels to predict therapeutic effect is less developed than for the measurement of plasma levels to assess adherence and tolerability, prescriber decision making would be improved if plasma levels were routinely measured to manage complicated cases. We have discussed this issue and the scientific evidence in more detail elsewhere (7).

For example, if a patient is not responding to treatment and antipsychotic plasma levels are undetectable, prescribers would recognize nonadherence as the cause of treatment failure and might switch to a long-acting injectable preparation or implement another proadherence intervention (7). However, if a patient is not responding to treatment but has antipsychotic plasma levels within the normal therapeutic range, prescribers would recognize true treatment failure and might switch to a different first-line antipsychotic drug or clozapine. Similarly, measurement of plasma levels would help prescribers determine whether intolerable side effects are the result of slow elimination of the drug (supratherapeutic levels) or high drug sensitivity (low normal or subtherapeutic levels), enabling implementation of the most appropriate intervention—that is, dose reduction or a switch to another drug, respectively (7). Thus the ability to make informed decisions in these complicated cases would increase the likelihood that patients receive effective and tolerable antipsychotic treatment.

The Payer Perspective

Payers might be interested in promoting the use of antipsychotic plasma level measurement to guide prescribing decisions and deliver higher-value care. Health care costs are two to six times higher for patients with poorly controlled schizophrenia compared with their peers whose symptoms are better controlled (8), primarily because of the higher risk of costly hospitalizations. Public payers would be the main beneficiaries of more accurate identification of the cause of complicated courses of antipsychotic treatment afforded by the targeted use of plasma level measurement for those patients, largely because Medicaid and Medicare cover the cost of care for most individuals with schizophrenia. In addition, state Medicaid budgets can be negatively affected by social assistance costs and criminal justice system costs for this population, which are financed by state revenues. A model based on published evidence, for example, estimated that improved antipsychotic adherence could yield $1,580 annual savings per patient in 2013 dollars to state Medicaid programs because of reductions in health care and criminal justice costs (9).

Public payers that operate under strict annual budget constraints and have discretion over which services to cover, such as Medicaid programs and the Veterans Health Administration, may be particularly interested in incorporating plasma level measurement into the routine care of people who are either not responding to standard antipsychotic treatment or are exhibiting intolerable side effects.

The Role of Payment Reform

An important trend in U.S. health care is the reform of the prevailing fee-for-service payment model and the emergence of value-based payment (VBP) models that hold provider organizations accountable for the overall cost, quality, and experience of the population under their care. Because of this trend, the payer-provider distinction is beginning to blur because providers are at least partially exposed to the overall cost of care and are thus incentivized to improve efficiency. An early form of this new payment system is the accountable care organization (ACO), in which groups of physicians, hospitals, and health systems contract with the Centers for Medicare and Medicaid Services (CMS) to provide care for a Medicare patient population and receive a portion of any savings achieved through improvements in quality of care or care coordination. Although CMS’s initial Pioneer ACO program has ended, the more permanent Medicare Shared Savings Program was estimated to cover more than seven million beneficiaries in 2016 and seems to have generally resulted in better care quality and lower costs (10).

The 2015 Medicare Access and Children’s Health Insurance Program Reauthorization Act continued this trend by furthering the development of new Medicare payment and delivery models under the new Medicare Merit-based Incentive Payment System (MIPS) and the so-called Medicare alternative payment models (APMs). MIPS provides performance-based adjustments to Medicare fee-for-service payments, and APMs are risk-sharing models that apply to a specific clinical condition, care episode, or population. These efforts at the federal level are mirrored by Medicaid reforms, such as the Delivery System Reform Incentive Payment programs under the Section 1115 waiver program, which vary by state but often contain steps toward VBP models (11). Although many of these VBP initiatives have applied to all patients, in some states, VBP models have included schizophrenia-specific quality measures as part of their definition of value; for example, Pennsylvania's Medicaid program includes adherence to antipsychotics for people with schizophrenia among its performance measures for eligible managed care organizations (12). Commercial carriers have also experimented with VBP models, as exemplified by the alternative quality contract of Blue Cross–Blue Shield of Massachusetts.

Although the broader policy of the new administration toward payment reform is still emerging, it seems unlikely that the overall trend toward greater accountability of providers will be reversed. Thus providers will become increasingly incentivized to manage population-level cost through better care. In the case of schizophrenia care, measurement of antipsychotic plasma levels may be a valuable tool to optimize antipsychotic medication management for the sizable portion of patients with complicated courses of antipsychotic treatment. Of note, there is already a nationally endorsed quality measure on adherence to antipsychotic drugs that is part of the measure sets of public and private payers (13).

Barriers to the Measurement of Antipsychotic Plasma Levels in Routine Care

Despite the potential of plasma level measurement to help prescribers manage patients with complex conditions, it is rarely used in schizophrenia care, even in well-resourced delivery systems (14), a reality that contrasts with the routine use of plasma level measurement in other areas of psychiatry. The reasons for its underuse in schizophrenia are not well understood, but it is possible that low use breeds lack of familiarity with the evolving scientific evidence, which in turn amplifies the underuse. Limited access to laboratory services and slow turnaround of results (15) may also contribute. In addition, payers may be reluctant to reimburse for an additional test, when the evidence base for its cost-effectiveness is still emerging.

Conclusions

As payers and providers switch to VBP models, there is a need for tools that help prescribers better manage their patient populations while also controlling costs. More research is needed on the use of plasma level measurement to predict therapeutic effect and on the cost-effectiveness of this diagnostic tool. However, improvements in disease management enabled by antipsychotic plasma level information have the potential to improve outcomes for patients with complicated treatment courses and thus improve the value of schizophrenia care. For patients with good response and tolerance to treatment and those experiencing intolerable side effects in the absence of treatment response, routine plasma level management would not provide any additional value to the payer.