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The detection of depression in medical setting: a study with PRIME-MD

Fraguas, Renerio Jr; Henriques, Sergio Gonsalves Jr; De Lucia, Mara S; Iosifescu, Dan V; Schwartz, Faye H; Menezes, Paulo Rossi; Gattaz, Wagner Farid; Martins, Milton Arruda
BACKGROUND: Studies investigating the performance of instruments to detect major depressive disorder (MDD) have reported inconsistent results. Subsyndromal depression (SD) has also been associated to increased morbidity, and little is known about its detection in primary care setting. This study aimed to investigate the performance of the Primary Care Evaluation of Mental Disorders (PRIME-MD) to detect MDD and any depression (threshold at SD) in an outpatient unit of a teaching general hospital. METHODS: Nineteen primary care physicians using the PRIME-MD evaluated 577 patients, 240 of them (75% female; mean age, 40.0 +/- 14.4), including all with MDD and a randomly subset of those without MDD, were evaluated by 11 psychiatrists using the Structured Clinical Interview Axis I Disorders, Patient Version (SCIDI/P) for DSM-IV as the standard instrument. RESULTS: The kappa between the PRIME-MD and the SCID was 0.42 for the diagnosis of any depression and 0.32 for MDD. The distribution of the number of depressive symptoms per patient suggested the existence of a continuum between SD and MDD, and a high frequency of subjects with 4-6 symptoms (close to the cutoff for the diagnosis of MDD). LIMITATIONS: The sample has a modest size and is a subset of an original one. CONCLUSION: A continuum between SD and MDD may in part explain the relatively low agreement for the diagnosis of MDD in our sample and possibly in other studies. Studies investigating the performance of screening instruments to detect MDD, should consider the relevance of identifying SD, and the influence of the distribution of the number of depressive symptoms in their results.
PMID: 16427132
ISSN: 0165-0327
CID: 2389752

Clinical characteristics of depressed patients with comorbid diabetes mellitus

Petersen, Timothy; Iosifescu, Dan V; Papakostas, George I; Shear, Deborah L; Fava, Maurizio
Both diabetes and depression are highly prevalent. Patients with diabetes experience higher rates of depression compared to the general population. When present, depression is associated with an increase in the morbidity and mortality of diabetes, suggesting the importance of treatment in this population. The objective of the present study was to characterize depressive characteristics in depressed patients with and without comorbid diabetes. Seventeen patients with type 1 or type 2 diabetes were drawn from outpatient clinical trials. Depressed patients without diabetes were identified from the same studies. Unpaired t-tests and multiple chi-square analyses were used to compare demographic and clinical characteristics between the samples. Diabetic patients in our sample were more depressed and reported lower levels of somatic well-being and contentment compared to non-diabetic patients. The samples did not differ significantly along other dimensions of depression, including course of illness, response to previous treatments and comorbid conditions. These findings suggest that depressed diabetic patients are more similar than not to non-diabetic depressed patients, although important differences exist.
PMID: 16317316
ISSN: 0268-1315
CID: 2389762

A description of next-step switching versus augmentation practices for outpatients with treatment-resistant major depressive disorder enrolled in an academic specialty clinic

Papakostas, George I; Petersen, Timothy J; Green, Cassandra; Iosifescu, Dan V; Yeung, Albert S; Nierenberg, Andrew A; Fava, Maurizio; Posternak, Michael A
BACKGROUND: There is a paucity of naturalistic studies from depression specialty clinics describing the next-step (augmentation versus switching) practices of clinicians for outpatients with major depressive disorder (MDD) resistant to an antidepressant trial of adequate dose and duration. METHODS: Eighty-five MDD outpatients enrolled in one of two specialty clinics, who had not achieved remission after a first adequate prospective antidepressant trial conducted at the clinic underwent either augmentation (n = 36) or switching (n=49) of their antidepressant regimen. Outcome was defined with the use of the Clinical Global Impressions (CGI) Scale. RESULTS: Nonresponders (CGI-I>3) following the first antidepressant trial were more likely to have their treatment switched than patients who experienced incomplete response (CGI-I<4, CGI-S>1) (67.2% versus 28.5%, p = 0.001). Incomplete responders during the first trial who went on to receive augmentation had higher remission rates (60.0% versus 0%, p=0.01), lower endpoint depression severity scores (1.8 +/- 1.1 versus 3.3 +/- 0.8, p = 0.01) and greater clinical improvement scores (1.6 +/- 1.1 versus 3.0 +/- 0.0, p=0.03) than incomplete responders who had their antidepressant regimen switched. Although nonresponders to the first treatment who were switched experienced greater symptom improvement than nonresponders who were augmented (2.7 +/- 1.1 versus 3.4 +/- 1.2, p=0.03), there was no significant difference (p>0.05) between these two groups with respect to remission rates (18.6% versus 14.2%, respectively) and endpoint depressive severity (3.0 +/- 1.4 versus 3.4 +/- 1.4, respectively). CONCLUSIONS: In this nonrandomized, naturalistic treatment setting, nonresponders to an adequate, prospective antidepressant trial were more likely to have their antidepressant regimen switched, while patients with incomplete response during the first trial were more likely to have their regimen augmented. In addition, patients with incomplete response who had their treatment augmented had better outcome than patients with incomplete response who had their treatment switched.
PMID: 16433058
ISSN: 1040-1237
CID: 2389742

Brain MRI white matter hyperintensities and one-carbon cycle metabolism in non-geriatric outpatients with major depressive disorder (Part I)

Iosifescu, Dan V; Papakostas, George I; Lyoo, In Kyoon; Lee, Ho Kyu; Renshaw, Perry F; Alpert, Jonathan E; Nierenberg, Andrew; Fava, Maurizio
The objective of the present work was to study the interrelationship between white matter hyperintensities (WMHs), cardiovascular risk factors and elements of the one-carbon cycle including serum folate, vitamin B12, and homocysteine levels in a relatively young sample of outpatients with major depressive disorder (MDD), and to compare the severity of white matter hyperintensities in MDD patients and healthy volunteers. Fifty MDD outpatients (34% women, age 40.6+/-10.3 years), free of psychotropic medications for at least 2 weeks before enrollment, underwent magnetic resonance imaging (MRI) scans of the brain to detect T2 WMHs and also had (1) serum folate, vitamin B12, homocysteine and cholesterol levels measured, and (2) cardiovascular risk factors assessed during the same study visit. Thirty-five healthy comparison subjects (40% women, age 39.2+/-9.8 years) also underwent brain MRI scans. Hypofolatemia, hypertension and age independently predicted a greater severity of total brain WMHs. Separately, the same factors also predicted a greater severity of subcortical WMHs. Hypofolatemic and hypertensive patients had more severe WMHs than normal controls. In light of the adverse impact of WMHs on a number of health-related outcomes later in life, hypofolatemia and hypertension may represent modifiable risk factors to prevent the occurrence of such adverse outcomes.
PMID: 16298109
ISSN: 0165-1781
CID: 2389772

Brain MRI white matter hyperintensities and one-carbon cycle metabolism in non-geriatric outpatients with major depressive disorder (Part II)

Papakostas, George I; Iosifescu, Dan V; Renshaw, Perry F; Lyoo, In Kyoon; Lee, Ho Kyu; Alpert, Jonathan E; Nierenberg, Andrew A; Fava, Maurizio
The objective of this study was to investigate the relative impact of brain white matter hyperintensities (WMHs), cardiovascular risk factors and elements of the one-carbon cycle metabolism (including serum folate, vitamin B12 and homocysteine levels) on the outcome of antidepressant treatment in non-elderly subjects with major depressive disorder (MDD). Fifty MDD subjects were administered brain magnetic resonance imaging (MRI) scans at 1.5 T to detect T2 WMHs. The severity of brain WMHs was classified with the Fazekas scale (range=0-3). We assessed cardiovascular risk factors in all MDD subjects (age, gender, smoking, diabetes, family history, hypertension, cholesterol). MDD patients also had serum folate, vitamin B12 and homocysteine levels measured. All MDD subjects received treatment with fluoxetine 20 mg/day for 8 weeks. In a logistic regression, the severity of subcortical WMHs and the presence of hypofolatemia were independent predictors of lack of clinical response to antidepressant treatment. Separately, hypofolatemia also predicted lack of remission to antidepressant treatment. These associations were independent of the presence of smoking, diabetes, family history, hypercholesterolemia, hyperhomocysteinemia and low B12 levels. Although preliminary, the results of the present work suggest that subcortical brain WMHs and hypofolatemia may have an independent negative impact on the likelihood of responding to antidepressant treatment in non-geriatric subjects with MDD.
PMID: 16297603
ISSN: 0165-1781
CID: 2389782

Cardiovascular risk factors may moderate pharmacological treatment effects in major depressive disorder

Iosifescu, Dan V; Clementi-Craven, Nicoletta; Fraguas, Renerio; Papakostas, George I; Petersen, Timothy; Alpert, Jonathan E; Nierenberg, Andrew A; Fava, Maurizio
OBJECTIVE: An increased association between depression and cardiovascular disease, as well as cardiovascular risk factors, led to the "vascular depression" hypothesis. This subtype of depression is postulated to have a different clinical presentation and to be more treatment-resistant. In this study, we measured the impact of cardiovascular risk factors on the outcome of antidepressant treatment in major depressive disorder (MDD). METHOD: We enrolled 348 MDD subjects, ages 19 to 65 years, in an 8-week treatment study with 20 mg fluoxetine per day. We recorded for each subject 6 cardiovascular risk factors: age (male > or =45, female > or =55), smoking, family history, hypertension, diabetes, hypercholesterolemia; and we defined a cardiovascular risk score (range, 0-6) by the number of risk factors present. Treatment outcome was measured as response (> or =50% improvement on the 17-item Hamilton Rating Scale for Depression [Ham-D-17]) and remission (final Ham-D-17< or =7). RESULTS: In logistic regression analyses, the cardiovascular risk score was significantly associated with treatment nonresponse and lack of remission when adjusting for age of onset of MDD and baseline severity of depression. The cardiovascular risk score remained significantly associated with treatment nonresponse when we additionally controlled for overall medical burden (measured with the Cumulative Illness Rating Scale). Among individual cardiovascular risk factors, elevated total cholesterol was a significant predictor of treatment nonresponse and lack of remission. CONCLUSION: Cardiovascular risk factors may have negative effects on the course of treatment in MDD. These results support the concept of "vascular depression" in younger subjects.
PMID: 16204427
ISSN: 1534-7796
CID: 2389792

An open study of triiodothyronine augmentation of selective serotonin reuptake inhibitors in treatment-resistant major depressive disorder

Iosifescu, Dan V; Nierenberg, Andrew A; Mischoulon, David; Perlis, Roy H; Papakostas, George I; Ryan, Julie L; Alpert, Jonathan E; Fava, Maurizio
OBJECTIVE: In an open trial, we investigated the efficacy of triiodothyronine (T(3)) adjuvant to selective serotonin reuptake inhibitors (SSRIs) in subjects with major depressive disorder (MDD) resistant to SSRI treatment. METHOD: Twenty subjects who met DSM-IV criteria for MDD (mean +/- SD age = 44.3 +/- 10.3 years; 55% [N = 11] women) and had failed to respond to a course of treatment of at least 8 weeks with an SSRI antidepressant were enrolled in a 4-week open-label augmentation treatment with T(3) 50 microg/day. Atypical and melancholic sub-types of MDD were diagnosed using Structured Clinical Interview for DSM-IV Axis I Disorders criteria. We administered the 17-item Hamilton Rating Scale for Depression (HAM-D-17) 4 times during the study (which was conducted between 2001 and 2003). RESULTS: During T(3) augmentation, the severity of depression decreased from an initial mean +/- SD HAM-D-17 score of 20.5 +/- 3.6 to a final HAM-D-17 score of 14.0 +/- 7.1 (p < .001). Seven subjects (35.0%) were treatment responders (HAM-D-17 reduction >or= 50%), and 6 subjects (30.0%) achieved clinical remission (final HAM-D-17
PMID: 16086620
ISSN: 0160-6689
CID: 2389802

Empirical testing of two models for staging antidepressant treatment resistance

Petersen, Timothy; Papakostas, George I; Posternak, Michael A; Kant, Alexis; Guyker, Wendy M; Iosifescu, Dan V; Yeung, Albert S; Nierenberg, Andrew A; Fava, Maurizio
BACKGROUND: An increasing amount of attention has been paid to treatment resistant depression. Although it is quite common to observe nonremission to not just one but consecutive antidepressant treatments during a major depressive episode, a relationship between the likelihood of achieving remission and one's degree of resistance is not clearly known at this time. This study was undertaken to empirically test 2 recent models for staging treatment resistance. MATERIALS AND METHODS: Psychiatrists from 2 academic sites reviewed charts of patients on their caseloads. Clinical Global Impressions-Severity (CGI-S) and Clinical Global Impressions-Improvement (CGI-I) scales were used to measure severity of depression and response to treatment, and 2 treatment-resistant staging scores were classified for each patient using the Massachusetts General Hospital staging method (MGH-S) and the Thase and Rush staging method (TR-S). RESULTS: Out of the 115 patient records reviewed, 58 (49.6%) patients remitted at some point during treatment. There was a significant positive correlation between the 2 staging scores, and logistic regression results indicated that greater MGH-S scores, but not TR-S scores, predicted nonremission. CONCLUSIONS: This study suggests that the hierarchical manner in which the field has typically gauged levels of treatment resistance may not be strongly supported by empirical evidence. This study suggests that the MGH staging model may offer some advantages over the staging method by Thase and Rush, as it generates a continuous score that considers both number of trials and intensity/optimization of each trial.
PMID: 16012276
ISSN: 0271-0749
CID: 2389812

Tridimensional personality questionnaire factors in major depressive disorder: relationship to anxiety disorder comorbidity and age of onset

Ongur, Dost; Farabaugh, Amy; Iosifescu, Dan V; Perlis, Roy; Fava, Maurizio
OBJECTIVE: We used the Tridimensional Personality Questionnaire (TPQ) to study the relationship between temperamental traits and comorbid anxiety disorders as well as age of onset of major depressive disorder (MDD) in 263 patients with MDD. METHODS: Patients recruited for a large clinical study on MDD underwent a Structured Clinical Interview for DSM-III-R assessment and were administered the self-rated TPQ [mean age = 39.5 +/- 10.5 years, women = 138 (53%), initial 17-item Hamilton Rating Scale for Depression (HAM-D-17) score = 19.6 +/- 3.4]. The TPQ was scored for three previously identified factors -- harm avoidance (HA), novelty seeking (NS), and reward dependence (RD). Multiple linear regression methods were used to evaluate the relationship between TPQ factors and each comorbid anxiety disorder as well as between early-- vs. late-onset MDD, after controlling for age, gender and initial HAM-D-17 score (when these were related to the dependent variable in simple regressions). RESULTS: Social anxiety disorder in MDD was strongly associated with higher scores on HA and lower scores on NS and RD (t = 5.4, p < 0.0001; t = 2.6, p = 0.009; t = 2.2, p = 0.028, respectively). A diagnosis of generalized anxiety disorder in MDD was significantly related to higher HA scores (t = 2.8, p = 0.006). The presence of comorbid obsessive-compulsive disorder was associated with lower NS scores (t = 2.3, p = 0.023) as was that of comorbid panic disorder (t = 2.0, p = 0.051). Finally, the presence of simple phobias was associated with lower scores on RD (t = 2.4, p = 0.016). HA scores were higher in patients with early onset of MDD (adjusted p = 0.05). Early versus late onset of MDD was not significantly related to NS or RD scores. LIMITATIONS: Since our sample consisted of moderately depressed outpatients, our ability to generalize our findings to other populations is limited. CONCLUSIONS: Features of temperament are related to patterns of anxiety disorder comorbidity and age of onset among patients with MDD. Higher levels of HA and lower levels of RD and NS were associated with an increased risk of anxiety disorder comorbidity in our sample. HA may also be related to early onset of depression.
PMID: 15832068
ISSN: 0033-3190
CID: 2389822

Obesity among outpatients with major depressive disorder

Papakostas, George I; Petersen, Timothy; Iosifescu, Dan V; Burns, Alana M; Nierenberg, Andrew A; Alpert, Jonathan E; Rosenbaum, Jerrold F; Fava, Maurizio
Studies focusing on the prevalence of obesity in Major Depressive Disorder (MDD), or the impact of excess body fat on the treatment of MDD are lacking. The aim of the present work is to systematically study obesity in MDD outpatients. A total of 369 MDD outpatients enrolled in an 8-wk trial of 20 mg fluoxetine had height and weight measured at baseline. We then examined: (1) the prevalence of being overweight or obese, (2) the relationship between obesity and a number of demographic and clinical variables, and, (3) the relationship between relative body weight and obesity with clinical response. We found that more than 50% of patients were overweight [body mass index (BMI) > or =2 5 kg/m2], while 20% were obese (BMI > or = 30 kg/m2). Obese patients presented with worse somatic well-being scores than non-obese MDD patients, but they did not differ with respect to depression severity, anxiety, somatic complaints, hopelessness or hostility. Greater relative body weight, but not obesity, predicted non-response. In conclusion, greater relative body weight was found to place MDD outpatients at risk for fluoxetine resistance.
PMID: 15361263
ISSN: 1461-1457
CID: 2389832