To assess the benefit of sibutramine hydrochloride monohydrate within a weight management program. 

Prospective randomized controlled trial in a health maintenance organization. 

Obese patients (n = 588) starting a weight management program were enrolled. Patients were randomly assigned to participate in the program alone or to participate in the program and receive sibutramine for 12 months. Outcome measures were change in weight, body mass index (BMI), percentage body fat, serum lipids, serum glucose, and blood pressure. 

At baseline, there was a younger age and higher weight, BMI, and waist circumference in the drug group. There was more degenerative joint disease in the nondrug group. The mean weight loss at 6 months was 6.8 kg (95% confidence interval [CI], &#8722;7.4 to &#8722;6.1 kg) in the drug group vs 3.1 kg (95% CI, &#8722;3.8 to &#8722;2.4 kg) (P < .001) in the nondrug group. Weight loss was maintained at 12 months. Significant reductions in BMI, body fat, and waist circumference occurred in the drug group. There were no significant changes in laboratory values or blood pressure. Patients taking sibutramine experienced a significant increase in heart rate (1.7 beats/min [95% CI, 0.5â€“2.9 beats/min] vs &#8722;0.4 beats/min [95% CI, &#8722;1.5 to 0.8 beats/min]; P <.004). 

In this managed care setting, the effectiveness and safety of sibutramine were similar to those observed in randomized, doubleâ€“blind clinical efficacy trials. 

(Am J Manag Care. 2004;10:369â€“376)

The prevalence of overweight (body mass index [BMI], calculated as weight in kilograms divided by the square of height in meters, &#8805;25) and obese (BMI, &#8805;30) adults in the United States continues to increase. The most recent data from the continuous National Health and Nutrition Examination Survey show a significant increase in the age—adjusted prevalence of obesity (22.9% in National Health and Nutrition Examination Survey III [1988—1994], increasing to 30.5% in 1999—2000). This surveillance also showed a significant increase in the prevalence of overweight (55.9% in National Health and Nutrition Examination Survey III, compared with 64.5% in 1999—2000).

Obesity is associated with significant costs and comorbidities.

In 1995, the total costs of obesity were estimated at $95 billion.

Obesity is a major risk factor for comorbidities, including hypertension, hypercholesterolemia, type 2 diabetes mellitus, coronary artery disease, stroke, gallbladder disease, musculoskeletal disorders, certain cancers, as well as all—cause mortality.

In managed care, health plan members are similar to the general population with regard to obesity and its attendant comorbidities. For example, unpublished data from Kaiser Permanente of Colorado suggest that about 22% of the adult health plan members are obese (J.A.M.). 

Sibutramine hydrochloride monohydrate (Meridia, Abbott Laboratories, Inc) inhibits norepinephrine and serotonin reuptake, resulting in enhanced satiety and weight loss. In animals, the drug also increases thermogenesis through central activation of efferent sympathetic activity.

The efficacy of sibutramine in inducing and maintaining weight loss has been established for up to 2 years in randomized, double—blind, placebo—controlled studies.

 (USPSTF) has recently published evidence—based recommendations for screening and interventions for obesity in adults. These recommendations state that obese individuals should be offered a program that includes intensive counseling and behavior interventions to promote sustained weight loss. The USPSTF also recommends that pharmacologic agents should be used in conjunction with a program that includes significant lifestyle modification. The principal objective of our study was to determine the clinical effectiveness of sibutramine in the setting of a weight management program in a managed care environment. 

This prospective, randomized, controlled trial involved obese patients enrolled in the Kaiser Permanente Weight Management Program (KPWMP). Enrollment occurred from January 1999 through June 2000. Eligible patients were 18 years of age or older, willing to enroll in the KPWMP, willing and able to give informed consent, and had a BMI of 30 or higher. Patients with a BMI of 27 to 29.9 were eligible for enrollment only if they had 1 or more of the following comorbidities: diabetes mellitus with or without drug therapy, hypertension treated with drug therapy, or hyperlipidemia treated with drug therapy. 

Patients were excluded from the study if they had taken a prescription weight loss agent within 6 months; had a history of coronary artery disease, congestive heart failure, cardiac arrhythmia, or stroke; had uncontrolled hypertension (mean blood pressure [BP] >145/95 mm Hg, or isolated mean systolic BP [SBP] >160 mm Hg with diastolic BP [DBP] <95 mm Hg, or isolated mean DBP >95 mm Hg with SBP <145 mm Hg); a mean resting heart rate of greater than 100 beats/min (bpm); or 1 of the contraindications to sibutramine listed in the product labeling. Other exclusions included narrow—angle glaucoma, severe renal impairment (creatinine clearance, &#8804;30 mL/min [&#8804;0.50 mL/s]), severe hepatic dysfunction (liver function test results, &#8805;3 times the upper limit of normal), obesity of organic origin (eg, untreated or uncontrolled hypothyroidism), seizures, other medical conditions that placed them at increased medical risk by participating in the study (as determined by the study physician), previous participation in this study, participation in KPWMP or any of the required American Heart Association (AHA) classes within the past 6 months, and inability to read English. Patients were excluded if they were pregnant, planning a pregnancy during the study, or breast—feeding. Finally, patients were also excluded if they were taking any of the following medications: selective serotonin reuptake inhibitors, St John's wort, sumatriptan succinate or related agents, ergotamine tartrate, lithium, fentanyl citrate, pentazocine, meperidine hydrochloride, dextromethorphan, tryptophan, and cisapride. 

The study was reviewed and approved by the Kaiser Foundation Research Institute Institutional Review Board. All patients provided written informed consent before study enrollment. 

On enrollment in the KPWMP, patients were invited to participate in the study. Patients were randomized to receive sibutramine or no drug therapy, but all patients participated in the KPWMP. The KPWMP is a physiciansupervised, multidisciplinary program. Patients paid $100 for the program consisting of 5 monitored-care visits with a prevention specialist (served as study coordinators) and 2 weight management seminars chosen from a menu of 20 seminars. Study data collection was coordinated with the monitored care visits. All study patients also participated in 20 weeks of educational programs offered by the AHA. The Point of Change disease management program (program name is now Meridia Milestones, Abbott Laboratories, Inc) was available to patients taking sibutramine. 

Patients had financial commitments to participate in the study. Participants paid for the AHA classes ($140) and the KPWMP ($100). Participants who completed 6 months of the study received a $50 gift check. Those patients who completed 12 months of the study received an additional $100 gift check. Patients randomized to sibutramine paid retail price for the drug and were later reimbursed for 75% of the cost on presentation of the receipt. 

Randomization to drug or nondrug treatment arms was completed using a computer—generated random numbers table. Study assignments were placed in envelopes that were opened at the end of the baseline visit by the study coordinator. Patients and investigators were aware of study group assignment. 

Study visits for all patients occurred at baseline and at 3, 6, 9, and 12 months. At study visits, demographics, weight, height, body fat, BP, heart rate, and waist and hip circumference were collected. Weight was measured (and BMI calculated) using the Tanita TBF—305 (Tanita Corporation of America, Inc, Arlington Heights, Ill) bioelectrical impedance technology body fat analyzer. Percentage body fat was measured by the FUTREX—5000 (FUTREX, Inc, Gaithersburg, Md), which uses near infrared light technology. Vital signs were measured after the patient had been sitting for 5 minutes. Blood pressure and heart rate were measured twice at 2—minute intervals and averaged. Baseline laboratories included fasting glucose and fasting lipid profile. Hemoglobin A

 levels were obtained in patients with diabetes mellitus. Laboratory evaluations were repeated at 6 and 12 months. As part of standard care, the Zung Self—Rating Depression Scale was used to screen patients for depression.

Patients randomized to receive sibutramine received a physical examination by a KPWMP physician at baseline and then received a prescription for 10 mg of sibutramine to be taken once daily. These patients had a safety visit at 4 weeks to check vital signs and weight. If 4 pounds (1.8 kg) were not lost in the first 4 weeks, the dosage was increased to 15 mg daily. The dosage was not increased if the patient lost more than 10 pounds (4.5 kg) by the 4—week visit. The dosage was decreased by 5 mg daily if significant changes in BP (BP >150/100 mm Hg, SBP >160 mm Hg with a DBP <100 mm Hg, &#8805;20 mm Hg increase from baseline in SBP, or &#8805;15 mm Hg increase from baseline in DBP) or heart rate (>100 bpm or an increase of &#8805;15 bpm from baseline) occurred or if intolerable adverse events (AEs) were experienced. The higher dosage could be resumed after 2 weeks if the AE resolved or if changes in vital signs normalized. The dosage of sibutramine could be increased to 15 mg daily at 3 or 6 months, but not after 6 months. The KPWMP physician, study coordinators, and investigators were responsible for study—related examinations, prescribing of sibutramine if applicable, and monitoring study-related variables (ie, BP and heart rate). Drug treatment and control of concomitant medical conditions continued under the patients' primary care and other providers. 

At each visit, patients in both study groups were asked whether they had an AE to report. The study coordinator and investigators evaluated the severity and potential relation of the AE to sibutramine use. If the AE was emergent or serious, the institutional review board and the study sponsor were notified. 

The primary outcome measure was change in weight. Secondary outcomes included changes in the following: (1) BMI; (2) percentage body fat; (3) serum high—density lipoprotein cholesterol, low—density lipoprotein cholesterol, and triglycerides; (4) serum glucose; and (5) BP. 

A sample size of 285 in each group was determined as adequate to detect a 10% difference in change in weight between groups (2—tailed test), with &#945; = .05 and a power of 75%. To accommodate dropouts, the target enrollment was 700 patients to obtain 570 evaluable subjects. Evaluable subjects were defined as subjects who retained membership with Kaiser Permanente of Colorado for the 6— and 12—month follow—ups, received at least 1 dose of sibutramine (if randomized to drug), and had a body weight recorded at least 4 weeks after randomization. To assess differences between treatment groups at baseline, 

All data were analyzed using an intention—to—treat approach. Missing data from any period were replaced by data from the last available recorded visit. Inferential analyses on continuous variables were performed using general linear model techniques in SAS 

with 2 groups: sibutramine plus KPWMP and KPWMP alone. Adjustments were made for age, sex, and significant baseline differences between the 2 groups. Differences between the 2 groups for categorical variables were analyzed using &#967;

 tests. Pharmacy compliance with sibutramine was determined from pharmacy medication dispensing or refill records. Compliance was calculated using the amount of medication obtained, date of dispensing, and enrollment or disenrollment dates. Compliance was calculated as 1 minus the number of days without medication. 

Coding Symbols for Thesaurus of Adverse Reaction Terms

Adverse events experienced during the 12—month study and within 30 days following the last study visit were recorded. Adverse events were recorded in patients who may not have been included in the intention—to—treat efficacy analyses. Events were coded and analyzed using 

Significance was determined by comparing groups using a &#967;

 test, with a Fisher exact test for small expected cell size if applicable. 

Patients (n = 1564) were invited to participate in the study; 976 patients did not participate, primarily because of lack of interest. The second most frequent reason for not participating was that patients were taking selective serotonin reuptake inhibitor medication (an exclusion criteria). Randomization occurred at baseline for the entire study sample (ie, evaluable and nonevaluable patients). Five hundred eighty—eight patients were enrolled and randomized (296 in the drug group and 292 in the nondrug group). Further information about patients not included in the analysis is available from the authors. 

Demographics, clinical characteristics, and comorbidities of evaluable patients at baseline are given in 

. There was a significant difference in age between the 2 evaluable groups at baseline. Weight, BMI, and waist circumference were significantly higher in the drug group. These differences did not exist when all randomized (evaluable and nonevaluable) patients were included, attesting to the effectiveness of our randomization procedure. The incidence of degenerative joint disease was significantly higher in the nondrug group. The mean (SD) weight in the drug group was 108.2 (22.7) kg (range, 69.5—188.2 kg) compared with 103.5 (18.5) kg (range, 68.2—172.3 kg) in the nondrug group (

 = .05). The mean (SD) BMI in the drug group was 38.6 (7.0) (range, 30.0—68.6) compared with 36.8 (5.6) (range, 27.9—56.8) in the nondrug group (

 = .01). The mean (SD) waist circumference in the drug group was 109.7 (17.3) cm (range, 71.1—167.6 cm) compared with 106.4 (14.0) cm (range, 73.7—154.9 cm) in the nondrug group (

 = .03). There were larger percentages of patients in the BMI categories of 35 to 39.9 and 40 or higher enrolled in the drug group (

Although patients identified with known depression through selective serotonin reuptake inhibitor prescriptions were excluded from study participation, large numbers of patients were mildly to moderately depressed on study entry. Notably, 39.4% and 37.0% of patients in the nondrug and drug groups, respectively, had significant symptoms of depression (Self—Rating Depression Scale score, &#8805;50). Mean Self—Rating Depression Scale scores between the 2 study groups were not different. 

The mean weight loss from baseline to 6 months was significantly greater in the drug group (6.8 kg [95% confidence interval {CI}, &#8722;7.4 to &#8722;6.1 kg] vs 3.1 kg [95% CI, &#8722;3.8 to &#8722;2.4 kg] for the nondrug group; 

<.001). Significantly greater decreases in percentage weight loss, BMI, percentage body fat, and waist circumference were seen in the drug group compared with the nondrug group at 6 months (

). The percentage change in weight in the drug group was greater than in the nondrug group for all BMI categories. For the BMI category of less than 35, the mean (SD) percentage change in weight for the drug group was &#8722;6.7% (6.8%) vs &#8722;1.5% (4.4%) for the nondrug group (BMI of 35—39.9, &#8722;6.2% [6.4%] for the drug group vs &#8722;2.3% [4.8%] for the nondrug group; and BMI of &#8805;40, &#8722;5.2% [6.7%] for the drug group vs &#8722;3.1% [7.6%] for the nondrug group). 

Most weight loss occurred during the first 6 months of study participation for both groups. The mean change in weight from 6 to 12 months was 0.50 kg (95% CI, &#8722;0.01 to 0.90 kg) (range, &#8722;23.60 to 13.20 kg) for the drug group vs 0.6 kg (95% CI, 0.1—1.1 kg) (range, &#8722;20.5 to 17.3 kg) for the nondrug group (

 = .51). The net effect on weight from baseline to 12 months was a mean weight loss of 6.2 kg (95% CI, &#8722;7.1 to &#8722;5.4 kg) (range, &#8722;38.6 to 8.9 kg) for the drug group vs 2.3 kg (95% CI, &#8722;3.1 to &#8722;1.5 kg) (range, &#8722;35.9 to 9.1 kg) for the nondrug group (

 < .001). Body mass index and percentage body fat did not significantly change between 6 and 12 months (mean change in BMI, 0.20 [95% CI, &#8722;0.01 to 0.30] for the drug group and 0.20 [95% CI, &#8722;0.03 to 0.40] for the nondrug group; 

 = .73; and mean change in percentage body fat, &#8722;0.1% [95% CI, &#8722;0.5% to 0.3%] for the drug group and 0.2% [95% CI, &#8722;0.4% to 0.7%] for the nondrug group; 

Significantly more patients in the drug group experienced a 5% or greater weight loss at 12 months (47.3% vs 19.1%, 

). Patients who completed 6 months of the study showed similar results to the intention—to—treat analyses (ie, significantly greater decreases in weight, BMI, percentage body fat, and waist circumference for patients in the drug group). 

There were no significant changes at 6 months in either group for total cholesterol, triglycerides, high—density lipoprotein cholesterol, low—density lipoprotein (LDL) cholesterol, glucose, or hemoglobin A

 among patients with diabetes mellitus. The mean increase in total cholesterol was 0.4 mg/dL (0.01 mmol/L) (95% CI, &#8722; 2.5 to 3.3 mg/dL [&#8722;0.07 to 0.09 mmol/L]) in the drug group vs 1.8 mg/dL (0.05 mmol/L) (95% CI, &#8722;1.4 to 5.0 mg/dL [&#8722;0.04 to 0.13 mmol/L]) in the nondrug group (

 = .38). The mean decrease in triglycerides was 13.1 mg/dL (0.15 mmol/L) (95% CI, &#8722;21.6 to &#8722;4.6 mg/dL [&#8722; 0.24 to &#8722;0.05 mmol/L]) in the drug group compared with 7.8 mg/dL (0.09 mmol/L) (95% CI, &#8722;16.3 to 0.7 mg/dL [&#8722;0.18 to 0.008 mmol/L]) in the nondrug group (

 = .35). The mean increase in high—density lipoprotein cholesterol was 0.5 mg/dL (0.01 mmol/L) (95% CI, &#8722;0.4 to 1.3 mg/dL [&#8722;0.01 to 0.03 mmol/L]) in the drug group vs 0.4 mg/dL (0.01 mmol/L) (95% CI, &#8722;0.9 to 1.6 mg/dL [&#8722;0.02 to 0.04 mmol/L]) in the nondrug group (

 = .87). The mean increase in LDL cholesterol was 0.9 mg/dL (0.02 mmol/L) (95% CI, &#8722;1.7 to 3.5 mg/dL [&#8722;0.04 to 0.09 mmol/L]) in the drug group vs 2.6 mg/dL (0.07 mmol/L) (95% CI, &#8722;0.2 to 5.4 mg/dL [&#8722;0.005 to 0.14 mmol/L]) in the nondrug group (

 = .39). The mean decrease in glucose was 0.7 mg/dL (0.04 mmol/L) (95% CI, &#8722;3.7 to 2.2 mg/dL [&#8722;0.21 to 0.12 mmol/L]) in the drug group vs 2.5 mg/dL (0.1 mmol/L) (95% CI, &#8722;5.3 to 0.3 mg/dL [&#8722;0.3 to 0.02 mmol/L]) in the nondrug group (

 = .30). No significant changes in blood chemistries were seen at 12 months. 

No significant changes occurred in BP from baseline to 6 months in either group (SBP mean change, &#8722;1.4 mm Hg [95% CI, &#8722;2.7 to &#8722;0.1 mm Hg] for the drug group and &#8722;2.1 mm Hg [95% CI, &#8722;3.5 to &#8722;0.7 mm Hg] for the nondrug group; 

 = .63; and DBP mean change, &#8722;0.9 mm Hg [95% CI, &#8722;1.9 to 0.2 mm Hg] for the drug group and &#8722;1.7 mm Hg [95% CI, &#8722;2.9 to &#8722;0.5 mm Hg] for the nondrug group; 

 = .35). No significant changes were observed at 12 months. Patients in the drug group experienced a significant increase in heart rate from baseline to 6 months (1.7 bpm [95% CI, 0.5—2.9 bpm] for the drug group vs &#8722;0.4 bpm [95% CI, &#8722;1.5 to 0.8 bpm] for the nondrug group; 

 = .004). This significant increase in heart rate continued at 12 months (1.1 bpm [95% CI, &#8722;0.1 to 2.4 bpm] for the drug group vs &#8722;1.1 bpm [95% CI, &#8722;2.2 to 0.1 bpm] for the nondrug group; 

 = .01). Compliance for patients taking sibutramine averaged 76%. During the study, the percentage of patients in the drug group who had documented degenerative joint disease increased to a percentage similar to that seen at baseline in the nondrug group, resulting in no significant difference in the incidence of degenerative joint disease or any other comorbidity between the 2 groups at 12 months. 

Adverse events (n = 552) were reported in 230 patients initially randomized to receive sibutramine. Adverse events were similar to those reported in sibutramine package labeling, including dry mouth, tachycardia, constipation, hypertension, insomnia, and headache.

 gives the AEs that were significantly greater for patients receiving sibutramine therapy. Thirty—seven patients (12.5%) receiving sibutramine had treatment discontinued as a result of 43 reported AEs (6 [2.0%] with constipation, 6 [2.0%] with hypertension, 4 [1.4%] with tachycardia, 3 [1.0%] with headache, 3 [1.0%] with chest pain, 2 [0.7%] with insomnia, 2 [0.7%] with dizziness, 2 [0.7%] with hemorrhoidal or rectal events, 2 [0.7%] with rash, and 13 [4.4%] with miscellaneous events). Sibutramine dosage was reduced most commonly as a result of hypertension (n = 20), tachycardia (n = 16), appetite increase (n = 11), and headache (n = 6). 

Thirty—three serious AEs were reported in 30 patients in the drug group, and 21 serious AEs were reported in 18 patients in the nondrug group. Five patients (1.7%) experienced serious AEs indicated as possibly or probably related to sibutramine. One patient received a cholecystectomy for cholelithiasis. Another patient was evaluated for chest pain that was determined to be noncardiac. One patient in the drug group was admitted to an inpatient psychiatric facility for suicidal depression. Two patients were evaluated in the emergency department, 1 for hypertension and 1 for hemorrhoidal pain. 

Obesity is a devastating medical condition.

 The clinical and economic burden of obesity has been estimated in the managed care environment. In a cost—of—illness model, healthcare costs due to obesity were estimated to be almost $350 million annually.

A 5% to 10% weight loss can decrease the associated medical risks.

Our study in this managed care environment demonstrated that patients enrolled in a weight management program who took sibutramine lost significantly more weight than participants in the same program who did not receive medication (6.8 vs 3.1 kg). The results in the drug group are similar to those obtained from previous studies 

with sibutramine, despite our unique managed care study environment. We believe this study setting is more comparable to a usual care environment compared with traditional clinical trial settings. The amount of weight loss observed in patients who were in the weight management program testifies to the effectiveness of the program, with increased benefit with the addition of drug therapy. 

The methods and results from this trial are consistent with recent evidence—based recommendations from the USPSTF.

These recommendations state that there is fair to good evidence that patients involved in intense (>1 person—to—person session per month for at least the first 3 months) counseling and behavioral interventions can achieve modest, sustained weight loss (3—5 kg for &#8805;1 year). In our trial, which included the KPWMP seminars, monitored care visits, and AHA classes, the USPSTF definition of high intensity was met. Weight loss was similar to that suggested by the USPSTF. These recommendations also state that pharmacologic treatment for obesity should be used as part of a program that includes lifestyle modification. This is an important consideration for managed care organizations considering the use of drug therapy for obesity or the development of a weight management program. 

Similar to randomized, double—blind, placebo—controlled trials with sibutramine, most weight loss occurred during the first 6 months of therapy.

The role of the medication after 6 months was to maintain the weight previously lost and to prevent weight gain. There was a small amount of weight regain observed in both groups from 6 to 12 months. The minimal weight regain in the nondrug group again attests to the efficacy of the weight management program. The mean percentage weight loss in patients taking sibutramine exceeds the amount of weight loss thought to produce clinical improvements in obesity—related conditions.

Almost 3 times as many patients who received sibutramine lost 5% or more of their body weight compared with patients who did not receive drug therapy. Whether this weight loss can be maintained with continuation or after discontinuation of the drug is not known. One trial demonstrated that patients who initially lost greater than 5% of their body weight after 6 months of sibutramine were able to maintain that weight loss for an additional 18 months with continued therapy.

Obesity—related comorbidities were not reduced in this 1—year study. There were no significant changes in lipid variables or fasting glucose levels, despite weight loss. Most trials with sibutramine have not demonstrated clinically significant decreases in total or LDL cholesterol.

The number of patients with diabetes mellitus in our study population was too small to evaluate effect on diabetes mellitus control. Approximately 35% of patients in our study had hypertension. Small decreases in SBP and DBP were observed, but these were not significantly different between groups. The study sample size was determined on the basis of the primary outcome; therefore, our study could have lacked the power to detect changes in comorbid conditions or laboratory variables. In addition, ongoing treatment for concomitant medical conditions outside the study was not controlled for and could have precluded us from finding significant changes. 

Adverse events with sibutramine were similar to those reported in the package labeling, but the incidence of several of these events in this study was higher.

This could be because this study was not blinded and patients were asked at each visit to report any new symptoms. A significant increase in heart rate was noted in patients taking sibutramine, but this was less than the increase reported in other sibutramine trials.

The increase in heart rate is consistent with the sympathomimetic properties of sibutramine. Blood pressure decreases related to weight loss might not have been observed because of sibutramine's potential to raise BP. The incidence of patients discontinuing sibutramine because of increases in BP or heart rate was low. 

Articles

CLINICAL

The Long-term Outcomes of Sibutramine Effectiveness on Weight (LOSE Weight) Study: Evaluating the Role of Drug Therapy Within a Weight Management Program in a Group-Model Health Maintenance Organizati

To determine the costs of antidepressant medications used during inadequate treatment.

Retrospective database analysis of pharmacy claims made by patients who were treated under routine clinical conditions from July 1, 1999, through September 30, 2002.

Our participants included 21 632 patients enrolled in a commercial HMO who had a primary care physician associated with our healthcare system. Patients never receiving at least a minimum likely effective antidepressant dose for at least 90 days were defined as having inadequate treatment. This study calculated the costs of antidepressants involved with inadequate treatment at the level of the patient and the medication trial.

A majority of patients (51%) received inadequate treatment. Of overall antidepressant costs, 16% were incurred during trials for patients never adequately treated. The majority of inadequate trials were short and unlikely to have been effective. Most patients (64%) had only a single trial of antidepressants. Venlafaxine, fluoxetine, and sertraline had significantly lower firsttrial inadequacy rates compared with the most commonly prescribed agent, citalopram.

Improved patient care quality and lower antidepressant costs could result if clinicians and healthcare systems focus on reducing short trial rates. Initiating treatment with agents least likely to be discontinued prematurely may be helpful.

Antidepressants are among the most frequently prescribed medications in the United States, accounting for approximately 14% of the total US outpatient pharmacy costs in 2000.

 Antidepressant use rates and costs are projected to increase throughout the coming decade,

 driven in large part by the increasing recognition and treatment of both mood and anxiety disorders by physicians in general medical settings.

 Despite the high frequency of antidepressant use, concerns have been raised regarding the effectiveness of current prescribing practices.

The goals of antidepressant treatment for mood disorders are full remission of symptoms and prevention of relapse. Doses need to be sufficient to produce symptom resolution, and treatment needs to continue for a sufficient duration (4-12 months beyond symptom resolution) to reduce the likelihood of relapse.

 Courses of treatment failing to meet these targets are likely to be suboptimal and can be regarded as inadequate treatment trials.

Treatment goals for the use of antidepressants in patients with anxiety disorders are very similar, and guidelines for anxiety disorders have minimum dose and duration targets

 nearly identical to those in mood disorder guidelines. Mood and anxiety symptoms frequently appear together in patients in general medical settings,

 and primary care physicians (PCPs) base decisions to use antidepressants more on symptom severity than on diagnosis.

 Because underdiagnosis and undertreatment of mood and anxiety disorders are common,

 and rates of false-positive diagnosis by PCPs of mood, anxiety, and other mental disorders are relatively low,

 provision of antidepressant medication for patients without an appropriate indication is unusual.

 These factors argue in favor of including a broad spectrum of patients receiving antidepressants when undertaking an assessment of antidepressant treatment.

Rates of inadequate antidepressant treatment are high in part because many patients discontinue treatment early.

 Little attention has been devoted to the costs incurred by healthcare systems and HMOs in payment of pharmacy claims made by covered patients who use antidepressants for short, inadequate courses of treatment.

 We hypothesized that a large fraction of the total acquisition cost of antidepressants was associated with treatment considered inadequate due to premature discontinuation. To evaluate this hypothesis, we conducted a retrospective analysis of antidepressant use patterns and their associated acquisition costs for patients prescribed antidepressants in a large HMO.

We analyzed pharmacy records from an HMO from July 1, 1999, through September 30, 2002. Patients in this dataset had a PCP in the Partners HealthCare System, a network of academic and community PCPs and specialists in Eastern Massachusetts.

No formulary restrictions, mental health carve-out, or depression management program impacted the study population during the time the data were collected. There was a 3-tier drug copayment program. This program varied by employer; but in general, during 2002, most patients paid $5-$10 per month for generic antidepressants, which were in the lowest tier; $20 for most other antidepressants; and $35 for weekly brand-name fluoxetine, the only antidepressant in the top tier.

Prescription records showing the fill date, drug name, dose, number of pills supplied, and name of prescriber from retail and mail order pharmacies were collected. After correction of data entry errors, 2.61 million prescription records for 161 132 patients with costs totaling $95.6 million were available for analysis.

A total of 26 414 patients (16.4% of the patients in the database) received 230 924 antidepressant prescriptions (8.9% of total prescriptions). These antidepressant prescriptions totaled $16.0 million (17.0% of total pharmacy costs for all medications). Copayment costs incurred by patients were unavailable; hence, they were not included in this analysis.

An individual treatment trial was defined as 1 or more continuous prescriptions of the same antidepressant. If a gap of more than 120 days between prescriptions occurred, a new trial was considered to have begun unless the prescription written before the gap provided sufficient days of medication therapy to bridge the gap period.

Tricyclic antidepressants (TCAs) and trazodone in low doses are commonly used for treatment of chronic pain, insomnia, and other conditions for which mood disorder guideline concordance is not relevant. We eliminated the 5584 trials involving only low-dose TCAs or trazodone, excluding 2572 (9.7%) patients. The excluded trials represented only $47 200 or 0.3% of all of the antidepressant pharmacy costs. 

Data on enrollment duration were available for most members (99.1%) in the database. When we did not have enrollment data, we used pharmacy fill dates as proxies for enrollment periods. Patients without evidence of more than 180 days of membership in the plan were eliminated from the analysis.

After excluding low-dose TCA and trazodone trials and patients with short enrollment periods, 21 632 patients remained for analysis. A total of 203 081 antidepressant pharmacy records remained; the corresponding total cost of the medication was $15.6 million.

Treatments that failed to achieve use of minimum likely effective doses and/or were prematurely discontinued were defined as inadequate. The minimum likely effective dose for each agent (Table 1) was derived from literature review and practice guidelines.

 To make comparisons between agents, all antidepressants were first adjusted to a "fluoxetine equivalence" based on equating their minimum daily dose as displayed in Table 1 to 20 mg of fluoxetine. We then examined patterns of use. The distribution of actual mean daily dose based on an expected use of 20-mg fluoxetine equivalents per day showed a close clustering between 18.75 and 20 mg/day. A mean daily dose of approximately 18.75 mg is achieved if patients miss 2 daily doses in a 30-day period. We set the minimum threshold for dose adequacy at 18.75 mg of fluoxetine equivalents per day, as this allowed patients with less-than-perfect adherence still to be considered as receiving an adequate dose, while also reflecting the gap between this pattern of use and the cluster reflecting use of lower doses.

We examined every period within a trial, beginning and ending with a prescription fill date, and calculated the average daily dose and the cumulative length of the trial for each of these periods, looking for at least 1 90-day period during which our minimum daily average dose was achieved. Thus, patients could have a period of dose titration at the beginning of a trial and still achieve adequacy by having at least 90 days in the middle of the trial during which they received an adequate dose. The last prescription in a trial was used only to indicate the date by which the medication in the previous prescription had been consumed. Pills dispensed in the final prescription were not included in our calculations because we could neither assume that all of these pills were consumed, nor know the time period it took for their consumption. Patients with more than 1 treatment trial were considered to have had adequate treatment if any 1 of their trials met adequacy criteria.

Patients were divided into 2 groups: those who received at least 1 period of adequate treatment and those who never received adequate treatment. All of the trials for patients who never received adequate treatment are grouped into "all trials for inadequately treated patients" (

). In contrast, "all trials for adequately treated patients" included some inadequate trials. This is because patients with adequate treatment may have had some trials that were inadequate. For example, a patient may have had a short trial, been switched to another agent, and had an adequate trial of the second agent. Within these 2 groups of patients, we stratified trials by trial duration.

Every pharmacy record specified the prescribing physician and patient's PCP. Prescribers were assigned to 1 of 3 categories: PCPs, psychiatric specialists, or "other." Others were nonpsychiatric specialists, hospital residents, unknown doctors, and those records with invalid and/or unidentified Drug Enforcement Administration numbers. Within the "other" category, the largest group was nonpsychiatric specialists (50.0%).

"No refill trials" involved only a single prescription. More than 82% of these single prescription trials were for fewer than 90 pills, and 50% of these prescriptions were for 30 pills or fewer. Trials between 0 and 90 days were defined as having at least 1 refill but no refills beyond a 90-day cutoff. Trials in this group were sufficiently below duration guidelines for mood and anxiety disorders that it was unlikely that treatment during these trials was effective.

Trials of at least 90 days but fewer than 180 days were considered adequate if the minimum dose threshold was reached for at least 90 days. Although these trials were shorter than suggested by most guidelines, there was at least a reasonable chance, across a population, that some benefit would have been achieved. Trials of more than 180 days were generally considered guideline concordant for mood and anxiety disorders if they included sufficient sustained doses. By further subdividing these longer trials, we also were able to assess the costs and frequency of those trials extending beyond typical recommendations, a target of some cost-control strategies.

Each pharmacy record included a cost variable indicating the amount the HMO reimbursed the pharmacy. This was the sum of the price paid by health plan for the drug plus a small administrative reimbursement (usually $0.28), minus the cost of the copayment made by the plan member. We used this cost variable for all cost calculations in this paper. For each trial, the cost of each prescription filled during the trial was summed to provide the total cost of the trial. In evaluating adequacy rates for individual antidepressant products, we limited our analysis to the first trial for each patient.

We used SAS software version 8.0 for all analyses (SAS Institute Inc, Cary, NC). We performed descriptive comparisons of adequacy rates by antidepressant type, with adequacy rates calculated as the ratio of the number of patients with adequate trials to the total number of patients with trials. Multivariate logistic regression models were used to assess statistically significant predictors of inadequate antidepressant treatment, including physician specialty, patient age and sex, and specific antidepressant drug. In regression models, we evaluated a variety of small incremental changes in dose and duration, and noted no significant change in our findings. Doubling and tripling the minimum likely effective dose produced a significant change in adequacy outcomes, and these results for several of the most common drugs are displayed in the 

. We calculated adjusted odds ratios and 95% confidence intervals, and considered a 2-tailed 

 value of <.05 to be statistically significant.

We evaluated patients treated with antidepressants. These patients received 34 281 distinct antidepressant trials. On a patient level of analysis, 51% received inadequate treatment. These patients received 45.2% of all trials (Table 2). Costs of these trials to the health plan were $2.4 million, representing 15% of the total $15.6 million spent on antidepressants.

Categorized by trial length, the largest group of trials were single-prescription trials for inadequately treated patients (21.4%). As expected, longer trials, on average, cost more than shorter trials. Trials of the same length cost more if they were for adequately treated patients (Table 2).

In this study, the number of patients who had only a single trial was 13 863 (64%). The remaining 7769 (36%) patients received multiple trials: 4859 (22%) received 2 trials, 1755 (8%) received 3 trials, and 1155 (5%) received more than 3 trials.

In order to provide a fair comparison between agents, only the first trial each patient received was included in the analysis to determine rates of adequacy of individual drugs (

). Among drugs with more than 250 trials, those with the lowest rates of inadequacy were venlafaxine, fluoxetine, sertraline, citalopram, and mirtazapine. Compared with citalopram (the most frequently prescribed drug in the Partners system), venlafaxine, fluoxetine, and sertraline all had first-trial rates of inadequacy significantly lower than that of citalopram. Drugs with the highest rates of first-trial inadequacy were trazodone, amitriptyline, and bupropion. Nefazodone, paroxetine, and nortriptyline had rates of adequacy similar to that of citalopram.

In multivariate regression analyses accounting for confounding factors (including age, sex, antidepressant prescribed, and prescriber type), younger age but not sex was a significant predictor of treatment inadequacy (

). The strongest predictors of inadequate treatment were use of amitriptyline or trazodone. Trials for patients under the age of 20 years also were likely to be inadequate. Predictors of adequacy included use of fluoxetine, sertraline, or venlafaxine. Those trials prescribed by more than 1 prescriber type were less likely to be inadequate than those prescribed by a single prescriber type. Trials with prescriptions written by PCPs or other specialists alone were more likely to be inadequate than those with psychiatrists prescribing alone.

To determine whether prior antidepressant use impacted the likelihood of adequacy for subsequent trials, we examined the 3787 patients (17% of the 21 632 patients originally analyzed) who began a trial after the midpoint of the observation period and who had been represented in the dataset for the entire period. This revealed that prior antidepressant use made a trial significantly less likely to be inadequate compared with no prior antidepressant use. Limits in our sample size did not allow us to consider the potential impact of prior trials as a factor in the comparison of inadequacy among agents.

We considered how many additional patients would have had an adequate trial if we included the final prescription in the analysis. If all pills in the final prescription of multiprescription trials were consumed at a rate of 1 pill per day, an additional 1315 patients (6%) would have received adequate treatment, and the overall rate of adequacy would have increased from 49% to 55%. However, this is very likely to overstate the impact of including final prescriptions because not all tablets are likely to be consumed, and even if they are, they may not be consumed quickly enough so that the mean dose per day remains adequate.

We conducted an additional analysis to determine the impact of removing TCAs and trazodone, because it is possible that these agents may be used for purposes other than treating anxiety or depression. This removed only 859 patients (4%) and resulted in only a modest increase in treatment adequacy, from 49.0% to 49.8%. The percentage of antidepressant costs for patients never treated adequately remained at 15%.

This retrospective analysis of antidepressant use in routine clinical conditions found that inadequate treatment is very common, and that a substantial portion of antidepressant acquisition costs are spent in ways unlikely to produce desired outcomes.

A majority (51%) of patients had only inadequate treatment. That is, at no time during the 39 months of observation did they simultaneously receive treatment that achieved dose and duration minimums. Resources expended on medications used by these patients represent 15% of total antidepressant costs. Given the evidence suggesting that, on a population basis, treatment failing to attain minimal guideline standards is unlikely to produce optimal outcomes,

 these resources may be regarded as having been expended suboptimally.

Spending for inadequate treatment was almost certainly suboptimal in cases where patients had only 1 prescription and this prescription was never refilled. It is unlikely that patients receiving very short (0-30 days of duration) trials achieve sustained medication-induced symptom remission, and protection against relapse is low.

 Single prescriptions (where no subsequent refills or prescriptions for a different antidepressant appeared) accounted for 21% of all trials, and 3% of total costs.

Various strategies, such as PCPs instructing patients about the importance of continuation

 may reduce rates of inadequate treatment. Our findings suggest that strategies focused on reducing the likelihood of short trials also may reduce rates of inadequate treatment. Such strategies would impact a large number of patients. They may reduce the medication acquisition costs associated with inadequate treatment, and thereby reduce suboptimal, potentially wasted expenditures. These strategies would support both quality improvement and cost-control goals, and should be considered by healthcare systems.

One way to reduce the prevalence of short trials may be to increase the use of agents with lower inadequacy rates (ie, those least likely to be prematurely discontinued). Comparing inadequacy rates across agents may be helpful in identifying these agents. We found that venlafaxine, sertraline, and fluoxetine were significantly less likely than other commonly used agents to be discontinued prematurely.

Several limitations must be considered before our findings can be used to guide the choice of antidepressant agent. We were not able to determine why venlafaxine, sertraline, and fluoxetine had lower inadequacy rates than the commonly used reference agent, citalopram, or the less commonly prescribed agents. Our comparison among agents was based only on first trials and required only that patients use minimum likely effective doses. Treatment episodes meeting minimum dosage and duration thresholds do not necessarily produce optimal outcomes, and lower inadequacy rates do not guarantee the best outcomes. Truly optimizing outcomes may frequently require doses beyond these minimal levels. In our analysis, several drugs, including venlafaxine, were most likely to be used at doses above the minimum. This may suggest that a larger fraction of patients treated with these drugs may require doses higher than the doses used in our analysis. Although each agent's minimum likely effective dose was based on expert consensus and manufacturers' guidelines, efficacy and effectiveness data supporting these thresholds are limited.

Healthcare organizations seeking to control costs may encourage the use of antidepressants with the lowest acquisition costs. Many currently use this strategy, but its value remains unproven. If inexpensive agents such as TCAs have high inadequacy rates, choosing these agents may reduce quality. Total costs of care (as opposed to costs of purchasing medications) may not increase when agents less likely to be prematurely discontinued (eg, agents with low inadequacy rates) are used, even if such agents are relatively expensive.

 Consideration of relative inadequacy (and eventually adequacy) rates for various medications may assist healthcare organizations in making informed choices of preferred agents.

The 49% of patients who received adequate treatment accounted for 55% of trials and 85% of antidepressant acquisition costs. Some of the patients in this group (44%) had multiple trials. Among these were trials that were inadequate (18% of total trials). These typically were short trials for patients who went on to adequate treatment, often after being switched to a different medication. These trials made up only a small fraction (6%) of antidepressant costs. In contrast to spending for patients who never had adequate treatment, money spent on short trials for patients with switches and adequate treatment may not represent suboptimal use of resources. This is because some amount of switching may be inevitable, and may be appropriate, so long as the patient eventually receives adequate treatment with desired outcomes.

 It may not be reasonable to focus on trying to reduce this segment of antidepressant spending.

Costs of Antidepressant Medications Associated With Inadequate Treatment

Poor diet and physical inactivity contribute to ill health and deteriorating quality of life in such important ways that few institutions or individuals are unaffected. Diabetes, hypertension, stroke, heart disease, and cancer begin the list of complications of these components of modern lifestyle, but obesity is the most evident. 

Two thirds of the population is now overweight or obese. Joining direct healthcare costs with lost productivity and other work-related variables, obesity is estimated to cost the nation $75-$112 billion annually. Hidden behind these numbers is tremendous human suffering, in both adults and children. Children under age 10 suffer from Type 2 diabetes, making "adult onset diabetes" an obsolete term. Children so affected could have advanced coronary disease, be blind, or die by age 30.

The question has now been raised whether our children will be the first generation in the nation's history to lead shorter lives than their parents. Under such conditions, it is natural to ask whether the best course of action is treatment, prevention, or both. 

It is essential that obese individuals receive compassionate and effective treatment. Two papers in this issue of the 

 reflect nicely on what can be expected from state-of-the-art approaches to obesity. Porter et al offer a more "real world" test of pharmacotherapy than what is seen typically in controlled clinical trials, testing a lifestyle change program with and without medication in a health maintenance organization.

Sibutramine, a serotonin and norepinephrine re-uptake inhibitor, produced a modest but significant advantage for the group taking the drug (3.1 kg average weight loss for the no-drug group vs. 6.8 kg for those receiving drug). Those taking the drug lost about 6% of their initial body weight. Weight losses of this magnitude are helpful in that even small losses can affect risk factors, but of course leave patients far from their desired weight (a 6% loss in a 200 pound woman would leave her at 188 pounds). The cost per pound lost to the patients and the HMO were not reported. 

The Porter et al study is typical of drug studies for obesity, although typical weight losses are generally higher. Patients lose 5% to 15% of initial body weight, risk factors improve on average, but relapse becomes an issue when drugs are withdrawn. Pharmacotherapy is now considered a viable treatment for helping reduce risk in overweight individuals. 

The paper by Jeffery et al is an important product of the fruitful collaboration by Jeffery and colleagues at the University of Minnesota and Pronk and colleagues at HealthPartners in Minneapolis.

The authors used clinic fliers, mailings, and physician referral in hopes of recruiting a cross section of members of a managed care organization (MCO) for a weight management program. Members who expressed interest, compared to members in general, were more likely to be minority and female, to have poorer diets, and have higher levels of binge eating. They were also heavier, but reported more physical activity. The authors expressed disappointment at not recruiting a true cross section of the membership, but rightfully noted the impressive number of people willing to be enrolled in a program. This paper helps define recruitment strategies, which will be central to delivering treatment. 

Still, treating obesity is a challenging enterprise. In order to produce weight losses of medical consequence, treatment is typically intensive and expensive. An argument can be made that intervening by any method is cost effective (costs are justified by improved health outcomes), but treatment is costly nonetheless. The question, then, is whether treatment can reduce the prevalence of obesity in a population or whether prevention must become a priority. 

Treatment is not now, and may never be, a means of reducing the impact of obesity as a public health problem. For every "case" removed by treatment from the population of overweight individuals, thousands more may be joining the obese population because of the toxic food and physical inactivity environment. Stated simply, the environment all Americans face produces obesity at record rates and treatment is not powerful or inexpensive enough to keep up. 

Managed care organizations, therefore, have a clear stake in preventing obesity. Preventive services offered to members might be a start. If those at risk for weight gain can be identified and be recruited into a lifestyle coaching program, perhaps some obesity can be prevented. Work with children and with groups like pregnant mothers might be especially important in this regard. Sadly, there is not much research to help guide such efforts. 

Prevention at the national level, while seemingly best left to politicians and public health experts, may well be an important priority for those in the world of managed care. Here's why. Only so much can be done in the clinical setting, and when daily life for Americans involves a tidal wave of food advertisements, high-calorie food available as never before, soft drinks, snack foods, and declining physical education in schools, few children walking or biking to school, and hundreds of other environmental "toxins," high levels of obesity are the likely consequence. 

Changing the environment through public policy may be the most effective means of preventing obesity, and such changes could benefit the healthcare system in general and MCOs in particular. It remains to be seen whether managed care will mobilize nationally, locally, or both, to address public policy in ways that will improve the environment and prevent obesity. 

Why would mobilization even be necessary for such a widely recognized problem? Bias and stigma directed at overweight people is a first possible explanation.

Because obesity is blamed on the people who have it, and the condition itself is stigmatized, attention to obesity has lagged far behind what would be expected given its public health impact. 

A second barrier is a thorny issue that confronts the food industry. If the American population were to reduce to normal weight, the number of calories, and hence the amount of food sold every day must decline significantly.

The industry could recoup the loss to some extent by shifting to production of healthy foods, but if total intake declines, the bare fact is that less food will be sold. In order to protect profits, it is understandable that the industry defends practices that are coming under increasing scrutiny. 

The average American child sees 10 000 food advertisements per year on television alone, nearly all for fast foods, soft drinks, candy, sugared cereals, etc.

Children are a multi-billion dollar target group themselves, and of course, grow to be adult consumers. Soft drink and snack food companies have worked for years to offer their products in schools. The industry defends both practices, saying that food advertising affects only brand choice and not consumption of foods like soft drinks, and that offering soft drinks and snack foods helps education (a vice president of Coca Cola sits on the Board of Directors of the National PTA). It is against this backdrop that health institutions, including MCOs, must pick up the pieces when the population falls ill. 

In addition to offering and supporting treatment and care for obese individuals, organizations like MCOs might consider supporting and even initiating social changes that could aid in the prevention of obesity. Among the opportunities would be to support local, state, and federal efforts to: 

Decrease or eliminate soft drinks and snack foods in schools

Improve school lunches and integrate education on nutrition and physical activity into classes, into the cafeteria experience, etc.

Foster the design of communities to encourage and permit physical activity

Regulate food advertising aimed at children

Additional ideas might also be considered,

but the first step is to emphasize prevention, understand that children may be the most important group to address initially, and advocate for changes in the interest of public health. There might then be hope we can dampen the toll obesity takes on the health and well-being of the nation. 

From the Departments of Psychology and Epidemiology and Public Health, Yale University, New Haven, CT. 

Address correspondence to: Kelly D. Brownell, PhD, Department of Psychology, Yale University, Box 208205, New Haven, CT 06520-8205. E-mail: 

 Childhood obesity: public health crisis, common sense cure.

Natural history of Type 2 diabetes diagnosed in childhood; long-term follow-up in young adult years. Paper presented at: Annual Meeting of the American Diabetes Association, June 2002; San Francisco, Calif. 

3. Porter JA, Raebel MA, Conner DA, et al.

 The Long-term Outcomes of Sibutramine Effectiveness on Weight (LOSE Weight) Study: Evaluating the role of drug therapy within a weight management program in a group-model health maintenance organization. 

4. Jeffrey RW, McGuire MT, Brelje KL, et al.

 Recruitment to mail and telephone interventions for obesity in a managed care environment: The Weigh-to-Be Project. 

Food Politics: How the Food Industry Influences Nutrition and Health.

 Berkeley, Calif: University of California Press, 2002. 

 New York: Contemporary Books (McGraw Hill), 2004. 

EDITORIAL

Obesity and Managed Care: A Role for Activism and Advocacy?

Although clinical practice guidelines are widely accepted as â€œbest practices,â€ provider compliance remains low. 

 To examine the relationship between providersâ€™ behavioral intentions and their compliance with practice guidelines; to assess the impact of perceived barriers that were most inhibiting to compliance; and to examine the ability of factors in the Physician Guideline Compliance Model to predict intention to comply and compliance with guidelines implemented at specific practice sites. 

Survey research methods were used to assess effects of antecedents (attitudes, subjective norms, past behavior, and perceived behavioral control) on providersâ€™ intentions to comply and compliance with clinical practice guidelines. Provider survey I was conducted at the time of guideline introduction and survey II 4 months after implementation. 

Scores for the antecedents to behavior and behavioral intention reflected favorable responses toward the use of guidelines. The mean self-reported compliance behavior was 65%, whereas compliance as assessed by chart review was 54%. Approximately 68% of the variance in the physiciansâ€™ behavioral intentions was accounted for by variables included in the Physician Guideline Compliance Model. A significant negative correlation was found between perceived barriers and self-reported behavior but not between perceived barriers and chart-review-assessed behavior. 

Some variables, particularly perceived barriers to guideline implementation, predicted a providerâ€™s practice intentions and self-reported behavior. Future guideline intervention efforts should identify and reduce these barriers to guideline compliance prior to implementation. 

The demand is ever increasing from patients, patient advocate groups, government regulatory agencies, and employer groups for cost-effective, high-quality patient care. Because quality is largely determined by the daily clinical decisions of practitioners, interest has grown in finding ways to influence providers' decision-making processes. One way of influencing clinical decision making is through the development and implementation of evidence-based clinical practice guidelines. Although numerous healthcare organizations, health plans, and individual researchers promote the development and utilization of guidelines,

 research findings demonstrate that even with educational programs and incentives for compliance, practitioners often fail to use guidelines in daily practice.

 Studies have attempted to identify reasons for practitioners' general failure to follow evidence-based guidelines. However, research using a theoretical foundation for understanding and predicting physician behavior has been limited. 

A review of literature on barriers to guideline adherence identified a lack of knowledge on the part of physicians as the most frequently investigated barrier.

 Other barriers examined in empirical work were found to include low self-efficacy and negative outcome expectancy beliefs on the part of physicians, as well as patient barriers and environmental barriers such as lack of time and insufficient staff support.

 Other studies have indicated that failure to adhere to guidelines is sometimes a conscious decision based on disagreement with what is the best practice for a particular patient or situation,

 which may be a particularly relevant scenario when guidelines lag behind "cutting-edge" practice.

While much of the research that has evaluated efforts to improve utilization of practice guidelines has been empirical, several investigators have described a conceptual framework for examining implementation of guidelines. Kitson and associates

 developed a framework for conceptualizing implementation of evidence-based practices. The factors included in their model were (a) the nature of the evidence supporting the guideline; (b) the context, including the work culture and leadership in the organization; and (c) the support from others in the environment. Although valuable in examining the implementation process, their framework is not based specifically on an established theory of behavior change and, as acknowledged by the authors, requires validation through empirical testing. In addition to this work, Pathman and colleagues

June 2004

The Long-term Outcomes of Sibutramine Effectiveness on Weight (LOSE Weight) Study: Evaluating the Role of Drug Therapy Within a Weight Management Program in a Group-Model Health Maintenance Organizati

Costs of Antidepressant Medications Associated With Inadequate Treatment

Obesity and Managed Care: A Role for Activism and Advocacy?

Predicting Physician Guideline Compliance: An Assessment of Motivators and Perceived Barriers

Recruitment to Mail and Telephone Interventions for Obesity in a Managed Care Environment: The Weigh-To-Be Project

Willingness to Recommend a Health Plan: Who Is Dissatisfied and What Don't They Like?