PURPOSE: Some studies suggest that anthropometric measures of abdominal obesity may be superior to body mass index (BMI) for the prediction of cardiometabolic risk factors; however, most studies have been cross-sectional. Our aim was to prospectively examine the association of change in BMI, waist-to-hip ratio (WHR), waist circumference (WC), and waist circumference-to-height ratio (WCHtR) with change in markers of cardiometabolic risk in a population of postmenopausal women. METHODS: We used a subsample of participants in the Women's Health Initiative aged 50 to 79 years at entry with available fasting blood samples and anthropometric measurements obtained at multiple time points over 12.8 years of follow-up (n = 2672). The blood samples were used to measure blood glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides at baseline, and at years 1, 3, and 6. We conducted mixed-effects linear regression analyses to examine associations at baseline and longitudinal associations between change in anthropometric measures and change in cardiometabolic risk factors, adjusting for covariates. RESULTS: In longitudinal analyses, change in BMI, WC, and WCHtR robustly predicted change in cardiometabolic risk, whereas change in WHR did not. The strongest associations were seen for change in triglycerides, glucose, and HDL-C (inverse association). CONCLUSION: Increase in BMI, WC, and WCHtR strongly predicted increases in serum triglycerides and glucose, and reduced HDL-C. WC and WCHtR were superior to BMI in predicting serum glucose, HDL-C, and triglycerides. WCHtR was superior to WC only in predicting serum glucose. BMI, WC, and WCHtR were all superior to WHR.

CONTEXT: Evidence for the efficacy of combination pharmacotherapy has been limited and without positive trials in geriatric patients with major depression (MD) with psychotic features. OBJECTIVES: To compare remission rates of MD with psychotic features in those treated with a combination of atypical antipsychotic medication plus a serotonin reuptake inhibitor with those treated with antipsychotic monotherapy; and to compare response by age. DESIGN: Twelve-week, double-blind, randomized, controlled trial. SETTING: Clinical services of 4 academic sites. Patients Two hundred fifty-nine subjects with MD with psychotic features randomized by age (<60 or > or =60 years) (mean [standard deviation (SD)], 41.3 [10.8] years in 117 younger adults vs 71.7 [7.8] years in 142 geriatric participants). Intervention Target doses of 15 to 20 mg of olanzapine per day plus masked sertraline or placebo at 150 to 200 mg per day. Main Outcome Measure Remission rates of MD with psychotic features. RESULTS: Treatment with olanzapine/sertraline was associated with higher remission rates during the trial than olanzapine/placebo (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.12-1.47; P < .001); 41.9% of subjects who underwent combination therapy were in remission at their last assessment compared with 23.9% of subjects treated with monotherapy (chi(2)(1) = 9.53, P = .002). Combination therapy was comparably superior in both younger (OR, 1.25; 95% CI, 1.05-1.50; P = .02) and older (OR, 1.34; 95% CI, 1.09-1.66; P = .01) adults. Overall, tolerability was comparable across age groups. Both age groups had significant increases in cholesterol and triglyceride concentrations, but statistically significant increases in glucose occurred only in younger adults. Younger adults gained significantly more weight than older subjects (mean [SD], 6.5 [6.6] kg vs 3.3 [4.9] kg, P = .001). CONCLUSIONS: Combination pharmacotherapy is efficacious for the treatment of MD with psychotic features. Future research must determine the benefits vs risks of continuing atypical antipsychotic medications beyond 12 weeks. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00056472.

CONTEXT: Evidence for the efficacy of combination pharmacotherapy has been limited and without positive trials in geriatric patients with major depression (MD) with psychotic features. OBJECTIVES: To compare remission rates of MD with psychotic features in those treated with a combination of atypical antipsychotic medication plus a serotonin reuptake inhibitor with those treated with antipsychotic monotherapy; and to compare response by age. DESIGN: Twelve-week, double-blind, randomized, controlled trial. SETTING: Clinical services of 4 academic sites. Patients Two hundred fifty-nine subjects with MD with psychotic features randomized by age ( or =60 years) (mean [standard deviation (SD)], 41.3 [10.8] years in 117 younger adults vs 71.7 [7.8] years in 142 geriatric participants). Intervention Target doses of 15 to 20 mg of olanzapine per day plus masked sertraline or placebo at 150 to 200 mg per day. Main Outcome Measure Remission rates of MD with psychotic features. RESULTS: Treatment with olanzapine/sertraline was associated with higher remission rates during the trial than olanzapine/placebo (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.12-1.47; P < .001); 41.9% of subjects who underwent combination therapy were in remission at their last assessment compared with 23.9% of subjects treated with monotherapy (chi(2)(1) = 9.53, P = .002). Combination therapy was comparably superior in both younger (OR, 1.25; 95% CI, 1.05-1.50; P = .02) and older (OR, 1.34; 95% CI, 1.09-1.66; P = .01) adults. Overall, tolerability was comparable across age groups. Both age groups had significant increases in cholesterol and triglyceride concentrations, but statistically significant increases in glucose occurred only in younger adults. Younger adults gained significantly more weight than older subjects (mean [SD], 6.5 [6.6] kg vs 3.3 [4.9] kg, P = .001). CONCLUSIONS: Combination pharmacotherapy is efficacious for the treatment of MD with psychotic features. Future research must determine the benefits vs risks of continuing atypical antipsychotic medications beyond 12 weeks. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00056472.

The independent association of age and other factors with suicidality in patients with major depression with psychotic features was examined. Of the 183 study participants, 21% had a suicide attempt during the current episode. Male gender, Hispanic background, past suicide attempt, higher depression scores, and higher cognitive scores were each independently associated with greater intensity of current suicidality. Older age was independently associated with a lower risk of a lifetime suicide attempt. These findings reinforce the evidence that patients with psychotic depression are at high risk for suicide and underscore the importance of examining correlates of suicidality specific to patients with psychotic depression.

BACKGROUND: Among patients with major depression with psychotic features, little is known about the extent to which those with and without somatic delusions differ. METHODS: The first 183 participants in the STOP-PD study were divided into two groups based on the presence or absence of somatic delusions and were compared on multiple demographic and clinical characteristics. RESULTS: In the multivariate analysis, those with somatic delusions reported more somatic symptoms, rated their health as worse, and were less likely to have persecutory delusions. CONCLUSIONS: Based on the methods we used, we could not detect meaningful differences between subjects with and without somatic delusions. This suggests that the presence of irrational somatic ideation does not define a distinct clinical subgroup among patients with psychotic depression. This finding needs to be replicated.

Weight gain has often been associated with olanzapine treatment, yet little is known about the influence of patient age or cumulative dose on olanzapine-associated weight gain. The first 118 participants in the National Institutes of Mental Health Study of the Pharmacotherapy of Psychotic Depression randomized clinical trial (ClinicalTrials.gov Registration NCT00056472) completing at least 4 weeks of treatment with olanzapine were analyzed to determine the relationship between weight gain, age, and cumulative olanzapine dose. Younger (age 18-59 years) and older (age 60+ years) participants received open-label olanzapine and either sertraline or placebo for up to 12 weeks. Linear mixed effect regression modeling was used to determine the effects of age and cumulative olanzapine dose on weight gain, controlling for potential confounders. Age was observed to have a significant negative association with weight gain (P=0.01), even after controlling for differences in cumulative dose and baseline body mass index. Each 10-year increase in age was associated with a decrease in mean weight gain over 12 weeks of approximately 0.6 kg (95% confidence interval: 0.14-1.05 kg). Cumulative olanzapine dose was also significantly associated with weight gain (P<0.0001). Approximately 60% of completers of the 12-week trial experienced clinically significant weight gain (> or =7% of baseline weight).

BACKGROUND: Major depressive disorder with psychotic features (psychotic depression), though occurring relatively frequently in the general population, is a commonly missed psychiatric diagnosis. OBJECTIVE: To ascertain accuracy of diagnosis of psychotic depression among inpatients at 4 academic medical centers and explore whether presenting symptoms, treatment setting, and physician's level of training affect the accuracy of diagnosis. METHOD: The medical records of 65 patients who met DSM-IV criteria for psychotic depression following systematic assessment were analyzed to ascertain the concordance between chart diagnoses and research diagnoses arrived at using the Structured Clinical Interview for DSM-IV. The patients were participants in the National Institute of Mental Health Study of Pharmacotherapy of Psychotic Depression, conducted from December 28, 2002, through June 18, 2004, at 4 academic medical centers. For each patient's hospital visit, separate standardized data forms were completed on the basis of each physician's assessment of the patient prior to screening for the study. Hospital records from the emergency room and from admission to psychiatric units were reviewed. Among these 65 patients, 130 chart diagnoses had been made. RESULTS: Psychotic depression had not been diagnosed prior to research assessments for 27% of the 130 diagnoses in our sample. The 3 most common diagnoses assigned to patients meeting research criteria for psychotic depression were major depressive disorder without psychotic features, depression not otherwise specified, and mood disorder not otherwise specified. Failure to identify psychotic depression was more likely when symptoms of depressed mood, hallucinations, or delusions were not noted in the medical record (all p < .005). The accuracy of diagnoses was greater on inpatient units than in emergency rooms (chi(2) = 7.64, p < .01). CONCLUSION: The diagnosis of psychotic depression is frequently missed in emergency room and inpatient settings. The findings of this study are sobering given the serious morbidity and mortality of psychotic depression and the implications for treatment if an inaccurate diagnosis is made. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00056472.

OBJECTIVE: Practice guidelines recommend the use of a combination of an antidepressant and an antipsychotic for the pharmacologic treatment of major depressive disorder with psychotic features (MD-Psy). We assessed the extent to which the pharmacotherapy received by patients with MD-Psy under usual care conforms to these recommendations. METHOD: We assessed the pharmacotherapy received under usual care conditions by 100 patients with MD-Psy prior to enrollment in STOP-PD (Study of the Pharmacotherapy of Psychotic Depression), a 12-week randomized, controlled trial comparing olanzapine plus sertraline to olanzapine plus placebo. Our assessment took place from January 2003 to May 2004. The strength of antidepressant trials was rated using the Antidepressant Treatment History Form (ATHF). The strength of antipsychotic trials or combinations of antidepressants and antipsychotics was rated using a modified version of the ATHF. We also determined whether the strength of antipsychotic or combination trials was associated with age, the duration of the current depressive episode, medical burden, cognitive status, or the severity of depressive or psychotic symptoms. RESULTS: Most patients with MD-Psy were treated with antidepressants (N = 82, 82%) or antipsychotics (N = 65, 65%). About half of the patients (N = 48, 48%) received therapeutic doses of an antidepressant; 10% (N = 10) received an intermediate dose of an antipsychotic, and 6% (N = 6) received a high dose. Overall, only 5% (N = 5) received a combination of an adequate dose of an antidepressant and a high dose of an antipsychotic. The strength of both antipsychotic trials (p = .021) and combination trials (p = .039) was significantly associated only with a longer duration of the current depressive episode. CONCLUSIONS: These findings show a persisting low use of antipsychotics in the treatment of MD-Psy. Given the high morbidity rates associated with MD-Psy, it is important to continue to educate clinicians regarding its identification and treatment. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT00056472.

BACKGROUND: Although delusions are the hallmark of major depression with psychotic features, a scale to measure the intensity of beliefs across multiple delusional domains in this condition has been unavailable. The development and assessment of the Delusional Assessment Scale (DAS) are described. METHODS: Scale items were selected initially based on previous studies of delusional ideation in schizophrenia. A three-point item to assess mood congruence was added. A 15-item scale was assessed in 92 subjects participating in the four-site collaborative study of the pharmacotherapy of major depression with psychotic features. Maximum likelihood method was used to determine scale factors. The internal consistency of these factors was determined. Comparisons between scale scores and ratings from the Brief Psychiatric Rating Scale (BPRS) (Overall and Gorham 1962) were used to assess convergent and discriminant validity. RESULTS: The data were fit by a five-factors model (impact, conviction, disorganization, bizarreness, and extension). Inter-rater reliability of the five factors ranged from .77 for conviction and .74 for impact to .37 for disorganization. Internal consistency for each of the five factors was > or =.72. Scores on specific domains were significantly correlated with the BPRS unusual thought content item and positive symptom subscale scores. CONCLUSIONS: The DAS is a reliable measure of 5 delusional domains.