Eosinophil Depletion with Benralizumab for Eosinophilic Esophagitis.

BACKGROUND: Benralizumab is an eosinophil-depleting anti-interleukin-5 receptor α monoclonal antibody. The efficacy and safety of benralizumab in patients with eosinophilic esophagitis are unclear. METHODS: In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial, we assigned patients 12 to 65 years of age with symptomatic and histologically active eosinophilic esophagitis in a 1:1 ratio to receive subcutaneous benralizumab (30 mg) or placebo every 4 weeks. The two primary efficacy end points were histologic response (≤6 eosinophils per high-power field) and the change from baseline in the score on the Dysphagia Symptom Questionnaire (DSQ; range, 0 to 84, with higher scores indicating more frequent or severe dysphagia) at week 24. RESULTS: A total of 211 patients underwent randomization: 104 were assigned to receive benralizumab, and 107 were assigned to receive placebo. At week 24, more patients had a histologic response with benralizumab than with placebo (87.4% vs. 6.5%; difference, 80.8 percentage points; 95% confidence interval [CI], 72.9 to 88.8; P<0.001). However, the change from baseline in the DSQ score did not differ significantly between the two groups (difference in least-squares means, 3.0 points; 95% CI, -1.4 to 7.4; P = 0.18). There was no substantial between-group difference in the change from baseline in the Eosinophilic Esophagitis Endoscopic Reference Score, which reflects endoscopic abnormalities. Adverse events were reported in 64.1% of the patients in the benralizumab group and in 61.7% of those in the placebo group. No patients discontinued the trial because of adverse events. CONCLUSIONS: In this trial involving patients 12 to 65 years of age with eosinophilic esophagitis, a histologic response (≤6 eosinophils per high-power field) occurred in significantly more patients in the benralizumab group than in the placebo group. However, treatment with benralizumab did not result in fewer or less severe dysphagia symptoms than placebo. (Funded by AstraZeneca; MESSINA ClinicalTrials.gov number, NCT04543409.).

Treating moderate-to-severe atopic dermatitis with benralizumab: results from the HILLIER study, a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: Atopic dermatitis (AD) is a chronic (long-lasting) skin disease that leads to dry, itchy, and swollen red spots, which can also be painful and flare up at any time. Some people with AD have a high number of eosinophils, a type of white blood cell, which are associated with worse disease. Medicated creams and lotions, prescribed by health care providers, are meant to reduce the symptoms of AD. For some people, these creams and lotions do not work. Benralizumab injection is a medication that reduces and removes eosinophils. A clinical trial called HILLER tested benralizumab to see if there was a difference in symptoms of AD after reducing or removing eosinophils. This article explains how benralizumab reduced eosinophils and the effect it had on AD symptoms in the HILLIER study. WHAT WERE THE MAIN CONCLUSIONS REPORTED BY THE RESEARCHERS?: Benralizumab reduced blood eosinophil numbers. However, benralizumab showed no evidence of treatment benefit on signs, symptoms, or severity of AD, as measured by three skin assessments compared with placebo. Benralizumab was well tolerated and had a safety profile that was consistent with previous studies. The five most commonly reported side effects were COVID-19 infection, upper respiratory tract infection, headache, swelling of the lymph nodes, and pink eye (conjunctivitis) in patients who received either benralizumab or placebo. WHAT ARE THE KEY TAKEAWAYS?: Benralizumab lowered the number of blood eosinophils without improving AD symptoms and was well tolerated.

Benralizumab does not elicit therapeutic effect in patients with chronic spontaneous urticaria: results from the phase 2b multinational, randomised, double-blind, placebo-controlled ARROYO trial.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a relatively common skin disease associated with hives and angio-oedema. Eosinophils play a role in CSU pathogenesis. Benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, has been shown to induce nearly complete depletion of eosinophils. OBJECTIVES: To determine the clinical efficacy and safety of benralizumab in patients with CSU who were symptomatic despite H1 antihistamine treatment. METHODS: The 24-week, randomised, double-blind, placebo-controlled, phase 2b portion of the ARROYO trial enrolled adult patients with CSU who were currently on H1 antihistamine treatment. Patients were randomised to one of five treatment groups according to benralizumab dose and regimen for a 24-week treatment period. The primary endpoint was change from baseline in ISS7 at Week 12. The key secondary endpoint was change from baseline in UAS7 at Week 12. Additional secondary endpoints included other metrics to assess CSU at Week 24; blood eosinophil levels; and pharmacokinetics and immunogenicity assessments. Exploratory subgroup analyses were conducted to explore responses according to demographics, clinical features and biomarkers. Safety was assessed in all treatment groups. RESULTS: Of 155 patients, 59 were randomised to benralizumab 30 mg, 56 to benralizumab 60 mg and 40 to placebo. Baseline and disease characteristics were consistent with what was expected for patients with CSU. There were no significant differences in change from baseline in ISS7 score at Week 12 between benralizumab and placebo (benralizumab 30 mg vs. placebo, least-squares mean difference -1.01, 95% confidence interval -3.28 to 1.26; benralizumab 60 mg vs. placebo, least-squares mean difference -1.79, 95% confidence interval -4.09 to 0.50) nor in change from baseline in UAS7 score at Week 12 between benralizumab and placebo (benralizumab 30 mg vs. placebo, P = 0.4016; benralizumab 60 mg vs. placebo, P = 0.0819). Depletion of blood eosinophil levels was observed at Week 24 in patients treated with benralizumab. All other secondary endpoints and exploratory/subgroup analyses indicated no significant differences between benralizumab and placebo. Safety results were consistent with the known profile of benralizumab. CONCLUSIONS: Although benralizumab resulted in near-complete depletion of blood eosinophils, there was no clinical benefit over placebo.

Characteristics, treatment patterns, health care resource utilization and costs in patients with bullous pemphigoid: A retrospective analysis of US health insurance claims data.

Background: Real-world data describing the impact of incident bullous pemphigoid (BP) on patients and health care resource utilization (HCRU) are limited. Objective: To examine characteristics, treatment patterns, HCRU, and costs for incident BP. Methods: Retrospective analysis of 2015 to 2019 US health insurance claims for patients ≥18 years with an incident BP diagnosis. Patients with BP were matched to those without on demographic and clinical characteristics. Statistics were descriptive. Results: The mean Charlson Comorbidity Index score was higher for patients with BP (n = 1108) than without (n = 4621) at baseline (mean [SD]: 3.3 [2.7] vs 2.8 [2.4]) and during follow-up (5.0 [4.9] vs 3.7 [3.0]). Hypertension, diabetes, skin ulcers, chronic pulmonary disease, dyslipidemia, sleep disorders, and congestive heart failure were higher with BP. Most patients with BP received antibiotics (>80%) and/or corticosteroids (>90%). Hospitalizations were more common (44.0% vs 17.1%) and monthly all-cause health care costs more than double ($3214 vs $1353) in patients with BP than without. Limitations: Diagnoses were based on billing codes. HCRU claims data may not reflect the true number of encounters. Conclusion: Incident BP is associated with considerable morbidity, HCRU, and costs. More effective, targeted treatments are needed to improve quality of life, while minimizing exposure to systemic corticosteroids.

Opioid utilization patterns among patients with cancer and non-cancer pain.

OBJECTIVE: Opioid pain medication continues to be an important treatment option for patients with moderate to severe cancer and non-cancer pain; however, limited evidence is available regarding differences in opioid use between these two populations. The objective of this analysis was to compare real-world opioid use patterns over time in these two populations. DESIGN: Retrospective analysis of administrative claims data. SETTING: HealthCore Integrated Research Environment database. PATIENTS: Adults with ≥1 opioid pharmacy claim (and a confirmed cancer diagnosis for the cancer pain cohort). MAIN OUTCOME MEASURES: Opioid doses and dose changes following the initial prescribed (index) dose were determined. RESULTS: In the cancer pain (n = 9,209) and non-cancer pain (n = 409,703) cohorts, median index opioid doses were 51.7 and 45.0 morphine-equivalent units (MEU), respectively, and median post-index opioid doses were 55.8 and 45.1 MEU for the cancer pain and non-cancer pain cohorts, respectively. The most common dose escalation in both groups was up to a dose doubling (cancer pain, 31.8 percent; non-cancer pain, 28.3 percent). The proportions of patients with dose increases exceeding two times the index dose were low and clinically comparable between cohorts (cancer pain, 9.9 percent; non-cancer pain, 7.4 percent). CONCLUSIONS: Opioid use was consistent between patients with cancer pain and non-cancer pain, including clinically comparable total daily opioid doses and consistent rates of dose escalations and chronic utilization. Opioid medications are an important element of cancer and non-cancer pain management; thus, access to appropriate therapies, use patterns, and risk assessment and management are important for both patient populations.

Translating Clinical Findings into the Patient's Perspective: Post-hoc Pooled Analysis of Bowel Movement Changes as a Predictor of Improvement in Patients' Opioid-induced Constipation Symptoms and Outcomes.

PURPOSE: Opioid-induced constipation (OIC) is a bothersome side effect of opioid use for the management of noncancer pain, affecting patients' health-related quality of life and chronic-pain management. The objective of this study was to examine the relationship between changes in the frequency of spontaneous bowel movements (SBMs) and changes in patient-reported outcomes (PROs) among patients with OIC treated with naloxegol. METHODS: Post hoc analyses were conducted using pooled data from two Phase III 12-week, placebo-controlled trials of naloxegol for the treatment of OIC (NCT01309841 and NCT01323790). Patients completed the Patient Assessment of Constipation-Quality of Life (PAC-QOL) and PAC-Symptoms (PAC-SYM) at each study visit, and the Straining Scale and Bristol Stool Scale (BSS) with each bowel movement for the study duration. Four subgroups were created based on improvements from baseline in mean frequency of SBMs per week: 0 or worse (no change), +1 SBM, +2 SBMs, and +≥3 SBMs. Spearman correlations assessed the association between mean SBM changes from baseline and mean changes from baseline in PROs; analysis of covariance was used to compare changes from baseline. FINDINGS: A total of 1337 patients with mean (SD) age of 52.2 (11.0) years were included in this analysis. The patient population was predominantly white (79.0%) and female (62.4%). At baseline, mean SBM frequency was 1.4 (1.0) per week. At study end, all 4 SBM-change subgroups experienced improvements in PAC-QOL, PAC-SYM, Straining Scale, and BSS scores, and these changes were significantly correlated with mean changes from baseline in SBMs per week. The subgroup of patients with an increase in SBMs of ≥3 per week experienced the greatest improvements in PROs. IMPLICATIONS: In these patients with OIC, an improvement in the frequency of SBMs by ≥3 per week was associated with consistent improvements in PROs, providing support for the use of improvements in SBMs as a clinical outcome surrogate for managing patients with OIC. Further research is needed to determine a threshold for change in SBMs that is clinically meaningful in both research and clinical settings. A key limitation was the post hoc nature of the study, which was not powered prospectively to examine these relationships.

Laxative utilization over time in chronic pain patients with opioid-induced constipation.

AIM: To determine laxative utilization over time among chronic noncancer pain patients with opioid-induced constipation (OIC). SETTING: A prospective longitudinal study conducted in the USA, Canada, Germany and UK. METHODS: Patients on daily opioid therapy for treatment of chronic noncancer pain with OIC were recruited from clinics to complete a survey at Baseline and weeks 2, 4, 6, 8, 12, 16, 20 and 24. RESULTS: 489 patients completed baseline with 452 completing one or more follow-up visits. 128 (28%) were nonlaxative users, 112 (25%) were insufficient laxative users and 212 (47%) were sufficient laxative users. The consistent sufficient laxative users reported the most bowel movements per week. CONCLUSION: The majority of OIC patients do not take or only intermittently take laxatives.

Opioid-induced constipation in patients with chronic noncancer pain in the USA, Canada, Germany, and the UK: descriptive analysis of baseline patient-reported outcomes and retrospective chart review.

BACKGROUND: The characteristics of patients who suffer from noncancer pain and opioid-induced constipation are not well understood. METHODS: Cross-sectional patient survey and chart review data from the baseline assessment of an ongoing longitudinal study in the USA, Canada, Germany, and the UK were evaluated via descriptive statistics. Participants had confirmation of daily opioid therapy ≥30 mg for ≥4 weeks and self-reported opioid-induced constipation. Response to laxatives was defined by classifying participants into categories of laxative use and evaluating the prevalence of inadequate response to one laxative agent and two or more agents from at least two different laxative classes. Outcomes included the Patient Assessment of Constipation-Symptoms, Work Productivity and Activity Impairment Questionnaire-Specific Health Problem, EuroQOL 5 Dimensions, and Global Assessment of Treatment Benefit, Satisfaction, and Willingness to Continue. RESULTS: Patients reported a mean of 1.4 bowel movements not preceded by laxatives and 3.7 bowel movements with laxative use per week; 83% wanted at least one bowel movement per day. Most commonly reported on Patient Assessment of Constipation-Symptoms were straining/squeezing to pass bowel movements (83%), bowel movements too hard (75%), flatulence (69%), and bloating (69%). Eighty-four percent were taking natural or behavioral therapies; 60% were taking at least one over-the-counter laxative; and 19% were taking at least one prescription laxative. Prevalence of inadequate response to one laxative agent was 94%; inadequate response to two or more agents from at least two different laxative classes was 27%. Mean Work Productivity and Activity Impairment Questionnaire-Specific Health Problem values for percent work time missed, percent impairment while working, and percent activity impairment were 9%, 32% (equivalent of 14 hours of lost productivity per week), and 38%. Mean EuroQOL 5 Dimensions index and visual analog scale scores were 0.49 and 50.6, respectively. Forty-four percent reported being satisfied with their treatment for constipation. CONCLUSION: Patients treated with opioids for noncancer pain commonly endure constipation symptoms that limit their work productivity and overall health-related quality of life while adhering to treatments that provide little relief. Further research is needed to identify more efficacious constipation therapies for this patient population.

Clinical manifestations, diagnosis, and empirical treatments for catatonia.

OBJECTIVE: Review the medical literature on the history and clinical features of catatonia so as to provide a contemporary clinical guide for successfully diagnosing and treating the various clinical forms of catatonia. DESIGN: RESULTS of MEDLINE computerized searches using search terms 'catatonia', 'treatment of catatonia', 'electroconvulsive therapy and catatonia', 'benzodiazepines and catatonia', clinical case reports, and book chapters covering the medical and psychiatric literature relevant to catatonia and its associated treatments were examined. SETTING: Academic medical center. PARTICIPANTS: None. MEASUREMENTS: None. RESULTS: Catatonia is a common but under-recognized clinical syndrome. No large-scale, controlled studies exist to determine the relative effectiveness of current treatments, including sedative-hypnotic medications (benzodiazepines or barbiturates), and electroconvulsive therapy (ECT). CONCLUSION: Despite the lack of large-scale, controlled studies, benzodiazepines appear to be an effective first-line treatment for catatonia. ECT is now often reserved as a second-line treatment despite more than 60 years of documented efficacy and safety. However, ECT should be viewed as a first-line intervention in cases of severe or malignant catatonias.

Propofol for the management of emergence agitation after electroconvulsive therapy: review of a case series.

We report the successful use of propofol in the management of a case series (n = 10) of patients with severe, treatment-resistant, postictal agitation (PIA) in the setting of electroconvulsive therapy (ECT). Despite prior inadequate response to intravenous midazolam and other agents, propofol therapy was highly effective with good control of PIA achieved in all cases. Propofol was well tolerated with occasional, transient, and reversible drops in blood the pressure being the only adverse event noted. The administration of propofol was also versatile being effective, as either a bolus or a bolus followed by an infusion. It appeared to be synergistic with existing therapy. Although further study is needed, these results suggest that propofol may be a very valuable additional agent for the ECT clinician in the management of PIA, which is a common entity in the setting of ECT.

Older adult report of change in depressive symptoms as a treatment decision tool.

OBJECTIVES: To evaluate patient reports of changes in depressive symptoms as information that can be used in treatment decision-making. DESIGN: Longitudinal cohort study. SETTING: The Prevention of Suicide in Primary Care Elderly: Collaborative Trial and the Primary Care Research in Substance Abuse and Mental Health for the Elderly trial, multisite studies investigating the effect of depression interventions on outcomes in primary care. PARTICIPANTS: Fifty-six patients aged 60 and older. MEASUREMENTS: Patient demographics were collected from patient reports. Symptoms of depression were measured using the Centers for Epidemiologic Studies Depression Scale (CES-D) and Hamilton Depression Scale (HAM-D). Changes in depressive symptoms were also measured using the Clinical Global Impressions of Change (CGI-C) as rated by patients in ongoing treatment. RESULTS: Patient ratings of CGI-C were significantly correlated with percentage improvement on the HAM-D as rated by the depression care manager (correlation coefficient (r)=0.44, P<.001) and percentage improvement on the CES-D (r=0.38, P=.005). The patient report of at least "much improved" predicted at least 50% treatment response based on HAM-D scale scores, with a sensitivity of 87.5% and a specificity of 74.2%. CONCLUSION: These findings suggest that patients are able to accurately report their degree of improvement in depressive symptoms. Patient report of at least "much improved" can be used as an estimate of at least 50% depression treatment response. In an era of increasingly fragmented clinical care, these findings demonstrate that older adult primary care patients can accurately self-report overall change in depressive symptoms. When results of repeated depression instruments are not available, patient report of depression treatment response can be used to inform depression treatment decision-making.

Outcomes of minor and subsyndromal depression among elderly patients in primary care settings.

BACKGROUND: Although depressive conditions in later life are a major public health problem, the outcomes of minor and subsyndromal depression are largely unknown. OBJECTIVE: To compare outcomes among patients with minor and subsyndromal depression, major depression, and no depression, and to examine putative outcome predictors. DESIGN: Cohort study. SETTING: Patients from primary care practices in greater New York City, and Philadelphia and Pittsburgh, Pennsylvania. PATIENTS: 622 patients who were at least 60 years of age and presented for treatment in primary care practices that provided usual care in a randomized, controlled trial of suicide prevention. Of the 441 (70.9%) patients who completed 1 year of follow-up, 122 had major depression, 205 had minor or subsyndromal depression, and 114 did not have depression at baseline. MEASUREMENTS: One year after a baseline evaluation, data were collected by using the following tools: Hamilton Depression Rating Scale, the depressive disorders section of the Structured Clinical Interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, fourth edition), Charlson Comorbidity Index, Multilevel Assessment Instrument for measuring instrumental activities of daily living, Physical Component Summary of the Medical Outcomes Study Short Form-36, and Duke Social Support Index. RESULTS: Patients with minor or subsyndromal depression had intermediate depressive and functional outcomes. Mean adjusted 1-year Hamilton depression score was 10.9 (95% CI, 9.6 to 12.2) for those with initial major depression, 7.0 (CI, 5.9 to 8.1) for those with minor or subsyndromal depression, and 2.9 (CI, 1.6 to 4.2) for those without depression (P < 0.001 for each paired comparison). Compared with patients who were not depressed, those who had minor or subsyndromal depression had a 5.5-fold risk (CI, 3.1-fold to 10.0-fold) for major depression at 1 year after controlling for demographic characteristics (P < 0.001). Cerebrovascular risk factors were not associated with a diagnosis of depression at 1 year after controlling for overall medical burden. Initial medical burden, self-rated health, and subjective social support were significant independent predictors of depression outcome. LIMITATIONS: Participants received care at practices that had personnel who had been given enhanced education about depression treatment; 29.1% of participants withdrew from the study before completing 1 year of follow-up. CONCLUSIONS: The intermediate outcomes of minor and subsyndromal depression demonstrate the clinical significance of these conditions and suggest that they are part of a spectrum of depressive illness. Greater medical burden, poor subjective health status, and poorer subjective social support confer a higher risk for poor outcome.

Older patients' aversion to antidepressants. A qualitative study.

BACKGROUND: Depression is common among older patients yet is often inadequately treated. Patient beliefs about antidepressants are known to affect treatment initiation and adherence, but are often not expressed in clinical settings. OBJECTIVE: To explore attitudes toward antidepressants in a sample of depressed, community-dwelling elders who were offered treatment. DESIGN. Cross-sectional, qualitative study utilizing semi-structured interviews. PARTICIPANTS: Primary care patients age 60 years and over with depression, from academic and community primary care practices of the University of Pennsylvania Health System and the Philadelphia Department of Veterans Affairs. Patients participated in either the Prevention of Suicide in Primary Care Elderly: Collaborative Trial or the Primary Care Research in Substance Abuse and Mental Health for the Elderly Trial. Sixty-eight patients were interviewed and responses from 42 participants with negative attitudes toward medication for depression were analyzed. MEASUREMENTS: Interviews were audiotaped, transcribed, and entered into a qualitative software program for coding and analysis. A multidisciplinary team of investigators coded the transcripts and identified key features of narratives expressing aversion to antidepressants. RESULTS: Four themes characterized resistance to antidepressants: (1) fear of dependence; (2) resistance to viewing depressive symptoms as a medical illness; (3) concern that antidepressants will prevent natural sadness; (4) prior negative experiences with medications for depression. CONCLUSIONS: Many elders resisted the use of antidepressants. Patients expressed concerns that seem to reflect their concept of depression as well as their specific concerns regarding antidepressants. These findings may enhance patient-provider communication about depression treatment in elders.

Customized anesthetic preservation of ictal threshold in electroconvulsive therapy: role of adjunctive remifentanil with etomidate.

We present a case of anesthesia for electroconvulsive (ECT) therapy that was complicated by emetic sensitivity to etomidate, fragile ictal threshold, and mild pseudocholinesterase deficiency. The anesthetic was designed in this patient taking all his issues in consideration. The mild pseudocholinesterase deficiency necessitated a (50-75%) reduction in succinylcholine dosage, careful monitoring of the train of four, and postictal amnestic coverage to prevent paralysis upon waking. The significant emetic response to etomidate prompted substitution to propofol and preemptive ondansetron. Propofol significantly raised the ictal threshold but significantly reduced the postprocedural emesis. Eventually, this clinical challenge was resolved with adjunctive use of low-dose etomidate and remifentanil. This combination preserved the ictal parameters, providing patient comfort, good clinical response, and therapeutic efficacy. Although seizure duration and quality often are restored with hyperventilation and caffeine, this case necessitated a return to etomidate for the restoration of satisfactory ictal parameters. Although this effect of remifentanil has been described with methohexital, and etomidate with alfentanil, to the best of our knowledge, this is the first reported case of adjunctive remifentanil with etomidate for preserving ictal threshold. The outpatient course of ECT was thus completed with all psychiatric and anesthetic goals satisfied: adequate seizure quality and duration, no paralysis upon waking, no post-ECT nausea and vomiting, and patient satisfaction. Anesthesiologists should be aware of factors influencing the seizure duration and, keeping in mind the coexisting medical conditions of the patient, adjustments should be made to get the best possible outcome.

Using the minimum data set 2.0 mood disturbance items as a self-report screening instrument for depression in nursing home residents.

OBJECTIVE: Seeking to enhance nursing home residents' involvement in their care, the authors examined whether the Minimum Data Set, Version 2.0 (MDS) Mood Disturbance items could be administered by self-report. They compared the MDS to the Geriatric Depression Scale (GDS) in terms of its association with depression diagnosis. METHODS: Subjects (N=204) were nursing home residents who were interviewed with a psychiatric diagnostic instrument, the GDS, and a self-report version of the MDS mood disturbance items. RESULTS: Analyses of variance and receiver operating characteristics analyses demonstrated that MDS items distinguished subjects with any versus no depression about as well as did the GDS. This pattern held within cognitive, gender, and ethnicity subgroups. CONCLUSION: The MDS Mood Disturbance items can be reliably and validly administered via self-report to persons scoring at least 12 on the Mini-Mental State Exam.

Probing the safety of medications in the frail elderly: evidence from a randomized clinical trial of sertraline and venlafaxine in depressed nursing home residents.

BACKGROUND: In nursing home residents and other frail elderly patients, old age and potential drug-drug and drug-disease interactions may affect the relative safety and efficacy of medications. The purpose of this study was to examine the efficacy and tolerability of venlafaxine and sertraline for the treatment of depression among nursing home residents. METHOD: The study was a 10-week randomized, double-blind, controlled trial of venlafaxine (doses up to 150 mg/day) versus sertraline (doses up to 100 mg/day) among 52 elderly nursing home residents with a DSM-IV depressive disorder and, at most, moderate dementia. The primary measure of outcome was the Hamilton Rating Scale for Depression (HAM-D). Adverse events were monitored and recorded systematically during the trial. RESULTS: Twelve subjects were discontinued due to serious adverse events (SAE), 5 were discontinued due to other significant side effects, and 2 withdrew consent. Tolerability estimated by the time to termination was lower for venlafaxine than sertraline for serious adverse events (log rank statistic = 5.28, p =.022), for serious adverse events or side effects (log rank statistic = 8.08, p =.005), or for serious adverse events, side effects, or withdrawal of consent (log rank statistic = 10.04, p =.002). Mean (SD) HAM-D scores at baseline were 20.2 (3.4) for sertraline and 20.3 (3.7) for venlafaxine; intent-to-treat endpoint HAM-D scores were 12.2 (5.1) and 15.7 (6.2) (F = 3.45; p =.069). There were no differences in categorical responses for the intent-to-treat sample or completers. CONCLUSION: In this frail elderly population, venlafaxine was less well tolerated and, possibly, less safe than sertraline without evidence for an increase in efficacy. This unexpected finding demonstrates the need for systematic research on the safety of drugs in the frail elderly.

Effect of increasing the dose and duration of sertraline trial in the treatment of depressed nursing home residents.

There has been limited research into defining what constitutes an adequate first-line antidepressant trial in elderly patients. The authors report the outcome of extended, high-dosage sertraline treatment in a sample of nursing home residents experiencing residual significant depressive symptoms after 10 weeks of treatment with sertraline at a final dosage of 100 mg/day. Subjects who had a Hamilton Depression Rating Scale score > or = 12 after 10 weeks of treatment with sertraline were eligible for the 8-week open-label extension phase, which involved titrating the sertraline dosage to 200 mg/day. The cumulative response rate was 52% for the extension phase, compared with 37% for the acute phase. Examining acute phase nonresponders, 39% responded during the extension phase. Rates of discontinuation due to adverse events were comparable in the 2 phases. Our findings suggest that an extended trial or high dosages of sertraline may benefit some depressed elderly patients with persistent depression after acute treatment.

The pilot study of a telephone disease management program for depression.

Most depressed patients are seen and treated exclusively by primary care clinicians. However, primary care patients with depression are often not adequately treated. The aims of this pilot study were to measure the impact of a telephone disease management program on patient outcome and clinician adherence to practice guidelines, measure the relationship of clinician adherence to patient outcome, and explore the measurement of patient adherence to clinician recommendations and its impact on patient outcomes. Thirty-five primary care practices in the University of Pennsylvania Health System were randomized to telephone disease management (TDM) or "usual care" (UC). All patients received a baseline and a 16-week follow-up clinical evaluation performed over the telephone. Those from TDM practices also received follow-up contact at least every 3 weeks, with formal evaluations at weeks 6 and 12. These interval contacts were designed to facilitate patient and clinician adherence to a treatment algorithm based on the Agency for Health Research and Quality (AHRQ) practice guidelines. Depressive symptoms evaluated with the Community Epidemiologic Survey of Depression (CES-D) scale as well as guideline adherence were the primary outcome measures. Sixty-one patients were enrolled in this pilot project. The overall effect for CES-D scores over time was significant, (P <.001), indicating that those participating in the trial (both TDM and UC groups) showed significant improvement. The interaction between intervention condition and time was also significant (P <.05), indicating that TDM patients improved significantly more over time than did UC patients. A greater proportion of TDM patients had CES-D scores <16 by Week 16 (66.7 versus 33.3%; chi(2), P <.05). The improvement in depression outcome for the TDM group was related to its impact on improving clinician adherence to depression treatment algorithms. The TDM pilot did not show a statistically significant effect on improving patient adherence to clinician recommendations, however. This preliminary data suggests that TDM for depression improves both clinician guideline adherence and patient outcomes in the acute phase of depression. The effect on patient outcome is at least partially explained by the effect of TDM on clinician adherence to depression treatment algorithms.