Polly Hitchcock Noël

A systematic review of newer pharmacotherapies for depression in adults: evidence report summary.

Depressive disorders, including major depression and dysthymia, are serious disabling illnesses. Approximately one in five persons is affected by a mood disorder at some point (1, 2). The attendant economic costs to society and personal burden to patients and families are enormous. In the United States, the estimated costs of treating depression and the costs incurred by lost productivity exceeded

The Effectiveness of Depression Care Management on Diabetes-Related Outcomes in Older Patients

44 billion in 1990 (3). The personal burden of depression includes higher mortality and impairment in multiple areas of functioning. The World Health Organization estimates that major depression is now the fourth most important cause worldwide of loss in disability-adjusted life-years and will be the second most important cause by 2020 (4, 5). In the late 1980s, the U.S. Department of Health and Human Services sponsored the development of standard treatment guidelines for major depression (6, 7). Since publication of the guidelines, widely publicized emphasis on recognizing and treating depression and development of many new pharmacotherapies have contributed to explosive growth in antidepressant prescribing and increasing pharmacy costs for health plans. Newer antidepressants and readily available herbal remedies have led to wider but sometimes confusing choices for clinicians. The purpose of this paper is to help clinicians make informed choices about antidepressants and herbal therapies for the treatment of depression. Because previous reviews have conclusively demonstrated the efficacy of older antidepressants, this paper focuses on 29 newer antidepressants and 3 herbal remedies (6, 8-11). Older antidepressants and psychosocial therapies are considered only when they are compared directly with a newer antidepressant. Our goal was to summarize data on the efficacy of newer antidepressants and herbal treatments compared with placebo, older antidepressants, and each other for a broad spectrum of depressive disorders. 1.0 Methods English-language and non-English-language literature was identified by using the Cochrane Collaboration Depression, Anxiety and Neurosis Groups specialized registry of 8451 clinical trial articles and from references of pertinent meta-analyses and consultation with experts (1, 6-8, 10, 12-54). The specialized registry contained trials addressing depression identified from multiple sources, including electronic databases, such as MEDLINE, EMBASE, PsychLIT, LILACS, Psyndex, SIGLE, CINAHL, Biological Abstracts, and The Cochrane Library; hand searches of 69 psychiatry-related journals; and contacts with 30 pharmaceutical companies. Sources were searched from 1980 to January 1998 to capture literature relevant to newly released antidepressants. The terms depression, depressive disorder, or dysthymic disorder were combined with a list of 32 specific newer antidepressants and herbal treatments to yield 1277 relevant records. The newer antidepressants are selective serotonin reuptake inhibitors (SSRIs); serotonin and noradrenaline reuptake inhibitors; selective norepinephrine reuptake inhibitors; reversible inhibitors of monoamine oxidase; 5-hydroxy-tryptophan (5-HT2) receptor antagonists; 5-HT1a receptor agonists; -aminobutyric acid (GABA) mimetics; dopamine reuptake inhibitors and antagonists; and herbal remedies, such as hypericum (Table 1). Randomized, controlled trials that were at least 6 weeks in duration; compared a newer antidepressant with another antidepressant (newer or older), placebo, or psychosocial intervention; involved participants with depressive disorders; and had a clinical outcome were reviewed. Two or more independent reviewers identified 315 such trials. Table 1. Classification and Dosage Range of Antidepressants Two persons independently abstracted data from each trial. Data were synthesized descriptively, with attention to participant and diagnostic descriptors; study design, including randomization method and blinding; intervention characteristics; and clinical outcomes. When the studies were conceptually homogenous, quantitative analyses were done by using an empirical Bayes random-effects estimator method. Conceptual homogeneity required similar trial design, comparison of similar drug classes, diagnostic homogeneity, and adequate numbers of trials to justify pooling. Statistical heterogeneity was evaluated by using the chi-square test for homogeneity and Galbraith plots to identify outliers. When statistical heterogeneity was identified, outlier studies were reviewed to identify possible reasons for heterogeneity and studies were reanalyzed without the outliers. Primary outcomes were symptomatic response rate, total discontinuation rates (dropouts), and rates of discontinuation because of adverse events. Secondary outcomes were health-related quality-of-life, functional status, and suicide. Response rates were defined as a 50% or greater improvement in symptoms as assessed by a depression symptoms rating scale or a rating of much or very much improved as assessed by a global assessment method. Response rates were computed by using a modified intention-to-treat approach. This approach computes response rates as the number of patients who stay in treatment and get better divided by the total number of randomly assigned patients. The modified intention-to-treat analysis produces an estimate of treatment effect that is conservative because it assumes that all persons who drop out of the study early receive no benefit. A sensitivity analysis was based on an end point method. In this method, the denominator for the risk ratio was the number of participants who completed follow-up or whose last observation was carried forward. Funnel plots with the Beggs rank-order correlation test and the Egger regression approach were used to estimate the possibility of publication bias whenever a quantitative meta-analysis was performed (54). Publication bias is the tendency of published studies to have different results (usually positive findings) from studies rejected from publication or never submitted for review (usually negative findings). More detailed methods and updates through September 1998 are available in the report on which this manuscript is based (55, 56). This study was funded by the Agency for Healthcare Research and Quality, which specified certain aspects of the study, such as a technical advisory panel and the report format. 2.0 Data Synthesis 2.1 Literature on Newer Antidepressants Three hundred fifteen randomized trials evaluated newer pharmacotherapies for depression. Because some trials had multiple treatment arms, the 315 trials yielded 355 pairwise comparisons. More than 90% of the trials focused on major depression (Table 2). Nine studies focused on dysthymia, a chronic mood disorder characterized by depressed mood for at least 2 years accompanied by two or more vegetative or psychological symptoms. Three studies each examined mixed-anxiety depression and subsyndromal depression, a less symptomatic, acute depression that causes less impairment in social or occupational functioning than major depression. Forty-four trials involved participants with heterogeneous groups of depressive disorders. Most studies (n =206) compared newer and older antidepressants. Serotonin reuptake inhibitors have been the most widely tested; 60 comparisons have been made with placebo, 123 with older antidepressants, and 36 with an SSRI or other newer agent. Table 2. Treatment Trials of Newer Antidepressants and Herbal Remedies More than 90% of the included trials were of short duration (6 to 8 weeks). Among trials reporting visit frequency, patients were seen weekly (62%), every other week (23%), monthly (5%), or on a schedule that varied over time. Trial reporting was often incomplete. Fewer than one third of studies described study settings, few studies described the nature and content of clinical interactions between providers and patients, and fewer than 10% described ethnic background or socioeconomic status of the participants. Of studies that described the study setting, 77 were based in mental health specialty practices and 27 were exclusively in primary care settings. Most studies reported whether recruitment involved inpatient or outpatient settings, and most (160 studies) were based in outpatient practices. Secondary outcomes (health-related quality-of-life, functional status, and suicide) were reported too infrequently for analysis. More than 90% of the randomized trials used double-blinded methods, but fewer than 5% reported whether blinding was successful. Few studies described the method of randomization or allocation and concealment. Approximately 30% of studies had relatively low dropout rates ( 20%), and approximately 20% reported dropout rates exceeding 40%. Analysis of adverse events was complicated by variability in data collection, including voluntary reporting, generic questioning, and standardized scales that may differ and affect the reliability of the overall estimates. 2.2 Major Depression: Newer Antidepressants for Initial Treatment The lifetime risk for major depressive disorder ranges from 10% to 25% for women and 5% to 12% for men, with a point prevalence rate of 5% to 9% for women and 2% to 3% for men (2, 6, 57). It affects persons of all ages, ethnicities, and socioeconomic circumstances. Major depression is characterized by at least 2 weeks of depressed mood or loss of interest or pleasure in nearly all activities (58). The person must experience at least four additional symptoms drawn from a list of vegetative (for example, loss of appetite) and psychological (for example, difficulty concentrating or making decisions) symptoms. In addition, the symptoms must cause clinically significant distress or impairment in social, occupational, or other areas of functioning. In the trials that we reviewed, the average severity of depression was moderate to moderately severe, as measured by a standard symptom rating scale (mean score, 24 [range, 14 to 32], stand

Depression Treatment in a Sample of 1,801 Depressed Older Adults in Primary Care

Context Many patients have both diabetes and depression. Some hypothesize that treating depression might improve diabetes outcomes. Contribution In this randomized trial, 12 months of depression care management for depressed patients with diabetes improved depression-related outcomes and increased the frequency of exercise. However, care management did not affect diet, diabetes medication adherence, glucose testing, or glycemic control. Cautions The study sample had reasonably good diabetes control at baseline. Whether patients with poorly controlled diabetes would benefit from depression care is not known. The Editors Major depression and dysthymic disorder affect 5% to 10% of older adults seen in primary care settings (1-3). Late-life depression is often chronic or recurrent (4-6) and is associated with substantial suffering, functional impairment, and diminished health-related quality of life (7). Diabetes mellitus affects 7.8% of all adults and almost 1 in 5 of those age 60 years and older (8). Individuals with diabetes mellitus have a 2-fold higher rate of major depression than those without diabetes (9, 10). Depression adversely affects the course of coexisting medical illness, contributing to increased symptom burden, functional impairment, and mortality (11, 12). For patients with diabetes mellitus, depression is associated with decreased glycemic control and increased number of micro- and macrovascular complications (13, 14). The mechanism of effect is not understood but may be related to depression-induced abnormalities in neuroendocrine and neurotransmitter function or decreased self-care behaviors (15-20). Integrating evidence-based depression care for persons with diabetes may improve both depression and diabetes outcomes. Three small randomized, controlled trials have studied the effect of treatment for depression on affective and glycemic outcomes in patients with depression and diabetes mellitus (21-23). These studies have consistently shown improvements in affective outcomes, but effects on glycemic control have been mixed. Primary care physicians are well positioned to provide integrated care for depression and diabetes mellitus but face many barriers. Controlled trials report that treatment for depression is efficacious in approximately 70% of persons who complete treatment compared with 30% of those who receive placebo (24). However, these results are difficult to replicate in routine primary care practice. Barriers to high-quality care include suboptimal recognition; inconsistent treatment with lack of close follow-up and monitoring; and organizational barriers, such as brief visits, poor integration with specialty mental health care, competing clinical priorities, and lack of decision support systems (25-27). Simple interventions, such as depression screening and physician education, have little impact on these barriers and patient outcomes (28-30). Treatment models that use a depression specialist working collaboratively with primary care physicians have shown clinically important improvement in patient outcomes (31-37). We recently reported robust effects of such a model for older adults with major depression or dysthymia (37). In this preplanned analysis, we evaluate the effects on affective and diabetes-specific outcomes. If effective care for depression also benefits adherence to self-care regimens, functional status, and other medical illness outcomes, it would add powerful quality-of-care and economic incentives for the dissemination and maintenance of these models. In addition, if effective care for depression improves self-care behaviors, it may also positively affect other chronic medical illnesses with important self-care components. For this prespecified subgroup analysis, we focused on older adults with clinical depression and coexisting diabetes mellitus. We hypothesized that the collaborative care intervention would improve affective symptoms, functional status, self-care behaviors, and glycemic control. In addition, we hypothesized that effects on glycemic control would be greatest for patients with baseline hemoglobin A1c values of 8.0% or greater. Methods The Improving MoodPromoting Access to Collaborative Treatment (IMPACT) study is a multisite randomized, controlled trial of a collaborative care intervention program for late-life depression in primary care (37, 38). Institutional review boards at participating sites approved study protocols, and all participants gave written informed consent. Patients Seven study sites representing 8 diverse health care organizations with a total of 18 primary care clinics in 5 states participated in the study. From July 1999 to August 2001, depressed older adults were recruited through referrals from primary care practitioners and other clinic staff or through systematic depression screening with a 2-item depression screener adapted from the Primary Care Evaluation of Mental Disorders (39). Of the 2190 patients referred to the study, 308 (14%) declined the initial eligibility screening or additional interviews, 54 (3%) had incomplete initial screenings, and 202 (9%) were ineligible because they were younger than 60 years of age or they did not plan to use the participating clinic over the coming 12 months. Of the 32908 patients approached for screening, 5246 (16%) declined the initial screening or follow-up interviews. A total of 1791 (5%) of the initial screenings were incomplete and 23233 (71%) of those screened were not eligible because they did not have one of the core depression symptoms (95%) or because of logistic reasons such as lack of transportation or access to a telephone (5%). The remaining 1626 (74%) of those referred and 2638 (8%) of those screened completed a computer-assisted structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), to assess whether patients met research diagnostic criteria for major depression or dysthymia (40). Inclusion criteria were age 60 years or older, plans to use one of the participating clinics as the main source of general medical care in the coming year, and a diagnosis of current major depression or dysthymic disorder according to the structured clinical interview for DSM-IV. Otherwise eligible persons were excluded because of a current drinking problem (a score of 2 on the CAGE questionnaire) (41), a history of bipolar disorder or psychosis (38), ongoing treatment with a psychiatrist, or severe cognitive impairment defined by a score less than 3 on a 6-item cognitive screener (42). We identified 2102 eligible older adults with major depression or dysthymic disorder, of whom 1801 (86%) enrolled in the study. As part of the structured baseline interview, enrolled patients were asked Has a doctor or another health care worker diagnosed you with or treated you for high blood sugar or diabetes in the past 3 years? The 417 patients who endorsed this question are the focus of the diabetes-specific analyses. After the baseline interview, we randomly assigned participants to the IMPACT intervention or usual care. The randomization was stratified by recruitment method (screening or referral) and clinic. Randomization information was contained in a set of numbered, sealed envelopes for each stratum that were used sequentially for newly enrolled patients at each clinic (38). Diagnoses were communicated to enrolled patients and their primary care physicians. Intervention Patients in the intervention group received a 20-minute educational videotape and a booklet about late-life depression and were encouraged to have an initial visit with a depression care manager at the primary care clinic (43, 44). Care managers were nurses or psychologists who were trained for the study as a depression clinical specialist (38, 45). During the initial visit, the depression clinical specialist conducted a clinical and psychosocial history, reviewed the educational materials, and discussed patient preferences for depression treatment (antidepressant medications or psychotherapy). New patients and patients needing treatment plan adjustments were discussed with a supervising team psychiatrist and a liaison primary care physician during a weekly team meeting. The depression clinical specialist then worked with the patient and his or her regular primary care provider to establish a treatment plan according to an evidence-based treatment algorithm (38). The IMPACT algorithm suggested an initial choice of an antidepressant (usually a selective serotonin reuptake inhibitor) or a course of Problem-Solving Treatment in Primary Care (PST-PC), which consisted of 6 to 8 brief sessions of structured psychotherapy for depression, delivered by the depression clinical specialist in primary care (46-49). For patients who were already receiving antidepressant medications but who were still depressed, the recommendation for partial responders was to increase the dose or augment the antidepressant with a trial of PSTPC; the recommendation for nonresponders was to switch to a different medication or use a trial of PSTPC. Depression clinical specialists also encouraged patients to increase behavioral activation and referred them to additional health or social services, as clinically indicated. The intervention did not specifically address diabetes mellitus or other coexisting medical illnesses. As care managers, depression clinical specialists attempted to follow patients for up to 12 months; they monitored treatment response with the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire (50) and a Web-based clinical information system (51). During the acute treatment phase, in-person or telephone follow-up contacts were suggested at least every other week. Patients who recovered from depression ( 50% reduction in the Patient Health Questionnaire score and <3 of 9 symptoms of major depression) were engaged in developing a relapse prevention plan and were then follo

Depression and Comorbid Illness in Elderly Primary Care Patients: Impact on Multiple Domains of Health Status and Well-being

OBJECTIVES: To examine rates and predictors of lifetime and recent depression treatment in a sample of 1,801 depressed older primary care patients

Treatment of depression improves physical functioning in older adults

PURPOSE Our objective was to examine the relative association of depression severity and chronicity, other comorbid psychiatric conditions, and coexisting medical illnesses with multiple domains of health status among primary care patients with clinical depression. METHODS We collected cross-sectional data as part of a treatment effectiveness trial that was conducted in 8 diverse health care organizations. Patients aged 60 years and older (N = 1,801) who met diagnostic criteria for major depression or dysthymia participated in a baseline survey. A survey instrument included questions on sociodemographic characteristics, depression severity and chronicity, neuroticism, and the presence of 11 common chronic medical illnesses, as well as questions screening for panic disorder and posttraumatic stress disorder. Measures of 4 general health indicators (physical and mental component scales of the SF-12, Sheehan Disability Index, and global quality of life) were included. We conducted separate mixed-effect regression linear models predicting each of the 4 general health indicators. RESULTS Depression severity was significantly associated with all 4 indicators of general health after controlling for sociodemographic differences, other psychological dysfunction, and the presence of 11 chronic medical conditions. Although study participants had an average of 3.8 chronic medical illnesses, depression severity made larger independent contributions to 3 of the 4 general health indicators (mental functional status, disability, and quality of life) than the medical comorbidities. CONCLUSIONS Recognition and treatment of depression has the potential to improve functioning and quality of life in spite of the presence of other medical comorbidities.

Continuity of care, self-management behaviors, and glucose control in patients with type 2 diabetes

Objectives: To determine the effect of collaborative care management for depression on physical functioning in older adults.

Collaborative care needs and preferences of primary care patients with multimorbidity

Background. The influence of continuity of care on outcomes of care for patients with type 2 diabetes is poorly understood. Objective. To examine the relationships between continuity, glucose control, and advancement through stages of change for selfmanagement behaviors. Design. Prospective cohort study. Setting. Five community health centers on the Texas‐Mexico border. Subjects. A random sample of 256 adults, 18 years of age and older with an established diagnosis of type 2 diabetes. Measures. Stage of change for diet and exercise were assessed during two patient interviews, averaging 18.9 months apart. Phlebotomy was performed at each interview to measure glycosolated hemoglobin (HbA1C). Medical records were abstracted for ambulatory care utilization. A continuity score was calculated based on the number of visits and number of providers seen. Results. Patients who advanced one or more stages of change for diet had higher levels of continuity. As continuity improved, the change in HbA1C was smaller. (r = –0.25; P <0.001) This relationship remained significant after controlling for number of visits, months since diagnosis, number of days in the study, duration of diabetes, and advancement in stage of change for diet. Advancement through stage of change for diet explained a significant amount of the variance in the relationship between continuity and HbA1C (t test = –11.33; P <0.01). Conclusions. Continuity of care with a primary care provider is associated with better glucose control among patients with type 2 diabetes. This relationship appears to be mediated by changes in patient behavior regarding diet.

Impact of Comorbid Panic and Posttraumatic Stress Disorder on Outcomes of Collaborative Care for Late-Life Depression in Primary Care

Objective  To explore the collaborative care needs and preferences in primary care patients with multiple chronic illnesses.

Management of overweight and obese adults

OBJECTIVE Comorbid anxiety disorders may result in worse depression treatment outcomes. The authors evaluated the effect of comorbid panic disorder and posttraumatic stress disorder (PTSD) on response to a collaborative-care intervention for late-life depression in primary care. METHODS A total of 1,801 older adults with depression were randomized to a collaborative-care depression treatment model versus usual care and assessed at baseline, 3, 6, and 12 months, comparing differences among participants with comorbid panic disorder (N=262) and PTSD (N=191) and those without such comorbid anxiety disorders. RESULTS At baseline, patients with comorbid anxiety reported higher levels of psychiatric and medical illness, greater functional impairment, and lower quality of life. Participants without comorbid anxiety who received collaborative care had early and lasting improvements in depression compared with those in usual care. Participants with comorbid panic disorder showed similar outcomes, whereas those with comorbid PTSD showed a more delayed response, requiring 12 months of intervention to show a significant effect. At 12 months, however, outcomes were comparable. Interactions of intervention status by comorbid PTSD or panic disorder were not statistically significant, suggesting that the collaborative-care model performed significantly better than usual care in depressed older adults both with and without comorbid anxiety. CONCLUSIONS Collaborative care is more effective than usual care for depressed older adults with and without comorbid panic disorder and PTSD, although a sustained treatment response was slower to emerge for participants with PTSD. Intensive and prolonged follow-up may be needed for depressed older adults with comorbid PTSD.

The Challenges of Multimorbidity from the Patient Perspective

New treatment strategies have failed to control the global increase in obesity. Here two scientists discuss common barriers that need to be overcome by both healthcare professionals and patients if weight reduction is to be achieved and maintained The 1980s and ‘90s witnessed alarming increases in obesity across the globe.1 This epidemic has not been slowed by new treatment strategies, leading some health professionals to doubt if they can help their patients. A recent audit documented wide variation in the management of overweight and obese patients in general practices in England and uncertainty about which treatments were most effective.2 Healthcare providers may fail to address obesity for many reasons, including cynicism about the efficacy of treatments, lack of time, perceived non-compliance of patients, and lack of training in counselling and motivating patients to change their behaviour. 3 4 Although the control of obesity ultimately requires population based strategies, doctors can and should provide effective individual care. We review evidence based recommendations for managing overweight and obese adults. #### Summary points We searched Medline (1966-March 2002) using the terms “obesity or overweight” and “practice guideline, systematic review, …