SUPPLEMENT TO CareCare · 2019-12-18 · Care M A N A G E D SUPPLEMENT TO July 2003 This MANAGED...

M A N A G E DSUPPLEMENT TO

SEEKING A BALANCE:

Weighing the Clinical and EconomicFactors of Depression and AnxietyManagement in Patient OutcomesProceedings of the Economic Working Group Advisory Board, March 2003

HIGHLIGHTS

• Health Care Benefits in the 21st Century:What Employers Are Facing; How They Are Responding

• Mental Health Support Needs: The Employer Perspective In Optimizing Clinical and Economic Outcomes

• MindSET: Tools to Implement A Behavioral Health Initiative In the Workplace

• PANEL DISCUSSION: Does HEDIS Affect Compliance,Length of Therapy, or Outcomes?

• An Economic Analysis of SSRI Length of Therapy

• Improved SSRI Tolerability and Increased Length of Therapy

CareCare

Volume 12, No. 7July 2003

Editor, MANAGED CARE

JOHN A. MARCILLE

Managing Editor, MANAGED CARE

Editor, Custom PublicationsMICHAEL D. DALZELL

Senior EditorFRANK DIAMOND

Senior Science EditorPAULA SIROIS

Senior Contributing EditorPATRICK MULLEN

Contributing editorsto this supplementANNE OSTROFF

AL LIEBSON

Design DirectorPHILIP DENLINGER

Editorial Advisory Board ChairmanALAN L. HILLMAN, MD, MBASenior FellowCenter for Health PolicyLeonard Davis Institute

of Health EconomicsUniversity of Pennsylvania, Philadelphia

PublisherTIMOTHY P. SEARCH, RPH

Director, New Product DevelopmentTIMOTHY J. STEZZI

Eastern Sales ManagerSCOTT MACDONALD

Senior Account ManagerBLAKE REBISZ

Midwest Sales ManagerTERRY HICKS

Director of Production ServicesWANETA PEART

MANAGED CARE (ISSN 1062-3388) is published monthlyby MediMedia USA, Inc. at 780 Township Line Road,Yard-ley, PA 19067. This is Volume 12, Issue 7. Periodicalpostage paid at Morrisville, Pa., and at additional mailingoffices. POSTMASTER: Send address changes to MAN-AGED CARE, 780 Township Line Road,Yardley, PA 19067.Prices: $10 per copy, $93 per year in the USA; $120 peryear elsewhere. Letters to the editor may be edited forlength and clarity. E-mail: [email protected]: (267) 685-2788; fax (267) 685-2966; circulation in-quiries (267) 685-2782. Copyright ©2003 MediMedia USA.

CareM A N A G E D

CareINTRODUCTION

MARK ZITTER, MBACEO, The Zitter Group

Depression is a common, costly, and chronic problem for af-fected individuals as well as for employers, the health care pro-fession, insurers, and other major stakeholders. Depression —

and its frequent concomitant disorder, anxiety — is an inherentlycomplex issue made all the more difficult by nonparity of mentalhealth benefits, social stigma, underdiagnosis, undertreatment, poorpatient compliance with medication regimens, and significant asso-ciated morbidity and mortality.

To discuss and debate ways in which unnecessary suffering can bereduced and avoidable morbidity and mortality decreased, membersof the Economic Working Group attended the second national ad-visory board meeting last March, in Scottsdale, Ariz. The group in-cludes advisers from every major discipline in managed markets:employers, managed care behavioral health specialists, primary carephysicians, quality assurance professionals, psychiatrists, pharmacydirectors, researchers, and insurers. Advisers with this breadth ofprofessional diversity and expertise contributed generously to dis-cussions on which this proceedings publication is based. The uniqueperspectives of these advisers are captured in display quotes through-out this publication.

From the employer viewpoint, we heard presentations by AnnetteBoyer, RPh, principal for Mercer Human Resource Consulting, andWayne Lednar, MD, PhD, vice president and director for CorporateMedical, Eastman Kodak Co. These presentations provided insightinto employers’ difficulties in sustaining profitability amid an in-creasingly challenging business environment.

Bob Binder from the GlaxoSmithKline Employer Group Segmentpresented a portfolio of tools developed by GSK to address employerconcerns and issues surrounding depression in the workplace.

A panel discussion provided a forum for three distinct voices: Ben-jamin Druss, MD, a quality-assurance professional; Larry Pesko, MS,ScD, RPh, a managed care pharmacy director; and David V. Sheehan,MD, MBA, a practicing psychiatrist. Each presented a unique per-spective regarding optimal treatment of patients with depression.

An economic analysis of patterns of antidepressant use and relatedcosts was presented by Tim Regan, RPh, CPh, and Thomas Bramley,RPh, PhD, from Applied Health Outcomes. Compelling evidence re-garding the excess cost associated with an antidepressant therapeu-tic regimen of fewer than 90 days, or an augment/switch scenario, wasdocumented with findings from a national database of 57 managedcare plans covering 33 million lives.

Sheehan concluded the weekend’s presentations with a review ofdata on controlled- versus immediate-release selective serotonin re-uptake inhibitors, their differing effects on adverse events and toler-ability, and how they influence length of therapy and patient out-comes.

PHOTOGRAPHS BY DENNY COLLINS

CareM A N A G E D

CareS U P P L E M E N T T O

July 2003

This MANAGED CARE supplement is supported by an unrestricted educational grant from GlaxoSmithKline.The material in this supplement has been independently peer reviewed.The reviewer has declared no conflicts of interest vis-à-vis the sponsor or this program.The sponsorplayed no role in the selection of the reviewer.

The opinions expressed herein are those of the Economic Working Group and do not necessarilyreflect the views of GlaxoSmithKline,The Zitter Group, MediMedia USA, Inc., or the publisher, editor,or editorial board of MANAGED CARE.

Clinical judgment must guide each clinician in weighing the benefits of treatment against the riskof toxicity. Dosages, indications, and methods of use for products referred to in this special supple-ment may reflect the clinical experience of the authors or may reflect the professional literature orother clinical sources and may not necessarily be the same as indicated on the approved packageinsert. Please consult the complete prescribing information on any products mentioned in thisspecial supplement before administering.

Seeking a Balance: Weighing the Clinical and Economic Factorsof Depression and Anxiety Management in Patient Outcomes

Proceedings of the Economic Working Group Advisory Board, March 2003, Scottsdale, Ariz.

Health Care Benefits in the 21st Century:What Employers Are Facing; How They Are Responding ...........................3ANNETTE BOYER, RPH

Mental Health Support Needs: The Employer Perspective in Optimizing Clinical and Economic Outcomes............................................8WAYNE M. LEDNAR, MD, PHD

MindSET: Tools to Implement a Behavioral Health Initiative in the Workplace ........................................11BOB BINDER

PANEL DISCUSSIONDoes HEDIS Affect Compliance,Length of Therapy, or Outcomes? .....................................................................13BENJAMIN DRUSS, MD; LARRY PESKO, MS, SCD, RPH; AND DAVID V. SHEEHAN, MD, MBA

An Economic Analysis of SSRI Length of Therapy .......................................20THOMAS BRAMLEY, RPH, PHD, AND TIM REGAN, RPH, CPH

Improved SSRI Tolerability and Increased Length of Therapy..................23DAVID V. SHEEHAN, MD, MBA

ABOUT THIS PUBLICATION

The objective of this supplement is to explore theperspectives of a host of professionals concerned

with treatment outcomes for patients with depression.To meet this objective, a diverse group of advisers wasassembled to present, debate, and exchange view-points on the clinical and economic consequences ofdepression.This group of professionals, with expertisein psychiatry, managed behavioral health, HEDIS, re-search, pharmacy, the employer segment, and primarycare, discussed the inherent conflicts among variousmarket segments — health plans, employers, practi-tioners, and the quality management arena.

Advisers explored how depression and anxiety aremanaged in the United States.When asked,“What is theone most pressing problem in managing depressionand anxiety” in their organizations, one third of advisersidentified the primary care physicians’ suboptimal man-agement of the disease; one third expressed concernover employers’ willingness to pay for quality outcomesin the treatment of patients with depression; and thelast third were split evenly on lack of patient compli-ance and total cost of treatment.

Advisers challenged each other on what constitutesappropriate length of therapy and reviewed nationaldata on health plan performance on the HEDIS anti-depressant medication management measures. Eco-nomic analyses repeatedly supported the overall costeffectiveness of a longer course of therapy.

Because funding comes from two major sources —the government and private employers — cost of careand the role that cost should play in making formularydecisions were examined from several key positions.

Advisers debated the importance of patient compli-ance and discussed strategies to optimize the pharma-ceutical regimen. Participants admitted that although itis easy to talk about what should be happening in thetreatment of patients with depression, the realities ofthe situation in health care today merit an informedmultidisciplinary discussion.This was the intent of theEconomic Working Group Advisory Board meeting thatwas facilitated by The Zitter Group. Because the focuswas on the treatment of depression and anxiety from apharmaceutical and medical perspective, other impor-tant treatment modalities, such as psychotherapy, werenot discussed in depth.The articles in this supplementare not intended to serve as a blueprint for the fullrange of treatment options available to clinicians.

PRIMARY FACULTYAnnette Boyer, RPh

PrincipalMercer Human Resource Consulting

Thomas Bramley, RPh, PhDConsultant/Health EconomistApplied Health Outcomes

Benjamin Druss, MDRosalynn Carter Chair in Mental HealthAssociate Professor of Public Health and PsychiatryRollins School of Public Health, Emory University

Wayne M. Lednar, MD, PhDVice President and Director, Corporate MedicalEastman Kodak Company

Larry Pesko, MS, ScD, RPhVice President, PharmacyLovelace Health Systems

Tim Regan, RPh, CPhSenior ManagerApplied Health Outcomes

David V. Sheehan, MD, MBAProfessor of PsychiatryUniversity of South Florida College of Medicine

Mark Zitter, MBACEOThe Zitter Group

SUPPORTING FACULTYBob Binder

Executive Account Manager, Employer TeamGlaxoSmithKline

DISCLOSURE OF SIGNIFICANT RELATIONSHIPSDavid V. Sheehan, MD, MBA, acknowledges grant and

research support from GlaxoSmithKline, as well as anadvisory and speakers bureau relationship with GlaxoSmithKline.

Tim S. Regan, RPh, CPh, acknowledges grant and re-search support from GlaxoSmithKline, as well as an ad-visory relationship with GlaxoSmithKline.

Thomas Bramley, RPh, PhD, acknowledges an advi-sory and consultant relationship with GlaxoSmithKline.

Sabah Chammas, MD, acknowledges an advisory andspeakers bureau relationship with GlaxoSmithKline.

Stacey Brennan, MD, acknowledges an advisory andspeakers bureau relationship with GlaxoSmithKline.

The following individuals acknowledge an advisoryrelationship with GlaxoSmithKline: Jonathon Book, MD;Wayne M. Lednar, MD, PhD; Larry Pesko, MS, ScD, RPh;and John Williams, MD.

The development of this supplement was supportedby GlaxoSmithKline, sponsor of the advisory boardmeeting from which the content was derived.

This supplement has undergone appropriate peer re-view by a qualified physician expert in mental health,selected by MANAGED CARE.

The content of this supplement was prepared fromthe transcripts of the Economic Working Group Advi-sory Board by Susan Keller, Senior Associate,The ZitterGroup.

2 MANAGED CARE / SUPPLEMENT

SUPPLEMENT / MANAGED CARE 3

Aslowing economy and a demand for increasedworkforce performance in the presence of re-duced staffing levels have resulted in significant

challenges for business today. High medical inflationadds to those challenges, making profitability for someemployers a daunting goal. Steeply rising medical costsresult from a number of factors, not the least of whichare an entitlement mentality and consumer demand forlife-enhancing services, new technologies,and emerging drug therapies.Another fac-tor contributing to medical inflation isthe rising average age of the labor forcewith its concomitant increase in rates ofhealth risks, such as stress, obesity, highblood pressure, and even poor self-care.Aging baby boomers have had a measur-able effect on the cost of health care. Forinstance, the average per-member, per-month (PMPM) cost of prescription drugsfor employees in their 20s is just over $100;in contrast, PMPM pharmacy costs are$442 for employees in their 40s and $992for employees in their 60s (AdvancePCSBenefits Barometer 2002). Consequently,employers are focusing closely on the costramifications of an aging workforce and the increasinguse of pharmaceutical products. Employer data indicatethat pharmaceutical use and cost increases are frequentlyassociated with gastric disorders, depression, and car-diovascular disease, conditions that are fairly common inthe baby boomer age group.

Because HMOs, with controls and access limitationsin place, have not consistently saved employers’ healthcare dollars, as was initially hoped, there has been a largemigration to nongatekeeper PPO products in the past fewyears. Significant industry consolidation has resulted inless bargaining power for employers. Rising medical costs— from 14 to 20 percent — have caused cost-shifting,whereby employees and unions have less negotiatingpower than they had previously to mitigate such trends.Pharmacy continues to be viewed by employers as a cost-

cutting target and is blamed for spikes in health care ex-penditures. Among employers, there is a heightenedscrutiny relative to drug utilization, particularly with re-gard to specialty or new drugs — including new genericdrugs — and of the movement from use of prescriptiondrugs to utilization of over-the-counter formulations.

Quantifying the rising cost trendMercer Human Resource Consulting

conducts one of the largest comprehensiveannual health-benefit surveys in the Uni-ted States. The Mercer National Survey ofEmployer-Sponsored Health Plans exam-ines cost trends and cost-management ini-tiatives regarding pharmacy and medicalbenefits among employers with 500 ormore workers. As illustrated in Figure 1,pharmacy benefit cost increases have beenin the double digits for the past severalyears, naturally a big concern for employ-ers. This is a manifestation of many com-plex and intertwined factors, includingincreased product costs and, especially,higher utilization. In 2001 and 2002, thepharmacy benefit trend decreased slightly;

that, however, was mainly because of cost shifting, the ad-dition of three-tier copayments, and the adoption of ag-gressive pharmacy-management strategies.

The issue of greatest concern here to employers is thatof rising pharmacy and medical expenditures. To furtherconfound the issue, the two cost centers are still in silos,or separated, within many organizations; overall, there-fore, it can be difficult for providers or insurers to demon-strate medical savings with increased pharmaceuticalexpenditure. Yet it also must be remembered thatpharmaceutical products represent approximately 15 to25 percent of the entire health care expenditure; directmedical expenses, about 75 to 85 percent. Therefore, thesame percentage increase in the medical benefit is actu-ally 3 to more than 5 times greater than the same increasein the pharmacy benefit.

FACULTY PRESENTATION

Health Care Benefits in the 21st Century:What Employers Are Facing;How They Are RespondingANNETTE BOYER, RPH

Mercer Human Resource Consulting

A N N E T T E B O Y E R , R P H

What influences employers’ decisions?

In the presence of escalatingcosts, employers must act. A num-ber of factors influence their re-sponses, including:

• Attitudes and beliefs• Data and evidence• Internal and external

influencers

Many employers believe thatpharmacy benefit costs are drivenby price increases from pharma-ceutical manufacturers and the in-creased use of new drugs as a resultof pharmaceutical marketing.They believe that new drugs areoverpriced and overutilized and that benefits derivedfrom drugs are often exaggerated. In reality, the data show

that about half of the rise in the drug trend is a direct re-sult of simple increased utilization of pharmaceuticalproducts, which is, in part, a reflection of pharmaceuti-cal agents used as first-line therapy and the use of moredrugs due to the increased age of the workforce. Unfor-tunately, much of the available data are summarized byprice and clinical-use markers and are not expressed inbusiness terms that employers can readily understand. Toconfound the problem, there is a dearth of good studieson pharmaceutical use and its effect on workforce health.

Influencers in employer decision making are both in-ternal and external to the organization. Internally, inmost organizations, human resources benefit managersare the primary points of contact. However, in large cor-porations with multiple work sites, a medical directorworking with a human resources group is also a promi-nent model. Unions have some influence, as do employ-ees. In general, chief financial officers and chief executiveofficers are less involved with employee health benefit de-cisions, but, depending on the size of the employer, dif-ferent mixed models exist.

Benefit consultants play a key role, educating em-ployers about trends and helping them to develop strat-egy. Another growth area includes business leaders,groups, and coalitions. For example, there is an emerg-ing trend for midsized employers to purchase pharmacybenefit services as a collective. Last year, three such col-lectives were developed solely to examine pharmacy pur-chasing. The question is: As these collectives get largerand more numerous, how much influence will they haveover formulary and health management decisions?

Employer actions to manage the pharmacy benefit

Employers are acting on several fronts to control thepharmacy benefit cost. These initiatives include membercost sharing, enhanced clinical management, and con-trolling pharmaceutical access; member cost sharing hasbeen the number one area that employers have focusedon over the past few years. Copayments are the most

common form of cost sharing; the majority of growth hasbeen in the three-tier copayment plan design (Table 1).As opposed to the copayment design, in which the em-ployee pays a fixed-dollar amount for a prescription, thenew dialogue is focused on coinsurance, where the em-ployee pays a percentage (generally around 20 percent)of the actual cost of the prescription. Employers thatwant employees to have more at stake financially are

FIGURE 1 Health benefit cost trends

Average annual cost increases for employers

SOURCE: MERCER/FOSTER HIGGINS NATIONAL SURVEY OF EMPLOYER-SPONSORED HEALTH PLANS, 2002


“Large employers with medical directors onstaff may have a clinical and a quality orienta-tion. They’ll be looking for the best way to bringall the data streams together to make rational decisions on quality. Many other employers,staffed with only a purchasing agent, are focused solely on cost and cost reductions.”

— WAYNE M. LEDNAR, MD, PHD

“At what point do you see a significant decreasein compliance when you drive up copaymentsor coinsurance? I believe I’ve seen data thatsuggest drop-off in the $30 range.”

— SCOTT SPROULL

Prescription drugsMedical benefits

1997

11.0%

0.4%

13.8%

5.7%

16.9%

7.0%

18.3%

6.6%

17.8%

12.1%

16.9%

14.7%

20%

15%

10%

5%

0%1998 1999 2000 2001 2002


slowly changing copayment plans into coinsurance de-signs.

Employers have yet to look closely at the relationshipbetween copayments and compliance with therapy;presently, they are focused on the percentage of the phar-macy benefit that they support. Currently, an 80/20 splitis still the most common. With some of the movementto the three-tier plan designs, however, and with new re-strictions on formularies, a minority of employees aresharing up to 50 percent of the pharmacy cost. Intuitively,this is a concern because of the potential effect on com-pliance; nevertheless, there are no credible studies avail-able to quantify the relationship.

Carve out or carve in?Nearly 70 percent of large em-

ployers carve out behavioral healthbenefits. The issue is one of inte-gration, particularly when thepharmacy benefit is also carvedout, which is true for about onethird of all large employers. Anemerging and promising trendamong a handful of large organi-zations is that when they are se-lecting a pharmacy benefit man-ager, a minimum requirement isthat the PBM provide data back toa data integrator. Even with dataintegration, there is virtually nostudy to show that carving out

these benefits actually saves money for the employer.The carve-out trend is a reflection of the cyclical natureof employer purchasing habits. There are 3- to 4-year pe-riods during which self-insured employers question howthe health plan is managing the benefit, so they carve outthe benefit. Then they become dissatisfied with how thePBM is managing, and they go back to a carved-in modelwith the health plan. The trend is now toward consider-ation of carve-ins.

The slight reduction in increases in the pharmacybenefit from a high of 18.3 percent in 2000 to 16.9 per-cent in 2002 was caused partially by employers’ adoptionof more aggressive clinical management programs, such

TABLE 1 Employer actions to manage the prescription drug benefit

Member cost share

Most prevalent plan designs Average copayments

Card Mail order Card Mail orderplans plans plans plans

No cost share 0% 2% – –Coinsurance 10% 5% – –Copayment 90% 93% – –Single copayment 5% 8% _ _Two-tier copayment 31% 31% $8/$18 $11/$24Three-tier copayment 51% 51% $10/$19/$35 $14/$27/$49

SOURCE: MERCER/FOSTER HIGGINS NATIONAL SURVEY OF EMPLOYER-SPONSORED HEALTH PLANS, 2002

FIGURE 2 Employer actions to manage the prescription drug benefit

Enhanced clinical management

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

199619982001

SOURCE: LILLY TAKEDA BENEFIT SURVEY

Drug utiliza-tion review

Formulary Priorauthorization

Therapeuticsubstitution

Manageddrug limits

Steptherapy

Doseoptimization

as managed drug limits, step therapy, and dosage opti-mization. Figure 2 illustrates various employer actions tomanage the pharmacy benefit clinically and the relativeprevalence of these initiatives.

Control of pharmaceutical access is yet another strat-egy utilized by employers to manage the pharmacy ben-efit. There are several major ways in which this happens:

• Exclusions of predefined discretionary drugs ordrug classes

• Approval of drugs for only certain indications• High copayments, delayed coverage, and/or

therapeutic class management

Utilization of any of these strategies does not meanthat employers are making formulary decisions, but thereare a number that make policy decisions. Particularlywithin the three-tier benefit, large organizations are start-ing to ask questions such as, “Does a drug or therapeu-tic class fit into the second tier or the third tier, and whateffect might that placement have on my workforce?”These are the types of questions on which clinical ben-efit consultants advise and assist benefit managers inthinking through the issues from a workplace perspec-tive. This type of interaction is new and emergent and isbeing reinforced particularly as new pharmaceuticalproducts are being launched.

Cost of workplace depressionAffecting 10 percent of the workforce in any given

year, depression is one issue that is brought to employ-ers’ attention through briefing papers from consultingfirms. In the United States, the annual cost associatedwith depression is $44 billion, much of which resultsfrom lost productivity. Expressed differently, that is 175million lost workdays and a high rate of short disability.When employers see statistics such as these, their inter-est is piqued, and they may begin to pay attention to op-portunities for managing depression better within theirwork forces.

Direct and indirect costs also can be expressed on an

average per-capita basis; the percentage of employeeswho miss workdays because of a variety of commonconditions is well established in the literature. Statisticssuch as those in Table 2 can be used as benchmarks tohelp employers understand how their organization com-pares nationally.

Productivity, although more difficult to measure, isalso of interest to employers. Models developed by Mer-cer and others suggest that it can be in the economic in-terest of the employer to allow a higher priced pharma-ceutical product on formulary to avert possible side effectsassociated with less costly drugs or over-the-counter prod-ucts. Side effects, such as drowsiness or lack of concentra-tion, although difficult to measure, are inherently associ-ated with a negative effect on productivity.

Employers yet to adopt DMMost employers with fewer than 20,000 employees

still do not offer disease management programs forarthritis, back pain, cancer, hypertension, depression, orother common conditions. About 25 percent of themmight offer disease management through their healthplans, but very few are offered through an independentvendor. This lack of disease management is a concern be-cause effective programs provide patient managementopportunities, education, follow-up, and integrated in-formation that all can be acted upon to improve both


TABLE 2 The national economic burden of five chronic conditions

Workers Estimated Total costsAverage with condition work loss for persons

per-capita missing costs with conditionhealth cost work days (in billions) (in billions)

Mood disorders $4,328 18% $11.5 $66.4Diabetes $5,646 10% $3.5 $57.6Cardiac disease $10,823 37% $3.8 $42.4Hypertension $4,073 8% $11.5 $121.8Asthma $2,779 20% $3.4 $31.2

SOURCE: DRUSS 2001

“Health plans realize that the majority of theirdepressed members are being treating in pri-mary care, in which the plan is bearing the cost.Nonetheless, they’ve carved out behavioralhealth care, and are questioning the incremen-tal value of providing additional disease man-agement specific to depression. Frankly, theyask us why the carved-out behavioral healthcompanies aren’t providing more disease man-agement to primary care physicians.”

— JOHN WILLIAMS, MD

clinical and economic outcomes. Yet, what employershave been focused on during the last couple of years arebenefit design, vendor selection, and vendor consolida-tion, all higher-level concerns that demonstrate a morerapid payback, in comparison with the specifics of dis-ease management.

Although employers understand that depression is animportant area of focus for both clinical and economicreasons, there are disconnections from and barriers to ap-propriate treatment. These include the following:

• Only one-third of individuals with a behavioralhealth problem seek care.

• Because of the stigma of mental illness, employeesdo not want their employers to know that they aredepressed.

• There is a lack of care coordination for patientswith depression.

• Restrictive formularies can reduce access to, andavailability of, antidepressants.

• Education for employers, employees, and evenhealth care providers is lacking.

Nevertheless, credible solutions are available. Newdrug therapies have proven treatment-success rates, andmore than 80 percent of them result in fewer side effectsthan older medications. In addition, behavioral healthvendors have been able to demonstrate a solid return oninvestment when innovative integrated programs areimplemented. With measurable results such as these, adiscussion of best practices becomes imperative.

From an employer perspective, consideration is nowbeing given to an in-network benefit with liberal or no-visit/no-day limits on behavioral health benefits. In aperfect world, physical health benefits on copaymentsand deductibles would be in parity with behavioral healthbenefits. Streamlined administration and performance-based contracting between employers and MCOs wouldfurther ensure quality of care. From a health-managementperspective, health promotion, member outreach, earlydetection and intervention, as well as primary care physi-

cian guidelines and care coordination are goals to inte-grate into current treatment programs. Unfortunately, anumber of employers are not yet thinking in these terms.

Results of early identification and intervention

When forward-thinking employers did implement adepression management initiative, they saw a decrease inshort-term disability and an increase in productivity,and this was important to them. The depression initia-tive also resulted in a 17 percent drop in office visits. Inaddition, for each $1 spent on depression treatment,there was a $3.50 savings on medical treatment. Thistype of health information — expressed in businessterms — really means something to the employer. Mea-surable results help employers see the benefit of early in-tervention, adequate identification and treatment, andthe link with improved economic outcomes. The con-tinuing challenge is to make this clinical/business link tolarge and small employers alike.

ReferenceAdvancePCS Benefits Barometer 2002. Irving, Texas: AdvancePCS.

Available at: «http://www.advancepcs.com/images/uploads/16.pdf». Accessed June 23, 2003.

Druss BG, Marcus SC, Olfson M, et al. Comparing the national eco-nomic burden of five chronic conditions. Health Aff. 2001;20(6):233–241.

“This meeting is a microcosm of what needs tohappen in a more formal, systematized way. Weneed to have a structured, ongoing dialogue be-tween the people who gather the data and thepurchasers, the people who are the end-users ofthose data. Perhaps what’s needed is a fair bro-ker, a consultant, who would use an employer’sown data, which they would trust, to commu-nicate the benefits of varying modes of treat-ment.” — BENJAMIN DRUSS, MD


From an employer’s perspective, how does a businessget better at managing disease — both clinicallyand economically — other than by focusing solely

on cost, with a goal of reduced spending? Depression andanxiety are extremely relevant issues for employers. Yet,companies such as Kodak are in the business of captur-ing and using images; health care is not a core compe-tency. Increasingly, many businesses are realizing thatthey need the help of all their partners toimprove management of disease, enhanceemployees’ quality of life, reduce — or atleast manage — costs, and sustain pro-ductivity at high levels.

Why anxiety and depression areimportant issues for business

Many businesses, even smaller ones, arebecoming increasingly global. They areno longer “mom-and-pop” operations insingle communities. Frequently, peoplewho work together serve on global vir-tual teams and have never met. Focusedon a business need or product develop-ment, they are in different countriesaround the world and bring to the projectdiverse cultural issues, backgrounds, andlanguages that might clash, especially when pressuresbuild and/or pace accelerates.

Work systems are changing. Companies are trying tomake systems more efficient with fewer resources and lessstaffing. With fewer people, everyone has to performmultiple tasks simultaneously and accomplish more.Most businesspersons carry a pager or cell phone, whichis rarely turned off, keeping them still “at work” even ifthey are not at their desks. Working in an office buildingfor a company is becoming a thing of the past. Withtheir laptops, people are working in airport lounges andout of the front seats of their cars. Employees are work-ing faster and longer, in spite of the fact that the work-force is older. The average age of the Kodak workforce isnow 46. In other industries, the average age can be years

older. A kind of relentless demand is being seen in the21st century that is becoming characteristic of manybusinesses, and in combination with family responsibil-ities, it produces a significant psychological burden onemployees as well as increasing rates of anxiety and de-pression.

Profitability is a key issue for companies today, becausefor every employee, a company must generate enough

cash to pay its costs and then have re-maining capital to return to sharehold-ers. In addition, for every employee, theremust be enough profitability to cover thehealth insurance costs of that employee,his or her family members, and the re-tirees for whom businesses carry financialresponsibilities. For Kodak, that is fivepeople for every single employee. Kodakhas two retirees for every active employee;General Motors has three, and in somecases, pays first-dollar coverage based onunion-negotiated agreements. Thus, em-ployers have a significant challenge, notonly to reduce costs but to improve thequality of care that employees and theirfamilies receive.

Managers and executives constitute aspecial group, because if they do not perform well or ifthey make poor or delayed business decisions, the con-sequences are enormous and unforgiving. Regardless ofa sagging global economy, managers are still expected tohave high-performance business outcomes. In addition,these workers typically are hypercompetitive, are drivento succeed, and perceive that they must be invincible,even though they are hurting inside. They frequentlyfeel an imbalance between their work and other aspectsof their lives, with work always taking precedence andrepresenting a continual source of demand and stress.

At Kodak, the worldwide goal is to have healthy em-ployees who are safe and productive, working where theydo not get hurt and where they can use their skills andtalents in an effective and sustainable way. This has be-


Mental Health Support Needs:The Employer’s Perspective in Optimizing Clinical and Economic OutcomesWAYNE M. LEDNAR, MD, PHDVice President and Director, Corporate Medical, Eastman Kodak Co.

W A Y N E M . L E D N A R ,M D , P H D


come a central statement that helps Kodak leaders judgewhat they should do to make certain that they create thiskind of environment, whether the workforce is age 50, age20 and mostly female, or decentralized.

“With good care, patients live longer and miti-gate the impact of comorbid conditions longer.One might make a compelling argument thathigh-quality care actually results in reducedoverall costs.” — JEFF WEILBURG, MD

Major drivers of absenteeismTable 1 lists a prioritization of reasons for absenteeism

that is derived from Kodak’s data, rather than the pub-lished literature. These are physician-diagnosed absencesof a calendar week or more, not 1- or 2-day absences fromcolds or flu. The population comprises all U.S. Kodak em-ployees. The real usefulness of this list of causes for em-ployee health-related absenteeism is that it puts psychi-atric issues on the map for business management.

For several years, mental health-related absences haveescalated in terms of prioritization and with respect toabsolute number of workdays lost. For example, in 1996,mental health-related absences were ranked seventh,with more than 5,000 workdays lost. In 2001, these ab-sences were ranked second in frequency, with more than13,000 workdays lost. To underscore this trend, thesedata do not capture the contribution of depression oranxiety as an associated comorbid condition; these areonly workdays missed because of a primary diagnosis ofanxiety, depression, and so forth. In addition, the popu-lation in 1996 consisted of an employee base of about50,000, in comparison with 28,000 in 2001. Thus, the de-nominator, representing the population, is decreasing,whereas the numerator, or the number of lost workdays,is increasing. Clearly, the current business environmentis contributing to a portion of the burden of morbiditythat is reflected in this trend.

Costs: direct and more directAlthough direct costs typically are defined as expendi-

tures for medical treatment, employers view indirect costs— overtime, the need for contract labor, missed productlaunches, defects, waste, lost sales, etc. — as very direct.

“I believe employers are looking for data thatsupport the concept that if you spend more andtreat the right patients with the right medi-cations, they get better and go back to work. Inother words, optimal timely treatment has anoverall positive impact on cost structure.”

— JOHN WILLIAMS, MD

Table 2 summarizes 2002 expense ratios for total medi-cal and pharmacy claims in the United States for Kodakemployees who are younger than 65, the employees’ fam-ily members, retirees who have not yet reached the agefor Medicare eligibility, and their family members. Thesimple message is that people spend more on medicaltreatment than on pharmaceutical products.

For example, for neoplasms, spending on medical careis nearly 5 times that for prescription drugs. Conversely,in behavioral health, there is a greater commonality indollars. Therefore, prioritizing spending in the absenceof prescription drug information would not result insignificant attention to psychiatric issues.Yet, the need ishigh. Looked at differently, a low expense ratio could beconstrued as an advantage, which illustrates that medicalcosts are reduced when patients with psychiatric disor-ders are adequately treated with medication.

Employers’ needs in behavioral health disease management

Employers offer health benefits to secure high-quality,cost-effective care for their employees. In return, they an-ticipate increased profitability from having healthier em-

TABLE 1 Causes of health-related absenteeism (≥7 or days in duration), 2002

1. Musculoskeletal disorders2. Injury3. Psychiatric disorders (including alcohol and

substance abuse)4. Circulatory disorders5. Neoplasms6. Digestive disorders7. Maternity leave8 Respiratory disorders

SOURCE: KODAK 2002

TABLE 2 Ratio of medical-treatmentclaims costs (inpatient and outpatient) to drug-treatmentcosts

Disorder type Ratio

Circulatory disorders 2.8Digestive tract disorders 2.2Musculoskeletal disorders 3.0Neoplasms 4.8Psychiatric disorders 1.3Respiratory tract disorders 2.8Endocrine, metabolic disorders 2.1

SOURCE: KODAK 2002


oriented system, the structure to support repeatedpatient counseling is not evident.

• Faced with an immediate pressure to reduce cost,employers have still not accepted that high-qualitycare is more cost effective. With credible data todemonstrate this, it is likely that employers will beresponsive to this fact. In business, good data drivegood decision making.

Early treatment: imperativeFirst and foremost, treatment of depression and anx-

iety needs to improve for the patient. In the absence ofan accurate diagnosis and good therapy, prolonged mor-bidity and disability will be the result. There will be un-necessary employer expense, absenteeism, and reducedproductivity. Exhaustion of the sick benefit can result inloss of employment. Improperly treated depression andanxiety can cause escalating social margination at homeas well as at work.

Early detection and intervention are appropriate rolesfor the employer and the work group. Supervisors gen-erally know their team members well and can be trainedto recognize signs of distress and constructively respondto them with help for the employee. Employers mustendorse a workplace in which people care about eachother and are prepared to offer support when needed.

“It seems there are models, such as EAPs [Em-ployee Assistance Programs], that would im-prove the treatment of depression; increaseawareness in the workplace; and get people ap-propriately screened, assessed, and referred intotreatment. In treating substance abuse, the EAPindustry is ahead of the rest of health care.”

— JONATHON BOOK, MD

To be accountable and active partners in decisionmaking, patients need information on cost as well as onexpected clinical outcomes. They must be made aware ofthe downside of noncompliance and that they, too, areresponsible for the success of their therapy. Employers,as well as patients, need to be very involved, in a way theynever have been before.

ReferenceEastman Kodak Co. Data on file.

ployees. Therefore, to the extent that treatment goals areexpressed only in medical terms, the employer’s needs arenot being fully met. Employers need to have the end re-sult of any initiative expressed in business terms thatthey can both understand and evaluate. Some of theseterms are: the return to work, for active employees; thereturn to school, for children; the return to independentliving, for retirees; and functional outcomes. Diseasemanagement goals, when expressed in these terms, areenforceable and understandable to employers.

“Within controlled population studies, we havebegun to see that if you treat people correctlyimmediately upon diagnosis, it may cost a greatdeal of money the first year. After the initialspike, however, cost for treatment — regardlessof diagnosis — falls and remains fairly con-stant. So, I believe that good care does savemoney, and the data to support that assertionare credible and growing.”

— LARRY PESKO, MS, SCD, RPH

In addition to treatment goals that lack functionalrelevance, there are several other practices in behavioralhealth that are of concern to employers. These include thefollowing:

• Most decisions are made by primary care physi-cians, who spend an average of 7 minutes of “face”time with each patient per visit.

• In a system in which specialization is highly en-dorsed, the patient’s benefits are frequently “carvedup,” and pharmacy benefit managers are not com-municating with behavioral health specialists, whoare not communicating with disease managementvendors, who are not communicating back to thehealth plan or the employer.

• Delayed interventions lead to unnecessary adverseclinical outcomes.

• There is inadequate use of evidence-based guide-lines.

• Reliance on medical claims data alone does notprovide adequate information for informed deci-sion making.

• Prescriptions are being written with little evidencethat counseling is occurring. Because the U.S. healthcare system is an acute-presentation, complaint-



At GlaxoSmithKline (GSK), the Employer GroupSegment works with national and major regionalemployers, unions, coalitions, and trust funds

with 50,000 employees or more. Unions alone represent16 million people. Eight account managers are dedicatedto building relationships and bringing awareness of men-tal health issues to this significant business segment. Theneeds of smaller employers also are taken into account.To effectively reach them, GSK has three additional ac-count managers that work solely with business coali-tions that represent 11,000 various employers and 33million employees within the United States.

By strengthening employer relationships across a spec-trum of work sites, the Employer Group Segment strives:

• To understand employer issues and concerns• To assist in measuring disease costs and drivers• To establish demonstration programs for optimum

health outcomes• To justify a balanced approach to employee health

care purchasing and management

A number of tools have been developed to accomplishthese tasks. For example, the MindSET program collec-tion is specific to mental health, particularly depressionand related anxiety disorders. The GSK Web site containsMindSET materials that employers can download andcustomize. Additional National Committee for QualityAssurance certified disease management programs arealso available through GSK’s Web site as part of this em-ployer initiative. With groups such as Tower Perrin, theGSK Employer Group Segment has created and refinedactuarial tools that can be utilized within employer seg-ments to understand the impact of depression and anx-iety on a particular business. Demonstration projectsare in place to test many of these tools.

The goal of MindSET is to measure costs associatedwith illness; for example, the program shows how absen-teeism affects a particular marketplace and demonstratesthe areas in which those costs might be reduced. Mind-SET can also be used to plan and implement behavioral

health interventions in the workplace. Utilization ofMindSET increases awareness of behavioral health is-sues, assists in Health Insurance Portability andAccountability Act-compliant screening to identifybehavioral health disorders, and promotes the use of be-havioral health benefits. MindSET consists of two fun-damental components: a Workplace Kit and an EconomicBurden of Depression in the Workplace Actuarial Model.

MindSET in the workplaceThe MindSET kit contains step-by-step implementa-

tion instructions on how to assess organizational needs,communicate with health plans, and arrange and im-plement a behavioral health initiative. Among other aids,the kit contains a PowerPoint presentation for a “Lunchand Learn” program and a variety of promotional ma-terials and tips to assist a local health coordinator to setup a health fair within the work site. Fact sheets andbrochures educate employers and employees about be-havioral health disorders and where to go for help.

Economic burden of depression in the workplace actuarial model

This actuarial model — developed in conjunctionwith Towers Perrin — evaluates an employer’s data toproduce a detailed, economic picture of the impact of de-pression in a particular workplace. It allows managed careorganizations and employers to estimate the direct medi-cal costs, as well as lost productivity costs, of depressionand related comorbid conditions, and then to assess theeconomic impact of treatment. The figure on the fol-lowing page represents data from an actual employerwith nearly 22,000 employees.

Demographically, the female-to-male ratio is ex-tremely close. In our sample, 1,360 employees have re-ceived diagnoses of depression and have been treatedaccordingly. In this output of the model, differentialcosts for the employees with depression versus thosewithout are broken down by category: lost productivity,prescription costs, and direct medical costs. The differ-ence is nearly $1,000 per employee. In the aggregate,


MindSET: Tools to Implement A Behavioral Health InitiativeIn the WorkplaceBOB BINDER

Executive Account Manager, Employer Team, GlaxoSmithKline

In addition, GSK has the abilityto perform outreach and to pro-vide education for communityphysicians, within the network, tomeet specific employer needs.

ConclusionMost employers are not so-

phisticated when it comes tohealth care issues: General Mo-tors spends its time concentrat-ing on cars; McDonald’s, mostlyon hamburgers. Corporationsthat are savvy about health careare the exception, not the rule.

First, it can be difficult to im-press on employers that doing“the right thing,” in terms of de-pression disease management, notonly is good for their employeesbut also is prudent from their owneconomic standpoint.

Second, there are some inher-ent conflicts between employers

and managed care, specifically in terms of how the twoentities view costs. Indirect costs that affect the em-ployer, such as absenteeism or presenteeism (when anemployee is in attendance but is either offering little orno value or, in fact, is having a negative effect on qual-ity or on the performance of others because of some im-pairment, such as illness, medication side effect, lack ofsleep, or substance abuse) are not normally consideredby the provider or health plan. That inherent conflict issomething to resolve, and the employer must be awareof this conflict with any of the plans and programs justdescribed.

Finally, some employers have expressed concern thatif they implement these projects, they will identify addi-tional people with untreated depression. Although theybelieve an accurate diagnosis is appropriate, they areconcerned that the added treatment burden will furtherescalate costs. What the Towers Perrin model demon-strates, however, is that if patients with depression aretreated adequately, they become a more economically at-tractive group, from a productivity and absenteeism per-spective, than those not treated at all.

ReferenceGlaxoSmithKline. Data on file.

based on the model’s calculations, this employer incurs$9,407,128 per year in incremental costs from depression,with 28,163 workdays lost. The potentially surprisingnews here is that this situation is not unusual, and em-ployers need to take action and use nonbranded modelssuch as these to help determine the exact impact of de-pression within their environments. Both the MindSETtools and the actuarial model are specifically designed tohelp employers reduce the impact of depression in agiven organization.

What employers can doEmployers are encouraged to implement a compre-

hensive depression management program. This entails:

• Initiation of stress management and depressioneducation programs to increase disease awarenessamong employees

• Education of supervisors to recognize the signs andsymptoms of depression

• Encouragement of employees to contact trainedemployee assistance program personnel for referralsfor diagnosis and treatment

• Ensuring that depression identification and educa-tion are integral parts of every health care initiative


Example: an average employer

Effect of depression on lost productivity, prescription costs,and direct medical costs:

Demographics:• 10,000 employees• 11,800 dependents• 21,800 covered lives total• 52:48 female-to-male ratio• Average employee age: 39• Average salary: $37,489• 1,360 employees with

depression• Copayments represent

typical cost-sharing provisions

Lost productivity

Prescription costs

Direct medical costs

Employeeswith depression

Employeeswithout depression

$941difference

$772

$294$163

$316

$1,713

$608

$320

$785

SOURCE: GLAXOSMITHKLINE


Depression increases morbidity, mortalityDepression complicates the prognosis for individuals

who suffer from comorbid conditions, such as coronaryartery disease, diabetes mellitus, stroke, and cancer(Takeshita 2002). Depression also creates an increasedrisk for development of those diseases among otherwisehealthy individuals.

In a study to examine the effect of depression on de-velopment of coronary heart disease (CHD) and its se-quelae, researchers found that men and women withprior depression had an increased risk of developingCHD: Adjusted odds ratios for CHD were 1.73 for de-pressed women and 1.71 for depressed men. Depressionalso increased the risk of mortality from CHD in men(Ferketich 2000).

Penninx (2001) found that the risk for cardiac mor-tality among persons with and without cardiac diseasewas significantly elevated among individuals with majorand even minor depression: Adjusted odds ratios forcardiac mortality (95 percent confidence interval) were

PANEL DISCUSSION

Does HEDIS Affect Compliance,Length of Therapy, or Outcomes?Panelists:

DAVID V. SHEEHAN, MD, MBA Professor of Psychiatry, University of South Florida College of Medicine

LARRY PESKO, MS, SCD, RPHVice President, Pharmacy, Lovelace Health Systems

BENJAMIN DRUSS, MDRosalynn Carter Chair in Mental Health and Associate Professor of Public Health and Psychiatry, Rollins School of Public Health, Emory University

The key issue of length of therapy isthe foundation of the three HealthPlan Employer Data and Informa-

tion Set (HEDIS) measures for anti-depressant medication management. Pa-tient compliance has a direct bearing onlength of therapy, which has a direct bear-ing on outcomes. The challenge is toimprove patient compliance with anti-depressant therapy. The picture is compli-cated by the fact that providers have dif-fering opinions and understandings of theHEDIS measures: Some consider them tobe a minimum requirement, whereas oth-ers think of them as the optimal goal oftherapy. Consequently, patients are beingtaken off therapy at the 6-month mark by physicians whoassume that this is what the HEDIS metric specifies.

This confusion has been the seed for development ofthe following presentations, which focus on the ramifi-cations of length of antidepressant therapy vis-à-vis theHEDIS metrics. The three participants are David Shee-han, MD, MBA, speaking as a “prolifically prescribing”psychiatrist; Larry Pesko, MS, ScD, RPh, as a “tightwad”managed care pharmacy director; and Benjamin Druss,MD, as a “bureaucratic” quality assurance professional.

VIEW OF A PRACTICING PSYCHIATRISTDavid V. Sheehan, MD, MBA

Depression has a profound effect on a spectrum of is-sues, including comorbid and chronic medical condi-tions; workplace productivity; risk of suicide; and cost toindividuals, health care providers, and society. The goalsof therapy for depression are remission, recovery, and re-lapse prevention. Each of these major aspects of thetreatment of depression is discussed in turn.

From left: Larry Pesko, David Sheehan, Benjamin Druss

3.0 for patients who suffer frommajor depression and 1.6 for thosewith minor depression.

Depression and suicideIn another study, Isacsson

(1996) used a large data set fromthe Swedish National Data Centerand examined suicide rates in de-pressed individuals who were ei-ther treated with antidepressantsor not treated. The treated popu-lation numbered approximately40,000, and the untreated popula-tion numbered 85,000. The calcu-lated risk for suicide in treated pa-tients with depression was 141 per100,000 person years; in the un-treated population, the risk was259 per 100,000 person years, or1.8 times higher. The authors con-cluded that antidepressants couldeffectively reduce the risk of suicide among depressed pa-tients.Yet, at that time, only 1 in 5 persons with major de-pression was treated with an antidepressant. Increasingthe use of these medications has had a reductive effect onsuicide rates in Sweden.

Depression and resource utilization for chronic medical conditions

As illustrated in Figure 1, the presence of depressionsignificantly increases expenditures among patients withcommon chronic medical conditions such as back pain,diabetes, headache/migraine, and heart failure. Thesedata are from the OCI1 database and include almost250,000 people (OCI 2001).

Katon (1990) administered the National Institute ofMental Health Diagnostic Interview Survey,Version 3A,to 119 patients who used health care resources extensively(so-called high utilizers of health care). Their findings in-clude the following: 70 percent had a lifetime history ofmajor depression; 23 percent, panic disorder; more than40 percent, generalized anxiety disorder; 24 percent,somatization disorder; and 25 percent, alcohol abuseand dependence. Katon concluded that high utilizerswith a psychiatric diagnosis represented a major costdriver — not of psychiatric overutilization but of generalmedical overutilization (Figure 2).

High cost of suboptimal treatmentIn a study published in 1996, Thompson evaluated

patterns of antidepressant use and their relationship tocost of care. Cumulative charges included costs for drugs,physician visits, hospital outpatient care, and hospital in-patient care. Patterns of antidepressant use were definedas early discontinuation (fewer than 60 days); switching/augmentation, or partial compliance (60 to 90 days);and more than 90 days of use. The early discontinuationgroup, which included patients who received 60 days orfewer of treatment with an antidepressant over a 12-month interval, incurred total overall costs of $5,610. Incontrast, those who were treated for more than 90 days,who were considered compliant and received at least 90days of therapy with their initial selective serotonin re-uptake inhibitor (no switching/augmentation), had thelowest overall mean cost, $3,393, over the 12-monthfollow-up period (Thompson 1996).

This study confirms the counterintuitive notion thatthere are higher overall health care costs for those takingmedications for a shorter time. The expectation might bethat there are higher costs among patients consumingmore medication, yet the inverse is true. The longer a pa-tient is taking medication, the lower the aggregate costsbecome.

Economic trendApplied Health Outcomes (AHO) corroborated

Thompson’s results using the TennCare Data Set. Thesedata cover 1.4 million lives and approximately 22,000 pa-tients taking antidepressants. AHO looked at the totalamount billed by month in a 12-month period, begin-ning with the initiation of an antidepressant course oftherapy (Figure 3).

This data set illustrates stabilization of charges after 6


FIGURE 1 Depression impact on total medical costs*

* ANNUAL MEDICAL COSTS PER PATIENT, BASED ON CLAIMS DATA FOR 229,776 PATIENTS, 1995–1998.

SOURCE: OCI 2001

$3,562

$5,881

$5,045

$7,913

$3,555

$5,571

$11,804

$14,942

Back pain

↑↑65%

↑↑ = % increase w/ depression

With depression

Without depression

↑↑57%

↑↑57%

↑↑27%

Diabetes

Headache

Migraine

1 OCI is an application service provider that owns thelargest private collection of integrated health benefits andrisk-management data.


months. Comparing the sixthmonth with the first, we can cal-culate a reduction of 15.9 percentin costs. At 6 months, however, aphysician might get a letter from the managed care company reit-erating that Agency for HealthcareResearch and Quality (AHRQ)guidelines recommend that pa-tients with depression be treatedfor 6 months. The implication ofthe letter is clear: A patient whohas been treated for 6 monthsshould discontinue the medi-cation. So what does the physiciando? He or she might discontinuethe patient’s therapy due to con-cern that his or her prescribingpatterns are being scrutinized,with possible personal financialrepercussions. If discontinuationoccurs, what are the likely scenar-ios? To determine the outcome ofdiscontinuation versus continua-tion of treatment, Geddes (2003)researched relapse prevention andexplored optimal length of ther-apy for antidepressants.

The Geddes studyTo determine long-term anti-

depressant treatment outcomes,data were collected from 31 ran-domized trials involving 4,410subjects. The patients, who hadresponded to acute treatment,were treated largely in 8-week tri-als and then were assigned to acontinuation treatment phase, in-tended to prevent relapse. At dis-continuation, whether it was at 6months, 1 year, or 2 years, patientswere monitored for at least 1 ad-ditional month. In view of the brevity of the follow-upperiod, this is a best-case outcome scenario. Had fol-low-up been longer, extrapolated to 2, 3, 4, 5, or 12months, the outcomes might have been worse, becausethey would include the people who suffered relapse dur-ing the more-extended time frame.

Geddes (2003) found, however, that continuing treat-ment with antidepressant medication reduced the oddsof relapse by 70 percent, in comparison with patients whodiscontinued therapy or who were given placebo. Onaverage, across all the data, 41 percent of patients takingplacebo suffered relapse, in comparison with 18 percent

taking antidepressants. In other words, the absolute riskof relapse is high when antidepressants are discontinued.

In reference to the stabilization of costs graph, this canmean that after 6 months, if a patient discontinues med-ications, there may be relapse within 1 or 2 months and,from an economic perspective, the patient is going tostart back at week 1 with exaggerated costs. If physiciansjust stay the course a bit longer and stabilize the patient,the frequency of visits to the psychiatrist or the primarycare physician actually decreases.

Geddes categorized patients into two primary groupsand two subsets of those groups. The primary group

FIGURE 3 Economic trend: ≥180 days of treatment

Total monthly amount billed

$600

$650

$700

$750

$800

$850

$900

1 2 3 4 5 6 7 8 9 10 11 12

SOURCE: APPLIED HEALTH OUTCOMES 2003

>180 days

Month

FIGURE 2 Lifetime mental disorders of distressed high utilizers of general medical care

N=119.

SOURCE: KATON 1990

Majordepression

Panicdisorder

Generalizedanxietydisorder

Somatizationdisorder

Alcoholabuse/

dependency

80

70

60

50

40

30

20

10

0

(%)

differentiation was based on either 1 or 2 years of treat-ment after randomization.Within these two groups, theyfurther distinguished patients on the basis of whetherthey had received 1 to 2 months or 4 to 6 months of treat-ment before the study. Geddes found that among patientswho had been treated for 2 years or more, those who hadundergone 1 to 2 months prior antidepressant treat-ment had a 33-percent rate of relapse during the trial,whereas those with 4 to 6 months of prior antidepressanttreatment had a 24-percent rate of relapse during thetrial. Rates of relapse for controls were 65 and 62 percent,respectively. Rates of relapse for patients with 1 year offollow-up were lower, as might be expected with a shorterperiod of observation.

The salient point here is the 9-percent difference (33versus 24 percent) in the rate of relapse between the twogroups treated for 2 years or more. This indicates that evena small difference in prior treatment has a positive effecton outcome. The overall message is that the longer pa-tients continue receiving treatment after an acute episodeof depression, the less likely they are to suffer relapse thanif they receive no appropriate treatment at all or if theydiscontinue their medication therapy after 12 months.

Getting patients into remissionThe goal of treatment of depression and anxiety dis-

orders is always remission, which is defined as 70 percentor more improvement according to a standardized in-strument. The definition of response is less precise. Insome of the published literature, response is defined as

34 percent or greater improvement; in other studies, it is50 percent improvement. Nevertheless, that is not goodenough and is the reason placebo “response rates”appearrobust. If the expectation for the outcome of active treat-ment is so poor, it is easy for a placebo to achieve whatappears to be a reasonable response.Yet, when standardsfor remission are set at 70 percent or more improve-ment, there is a significant difference between placeboand active treatment response rates. This concept isclearly illustrated in Figure 4, which shows placebo ver-sus active treatment with paroxetine during a 32-weekcourse of study among patients diagnosed with generalanxiety disorder.

Remission rates continue to increase throughout theentire length of the study, whereas rates among patientstaking placebo decline. At the end of 8 months of treat-ment, 70 percent of the patients experience 70 percent orbetter improvement, the previous definition of remis-sion. However, it takes an extended period of time to getthem to this level of improvement, and, of importance,remission can occur at any time (GlaxoSmithKline 2001).Therefore, patients must be maintained on treatmentfor a long period of time. The longer the treatment, thehigher is the likelihood of remission.

Rates of remission for patients with depression followa very similar pattern. For example, Thase found that in-complete remission is predictive of complete relapse. Heclassified patients into responders and “remitters” anddemonstrated that among remitters, the probability of re-maining symptom free was much higher. Patients who

were treated until they achievedremission had better outcomes atall time points than did those whowere not treated until they re-ceived remission; in addition, re-mitters were less likely to sufferrelapse (Thase 1992).

Recovery from major de-pression: 10-year follow-up

The longest study done by thefederal government on the ques-tion of recovery from major de-pression is the National Collabo-rative Depression Study, whichincludes a nationwide cohort ofpeople who received diagnoses ap-proximately 20 years ago with anindex episode of major depres-sion. The researchers assessed thecumulative probability of recov-ering from an index episode ofmajor depression. When re-searchers examined probability ofrecovery from a second, third,


FIGURE 4 Paroxetine long-term generalized anxiety disorder treatment

2 3 4 6 8 12Week

% o

f pat

ien

ts a

chie

vin

g re

mis

sio

n

16 20

**

*

** *

24 28 321

80

70

60

50

40

30

20

10

0

Phase 1: Single-blind

Paroxetine 20–50 mg(N=559 responders)

Randomization

Phase 2: Double-blind

Paroxetine (N=285)Placebo (N=274)

* p<.01 vs. placebo.Remission = Hamilton Anxiety Scale ≤7; last observed case forward data set.SOURCE: GLAXOSMITHKLINE


fourth, or even fifth episode, the proportion of patientswho recovered at any one point in time was similar to theothers. In addition, duration of recurrent major depres-sive episodes was relatively uniform, averaging approx-imately 20 weeks (Solomon 1997).

Recently, Keller (2002) assessed the cumulative prob-ability of recurrence after recovery from an episode of de-pression. He found that once a patient has experiencedthree episodes of depression, the probability that he orshe will suffer from another is 95 percent within 2 years.Because depression is a chronic illness, nearly everybodywho suffers an episode of major depression will eventu-ally experience another.

Therefore, the question is this: Why would any phar-macy benefits manager or any health plan assume thatpatients can discontinue antidepressant therapy and livehappily ever after, regardless of the HEDIS measures? Ar-bitrary discontinuation of medication is indefensible.There is no chronic disease in which a physician cantreat the condition, then stop the medication, and expectthe patient to live happily ever after. The data support-ing this conclusion are overwhelming.

VIEW OF A MANAGED CARE

PHARMACY DIRECTOR

Larry Pesko, MS, ScD, RPhMany of the studies in the literature are conducted

through the use of formal methods in sterile environ-ments that are removed from real-world practice. Thesestudies and clinical evaluations do not reflect the experi-ence or perspective of an integrated health system phar-macy director, a practicing clinician, or an average patient.

Bench research is well controlled, and investigatorsknow exactly what outcomes they are attempting to for-malize, but those outcomes frequently have little or noapplication to what goes on in the field. Field research,of course, is representative of what takes place in real life;however, in this type of research, it is very difficult to con-trol the variables. The following presentation is based onthe interface between some well-documented publishedliterature and how the results of those studies play out,or are interpreted, in a real-world scenario.

According to AHRQ statistics, the prevalence of majordepressive disorder ranges from 4.8 to 8.6 percent of thepopulation at any given time. These statistics, applied toa managed care plan that covers 250,000 lives, imply thatbetween 12,000 and 21,500 members will probably ex-perience some sort of major depressive disorder that ne-cessitates treatment, including treatment with anti-depression medications. To treat these health planmembers with major depressive disorder adequately, theAHRQ guideline on depression in primary care recom-mends that the acute treatment phase be of a sufficientlength to achieve remission of depressive symptoms, fol-

lowed by 4 to 9 months of chronic, or continuation,therapy to prevent recurrence.

The literature, however, supports the findings thatonly 40 to 70 percent of patients adhere to their anti-depressant drug regimen during the acute phase of ther-apy (Simon 1993) and that only 15 to 50 percent of pa-tients adhere to their antidepressant drug regimen duringthe continuation phase (Melfi 1998).

Economics of depression therapyTo put prevalence and adherence into economic terms,

the average cost to a health plan — after discounts — for1 year’s supply of antidepressant medication for one pa-tient is approximately $720. This amount is not an aver-age wholesale price or a fictitious number; it is based onreal-world data. When extrapolated to a health plan with250,000 members, the per-patient cost of antidepressanttherapy becomes an aggregate of about $6.7 million an-nually. These are real costs, fully discounted, for medi-cations only. Divided among all members of the healthplan, whether they have depression or not, this $6.7 mil-lion costs each member $26.80 annually.

These amounts are based on actual usage and are re-flected in the studies referenced previously. However, ifa health plan were to meet the current national guidelinesfor therapy, meaning that all patients with a diagnosis ofdepression would be given antidepressant medicationsand continue taking them for the acute and continuationphases of therapy, annual costs would rise to $53.60 foreach health plan member, double the current expense.

However focused a pharmacy director may be on costs,he or she will maintain that the most expensive drugs arethose that do not work or those that are not taken. Healthplans spend a great deal of money in treating depressedpatients, and yet outcomes remain inadequate. In manycases, less-than-optimal outcomes are a result of patientnoncompliance, defined as less than 75 percent of thecourse of therapy utilized within the period of timeunder consideration. If patients were compliant withevidence-based national recommendations on the opti-mal course of therapy, health plans would be far moresuccessful in lowering their overall medical costs, bene-fiting not only employers but also insurance companiesin terms of reduced medical expenses.

VIEW OF A QA EXPERTBenjamin Druss, MD

Making decisions about health care costs and qualityrelies on the use of data to the fullest extent possible andsimultaneously on the realization that all data have limit-ations. However imperfect, data form the basis of the fourcurrent guidelines on optimal length of antidepressanttherapy and were used in the development of all HEDISmeasures (Table 1 on page 18).

Despite having been developed almost a decade apart,all of these guidelines are actually quite similar. Theguideline that the National Committee for Quality As-surance, the authors of HEDIS, relied on most signifi-cantly — and the one most widely known — is that ofthe U.S. Agency for Health Care Policy and Research(AHCPR, now AHRQ) Depression Guideline in PrimaryCare. The AHCPR guideline recommends treatmentthroughout the acute phase, which is essentially the timeuntil remission of depressive symptoms. It further rec-ommends treatment during the continuation phase,which it defines as a second period lasting 4 to 9 months.Interestingly, all of these guidelines suggest discontinu-ing antidepressant therapy after the continuation pe-riod and then observing patients for recurrence of de-pressive symptoms. Maintenance therapy beyond thecontinuation period is recommended only for individ-uals at high risk, who are typically defined as patients whohave experienced recurrent depressions.

Recent literatureOne relevant and compelling look at the data can be

found in the article by Geddes (2003), referred to earlierby Sheehan.

Although Geddes addressed the benefits of antide-pressants in reducing the risk of relapse for at least 12months, the article does not make a strong recommen-dation to continue antidepressants after that period.Rather, it encourages clinicians to use their judgment inidentifying patients who seem to be at high risk, focus onthis subpopulation, and look into the issue of potentiallylowering the threshold for longer-term maintenancetreatment below that currently outlined in the four mainguidelines.

HEDIS antidepressant measuresThere are three evidence-based HEDIS antidepressant

measures. The first measure concerns the optimal num-ber of contacts that a depressed patient should have witha practitioner; the focus of this measure is the effectivemanagement of medications (see box, “Three HEDISAntidepressant Measures”). The second measure ad-

dresses the pattern of medication usage during the acutestage, or the first 3 months. With regard to this measure,there is broad consensus among practitioners. Accordingto the final measure, all adult members in whom a newepisode of depression is diagnosed should continue an-tidepressant therapy for a period of at least 6 months.This differs slightly from the AHCPR guideline that rec-ommends discontinuation of medication after 4 to 9months of continuation treatment: that is, treatmentafter remission of symptoms.

Health plan performance on HEDIS measuresRegardless of consensus on or clarity of the measures,

performance by participating HMOs is lackluster. Table2 summarizes 2002 performance data on the HEDIScontinuation phase measure. The HMOs that reportHEDIS data cover approximately 90 percent of the peo-ple in managed care plans in the United States; thus, re-sults can be considered representative of patterns of carenationwide among patients enrolled in commercial man-aged care plans.

Among plans that report performance on this mea-sure, less than 40 percent of people, on average, take anantidepressant throughout the 6-month continuationperiod. This is significant, because the guidelines rec-ommend that treatment continue throughout this phase.The debate arises with regard to the need for treatmentafter 6 months. Even in the highest-scoring plans — the75th percentile — less than 50 percent of patients whobegan taking a new antidepressant received the full 6months of treatment.

Another interesting fact about the HEDIS depressionmetrics is that their values are considerably lower thanoverall plan performance on the majority of other HEDISmeasures. For example, overall plan compliance withother general health metrics is approximately 60 percent,whereas depression compliance tends to be approxi-mately 40 to 50 percent.

As a wise man once said, “It’s better to light a candlethan to curse the darkness.” This aphorism can serve asa metaphor for the HEDIS measures. Before these mea-sures were developed in the late 1980s, health care prac-

titioners were indeed “fumblingaround in the dark” as far as mea-suring quality was concerned. Al-though HEDIS is still a work inprogress, it also can be viewed as avery viable attempt to balance datafrom research with measures thatcan and will be used in medicalpractice in the real world. Re-cently, a few major articles cri-tiquing HEDIS have been pub-lished. The authors of thesearticles have examined who actu-


TABLE 1 Guidelines for duration of medication use

Recommended continuation

Guideline Published period*

U.K. Defeat Depression Consensus 1992 4–6 monthsU.S. AHCPR Depression in Primary Care 1993 4–9 monthsAmerican Psychiatric Association 2000 4–5 monthsBritish Association for Psychopharmacology 2000 6 months

*All recommend maintenance therapy beyond this period only for individuals withrecurrent depression.


ally is complying with the mea-sures and whether clients are justdemanding the HEDIS data withlittle or no action being taken as aresult. Some of those criticismsare justified, but HEDIS is cer-tainly the best set of guidelinescurrently available, and it is farbetter than no attempt to measurequality at all. If there is no meansof measuring the quality of healthcare, all that can be determined iscost.

In summary, there seems to bea clear consensus among practi-tioners, as well as reports in theliterature such as Geddes’s study,that treatment should be main-tained through the acute phase(which is measured from remis-sion of symptoms) and then con-tinue for some time (typically atleast 6 months). There are ques-tions regarding the wisdom ofkeeping patients on antidepres-sant therapy after this continua-tion phase is complete. Geddes ad-vocated that more work be donein this area to evaluate the poten-tial benefits of continuing therapyafter that time. Finally, regardlessof whether patients need to con-tinue therapy after 6 months,health care providers certainlyhave to work hard just to achieve compliance in the acuteand continuation phases.

ReferencesApplied Health Outcomes. TennCare Length of Therapy validation

study. 2003. Data on file.Ferketich AK, Schwartzbaum JA, Frid DJ, et al. Depression as an an-

tecedent to heart disease among women and men in theNHANES I study. Arch Intern Med. 2000;160:1261–1268.

Geddes JR, Carney SM, Davies C, et al. Relapse prevention withantidepressant drug treatment in depressive disorders: asystematic review. Lancet. 2003;361:653–661.

GlaxoSmithKline. Data on file.Isacsson G, Bergman U, Rich CL. Epidemiological data suggest anti-

depressants reduce suicide risk among depressives. J AffectDisord. 1996;41:1–8.

Katon W,Von Korff M, Lin E, et al. Distressed high utilizers of medi-cal care. DSM-III-R diagnoses and treatment needs. Gen HospPsychiatry. 1990;12:355–362.

Keller MB. Rationale and options for the long-term treatment ofdepression. Hum Psychopharmacol. 2002;17(Suppl 1):S43–S46.

Melfi CA, Chawla AJ, Croghan TW, et al. The effects of adherenceto antidepressant treatment guidelines on relapse and recur-rence of depression. Arch Gen Psychiatry. 1998;55:1128–1132.

NCQA (National Committee for Quality Assurance). State ofHealth Care Quality, 2002.Available at: «http://www.ncqa.org/sohc2002». Accessed June 25, 2003.

NCQA. HEDIS 2003 Antidepressant Medication Measures. Wash-ington: NCQA.

OCI, Cheyenne, Wyo. Options and Choices Database, 2001.Penninx BW, Beekman AT, Honig A, et al. Depression and cardiac

mortality: results from a community-based longitudinal study.Arch Gen Psychiatry. 2001;58:221–227.

Simon GE, Von Korff M, Wagner EH, et al. Patterns of anti-depressant use in community practice. Gen Hosp Psychiatry.1993;15:399–408.

Solomon DA, Keller MB, Leon AC, et al. Recovery from major de-pression. A 10-year prospective follow-up across multipleepisodes. Arch Gen Psychiatry. 1997;54:1001–1006.

Takeshita J, Masaki K, Ahmed I, et al. Are depressive symptoms arisk factor for mortality in elderly Japanese American men?The Honolulu-Asia Aging Study. Am J Psychiatry. 2002;159:1127–1132.

Thase ME. Long-term treatments of recurrent depressive disorders.J Clin Psychiatry. 1992;53(Suppl):32–44.

Thompson D, Buesching D, Gregor KJ: Patterns of antidepressantuse and their relation to costs of care. Am J Managed Care.1996;2:1239–1246.

TABLE 2 Continuation measure: 2002 values for HMOs

% of members with a new episode of depression with at least 6 months of treatment

Health plan rank with antidepressant medications

25th percentile 33.7Median 39.675th percentile 46.0

SOURCE: NCQA 2002

Three HEDIS antidepressant measuresOptimal practitioner contacts for medication management. This issue

concerns the percentage of members age 18 and older as of the 120th day ofthe measurement year in whom a new episode of depression was diagnosed,who were treated with antidepressant medication, and who had at least threefollow-up contacts with a primary care practitioner or mental health practi-tioner during the 12-week acute phase. At least one of the three follow-up con-tacts must be with a prescribing practitioner (e.g., a licensed physician, a physi-cian assistant, or another practitioner with prescribing privileges).

Effective acute-phase treatment. This issue concerns the percentage ofmembers age 18 and older as of the 120th day of the measurement year inwhom a new episode of depression was diagnosed, who were treated with an-tidepressant medication, and who continued taking an antidepressant drugduring the entire 84-day (12-week) acute phase.

Effective continuation-phase treatment. This issue concerns the percent-age of members age 18 and older as of the 120th day of the measurement yearin whom a new episode of depression was diagnosed, who were treated withantidepressant medication, and who continued taking an antidepressant for atleast 180 days (6 months).

SOURCE: NCQA 2003

Two studies are presented here: the TennCare Data-base Study and a discontinuation analysis fromthe National Managed Care Database, managed by

Applied Health Outcomes and possibly the largestmanaged care data base on depression in the country.

The TennCare study was derived from a Tennesseemanaged Medicaid population of 1.4 million lives. Theobjectives for the study were to:

• Examine the relationship between length of therapyand total health care costs by using retrospectivemedical, behavioral health, and pharmacy claimsdata, and

• Evaluate the economic benefits of longer selectiveserotonin reuptake inhibitor (SSRI) antidepressanttherapy in a managed Medicaid population.

To quantify the economic burden of early discontin-uation, researchers in the TennCare Study modeled ele-ments of their methods after a study designed by Thomp-son (1996).

Thompson found that patients who were fully com-pliant and continued antidepressant therapy for 90 daysor longer had incurred $2,200 less in total annual healthcare costs than had patients who received therapy forfewer than 60 days. Thompson also found that the mostcostly cohort comprised patients with evidence of switch-ing or augmenting SSRI therapy ($7,590 annually). TheTennCare Study defined patient cohorts more broadly toinclude compliance with antidepressant therapy for fewerthan 90 days, 91 to 179 days, and more than 180 days —and examined the cost ramifications (Figure 1).

SSRI therapy in the TennCare population was dis-continued by 24 percent before 3 months and by 45 per-cent by 6 months. Only 34 percent of patients remainedcompliant and were still taking antidepressant therapymore than 180 days after the index prescription. Al-though the >180-day cohort and the augment/switchgroup had the highest monthly pharmacy charges —approximately $280 and $325, respectively — overallmedical charges for hospitalization, professional fees,physician visits, and outpatient care were lowest for the

>180-day cohort. Early discontinuation, therefore, is acostly issue from both an economic and a quality per-spective, inasmuch as persistency of antidepressant ther-apy is a HEDIS measure. The TennCare analysis also re-vealed that although costs do fluctuate during the first 6months of treatment for compliant patients, they stabi-lize at 6 to 7 months and remain stable at 12 months.With data such as these, the development of effective in-tervention strategies can begin to change inadequatepatterns of care and improve outcomes and costs in thetreatment of depression and anxiety.

Findings from the National Managed Care Database

One of the criticisms of the TennCare analysis was thatthe study population was not representative of thosefound in most managed care plans. To address that validconcern, a subsequent study was conducted with datafrom a much larger managed care population that in-cluded more than 33 million lives, 57 health plans, and750,000 patients receiving therapy with SSRIs (Bramley2003).

This geographically diverse study population isdeemed representative of national age and gender dis-tribution. Longitudinal integrated data, allowing for uti-lization and tracking of treatment patterns, were com-piled for analyses of time to discontinuation of therapy,cost of discontinuation, rates of discontinuation, andrates of switching and augmentation among patientstaking an immediate-release SSRI (Figure 2). A follow-up analysis was also conducted on discontinuation ratesof a controlled-release SSRI introduced after initial studycommencement.

Study inclusion criteriaAll subjects:• Were defined as “new starts,” which meant they had

taken no antidepressants for a 6-month period be-fore study enrollment

• Received a diagnosis of depression or anxiety; noother mental health disorders were included

• Were at least 18 years of age



An Economic Analysis of SSRI Length of TherapyTIM REGAN, RPH, CPH

THOMAS BRAMLEY, RPH, PHDApplied Health Outcomes

• Were continuously eligible for health plan mem-bership for 12 months after the index date

Among this national managed care population,discontinuation was defined as a medication treat-ment gap of 15 days or more. The two largest cohortswere the switch/augment group (34 percent) andthose who discontinued antidepressant therapy be-fore 60 days (30 percent). Among all the patients, in-cluding the switch/augment cohort, 72 percent ofpatients taking an immediate-release SSRI discon-tinued therapy before reaching the minimum 180days of treatment. Obviously, there is a problem withkeeping people on therapy, and it seems as though anumber of factors might influence that.

Medical cost by cohortNot surprisingly, total 6-month pharmacy costs for

all medications in addition to antidepressants werehighest for the >90-day cohort ($690) and lowest forthe <60-day cohort ($415). Switching/augmentingwas also in the upper range, at approximately $675for the 6-month follow-up period.

In terms of hospital costs incurred for any reason,a different picture emerges with regard to the >90-day cohort. In this case, their total 6-month hospi-tal costs are the lowest of all, at approximately $850,whereas the switch/augment cohort’s costs were thehighest, at $1,200. Therefore, hospital costs de-creased with persistency of SSRI therapy beyond 90days. In measuring total medical 6-month costs, theswitch/augment group was again the most costly, atjust over $1,700, and the >90-day cohort was the leastcostly, at less than $1,300.

Treatment patterns analysisThe initial study commenced Jan. 1, 2001, and a

treatment patterns analysis began April 1, 2002, co-inciding with the availability of the controlled-releaseSSRI antidepressant paroxetine.1 Two issues wereparticularly germane to this treatment patterns analy-sis: the effects of the controlled-release product onlength of therapy as well as on switching/augmentrates. The following analysis includes patients takingparoxetine (n=1,416) and patients taking immediate-release medications (n=45,128) over the same length oftime. The researchers found that throughout the studyperiod, 6 percent of patients taking paroxetine switchedor augmented therapy, compared to 11 percent of pa-tients taking an immediate-release product. This demon-strates a compelling 44 percent reduction in patientswho switched/augmented their SSRI therapy with parox-etine versus the immediate-release SSRIs.

A time-to-discontinuation analysis — illustrated inFigure 3, page 22 — evaluated the time between theindex date of April 1, 2002, and the discontinuation oftherapy, as defined by a gap of more than 15 days intherapy.

Beginning at 30 days, the discontinuation rate for pa-tients taking immediate-release SSRIs was 23 percenthigher than that for patients taking paroxetine.

One additional difference should be noted in study de-sign. The majority of manufacturers of immediate-release SSRIs participate in what are known as persis-


1 Throughout this article, “paroxetine” refers to Paxil CR.

FIGURE 1 TennCare sample distribution

Length of compliance with immediate-release SSRIs

FIGURE 2 MCO discontinuation and therapy-change rates

Time to discontinuation, immediate-release SSRIs

Augment/switch:21%

Switch/augment:34%

>180 days20%

90–179 days:11%

60–89days:5%

<60 days:30%

<90 days:24%

>180 days:34%

91–179 days:21%

SOURCE:THOMPSON 1996

SOURCE: BRAMLEY 2003

tency, or refill-reminder, programs with all the majorchain pharmacies, such as Eckerd, Rite-Aid, and Wal-greens. These programs would not, in all likelihood, af-fect switch/augment rates, but they do anecdotally havea rather significant effect on length of therapy. Theseprograms are designed so that after 30 days, if patientshave not filled their antidepressant prescriptions, they geta phone call from a pharmacist or a nurse. The caller ex-plains the importance of continuing to take the medica-tion and reiterates the reason it was prescribed initially.The caller encourages patients to refill their prescriptions,and, as a result, refill rates are extremely high, some-times doubling the expected length of therapy. Duringthe study period, however, paroxetine was not part of anysuch refill-reminder program. In view of this informa-tion, the 23 percent lower rate of discontinuing paroxe-tine not only is statistically significant but also may trans-late into even greater reductions in the future in

comparison with the immediate-release SSRIs.

The conclusion from this studyreinforces data from Thompsonand TennCare: approximately 50percent of patients who receivedimmediate-release SSRIs discon-tinued therapy within 90 days.

When people cannot continue on therapy for longerthan 90 days, or when they augment or switch, an eco-nomic penalty emerges. Conversely, as length of therapyincreases, there is evidence of decreased medical utiliza-tion. Patients taking paroxetine appear less likely tochange therapies and have greater persistency with ther-apy. This trend of better persistence is a viable proxy forimproved economic and clinical outcomes.

ReferencesBramley T, Eaddy M, Mauch B, Regan T. Treatment patterns and

time to treatment discontinuation with antidepressants: com-parison of a controlled-release formulation of paroxetine andimmediate-release selective serotonin reuptake inhibitors.Presentation to the Economic Working Group AdvisoryBoard, Phoenix, March 2003.

Thompson D, Buesching D, Gregor KJ. Patterns of antidepressantuse and their relation to costs of care. Am J Managed Care.1996;2:1239–1246.


FIGURE 3 Time-to-discontinuation analysis

Patients taking controlled-release paroxetine were 23% less likely to discontinue therapy (p=.0006). Index date: April 1, 2002.

“In psychiatry, there arecase management programsbeing developed. One thathas proved to be extremelyuseful is called the AssertiveCommunity Treatment forSchizophrenic Patients. Pro-grams such as these shouldbe considered as one of thesolutions for antidepressantnoncompliance as well.”

— SABAH CHAMMAS, MD

1 5 9 13 17 21 25 29 33 37 41 45 49 53 57 61 65 69 73 77 81 85 89 93 97 101 105 109 113 1170%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Immediate-release SSRIs (n=42,127)

Controlled-release paroxetine (n=1,190)

SOURCE: BRAMLEY 2003Days

Co

nti

nu

atio

n o

f th

erap

y

As anyone with a background in business wellknows, it is far more cost effective to retain an ex-isting customer than to secure a new one. The

same maxim can be translated into pre-scribed pharmaceuticals. For example, Lin(1995) studied Medicaid patients whowere prescribed antidepressants (selectiveserotonin reuptake inhibitors [SSRIs], tri-cyclic antidepressants [TCAs], and oth-ers) and determined their dropout ratesover a 6-month period. Lin found thatapproximately 28 percent of patients hadstopped taking their medications by week4, and 43 percent had stopped by week 9.At the end of 6 months, only 21.7 percentof patients were still taking their indexmedications. These are not isolated find-ings: Lin’s results (Figure 1) have beenreplicated by other researchers.

Dropout rates were slightly higher withthe tricyclic antidepressants than with the SSRIs, butoverall rates were cause for concern, particularly becausea great number of these patientsshould be taking antidepressantsover long periods. A practitioneror health care administratormight reasonably ask, “What isthe point of investing in depres-sion disease management pro-grams and prescribing medica-tions to patients if the majoritywill be noncompliant?”

To improve patient outcomes,the dropout rate must be re-duced and patient compliancewith length of therapy must beincreased. Given that patientsstop complying largely becauseof adverse side effects, a key char-acteristic for a new SSRI formu-lation became increased tolera-bility and reduced adverseeffects, especially nausea. This

led to the application of the Geomatrix technology.The Geomatrix technology provides a delivery system

that controls the amount, timing, and location of drugrelease; it has been favorably tolerated bypatients, and the rate of dropouts due toadverse effects is low in comparison withthat of dropout with placebo. The con-trolled-release (CR) paroxetine tablet hastwo basic components: the outer entericfilm-coated layer of the tablet, which con-sists of a degradable barrier, and the innerlayer, which contains the active drug. Thedegradable polymeric matrix controls thedissolution rate of paroxetine over a pe-riod of approximately 4 to 5 hours. Datasuggest that this unique pharmacokineticprofile has demonstrated benefits in termsof patient tolerability and reduced patientdropout rates. Once ingested, the CRparoxetine tablet travels down the diges-

tive tract to the stomach, where the active drug is pro-tected from degradation by the enteric coating, thus al-



Improved Tolerability And Increased Length of TherapyDAVID V. SHEEHAN, MD, MBAUniversity of South Florida College of Medicine

FIGURE 1 Compliance

High dropout rates undermine treatment success

ANTIDEPRESSANTS INCLUDE SSRIs,TCAs, AND “ATYPICALS”(N=46).SOURCE: LIN 1995

In a study of Medicaid patients prescribed antidepressants,21.7% remained on treatment for an adequate term of 6 months.

Week 4 Week 8 Week 12

High rate of early dropout antidepressant therapy in clinical practice

43%dropout

52%dropout

28%dropout

60

50

40

30

20

10

0

% o

f pat

ien

ts

D A V I D V. S H E E H A N ,M D , M B A

lowing absorption of the drug farther down in the smallintestine and reducing the nausea.

Adverse eventsThere are a number of pooled analyses with the CR

paroxetine: four in depression, three in panic disorder,

and one recently in social anxietydisorder. Others are still under in-vestigation. Figure 2 represents asummary of some of those data. Intreatment-emergent nausea, thereis an initial rise in the percentageof patients experiencing this ad-verse event and then a gradual de-cline until week 12, when virtuallyall cohorts report the same lowrate of nausea.

Overall rates of dropout due toadverse events in the pooled de-pression trials are illustrated inFigure 3. For placebo, dropout ratewas 5.8 percent; for CR paroxe-tine, 9.8 percent; and for immedi-ate-release (IR) paroxetine, 16.2percent. Those differences are sta-tistically significant, with a 40 per-cent reduction in dropout rate ofCR paroxetine in comparison withthe IR formulation.

Because depression has a 10percent prevalence in the popula-tion, a reduction in dropoutsamong this many people trans-lates into a much more favorableprofile in terms of compliance andlength of therapy.

EfficacyIn addition to greater tolerability, CR paroxetine seems

to provide efficacy equal to or greater than that of IRparoxetine, as measured by the Hamilton Depression(HAM-D) Rating Scale. A HAM-D score of 7 or less in-dicates remission, which is approximately equivalent to


FIGURE 2 Treatment-emergent nausea

* p<.05 CR VS. PAROXETINE.SOURCE: GLAXOSMITHKLINE

% o

f pat

ien

ts

FIGURE 3 Overall dropouts due to adverse events

* p=.0008 PAROXETINE VS. PLACEBO.SOURCE: GLAXOSMITHKLINE

“I would say, ‘Get it right thefirst time.’ Cost is probablynot the number one issuewith physicians. So, consid-ering that they are troubledby a large percentage of pa-tients coming back to thembecause they are having anadverse effect, if the prescrip-tion is the right one the firsttime, that will decrease thephysicians’ workloads andmake life simpler.”

— DENNIS GLICK, MD

1 2 3 4 120

5

10

15

20

25

30

35

40

45

50

14

23

4

10

15

47

9

3

7 6

2 2 1 2

0

2

4

6

8

10

12

14

16

18

5.8

9.8

16.2

Paroxetine CR

Paroxetine

Placebo

Placebo Paroxetine CR Paroxetine

*

% d

rop

ou

ts d

ue

to a

dve

rse

even

ts

*

an improvement of 70 percent ormore. Figure 4 illustrates statisti-cally significant results among co-horts of patients receiving CRparoxetine, IR paroxetine, orplacebo.

The observed (OC) cohort isobserved cases: that is, results frompatients who actually attended ateach visit. A last observation car-ried forward (LOCF) analysis in-cludes all patients who were randomly assigned to treat-ment and who returned for at least one on-treatmentvisit. For any patient who drops out of treatment ormisses a visit, his or her last observation is carried for-ward. In this way, all patients who took the effectivetreatment, including dropouts, are included in the finalanalysis. This is the most conservative analysis that canbe done in a clinical trial. It represents a worst-case sce-nario.

Weight gainAnother area of clinical interest in the treatment of de-

pression is weight change. The standard measure ofmeaningful weight change is an increase or decrease inbody weight by greater than 7 percent from baseline,which is, on average, equivalent to about a 10-pound

change in weight. With CR paroxetine, slightly morepeople lost 10 pounds than gained 10 pounds. In con-trast, data on the IR formulation indicate that more pa-tients gained than lost weight. This difference was not sta-tistically significant, but the study was not powered todetect weight shift. Some patients may favor CR over IRparoxetine for this reason.

In summary, the importance of patient compliancewith therapy cannot be overstated. Any formulation thatimproves compliance and increases length of antide-pressant therapy, resulting in overall lower utilization ofhealth care, should be carefully considered. An improvedadverse-event profile that translates into significantly re-duced dropout rates has a potentially enormous effectwhen extrapolated to the millions of sufferers of chronicdepression.

ReferencesGlaxoSmithKline, data on file.Lin EH, Von Korff M, Katon W, et al. The role of the primary care

physician in patients’ adherence to antidepressant therapy.Med Care. 1995;33(1):67–74.


FIGURE 4 Hamilton depression scale remission

Percentage of patients achieving Hamilton depression score ≤7

*p<.05 CR VS. PLACEBO.SOURCE: GLAXOSMITHKLINE

“There are good research data available in thepast few years that challenge the conventionalwisdom of starting with what appears to be anequally efficacious but lower-cost drug as first-line therapy. More and more data are showingclearly that starting with the best therapy firstfor a particular disease — whether surgery orpharmaceutical therapy — is less costly acrossall the conditions that the patient has.”

— BERNARD BLOOM, PHD

“When patients discontinueuse of one drug, typicallythey do not begin the seconddrug the next day. In fact,there’s an intermediate pe-riod of time when they areprobably untreated and cango into a clinical deteriora-tion, from which it is harderfor them to recover.”— WAYNE LEDNAR, MD, PHD

0

10

20

30

40

50

60 5653

44 45

3734

Paroxetine CR

Paroxetine

Placebo

*

Observed cohort Last observation carried forward

*

SUPPLEMENT TO CareCare · 2019-12-18 · Care M A N A G E D SUPPLEMENT TO July 2003 This MANAGED...

Documents

Transcript of SUPPLEMENT TO CareCare · 2019-12-18 · Care M A N A G E D SUPPLEMENT TO July 2003 This MANAGED...