Irene Romera

Factor analysis of the Zung self-rating depression scale in a large sample of patients with major depressive disorder in primary care

BackgroundThe aim of this study was to examine the symptomatic dimensions of depression in a large sample of patients with major depressive disorder (MDD) in the primary care (PC) setting by means of a factor analysis of the Zung self-rating depression scale (ZSDS).MethodsA factor analysis was performed, based on the polychoric correlations matrix, between ZSDS items using promax oblique rotation in 1049 PC patients with a diagnosis of MDD (DSM-IV).ResultsA clinical interpretable four-factor solution consisting of a core depressive factor (I); a cognitive factor (II); an anxiety factor (III) and a somatic factor (IV) was extracted. These factors accounted for 36.9% of the variance on the ZSDS. The 4-factor structure was validated and high coefficients of congruence were obtained (0.98, 0.95, 0.92 and 0.87 for factors I, II, III and IV, respectively). The model seemed to fit the data well with fit indexes within recommended ranges (GFI = 0.9330, AGFI = 0.9112 and RMR = 0.0843).ConclusionOur findings suggest that depressive symptoms in patients with MDD in the PC setting cluster into four dimensions: core depressive, cognitive, anxiety and somatic, by means of a factor analysis of the ZSDS. Further research is needed to identify possible diagnostic, therapeutic or prognostic implications of the different depressive symptomatic profiles.

Generalized anxiety disorder, with or without co-morbid major depressive disorder, in primary care: Prevalence of painful somatic symptoms, functioning and health status

BACKGROUND Painful physical symptoms (PPS) have received little attention in patients with generalized anxiety disorder (GAD). The objective of the present study was to assess the prevalence of PPS in patients with GAD vs patients with GAD and co-morbid major depressive disorder (MDD) and a control group (patients neither with GAD nor MDD). METHODS This is a cross-sectional, multi-center, epidemiological study, in primary care. Patients were screened for GAD (HADS-A), followed by a diagnosis confirmation (MINI). Patients were considered to have PPS when VAS overall pain score >30. Functioning and health status was assessed (SDS, EUROQoL-5D). Relationships between the presence of PPS and functioning and health status was analyzed (ANCOVA models). Results were adjusted for confounding factors. RESULTS Of 7152 patients, 1546 (22%) screened positive for GAD, 981 (14%) had confirmed GAD diagnosis, of whom 559 (8%) had GAD with co-morbid MDD and 422 (6%) had GAD alone. Of the 5292 (74%) patients screened negative for GAD, 336 (5%) were confirmed as controls. PPS in patients with GAD were twice as prevalent as in the control group: 59.0% vs. 28.3%; p<0.001. The presence of co-morbid MDD was associated with a significantly higher prevalence of PPS: 78.0% vs. 59.0%; p<0.001. PPS were significantly associated with functioning and health status impairment (p<0.001) both in GAD alone and in GAD and co-morbid MDD compared with controls. LIMITATIONS Results do not prove causal relationships. CONCLUSIONS Our results support the clinical relevance of PPS in patients suffering from GAD; therefore they need to be considered when evaluating the patient.

Optimal cutoff point of the Hamilton Rating Scale for Depression according to normal levels of social and occupational functioning

The main goal in the treatment of major depressive disorder (MDD) is to achieve remission, defined as the resolution of symptoms and the return to normal levels of functionality. However, the clinical assessment of remission is usually merely based on scores of symptomatic rating scales. One of the most widely used scales to measure remission is the HAM-D(17), in which remission is defined as a score ≤ 7. Nevertheless, several studies have shown that this cutoff could be too high when also functioning is considered. This is a post-hoc analysis of a 6-month prospective study, performed over a sample of 292 Spanish patients with MDD, in order to find the optimal cutoff in the HAM-D(17) scale, considering normal levels of functionality, evaluated by the SOFAS; by means of plotting Receiver Operating Characteristics (ROC) curves. Our results show that a score of ≤ 5 maximized both sensitivity and specificity for identifying normal levels of functionality with respect to other scores, and thus agree with previous works, which suggest that a cutoff ≤ 7 might be too high to consider remission in patients with MDD, when normal levels of functioning are taken into account.

Early switch strategy in patients with major depressive disorder: a double-blind, randomized study.

Objective Antidepressant switch is a commonly used strategy in the absence of an adequate response, but optimum timing is not well established. We compared the efficacy of an early and a conventional antidepressant switch strategy in patients with major depressive disorder. Methods Patients with no or minimal improvement (<30% reduction in baseline 17-item Hamilton Depression Rating Scale [HAMD17] score) after 4 weeks on escitalopram 10 mg/d were randomized to either early switch strategy with duloxetine 60 to 120 mg/d for 12 weeks (arm A) or conventional switch strategy (arm B): 4 further weeks on escitalopram 10 to 20 mg/d; then, in case of nonresponse (response, ≥50% reduction in HAMD17), switch to duloxetine 60 to 120 mg/d for 8 weeks, or continued escitalopram in responders. Co-primary end points were time to confirmed response and remission (HAMD17, ⩽7). Strategies were compared using Kaplan-Meier, logistic regression, and repeated-measures analyses. Results Sixty-seven percent (566 of 840) of patients showed no or minimal improvement and were randomized to arm A (282 patients) or arm B (284 patients). No between-strategy differences in time to confirmed response (25% Kaplan-Meier estimates, 3.9 vs 4.0 weeks, P = 0.213) or remission (6.0 vs 7.9 weeks, P = 0.075) were found. Rates of confirmed responders were similar (64.9% vs 64.1%); however, more patients randomized to early switch achieved confirmed remission (43.3% vs 35.6%; P = 0.048). Conclusions Although no differences in the primary end points were found, a higher remission rate was seen with the early switch strategy. Our findings suggest that further investigations to reevaluate the conventional approach to antidepressant switch strategy would be worthwhile.

Early vs. conventional switching of antidepressants in patients with MDD and moderate to severe pain: a double-blind randomized study.

BACKGROUND Concomitant painful physical symptoms in depressive patients frequently impair functioning and failure to treat these symptoms may adversely impact treatment outcomes of depression. Early vs. conventional switch of antidepressants were compared in patients with major depressive disorder (MDD) and moderate to severe pain. METHOD Pre-specified subgroup analysis of a 16-week, randomized, double-blind clinical study on MDD patients with >30 mm overall pain visual analog scale (VAS). Patients not achieving 30% reduction Hamilton Depression Rating Scale (HAM-D) after 4 weeks escitalopram (10 mg/day) were randomized to duloxetine 60-120 mg/day (early switch) or continued on escitalopram (conventional switch) with non-responders at week 8 switching to duloxetine. Endpoints were time to confirmed response and remission, VAS pain severity, and Sheehan disability scale (SDS). Switch strategies were compared using Kaplan-Meier, logistic regression, and repeated measures analyses. RESULTS No differences between early and conventional switching were found in time to confirmed response after randomization (3.9 vs. 4.1 weeks, p=0.511) or remission (6.0 vs. 8.0 weeks, p=0.238). Significantly lower VAS mean pain levels at for overall pain, headache, back pain, shoulder pain, interference with daily activities, and time being awake in pain were found for patients in the early switching group. Time to achieving normal functioning (SDS total score <6) was shorter in the early switching group (p=0.042). Safety results were comparable between switch strategies. CONCLUSIONS In MDD patients with moderate to severe painful physical symptoms not improving after 4 weeks of treatment with escitalopram, an earlier switch to duloxetine may lead to better pain and functional outcomes.

Following the results of the EMPA-REG OUTCOME trial with empagliflozin, is it possible to speak of a class effect?

Background The recently published cardiovascular outcomes data for the first sodium–glucose cotransporter 2 (SGLT2) inhibitor, empagliflozin, have shown cardiovascular safety and additional benefits in patients with type 2 diabetes and established cardiovascular disease. Empagliflozin showed lower rates of death from cardiovascular causes or from any causes and lower hospitalization rates from heart failure compared with placebo, both in addition to standard care. This commentary discusses the existence of a possible class effect considering the available evidence described for other SGLT2 inhibitors. Main text Empagliflozin, dapagliflozin and canagliflozin share the same mechanism of action, and it is a plausible hypothesis that some of the benefits of empagliflozin treatment could also be expected from other SGLT2 inhibitors. However, the rapid and persistent occurrence of cardiovascular benefits observed with empagliflozin and the different results shown by the three inhibitors in meta-analyses of some of their respective Phase II and III trials might suggest another possible mechanism of action, perhaps related to the different selectivity to inhibit SGLT-2 and other SGLT family members that these compounds present. Conclusion There is still lack of evidence to answer whether the cardiovascular benefits observed with empagliflozin in the EMPA-REG OUTCOME study could be seen as a “class effect”, which is also attributable to dapagliflozin and canagliflozin.

Different levels of lack of improvement at 4 weeks of escitalopram treatment as predictors of poor 8-week outcome in MDD

BACKGROUND Several post-hoc studies have shown that lack of early improvement reduces the chance of later response or remission. This post-hoc analysis evaluates different cut-off points of non-improvement at 4 weeks of escitalopram treatment to predict 8-week non-response and non-remission. METHOD This study consisted of MDD patients with an absence of improvement (<30% reduction in baseline score of the HAMD-17) at Week 4 of escitalopram treatment (10mg/day) that continued escitalopram treatment (10-20mg/day) for a further 4-week period (n=251). Predictive, sensitivity and specificity values for the several definitions of non-improvement (≤ 25%, ≤ 20% and ≤ 15% reduction in the HAMD-17 baseline total score) at 4 weeks were calculated. RESULTS Overall, 70.1% (176/251) of patients did not achieve response at Week 8 and 84.5% (212/251) did not achieve remission. The predictive value for non-response was high (71.4-74.3%) for all cut-off points of non-improvement tested. The respective values for non-remission were placed between 85.0% and 87.2%. LIMITATIONS This was a post-hoc subgroup analysis. The only drug assessed was escitalopram. CONCLUSIONS Our data indicate that an absence of improvement, <30% reduction in the HAMD-17, after 4 weeks of escitalopram treatment should prompt clinicians to consider a change in treatment strategy. Similar findings were previously reported for other antidepressants.

Empagliflozin in combination with oral agents in young and overweight/obese Type 2 diabetes mellitus patients: A pooled analysis of three randomized trials

AIMS This analysis aimed to evaluate efficacy and safety of empagliflozin in combination therapy in <65 y.o. patients, overweight/obese, and with uncontrolled T2DM. METHODS Pooled analysis from three phase-III trials, in <65 y.o. patients, with BMI 25-35kg/m2, and HbA1c ≥8% at baseline. Patients (N=439) were randomized to placebo (n=138), empagliflozin 10mg (n=160), or empagliflozin 25mg (n=141) once daily (24weeks) as add-on to metformin, to metformin plus sulfonylurea, or to pioglitazone ± metformin. RESULTS At week 24, adjusted mean (SE) changes from baseline in HbA1c were -0.19% (0.07) for placebo vs. -1.10% (0.07) and -1.10% (0.07) for empagliflozin 10 and 25mg, respectively (both p<0.001). Adjusted mean (SE) changes from baseline in weight were -0.33kg (0.21) for placebo vs. -1.94kg (0.19) and -2.14kg (0.20) for empagliflozin 10 and 25mg, respectively (both p<0.001). Adverse events were reported in 57.2% on placebo, 64.4% on empagliflozin 10mg and 59.6% on empagliflozin 25mg. Genital infection AEs were reported in 1.4% on placebo, 3.8% on empagliflozin 10mg, and 5.0% on empagliflozin 25mg. CONCLUSIONS In this specific population, empagliflozin in combination with other oral agents, significantly reduced HbA1c and body weight and was well tolerated.