The effects of soy milk and isoflavone supplements on cognitive performance in healthy, postmenopausal women.

RATIONALE: The decline in estrogen concentrations in women after menopause can contribute to health related changes including impairments in cognition, especially memory. Because of the health concerns related to hormone replacement therapy (HRT), alternative approaches to treat menopausal symptoms, such as nutritional supplements and/or diet containing isoflavones, are of interest. OBJECTIVES: This study investigated whether soy isoflavones (soy milk and supplement) could improve cognitive functioning in healthy, postmenopausal women. PARTICIPANTS, INTERVENTION AND DESIGN: A total of 79 postmenopausal women, 48-65 years of age, completed a double-blind, placebo-controlled trial in which they were randomly assigned to one of three experimental groups: cow's milk and a placebo supplement (control); soy milk and placebo supplement (soy milk, 72 mg isoflavones/day); or cow's milk and isoflavone supplement (isoflavone supplement, 70 mg isoflavones/day). MEASUREMENTS: Cognitive functioning was assessed using various cognitive tasks before the intervention (baseline) and after the intervention (test). RESULTS: In contrast to predictions, soy isoflavones did not improve selective attention (Stroop task), visual long-term memory (pattern recognition), short-term visuospatial memory (Benton Visual Retention Test), or visuo-spatial working memory (color match task). Also, the soy milk group showed a decline in verbal working memory (Digit Ordering Task) compared to the soy supplement and control groups. CONCLUSION: Soy isoflavones consumed as a food or supplement over a 16-week period did not improve or appreciably affect cognitive functioning in healthy, postmenopausal women.

Variation in pharmacy prescription refill adherence measures by type of oral antihyperglycaemic drug therapy in seniors in Nova Scotia, Canada.

OBJECTIVE: To examine the association between pharmacy prescription refill adherence by type of oral antihyperglycaemic medications used in seniors in Nova Scotia, Canada. RESEARCH DESIGN AND METHODS: Pharmacy and health care utilization data from April 1993 to March 1996 for Nova Scotia Seniors' Pharmacare beneficiaries treated with 1st and 2nd generation sulphonylureas and biguanides was analysed. Refill adherence was quantified by two proportions: number of days beneficiaries had a medication surplus compared with the total period of observation and gaps in treatment compared with the total period of observation. Analysis examined association of type of oral antihyperglycaemic agent and dosing on refill adherence, after adjustment for age, gender and hospital use. RESULTS: A total of 3358 beneficiaries met the study criteria. The mean refill adherence rate [continuous multiple-interval measure of medication availability (CMA)] was 86 +/- 0.4% SE and continuous measure of medication gaps (CMG) was 16 +/- 0.4% SE. Use of biguanides was associated with lower odds of having a medication surplus. The use of 2nd generation sulphonylureas and biguanides, and use of agents with a dosage frequency of more than one dose per day was associated with medication gaps. CONCLUSIONS: Many beneficiaries taking antihyperglycaemic agents adhered well to prescribed therapy. The proportion of days not covered by medications averaged 16%. Beneficiaries taking medications once a day were more likely to have good refill adherence. Further work is needed to compare prescription refill adherence rates with other adherence measures and clinical outcomes. These methods are useful for establishing baseline adherence, monitoring the success of programmes designed to improve adherence, and determining cost-effectiveness of drug regimens.

The need for an iterative process for assessing economic outcomes associated with SSRIs.

Pharmacotherapeutic advances in the treatment of depression have included the development of the selective serotonin reuptake inhibitors (SSRIs), thereby providing alternatives to tricyclic antidepressants. Concurrent with these events have been significant structural (e.g. pharmaceutical formularies) and regulatory (e.g. required pharmacoeconomic evaluations) changes in the delivery, financing, and oversight of healthcare programmes throughout the world. International cost-containment initiatives are increasingly mandating a demonstration of value for money, defined in terms of a measurable health and/or financial outcome, and, in the case of medicines, attributable to a given expenditure, for a given pharmacotherapeutic option. We examine the inherent strengths and weaknesses of 5 study designs used to discern and contrast financial outcomes stemming from the use of antidepressant pharmacotherapy for the treatment of depressive illness [randomised controlled trials (RCTs); meta-analyses; decision-analytical models (DAMs); retrospective database investigations; randomised naturalistic inquiry]. We argue that the economic appraisal of pharmacotherapy requires an iterative process extending from the developmental (RCTs; meta-analyses; DAMs) through to the postmarketing phase (database reviews; naturalistic inquiry), thereby resulting in a portfolio of evidence as to the safety, efficacy and effectiveness of a given pharmacotherapeutic category (e.g. SSRIs) and/or a specific medication. Database reviews, while nonrandomised, and prospective naturalistic inquiry afford greater insight into the patterns of use and financial merits of prescribing specific pharmacotherapeutic options for the treatment of depression within the context of clinical practice as compared with RCTs, meta-analyses and DAMs. The portfolio of evidence to date indicates that the first-line use of SSRIs in the treatment of depression is clinically warranted, and represents value for money.

Trends in the rate of depressive illness and use of antidepressant pharmacotherapy by ethnicity/race: an assessment of office-based visits in the United States, 1992-1997.

OBJECTIVE: This study was undertaken to determine ethnicity/race-specific (white, black, and Hispanic) population-adjusted rates of US office-based physician visits in which a diagnosis of a depressive disorder was recorded or in which a diagnosis of a depressive disorder was recorded and antidepressant pharmacotherapy was prescribed. METHODS: Data from the National Ambulatory Medical Care Survey for 1992 through 1997 were partitioned into three 2-year periods: 1992-1993, 1994-1995, and 1996-1997. For each 2-year period, data from office-based physician visits for patients aged 20 to 79 years were extracted to assess, by ethnicity/race, (1) the number of visits in which a diagnosis of a depressive illness was recorded (International Classification of Diseases, Ninth Revision, Clinical Modification codes 296.2-296.36, 300.4, or 311) and (2) the number of visits in which a diagnosis of a depressive illness was recorded and antidepressant pharmacotherapy was prescribed. We calculated ethnicity/race-specific rates (per 100 US population aged 20 to 79 years) of office-based visits in which a diagnosis of a depressive disorder was recorded and in which a diagnosis of a depressive disorder was recorded and antidepressant pharmacotherapy was prescribed. The specialty of the reporting physician and the proportion of patients receiving a selective serotonin reuptake inhibitor (SSRI) were also discerned. RESULTS: From 1992-1993 to 1996-1997, the rate of office-based visits (per 100 US population aged 20 to 79 years) in which a diagnosis of a depressive disorder was recorded increased 3.7% for whites (from 10.9 to 11.3; P = 0.001), 31.0% for blacks (from 4.2 to 5.5; P = 0.001), and 72.9% for Hispanics (from 4.8 to 8.3; P = 0.001). The rate of office-based visits in which a diagnosis of a depressive disorder was recorded and antidepressant pharmacotherapy was prescribed increased 18.5% for whites (from 6.5 to 7.7 per 100; P = 0.001), 38.5% for blacks (from 2.6 to 3.6 per 100; P = 0.001). and 106.7% for Hispanics (from 3.0 to 6.2 per 100; P = 0.001). Between 1992-1993 and 1996-1997, use of an SSRI increased among whites and blacks (from 50.0% to 65.8% and from 40.5% to 58.2%, respectively), but declined among Hispanics (from 51.4% to 48.6%; all comparisons P = 0.001). CONCLUSION: By 1996-1997, the population-adjusted rates for Hispanics were within a quartile of those observed for whites, whereas the rates for blacks remained at less than half those observed in whites. The observed divergence in population-adjusted rates by ethnicity/race may reflect the nature of the patient-physician relationship, sensitivity and specificity of diagnostic techniques and instruments, and the wider social context in which an office-based visit occurs, including access to and type of health insurance and coverage for mental health services.

[Antidepressant pharmacotherapy: a review of pharmaco-economic research]. / Pharmacothérapie antidépressive: une synthèse des recherches pharmaco-économiques.

Recent pharmacotherapeutic advances in the treatment of depression have included the development of selective serotonin reuptake inhibitors (SSRIs), thereby providing an alternative to tricyclic antidepressants (TCAs). SSRIs have achieved a rapid acceptance by prescribers worldwide due to a superior safety profile to that observed with the TCAs, and the potential for once daily administration. However, to date there exists limited data regarding the effect of antidepressant pharmacotherapy on health service expenditures. Herein, we review the inherent strengths and weaknesses of the five study designs which have been employed in the economic appraisal of antidepressant pharmacotherapy: randomized controlled trials; meta-analyses stemming from the results of controlled clinical trials; decision-analytical models predicated on results stemming from randomized clinical trials and/or meta-analyses; retrospective data archive investigations; and prospective randomized naturalistic inquiry. What emerges is the necessity of establishing a portfolio of evidence as to the safety, efficacy, and effectiveness of a given pharmacotherapeutic category (e.g. SSRIs) and/or a specific medication. Thus, the economic appraisal of antidepressant pharmacotherapy will require an iterative process extending from the developmental through post-marketing phase.

Economic appraisal of citalopram in the management of single-episode depression.

A retrospective intent-to-treat analysis (N = 1,339) was conducted to discern the natural course of antidepressant use and direct health service expenditures for the treatment of single-episode depression (DSM-IV code 296.20) among patients initiating antidepressant pharmacotherapy with either a tricyclic antidepressant (TCA) (amitriptyline, N = 237) or a selective serotonin reuptake inhibitor (SSRI) (citalopram, N = 71; fluoxetine, N = 411; paroxetine, N = 334; or sertraline, N = 286). Data were derived from the computer archive of a network-model health maintenance organization for the period of January 1, 1996, through April 30, 1999. Comparisons at the end of the 6-month post-period (180 days) were undertaken between cohorts initiating antidepressant pharmacotherapy with citalopram and each SSRI or TCA. Consistent with the intent-to-treat design, all accrued health service expenditures were assigned to the pharmacotherapeutic option initially prescribed. Multivariate models were adjusted for patient's age, gender, number of concomitant disease state processes, use of health services in the 6-month time frame (180 days) before initiating antidepressant pharmacotherapy, specialty of physician recording a diagnosis of single-episode depression, and the presence or absence of a previous diagnosis of single-episode depression and receipt of antidepressant pharmacotherapy. Patients initiating antidepressant pharmacotherapy with citalopram were far more likely to (1) have been diagnosed by a psychiatrist (37%; p < or = 0.05); (2) continue with the original pharmacotherapeutic option (79%) compared with patients originally prescribed amitriptyline (51%; chi2 = 17.29, df = 1, p < or = 0.05) or sertraline (65%; chi2 = 36.91, df = 1, p < or = 0.05); no significant difference was found compared with patients initiating antidepressant pharmacotherapy with paroxetine (72%; p = not significant [NS]) or fluoxetine (83%; p = NS); (3) obtain 90 days or more of antidepressant pharmacotherapy (86%) compared with those prescribed amitriptyline (69%; chi2 = 8.09, df = 1, p < or = 0.05); no significant difference was found compared with sertraline (77%), paroxetine (81%), or fluoxetine (84%); and (4) obtain 6 months (180 days) of antidepressant pharmacotherapy (68%) compared with those prescribed amitriptyline (39%; chi2 = 18.26, df = 1, p < or = 0.05) or sertraline (51%; chi2 = 6.02, df = 1, p < or = 0.05); no significant difference was found compared with paroxetine (56%) or fluoxetine (59%). Receipt of amitriptyline or sertraline as initial medication was associated with a per capita increase (p < or = 0.05) in health service utilization (17% and 9%, respectively) relative to citalopram. No significant difference (p > 0.05) in health service utilization was discerned between citalopram and either fluoxetine or paroxetine. Multivariate models adjusted for nonrandom assignment to the initial pharmacotherapeutic option confirmed these findings. Further research over a longer time course is warranted.

Ethnicity and the prescribing of antidepressant pharmacotherapy: 1992-1995.

Little is known about the prescribing pattern for antidepressant pharmacotherapy by ethnicity. The present study was designed to determine the rates of office-based visits documenting the utilization of antidepressant pharmacotherapy, a diagnosis of a depressive disorder, or both, among whites, blacks, and Hispanics age 20-79 years. Data from the National Ambulatory Medical Care Survey for 1992-93 and 1994-95 were utilized for this analysis. Comparing these time periods, we observed several trends: (1) The annualized mean rate per 100 US population of office-based visits documenting the use of antidepressant pharmacotherapy for any reason increased from 13.4 to 15.9 among whites (p < or = 0.0001) and from 6.5 to 7.7 among blacks (p < or = 0.0001), but remained unchanged at 7.3 for Hispanics (p > 0.05). (2) Documentation of a diagnosis of a depressive disorder increased for whites (10.9 to 12.0; p < or = 0.0001), for blacks (4.2 to 5.6; p < or = 0.0001), and for Hispanics (4.8 to 5.6; p < or = 0.0001). (3) The recording of a diagnosis of a depressive disorder in concert with the initial prescription or continuation of antidepressant pharmacotherapy also increased for whites (6.5 to 7.7; p < or = 0.0001), for blacks (2.6 to 3.4; p < or = 0.0001), and for Hispanics (3.0 to 3.2; p < or = 0.0001). We conclude that the rate of office-based visits documenting the utilization of antidepressant pharmacotherapy, a diagnosis of a depressive disorder, or both, was comparable among blacks and Hispanics by 1994-95, but was less than half the rate for whites in either time period examined. Further prospective research is required to discern the reasons for observed differences by ethnicity.

National trends in the prevalence of attention-deficit/hyperactivity disorder and the prescribing of methylphenidate among school-age children: 1990-1995.

It has been reported that during the past decade the prevalence of attention-deficit/hyperactivity disorder (ADHD) (ICD-9-CM code 314.00 or 314.01) and its pharmacologic treatment have increased dramatically in the United States. Herein, a single national data source is used to discern trends in the prevalence of U.S. office-based visits resulting in a diagnosis of ADHD, and trends in the prescribing of stimulant pharmacotherapy (including methylphenidate) for its treatment. Data from the National Ambulatory Medical Care Survey (NAMCS) for the years 1990 through 1995, for children aged 5 through 18 years, were utilized for this analysis. Results indicate that the number of office-based visits documenting a diagnosis of ADHD increased from 947,208 in 1990, to 2,357,833 in 1995. Between 1990 and 1995, the number of visits by girls diagnosed with ADHD rose 3.9-fold (p < 0.05), and the mean patient age increased by more than 1 year, from 9.7 in 1990, to 10.8 in 1995 (p < 0.05). The percentage of office-based visits resulting in a diagnosis of ADHD increased from 1.1% of all visits in this age group in 1990, to 2.8% by 1995. We discerned a 2.3-fold increase (p < 0.05) in the population-adjusted rate of office-based visits documenting a diagnosis of ADHD; a 2.9-fold increase (p < 0.05) in the population-adjusted rate of ADHD patients prescribed stimulant pharmacotherapy; and a 2.6-fold increase (p < 0.05) in the population-adjusted rate of ADHD patients prescribed methylphenidate.

Disease management: state of the art and future directions.

Disease management (DM) programs have become common in health systems, especially in managed care organizations and hospitals. These programs are designed to improve both the quality of care and the efficiency of health care delivery. However, there may be controversy about the most important outcomes to consider. Furthermore, the effectiveness of DM initiatives is largely undocumented in the literature. The purpose of this paper is to review the issues, methods, and outcomes involved in creating and instituting DM programs. To improve DM efforts within health systems, constructive relationships with practitioners need to be built by involving important individuals early in the process. It is hoped that evidence-based guidelines will further enhance DM efforts. Beneficial DM initiatives require a multidisciplinary focus of cooperation and willingness to share data between distinct professional groups. More thorough analysis of DM programs is needed in many health systems.

Economic appraisal of antidepressant pharmacotherapy: critical review of the literature and future directions.

In the United States, an estimated $44 billion is expended annually for the treatment, morbidity, and mortality associated with depression. Domestic and international cost-containment initiatives are mandating a demonstration of value for money defined in terms of a measurable health and/or financial outcome, and, in the case of medicines, attributable to a given expenditure for a given pharmacotherapeutic option. Recent pharmacotherapeutic advances in the treatment of depression have included the development of selective serotonin reuptake inhibitors (SSRIs), thereby providing an alternative to tricyclic antidepressants (TCAs). Herein, we review the pharmacoeconomic literature relative to antidepressant pharmacotherapy and identify issues for future inquiry.

Trends in the prescribing of antidepressant pharmacotherapy: office-based visits, 1990-1995.

Data from the National Ambulatory Medical Care Survey for the period 1990 through 1995 were used to discern the population-adjusted rate of office-based physician-patient encounters at which the prescribing or continuation of antidepressant pharmacotherapy (tricyclic antidepressants [TCAs], selective serotonin reuptake inhibitors [SSRIs], or others), a diagnosis of depression (International Classification of Diseases, 9th Revision, Clinical Modification codes 296.2 through 296.36, 300.4, or 311), or both were documented. National estimates of the number of office-based visits resulting in a prescription for or continuation of antidepressant pharmacotherapy for any purpose escalated from 16,534,268 in 1990 to 28,664,796 in 1995, a 73.4% increase. Although the number of office-based visits at which a diagnosis of depression was documented increased 23.2% during this period, the proportion of patients with a diagnosis of depression who were prescribed or continued antidepressant pharmacotherapy increased only 14.9%, from 52.1% in 1990 to 67.0% in 1995. Among patients with a diagnosis of depression, use of a TCA declined from 42.1% in 1990 to 24.9% in 1995. In contrast, use of an SSRI for the treatment of depression increased from 37.1% in 1990 to 64.6% in 1995. The rate of office-based visits at which the use of antidepressant pharmacotherapy for any purpose was documented increased from 6.7 per 100 US population in 1990 to 10.9 in 1995, a 62.7% increase; documentation of a diagnosis of depression increased from 6.1 per 100 US population in 1990 to 7.1 in 1995, a 16.4% increase; and the recording of a diagnosis of depression in concert with the prescribing or continuation of antidepressant pharmacotherapy increased from 3.2 per 100 US population in 1990 to 4.8 in 1995, a 50.0% increase. Further research is required to elucidate the effect of observed trends on clinical and financial outcomes.

Economic outcomes with antidepressant pharmacotherapy: a retrospective intent-to-treat analysis.

Herein we describe a retrospective intent-to-treat evaluation designed to compare the natural course of antidepressant utilization and direct health service expenditures for the treatment of a single episode of major depression among patients enrolled in a multistate network-model health maintenance organization and initially prescribed either a tricyclic antidepressant (amitriptyline or nortriptyline) or the serotonin selective reuptake inhibitor (SSRI) fluoxetine. Patient-level paid-claims data for the period July 1, 1988, through December 31, 1991, were abstracted. During the above time frame, fluoxetine was the only SSRI available in the United States. Patients prescribed amitriptyline were more than three times as likely to require a change in antidepressant pharmacotherapy (OR = 3.27, 95% CI = 2.31 to 5.49), while patients prescribed nortriptyline were nearly four times more likely to change medication (OR = 3.82, 95% CI = 2.74 to 6.83) relative to patients initially prescribed fluoxetine. Consistent with our intent-to-treat design, all accrued health service expenditures were assigned to the pharmacotherapeutic option initially prescribed. Multivariate analyses revealed that initiation of antidepressant pharmacotherapy with amitriptyline resulted in a 25.7% increase in per capita depression-related health service expenditures per year, while initiation of antidepressant pharmacotherapy with nortriptyline resulted in a 28.1% increase in per capita depression-related health service expenditures per year relative to patients initially prescribed fluoxetine. A financial break-even point was achieved at the conclusion of Month 5, at which time all three intent-to-treat cohorts had comparable health service expenditures in total. From a financial perspective, results stemming from this inquiry suggest that the initiation of antidepressant pharmacotherapy with an SSRI is warranted.

Antidepressant prescribing patterns: a comparison of blacks and whites in a medicaid population.

OBJECTIVE: This paper reports results stemming from a retrospective inquiry designed to determine the prescribing pattern of tricyclic antidepressants (TCAs) relative to selective serotonin reuptake inhibitors (SSRIs), and the subsequent effect on regimen adherence among African American (Black) and White beneficiaries enrolled in the state of South Carolina Medicaid programme. PATIENTS AND METHODS: Adjudicated patient-level paid-claims data for the time-frame 1 January 1990 to 31 December 1994 were abstracted resulting in a statewide cohort of 8596 ambulatory beneficiaries, 18 to 64 years of age, without receipt of antidepressant pharmacotherapy in the 1-year time-frame prior to initiating a regimen of either a TCA or SSRI, and remaining Medicaid-eligible for 1 year thereafter. RESULTS: Black race [odds ratio (OR) = 1.56, 95% confidence interval (CI) = 1.43 to 1.70], age 40 to 64 years (OR = 1.15, 95% CI = 1.06 to 1.26), and male gender (OR = 1.27, 95% CI = 1.14 to 1.41) were significant predictors of initiating antidepressant pharmacotherapy with a TCA. Relative to Whites, Blacks were found to be less likely to have obtained at least a 3-month (>/=90 days) supply of a TCA (22.1 vs 31.7%) or an SSRI (30.7 vs 36.1%), or to have obtained a 6-month (>/=180 days) supply of a TCA (6.4 vs 10.9%) or an SSRI (8.1 vs 13.2%). CONCLUSION: Further prospective research is required to discern the reasons for observed differences in prescribing and adherence patterns for antidepressant pharmacotherapy by age, gender and race, and to foster the development of educational programming designed to ensure clinically rational and equitable access to pharmacotherapeutic innovation.

What factors influence the prescribing of antidepressant pharmacotherapy? An assessment of national office-based encounters.

OBJECTIVE: This study was designed to identify: 1) predictors of antidepressant pharmacotherapy among patients diagnosed with depression; and 2) predictors of prescription for either a selective-serotonin reuptake inhibitor (SSRI), or a serotonin-norepinephrine reuptake inhibitor (SNRI). METHOD: Data from the 1995 National Ambulatory Medical Care Survey (NAMCS) were used to discern the number of office-based encounters documenting a diagnosis of depression (ICD-9-CM codes 296.2-296.36; 300.4; or 311) among patients eighteen years of age or older. Logistic regression-derived odds ratios (OR) and 95 percent confidence intervals (CI) were used to elucidate factors predictive of receipt of antidepressant pharmacotherapy, and, more specifically, factors predictive of receipt of an SSRI or an SNRI. Model variables included age (18-49 years as compared to > or = 50 years); race (white as compared to nonwhite, inclusive of Hispanics); gender; self-report of depression as a reason for the office-based encounter; and payer type (private insurance program as compared to public). RESULTS: Among the estimated 18,046,293 office-based visits resulting in a diagnosis of depression, 56.2 percent of patients self-reported depression as a reason for the office-based encounter; 67.5 percent were prescribed or continued a regimen of antidepressant pharmacotherapy; and 48.3 percent were prescribed an SSRI or an SNRI. Factors predictive of receipt of antidepressant pharmacotherapy included age less than fifty years (OR = 1.30, CI = 1.01-1.67); female gender (OR = 1.45, CI = 1.13-1.85); and self-report of depression as a reason for the office-based encounter (OR = 1.98, CI = 1.57-2.51). Factors predictive of receipt of an SSRI or an SNRI included age less than fifty years (OR = 1.31, CI = 1.03-1.65); female gender (OR = 1.55, CI = 1.23-1.95); and self-report of depression as a reason for the office-based encounter (OR = 1.56, CI = 1.25-1.95). In addition, having private insurance increased the likelihood of having been prescribed an SSRI or SNRI by 46 percent (OR = 1.46, CI = 1.13-1.89). CONCLUSIONS: Among patients with a diagnosis of depression, the pattern of prescribing antidepressant pharmacotherapy is influenced by a patient's age, gender, self-report of depression, and type of insurance coverage. Further research is required to discern the reasons for these observed effects and to advance clinically rational and equitable access to pharmacotherapeutic innovation.