| Table of Contents | Chapter II |
Drug benefits are the fastest growing major cost component both of private insurance and Medicaid, averaging 12.2% growth per year compared to 5.1% for total health spending (1993-1998).1 In 1997, $78.9 billion were spent on prescription drugs, representing 7% of total health care expenditures.2 More specifically, spending on the newer antidepressants such as fluoxetine, sertraline, and paroxetine increased by 240% between 1993 and 1998, representing 11.8% ($5 billion) of the total increase in drug expenditures over this time period.3
To slow the growth in pharmaceutical costs, health care payers have initiated utilization control mechanisms. Examples include restricted formularies (i.e., lists of pharmaceuticals approved for reimbursement that may include only the older, less expensive, and sometimes less effective medications), limits on the numbers of prescriptions or units allowed and prior authorization requirements for newer medications. In the case of substance abuse, many plans do not offer access to any substance abuse treatment, making pharmaceutical intervention much less likely or even impossible. To consumers, families, and mental health advocates these controls translate into denials of care.
In fact, many consumers, clinicians, and advocates believe that denying or reducing access to drugs may cost more in the long term. Instead of using effective pharmacotherapies early, consumers and advocates contend that precious time and money is wasted in older or less effective treatments. Consequently, the quality of their lives suffers. While criticism for using these practices often focuses on managed care organizations (MCOs), similar cost control measures exist in traditional insurance, including Medicaid.
New medications introduced in the last decade represent a significant advance in the effective treatment of mental illnesses. In general, the newer medications have proven efficacious in treating various mental disorders (particularly schizophrenia and major depression), with a noticeable reduction in, or absence of, the adverse side effects often associated with the older generation of psychiatric medications. These agents include Selective Serotonin Reuptake Inhibitors (SSRIs), other new generation antidepressants (e.g., nefazadone, venlafaxine, bupropion, mirtazapine), and atypical antipsychotics (e.g., risperidone, olanzapine, quetiapine). More specifically, newer generation drugs feature real-world effectiveness, ease of dosing, and improved safety.
Timely use of the most effective drug therapies can reduce the need for inpatient treatment and minimize the disabling effects of severe illnesses and disorders, such as schizophrenia and major depressive disorder. Furthermore, the milder side effects of many of the newer medications may ensure better compliance with therapy. Together, these factors can result in marked improvement in the productivity and quality of life for both the consumer and the consumer's family.
However, these newer medications are often substantially more expensive than the medications they are intended to replace. For example, the average wholesale price (AWP) for the antidepressant fluoxetine is $150.10 for a 30-day supply of an average therapeutic dose while a 30-day supply of the older antidepressant, amitriptyline, lists between $3.00 for a generic version and $5.00 for the branded version.
Although not formally related, this study benefited from prior work conducted by The Lewin Group on this topic for the Substance Abuse and Mental Health Services Administration (SAMHSA). In 1998, The Lewin Group conducted a trend analysis concerning the status of pharmacy benefits for behavioral health under public insurance.4 In that study, representatives from primary stakeholder groups were interviewed to determine the principal barriers in place that act to restrict access to the newer psychotropic medications. The trend paper summarized those findings and made an assessment of existing data sources and published literature to determine the extent to which the issues identified by the stakeholders could be (or had been) addressed from existing sources.
Until the present study, however, no primary research had been conducted on these questions. Most of the complaints were based on anecdotal experience. Nevertheless, such experiences did raise a clear policy concern as to whether health care payers have gone too far in controlling the utilization of pharmaceuticals. This is especially true as managed care programs assume increasing responsibility for caring for the severely mentally ill, and as the issue of mental health parity and the scope of desirable benefits are publicly debated and often legally mandated in various forms.
The Assistant Secretary for Planning and Evaluation (ASPE), United States Department of Health and Human Services and the National Institute of Mental Health (NIMH) commissioned the present study to identify, document, and assess the factors that affect access to and utilization of new generation antidepressant and antipsychotic medications. Three primary questions guided this assessment:
The study is designed to assist the U.S. Department of Health and Human Services to evaluate existing and proposed policies in this area by developing important insights and knowledge concerning the complex processes related to access, utilization, and coverage of newer psychotropic medications from a variety of perspectives. This study is also designed to identify clinical and health policy issues where further research is needed.
From its outset, this study was designed to answer the above questions by evaluating six principal issues that work together to influence the degree to which consumers have access to and are able to use the most up to date pharmaceutical therapies for mental illnesses. Broadly speaking, these issues include:
The antidepressants and antipsychotics of interest to this study are shown Exhibits I-1 and I-2, respectively, by generic and brand names. The principal antidepressants considered in this study include the Selective Serotonin Reupatke Inhibitors (SSRIs) and other newer antidepressants including venlafaxine, bupropion, nefazadone, and mirtazapine. These agents contrast with older classes of antidepressants, namely the Tricylcic Antidepressants (TCAs) and Monoamine Oxidase Inhibitors (MAOIs).
Pharmacotherapy is an important component of effective treatment of mental illness. Effective treatments for mental disorders date to the 1950s. For example, older antidepressants (e.g., TCAs) have proven to be effective; however, difficulties in dosing often lead to less than satisfactory results in common use (i.e., the "real world"). Furthermore, the lethal dose of TCAs is relatively low compared to the standard therapeutic dose. This danger is especially high for patients in crisis who may be suicide-prone. Newer agents such as SSRIs have generally proven as efficacious as the TCAs, and often have simpler (i.e. once a day) dosing and are far less lethal in overdose. They have also proven helpful in treating an array of other illnesses including obsessive-compulsive disorder, panic disorder, and social phobia.
Nonetheless, the side effect profiles of both TCAs and newer agents can be unpleasant. TCAs are associated with side effects such as constipation, dry mouth, urinary retention, and sedation, while SSRIs, carry the risk of sexual dysfunction, sleep disruptions, and increased anxiety. Venlafaxine has an associated risk of hypertension, while bupropion has a risk of seizures. In general, however, simpler dosing regimens and more acceptable side effect profiles for the newer drugs are thought to improve compliance and success.5
| Generic Name | Brand Names |
|---|---|
| Selective Serotonin Reuptake Inhibitors | |
| Citalopram | CelexaTM |
| Fluoxetine | Prozac® |
| Fluxvoxamine | Luvox® |
| Paroxetine | Paxil® |
| Sertraline | Zoloft® |
| Tricyclic Antidepressants (Representative) | |
| Amitriptyline | Elavil® |
| Desipramine | Norpramin® |
| Imipramine | Tofranil® |
| Nortriptyline | Pamelor® |
| Trazodone | Desyrel® |
| Monoamine Oxidase Inhibitors (MAOIs) | |
| Phenelzine | Nardil® |
| Tranylcypromine | Parnate® |
| Others | |
| Bupropion | Wellbutrin®, Wellbutrin® SR |
| Mirtazapine | Remeron® |
| Nefazadone | Serzone® |
| Venlafaxine | Effexor®, Effexor® XR |
The antipsychotic agents (Exhibit I-2) principally considered in this study include the archetype of the "atypical" antipsychotics, clozapine, together with three newer agents, risperidone, olanzapine, and quetiapine. These agents were designed to replace older generation pharmaceuticals including the phenothiazine class, haloperidol, and other miscellaneous antipsychotic agents.
| Generic Name | Brand Name |
|---|---|
| Atypical Antipsychotics | |
| Risperidone | Risperdal® |
| Olanzapine | Zyprexa® |
| Quetiapine | Seroquel® |
| Clozapine | Clozaril® |
| Typical Antipsychotics | |
| Haloperidol | Haldol® |
| Chlorpromazine | Thorazine® |
| Fluphenazine | Prolixin® |
Similarly, older antipsychotics (e.g., haloperidol, chlorpromazine) have proven effective for many patients. However, the duration of effect is often short-lived and these agents have no benefit for the so-called negative symptoms of schizophrenia, such as social withdrawal. The older agents are also associated with very high risks of extrapyramidal side effects (EPS) and tardive dyskinesia (TD) that often are associated with poor patient compliance and severe distress for both the patient and their families. The newer agents (e.g., risperidone, olanzapine, quetiapine) are generally as effective as the older agents and show promise in the treatment of negative symptoms. Clozapine has shown superior efficacy, especially in treatment-refractory patients. The newer agents typically have milder side effect profiles that may assist with compliance. Clozapine, however, is associated with a significant risk of agranulocytosis. Risperidone is not without some risk of EPS, while olanzapine is associated with weight gain, and quetiapine with somnolence.5
Based on previous reports and the 1998 trend analysis, a number of issues and factors had been identified that were used as an initial starting point to organize this research. The cost of newer medications has clearly been identified as a key issue. The increased costs associated with the development and use of the newer antidepressants and antipsychotics may pose significant barriers to their general and unrestricted use by consumers. From one perspective, the higher price of any new medication is justified as a means of recovering research and development costs. These costs include identifying a potential product and evaluating it through various required phases of pre-clinical and clinical testing that are needed to obtain formal approval of the drug from the Food and Drug Administration (FDA). This costly development and approval process typically takes several years, and no assurances exist that a marketable product will result. Even after FDA approval is obtained and the product is marketed, post-marketing issues may turn a profitable product into an unprofitable one.
Both public and private health care payers are also under considerable financial pressure, and may resist covering newer agents in an effort to control increasing prescription expenditures. Even if the clinical efficacy of a newer but more expensive medication is demonstrably superior to an older less costly medication, the cost-benefit decision point is not clear cut. Use of the less effective, but less expensive, medication may be defensible from the point of view that the added clinical value does not justify the higher cost of the newer medication on a routine basis.
However, the value of reduced or absent side effects and/or enhanced clinical efficacy may have cost implications that can counter-balance or offset the higher drug acquisition costs. Medications with fewer and/or more moderate side effects may improve patient compliance with therapy, which may lead to improved effectiveness when used in clinical practice. This improved real-world effectiveness may lead to improved day to day functioning while reducing other health care costs, such as those for physician or hospital visits.
While cost-savings and cost-effectiveness are often treated as equivalent, it is important to recognize that cost-savings do not accrue equally to all stakeholders. For example, health care payers reap the benefit of any savings in direct medical costs, while the consumer's interest lies in the most effective treatment with the mildest side effects, regardless of cost. Furthermore, the practice of administering budgets for individual health care sectors separately (e.g., pharmacy, psychiatric services, hospitals), often prevents health care payers from recognizing the overall net savings as individual service sectors struggle to manage their individual budgets.
Realistically, numerous factors affect the extent to which newer antidepressants and antipsychotics reach individuals who might benefit from them. Based on the 1998 trend analysis, it was thought that some of these factors would include:
These factors are likely to vary by the kind of insurance coverage or health care system being considered, plan organization, and the type of health delivery model used.
The present analysis was developed based on published literature, pharmaceutical claims, and primary research with stakeholders. It focuses on antidepressants and antipsychotics as general classes of pharmacotherapy, with emphasis on agents introduced to the US market after 1988. Chapters III -- V rely primarily on published literature and primary interviews. Chapter VI relies on Medicaid pharmaceutical claims, while Chapter VII relies on published literature. A description of each type of source follows.
Several individual searches of the databases MEDLINE and HEALTHSTAR were conducted in August 1999. All searches were limited to human subjects and English language. Cost studies were restricted to studies conducted in the United States, unless no studies for that agent were available. In this case, selected studies conducted in Europe or Canada were included. Relevant articles identified through the literature search were obtained and reviewed. Subsequent to this review, we collected additional literature cited in the reference section of the review articles. The formal literature review was supplemented by studies maintained in-house by our expert mental health services staff. Because the first of the pharmaceuticals of interest to this study was introduced in 1988 (fluoxetine, i.e., Prozac®), the literature searches were restricted to articles published from 1988.
These literature searches had several goals:
Quarterly, state level data on prescription drug utilization are available from the Health Care Financing Administration(now known as Centers for Medicare and Medicaid Services(CMS)) (HCFA(now known as CMS)). These data are reported at the National Drug Code (NDC) level, allowing analysis of utilization of individual pharmaceutical agents within the Medicaid system. While these data are representative of the US Medicaid population, state-level analyses are difficult in some States due to missing data. The completeness of the data is also compromised in States where Medicaid Managed Care has assigned the responsibility for paying for pharmaceuticals to the participating managed care organizations.
Although there are limitations in the data, The Lewin Group conducted time-series analysis of antidepressant and antipsychotic drug utilization data between 1985 and 1998 for 45 States. Data from six States were excluded for the following reasons:
The Lewin Group identified a set of key topics and issues that affect access to and utilization of antidepressant and antipsychotic medications that were not adequately discussed in the literature. These topics included, but were not restricted to:
The interview guides and survey instruments developed for this data collection are included in Appendix A. Exhibit I-3 presents the respondent organizations interviewed for this study. A fuller discussion of rationale for choosing each respondent is presented in Appendix B. A full list of all respondents is included in Appendix C.
| Key Informants | Number of Site Visits | Number of Telephone Interviews |
|---|---|---|
| Pharmaceutical companies | 3 | 2 |
| Managed behavioral health care companies | 1 | 2 |
| Large health maintenance organizations | 2 | 3 |
| Pharmacy Benefit Managers | 5 | |
| Employers | 3 | |
| Federal Programs | 2 | |
| State Medicaid Programs | 4 | |
| Department of Defense | 1 | 1 |
| Veterans Administration | 1 | 1 |
| State Mental Health Systems | 4 | |
| Provider Associations | 2 | |
| Consumer and Advocacy Associations | 2 | |
| Totals | 12 | 25 |
Following this introduction, Chapter II summarizes the principal findings of the study. Chapter III provides a detailed discussion of the distinctions between the concepts of "access" and "utilization" that underlie the entire report. Chapters IV and V detail the findings of the primary research interviews investigating the state of access to and utilization of newer antidepressant and antipsychotic medications during the term of this study (1998-1999). Chapter VI presents an analysis of Medicaid pharmaceutical claims designed to establish patterns of antidepressant and antipsychotic utilization by state Medicaid programs between 1995 and 1998. In addition this chapter compares utilization of these psychotherapeutics with the utilization of other classes of medications to gain insight into whether the uptake of newer psychotherapeutics by Medicaid is slower than for other classes. Chapter VII reviews the pharmacoeconomic literature for antidepressant and antipsychotic medications. Finally Chapter VIII highlights areas for further research and identifies key trends and potential issues that may raise policy concerns in the future.
| Table of Contents | Chapter II |
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Last updated August 20, 2000