Investigation of the antiphase dynamics of the orthogonally polarized passively Q-switched Nd:YLF laser.

The antiphase dynamics of Q-switched orthogonally polarized emissions have been thoroughly investigated. A Nd:YLF crystal with the anisotropic thermal lensing effect is used as the gain medium for achieving dual polarized laser. By using the Cr4+:YAG saturable absorber, the passively Q-switched output shows intriguing switching dynamics, where the number of pulses for both polarized components within one switching period is directly determined by the power ratio between the orthogonally polarized emissions. Experimental results reveal that the pulse energies of every single pulse for both orthogonally polarized states are equal with the maximum value of 223 µJ. The pulse durations for π- and σ-polarization are measured to be 15 ns and 11 ns and the corresponding peak power levels are up to 15.0 kW and 20.3 kW, respectively.

Evaluation of the impact of HIV serostatus, tobacco smoking and CD4 counts on epidermoid anal cancer survival.

Tobacco smoking and HIV infection increase the risk of epidermoid anal cancer (EAC). No published studies have examined smoking and EAC outcomes, and the literature is discrepant regarding outcomes of HIV-positive patients with EAC. The goal of this study was to examine smoking history, HIV status and outcomes in EAC patients. We conducted a retrospective analysis of adults with invasive EAC treated in the University of Washington hospital system from 1 January 1994 to 31 December 2008. Sixty-three patients were included. Forty-seven patients (75%) had primary chemoradiation, of whom 42 (89%) completed therapy. Two patients (3%) received radiotherapy alone. Fourteen patients (22%) underwent primary surgery, of whom 11 (79%) underwent tumour excision and three (21%) abdominoperineal resection (APR). We analysed smoking history, HIV status and CD4 count (≥ 200 cells/µL/<200 cells/µL for HIV-positive patients) versus outcomes. Forty-five patients (71%) were in remission, and 44 (70%) were alive at last follow-up. Overall survival was significantly better for never-smokers than for ever-smokers. There were no differences in outcomes according to HIV status or CD4 counts. Patients with anal cancer who smoke have worse overall survival than non-smoking patients. HIV infection does not appear to affect anal cancer outcomes.

Fusogenic membrane glycoproteins induce syncytia formation and death in vitro and in vivo: a potential therapy agent for lung cancer.

Fusogenic membrane glycoproteins (FMGs) are viral envelope proteins, which bind surface receptors and induce fusion of the cell membrane. An FMG-transfected cell will fuse with neighbor cells, thus forming syncytia that die within 5 days. In this report, plasmids encoding for FMGs from Human Endogenous Retrovirus-W (HERV-W) was compared with Gibbon Ape Leukemia Virus (GALV) and feline endogenous virus RD-114 (RD). These plasmids were transfected in human non-small-cell lung cancer (NSCLC) cells in vitro or directly injected into tumors in mice. All FMGs induced the formation of syncytia containing around 50 cells. HERV-W or GALV FMGs decreased up to 80% of cell viability in vitro and inhibited tumor growth in vivo (60-70% reduction). In contrast, RD FMG was not efficient. Apoptosis played a role in the death of the syncytia, but addition of the caspase inhibitor Z-VAD-fmk had no effect, suggesting that apoptosis is not the only mechanism responsible for FMG-induced cell death. Altogether, our results demonstrate that even at very low transfection efficiency, the antitumor activity of HERV-W FMG is as effective as that of GALV in vitro and in vivo for the treatment of human lung tumors.

Mental disorders among persons with arthritis: results from the World Mental Health Surveys.

BACKGROUND: Prior studies in the USA have reported higher rates of mental disorders among persons with arthritis but no cross-national studies have been conducted. In this study the prevalence of specific mental disorders among persons with arthritis was estimated and their association with arthritis across diverse countries assessed. METHOD: The study was a series of cross-sectional population sample surveys. Eighteen population surveys of household-residing adults were carried out in 17 countries in different regions of the world. Most were carried out between 2001 and 2002, but others were completed as late as 2007. Mental disorders were assessed with the World Health Organization (WHO) World Mental Health-Composite International Diagnostic Interview (WMH-CIDI). Arthritis was ascertained by self-report. The association of anxiety disorders, mood disorders and alcohol use disorders with arthritis was assessed, controlling for age and sex. Prevalence rates for specific mental disorders among persons with and without arthritis were calculated and odds ratios (ORs) with 95% confidence intervals were used to estimate the association. RESULTS: After adjusting for age and sex, specific mood and anxiety disorders occurred among persons with arthritis at higher rates than among persons without arthritis. Alcohol abuse/dependence showed a weaker and less consistent association with arthritis. The pooled estimates of the age- and sex-adjusted ORs were about 1.9 for mood disorders and for anxiety disorders and about 1.5 for alcohol abuse/dependence among persons with versus without arthritis. The pattern of association between specific mood and anxiety disorders and arthritis was similar across countries. CONCLUSIONS: Mood and anxiety disorders occur with greater frequency among persons with arthritis than those without arthritis across diverse countries. The strength of association of specific mood and anxiety disorders with arthritis was generally consistent across disorders and across countries.

Cost-effectiveness of a collaborative care program for primary care patients with persistent depression.

OBJECTIVE: The authors evaluated the incremental cost-effectiveness of stepped collaborative care for patients with persistent depressive symptoms after usual primary care management. METHOD: Primary care patients initiating antidepressant treatment completed a standardized telephone assessment 6-8 weeks after the initial prescription. Those with persistent major depression or significant subthreshold depressive symptoms were randomly assigned to continued usual care or collaborative care. The collaborative care included systematic patient education, an initial visit with a consulting psychiatrist, 2-4 months of shared care by the psychiatrist and primary care physician, and monitoring of follow-up visits and adherence to medication regimen. Clinical outcomes were assessed through blinded telephone assessments at 1, 3, and 6 months. Health services utilization and costs were assessed through health plan claims and accounting data. RESULTS: Patients receiving collaborative care experienced a mean of 16.7 additional depression-free days over 6 months. The mean incremental cost of depression treatment in this program was $357. The additional cost was attributable to greater expenditures for antidepressant prescriptions and outpatient visits. No offsetting decrease in use of other health services was observed. The incremental cost-effectiveness was $21.44 per depression-free day. CONCLUSIONS: A stepped collaborative care program for depressed primary care patients led to substantial increases in treatment effectiveness and moderate increases in costs. These findings are consistent with those of other randomized trials. Improving outcomes of depression treatment in primary care requires investment of additional resources, but the return on this investment is comparable to that of many other widely accepted medical interventions.

Does physician education on depression management improve treatment in primary care?

OBJECTIVE: To assess the effect of physician training on management of depression. DESIGN: Primary care physicians were randomly assigned to a depression management intervention that included an educational program. A before-and-after design evaluated physician practices for patients not enrolled in the intervention trial. SETTING: One hundred nine primary care physicians in 2 health maintenance organizations located in the Midwest and Northwest regions of the United States. PATIENTS/PARTICIPANTS: Computerized pharmacy and visit data from a group of 124,893 patients who received visits or prescriptions from intervention and usual care physicians. INTERVENTIONS: Primary care physicians received education on diagnosis and optimal management of depression over a 3-month training period. Methods of education included small group interactive discussions, expert demonstrations, role-play, and academic detailing of pharmacotherapy, criteria for urgent psychiatric referrals, and case reviews with psychiatric consultants. MEASUREMENTS AND MAIN RESULTS: Pharmacy and visit data provided indicators of physician management of depression: rate of newly diagnosed depression, new prescription of antidepressant medication, and duration of pharmacotherapy. One year after the training period, intervention and usual care physicians did not differ significantly in the rate of new depression diagnosis (P =.95) or new prescription of antidepressant medicines (P =.10). Meanwhile, patients of intervention physicians did not differ from patients of usual care physicians in adequacy of pharmacotherapy (P =.53) as measured by 12 weeks of continuous antidepressant treatment. CONCLUSIONS: After education on optimal management of depression, intervention physicians did not differ from their usual care colleagues in depression diagnosis or pharmacotherapy.

Can depression treatment in primary care reduce disability? A stepped care approach.

OBJECTIVE: To assess effects of stepped collaborative care depression intervention on disability. DESIGN: Randomized controlled trial. SETTING: Four primary care clinics of a large health maintenance organization. PATIENTS: Two hundred twenty-eight patients with either 4 or more persistent major depressive symptoms or a score of 1.5 or greater on the Hopkins Symptom Checklist. Depression items were randomized to stepped care intervention or usual care 6 to 8 weeks after initiating antidepressant medication. INTERVENTION: Augmented treatment of persistently depressed patients by an on-site psychiatrist collaborating with primary care physicians. Treatment included patient education, adjustment of pharmacotherapy, and proactive monitoring of outcomes. MAIN OUTCOME MEASURES: Baseline, 1-, 3-, and 6-month assessments of the Sheehan Disability Scale and the social function and role limitation subscales of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). RESULTS: Patients who received the depression intervention experienced less interference in their family, work, and social activities than patients receiving usual primary care (Sheehan Disability Scale, z = 2.23; P =.025). Patients receiving intervention also reported a trend toward more improvement in SF-36-defined social functioning than patients receiving usual care (z = 1.63, P =.10), but there was no significant difference in role performance (z = 0.07, P =.94). CONCLUSIONS: Significant disability accompanied depression in this persistently depressed group. The stepped care intervention resulted in small to moderate functional improvements for these primary care patients. Arch Fam Med. 2000;9:1052-1058

Low-intensity treatment of depression in primary care: is it problematic?

The aim of this study was to examine patterns of care and outcomes of depressed patients under primary care during acute phase treatment. A cohort of depressed patients was assessed 6-8 weeks after starting pharmacotherapy in four large primary care clinics in a health maintenance organization. These patients (n = 1671) were receiving antidepressant treatment for a new episode of depression. To calculate main outcome measures, Structured Clinical Interview for Depression evaluated prior history and current depression status. Visit and pharmacy refill data described use of health services and antidepressant medication. Six to eight weeks after starting antidepressant therapy, 33.2% of patients had 0-3 depressive symptoms and no prior history of depression, an additional 42.3% also reported 0-3 symptoms but were at high risk of relapse, and 24. 5% were persistently depressed with 4 or more depressive symptoms. In the initial 6 weeks of treatment, these three groups showed similar use of antidepressant medication and health services. About 50% in each group had no follow-up visit for depression and 32%-42% had not refilled their antidepressant prescription. In general, depressed patients under primary care obtained low-intensity pharmacotherapy and inconsistent follow-up visits during initial acute phase treatment. Six weeks after starting antidepressant medicine, many were still symptomatic or recovered but had a high risk of depression relapse. Patients with unfavorable outcomes did not receive more intensive management than the one-third who had favorable outcomes.

Randomized trial of a depression management program in high utilizers of medical care.

BACKGROUND: High utilizers of nonpsychiatric health care services have disproportionally high rates of undiagnosed or undertreated depression. OBJECTIVE: To determine the impact of offering a systematic primary care-based depression treatment program to depressed "high utilizers" not in active treatment. DESIGN: Randomized clinical trial. SETTING: One hundred sixty-three primary care practices in 3 health maintenance organizations located in different geographic regions of the United States. PATIENTS: A group of 1465 health maintenance organization members were identified as depressed high utilizers using a 2-stage telephone screening process. Eligibility criteria were met by 410 patients and 407 agreed to enroll: 218 in the depression management program (DMP) practices and 189 in the usual care (UC) group. INTERVENTION: The DMP included patient education materials, physician education programs, telephone-based treatment coordination, and antidepressant pharmacotherapy initiated and managed by patients' primary care physicians. MAIN OUTCOME MEASURES: Depression severity was measured using the Hamilton Depression Rating Scale (Ham-D) and functional status using the Medical Outcomes Study 20-item short form (SF-20) subscales. Outpatient visit and hospitalization rates were measured using the health plan's encounter data. RESULTS: Based on an intent-to-treat analysis, at least 3 antidepressant prescriptions were filled in the first 6 months by 151 (69.3%) of 218 of DMP patients vs 35 (18.5%) of 189 in UC (P < .001). Improvements in Ham-D scores were significantly greater in the intervention group at 6 weeks (P = .04), 3 months (P = .02), 6 months (P < .001), and 12 months (P < .001). At 12 months, DMP intervention patients were more improved than UC patients on the mental health, social functioning, and general health perceptions scales of the SF-20 (P < .05 for all). CONCLUSION: In depressed high utilizers not already in active treatment, a systematic primary care-based treatment program can substantially increase adequate antidepressant treatment, decrease depression severity, and improve general health status compared with usual care.

Cytochrome CYP sources of N-alkylprotoporphyrin IX after administration of porphyrinogenic xenobiotics to rats.

Cytochrome P-450 (CYP) 3A2 and CYP2C11 are sources of 70 and 30%, respectively, of N-vinylprotoporphyrin IX (N-vinylPP) formation after administration of 3-[(arylthio)ethyl]sydnone (TTMS) to rats. Female rats receiving TTMS were pretreated with dexamethasone, which induces CYP3A1 preferentially to CYP3A2. The resulting 12-fold increase in N-vinylPP formation showed that CYP3A1 was also a source of N-vinylPP. Phenobarbital (PB) pretreatment, which induces CYP2B1/2 and 3A1/2 in male rats, increased N-vinylPP formation after TTMS administration. Troleandomycin, a selective CYP3A inhibitor, was unable to decrease TTMS-mediated N-vinylPP formation in PB-treated male rats, indicating that CYP2B1/2 were sources of N-vinylPP. This conclusion was supported by demonstrating a 15-fold increase in TTMSinduced N-vinylPP formation in female rats after CYP2B1/2 induction with PB pretreatment. Allylispropylacetamide (AIA) inactivates rat CYP2B1/2, 2C6, 2C7, 2C11, and 3A1/2. Troleandomycin was unable to decrease N-AIA protoporphyrin IX adduct (N-AIAPP) formation, showing that CYP3A1/2 were not susceptible to AIA-mediated N-alkylation. N-AIAPP formation in females was approximately 30% of that in males, and thus we attribute 30% of N-AIAPP formation in males to the non-gender-specific isozymes (CYP2C6, 2C7, and/or 2B1/2), whereas approximately 70% originates from CYP2C11. PB treatment in female rats resulted in a 5-fold increase in N-AIAPP formation, showing that CYP2B1/2 were also susceptible to N-alkylation mediated by AIA. 1-Aminobenzotriazole elicited formation of equivalent amounts of N'N-aryl bridged protoporphyrin IX in male and female rat liver, demonstrating that nonselective mechanism-based inactivation is accompanied by nonselective conversion of the CYP heme moieties to N'N-aryl bridged protoporphyrin IX.

Diagnosis of depression by primary care physicians versus a structured diagnostic interview. Understanding discordance.

In this paper, false-negative and false-positive cases of depressive illness are examined, differentiating levels of disagreement between a primary care physician's diagnosis and a standardized research diagnosis. Two stratified random samples of primary care patients in Seattle, USA (N = 373) and Groningen, The Netherlands (N = 340) were examined with the Composite International Diagnostic Interview-Primary Health Care Version (CIDI-PHC). Physician's severity ratings and diagnosis of psychological disorder were obtained. Three levels of disagreement between physician and CIDI diagnosis were distinguished: 1) complete disagreement about the presence of psychiatric symptoms (true false-negative and true false-positive patients); 2) disagreement over severity of recognized psychological illness (underestimated or overestimated); and 3) disagreement over the specific psychiatric diagnosis among those given a diagnosis (misdiagnosed or given another CIDI diagnosis). All three levels of disagreement were common. Only 27% of the false-negative cases were due to complete disagreement (true false-negatives), and 55% of the false-positives were due to complete disagreement (true false-positives). The true false-negative patients were younger, more often employed, rated their own health more favorably, visited their doctor for a somatic complaint and made fewer visits than the underestimated, misdiagnosed, and concordant positive patients. Complete disagreement in depressive diagnoses between the primary care physician and research interview is not as frequent as indicated by an undifferentiated false-negative/ false-positive analysis. Differentiating levels of disagreement does more justice to diagnostic practice in primary care and provides guidance on how to improve the diagnostic accuracy of primary care physicians.

Can enhanced acute-phase treatment of depression improve long-term outcomes? A report of randomized trials in primary care.

OBJECTIVE: The authors' goal was to determine whether improved outcomes from enhanced acute-phase (3-month) treatment for depression in primary care persisted. METHOD: They conducted a 19-month follow-up assessment of 156 patients with major depression in the Collaborative Care intervention trials, which had found greater improvements in treatment adherence and depressive symptoms at 4 and 7 months for patients given enhanced acute-phase treatment than for patients given routine treatment in a primary care setting. Sixty-three of the 116 patients who completed the follow-up assessment had received enhanced treatment, and 53 had received routine treatment in primary care. The Inventory for Depressive Symptomatology and the Hopkins Symptom Checklist were used to measure depressive symptoms. Automated pharmacy data and self-reports were used to assess adherence to and adequacy of pharmacotherapy. RESULTS: At 19 months, the patients who had received enhanced acute-phase treatment did not differ from those who had received routine primary care treatment in clinical outcomes or quality of pharmacotherapy. CONCLUSIONS: Even though enhanced acute-phase treatment of depression in primary care resulted in better treatment adherence and better clinical outcomes at 4 and 7 months, these improvements failed to persist over the following year. Continued enhancement of depression treatment may be needed to ensure better long-term results.

Relapse of depression in primary care. Rate and clinical predictors.

OBJECTIVE: To determine the clinical predictors and rate of relapse for major depression in primary care. DESIGN: A cohort study of subjects in 2 randomized trials of depressed patients diagnosed and prescribed antidepressant medicine by primary care physicians. Baseline, 7-month, and 19-month assessments were conducted. SETTING: A large primary care clinic of a staff-model health maintenance organization. PATIENTS: Two hundred fifty-one primary care patients who did not satisfy Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) criteria for major depression at 7 months. MAIN OUTCOME MEASURES: Relapse was defined as (1) satisfying DSM-III-R criteria for major depression at 19 months, or (2) reporting an interval episode of 2 weeks or more of depressed mood and symptoms between 7 and 19 months. Predictors examined included demographic characteristics, medical comorbidity, disability, and psychological symptoms. Depressive symptoms were measured by Inventory of Depressive Symptoms and Hopkins Symptoms Checklist. RESULTS: Of the patients, 37.1% reported relapse of depression in the 12-month relapse-risk period. The 2 major risk factors associated with relapse were (1) persistence of subthreshold depressive symptoms 7 months after the initiation of antidepressant therapy (odds ratio, 3.3; 95% confidence interval, 2.74-3.93) and (2) history of 2 or more episodes of major depression, or chronic mood symptoms for 2 years (odds ratio, 2.1; 95% confidence interval, 1.41-2.76). Patients with both risk factors were approximately 3 times more likely to relapse than patients with neither. CONCLUSIONS: The relapse rate among primary care patients treated for depression approached that of specialty samples, with more than one third reporting relapse in 1 year. Clinical characteristics can help target high-risk patients for relapse prevention efforts.

Treatment costs, cost offset, and cost-effectiveness of collaborative management of depression.

OBJECTIVE: The report estimates the treatment costs, cost-offset effects, and cost-effectiveness of Collaborative Care of depressive illness in primary care. STUDY DESIGN: Treatment costs, cost-offset effects, and cost-effectiveness were assessed in two randomized, controlled trials. In the first randomized trail (N = 217), consulting psychiatrists provide enhanced management of pharmacotherapy and brief psychoeducational interventions to enhance adherence. In the second randomized trial (N = 153). Collaborative Care was implemented through brief cognitive-behavioral therapy and enhanced patient education. Consulting psychologist provided brief psychotherapy supplemented by educational materials and enhanced pharmacotherapy management. RESULTS: Collaborative Care increased the costs of treating depression largely because of the extra visits required to provide the interventions. There was a modest cost offset due to reduced use of specialty mental health services among Collaborative Care patients, but costs of ambulatory medical care services did not differ significantly between the intervention and control groups. Among patients with major depression there was a modest increase in cost-effectiveness. The cost per patient successfully treated was lower for Collaborative Care than for Usual Care patients. For patients with minor depression. Collaborative Care was more costly and not more cost-effective than Usual Care. CONCLUSIONS: Collaborative Care increased depression treatment costs and improved the cost-effectiveness of treatment for patients with major depression. A cost offset in specialty mental health costs, but not medical care costs, was observed. Collaborative Care may provide a means of increasing the value of treatment services for major depression.

Achieving guidelines for the treatment of depression in primary care: is physician education enough?

OBJECTIVES: The authors examine whether physician education has enduring effects on treatment of depression. METHODS: Depressed primary care patients initiating antidepressant treatment from primary care clinics of a staff-model health maintenance organization were studied. Quasi-experimental and before-and-after comparisons of physician practices, supplemented with patient surveys, were used to compare the process of care and depression outcomes. Intervention consisted of extensive physician education that spanned a 12-month period. This included case-by-case consultations, didactics, academic detailing (eg, clearly stating the educational and behavioral objectives to individual physicians), and role-play of optimal treatment. Main outcome measures were divided into two groups. Quasi-experimental samples included: (1) antidepressant medication selection and (2) adequacy (dosage and duration) of pharmacotherapy. Survey samples included: (3) intensity of follow-up; (4) physician delivered educational messages regarding depression treatment; (5) patient satisfaction; and (6) depression outcomes. RESULTS: No lasting educational effect was observed consistently in any of the outcomes measured. CONCLUSIONS: There was no enduring improvement in the treatment of depression for primary care patients. Depression treatment guidelines were achieved contemporaneously, however, for intervention patients enrolled in a multifaceted program of collaborative care during the training period. These results suggest that continuing programs of reorganized service delivery to support the role of a primary care physician (eg, on-site mental health personnel, close monitoring of patient progress and adherence), in addition to physician training, are essential for the success of guideline implementation.

Outcomes of "inadequate" antidepressant treatment.

OBJECTIVE: To examine outcomes of primary care patients receiving low levels of antidepressant treatment. DESIGN: Cohort study comparing patients receiving anti-depressant treatment within and below the recommended dosing range. SETTING: Primary care clinics of a staff-model health maintenance organization. PATIENTS: Primary care patients initiating antidepressant treatment for depression. MEASUREMENTS AND MAIN RESULTS: Of 88 patients beginning antidepressant treatment, 49 (56%) used "adequate" doses for 30 days or more. Likelihood of "adequate" pharmacotherapy was not related to patient age, gender, medical comorbidity, or baseline depression severity. All the patients showed substantial clinical improvement after four months. Compared with those using "adequate" pharmacotherapy, the patients receiving low-intensity treatment had lower likelihood of clinical response (64% vs 84%; chi-square = 4.44; df = 1; p = 0.035). At four months, however, those receiving low-intensity and those receiving higher-intensity treatment did not differ significantly in either the score on the 20-item Symptom Checklist depression scale (18.91 and 15.72, respectively; F = 1.45; df = 1.86; p = 0.23) or the proportion with persistence of major depression (10% and 4%, respectively; chi-square = 1.30; df = 1; p = 0.25). A replication sample of 157 patients (assessed only at baseline and four months) yielded similar results. CONCLUSIONS: While the patients receiving recommended levels of pharmacotherapy showed somewhat higher improvement rates, many of the patients receiving "inadequate" treatment experienced good short-term outcomes. Efforts to increase the intensity of depression treatment in primary care should focus on the subgroup of patients who fail to respond to initial treatment.

Application of multivariable optimal discriminant analysis in general internal medicine.

OBJECTIVE: To illustrate the use of multivariable optimal discriminant analysis (MultiODA). DESIGN: Data from four previously published studies were reanalyzed using MultiODA. The original analysis was Fisher's linear discriminant analysis (FLDA) for two studies and logistic regression analysis (LRA) for two studies. MEASUREMENTS AND MAIN RESULTS: In Study 1, FLDA achieved an overall percentage accuracy in classification (PAC) for the training sample of 69.9%, compared with 73.5% for MultiODA. In Study 2, the LRA model required three attributes to achieve a 76.1% overall PAC for the training sample and a 79.4% overall PAC for the hold-out sample. Using only two attributes, the MultiODA model achieved similar values. In Study 3, the FLDA model achieved an overall PAC of 82.5%, compared with 87.5% for the MultiODA model. In Study 4, MultiODA identified a two-attribute model that achieved a 93.3% overall training PAC, when an LRA model could not be developed. CONCLUSIONS: MultiODA identified: a superior training model (Study 1); a more parsimonious model that achieved superior overall training and identical hold-out PAC (Study 2); a model that achieved a higher hold-out PAC (Study 3); and a two-attribute model that achieved a relatively high PAC when a multivariable LRA model could not be obtained (Study 4). These findings suggest that MultiODA has the potential to improve the accuracy of predictions made in general internal medicine research.

The role of the primary care physician in patients' adherence to antidepressant therapy.

In this study, the authors attempted to determine predictors of adherence to antidepressant therapy and to identify specific educational messages, side effects, and features of doctor-patient collaboration that influence adherence. Patients newly prescribed antidepressants for depression at a health maintenance organization were identified by using automated pharmacy data and medical records review. Patients (n = 155) were interviewed 1 and 4 months after starting antidepressant medication. Approximately 28% of patients stopped taking antidepressants during the first month of therapy, and 44% had stopped taking them by the third month of therapy. Patients who received the following five specific educational messages--1) take the medication daily; 2) antidepressants must be taken for 2 to 4 weeks for a noticeable effect; 3) continue to take medicine even if feeling better; 4) do not stop taking antidepressant without checking with the physician; and 5) specific instructions regarding what to do to resolve questions regarding antidepressants--were more likely to comply during the first month of antidepressant therapy. Asking about prior experience with antidepressants and discussions about scheduling pleasant activities also were related to early adherence. Side effects, only at severe levels, were associated with early noncompliance. Neuroticism, depression severity, and other patient characteristics did not predict adherence. Primary care physicians may be able to enhance adherence to antidepressant therapy by simple and specific educational messages easily integrated into primary care visits.

Disability and depression among high utilizers of health care. A longitudinal analysis.

We evaluated, among depressed medical patients who are high utilizers of health care, whether improved vs unimproved depression is associated with differences in the course of functional disability. At baseline, 6 months, and 12 months, depression and disability were assessed among a sample of enrollees in health maintenance organizations (N = 145) in the top decile of users of ambulatory health care who exceeded the 70th percentile of health maintenance organization population norms for depression. Improved depression was defined as a reduction of at least one third in depressive symptoms averaged across the two follow-up times. At the 12-month follow-up, persons with severe-improved depression experienced a 36% reduction in disability days (79 days per year to 51 days per year) and a 45% reduction in disability score. Persons with moderate-improved depression experienced a 72% reduction in disability days (62 days per year to 18 days per year) and a 40% reduction in disability score. In contrast, persons with severe-unimproved depression reported 134 disability days per year at baseline, while persons with moderate-unimproved depression reported 77 disability days per year at baseline. Neither group with unimproved depression showed improvement in either disability days or disability score during the 1-year follow-up period. High utilizers of health care with severe-unimproved depression were more likely to have current major depression and to be unemployed. Improved (relative to unimproved) depression was associated with borderline differences in the severity of physical disease and in the percent married. We conclude that depression and disability showed synchrony in change over time. However, depression and disability may show synchrony in change with disability because both depression and disability are controlled by some other factor that influences the chronicity of depression (eg, chronic disease or personality disorder). The finding of synchronous change of depression and disability provides a rationale for randomized controlled trials of depression treatments among depressed and disabled medical patients to determine whether psychiatric intervention might improve functional status in such patients. Such research is needed to determine whether there is a causal relationship between depression offset and reductions in functional disability.