Baseline Hamilton Rating Scale For Depression Score Research Articles

C-Reactive Protein As A Response Indicator In Drug-Naïve Patients With Major Depressive Disorder: A Hospital-Based Study

Abstract Objective: C-reactive protein (CRP) is an indicator of the inflammatory process in the body, and is associated with the pathogenesis of depression through its purported effect on neurotransmitter function in the brain. Current research aims to study the relationship between the levels of CRP and the rate of remission of major depressive disorder with first-line antidepressant therapy. Methods: This hospital-based prospective study included thirty patients by purposive sampling technique. Patients with first-episode MDD with no history of antidepressant exposure and other medical comorbidity were recruited for pharmacotherapy with escitalopram, a first-line antidepressant. Patients taking antidepressants, anti-inflammatory medicines, having co-morbid conditions or other psychiatric conditions were excluded. The baseline CRP levels were measured and depressive symptoms were evaluated using the Hamilton Rating Scale for Depression (HRSD) at weeks 0, 6 and 12. The patients with low (≤5 mg/l) and high (>5 mg/l) CRP levels were compared for remission rates at week 12 using Kaplan–Meier survival analysis. Results: Amongst the 30 cases, 11(36.7%) were males and 19(63.3%) were female patients. The mean age was 35.95±7.85 years. Both groups were matched concerning age, gender, BMI and baseline HRSD score (p>0.05). As per Kaplan–Meier survival analysis, a significantly higher proportion of patients had remission of MDD at the 12th week having CRP levels ≤5 mg/l than the patients with CRP levels >5 mg/dl (p=0.002). Conclusion: This research concluded that after an adequate trial with a standard antidepressant, higher levels of CRP could lead to poorer remission rates in MDD subjects and could represent a sub-group of patients with treatment resistance.

Frailty and Depression in Late Life: A High-Risk Comorbidity With Distinctive Clinical Presentation and Poor Antidepressant Response.

To investigate the longitudinal relationship between physical frailty, the clinical representation of accelerated biological aging, and antidepressant medication response in older adults with depressive illness. An 8-week randomized placebo-controlled trial (escitalopram or duloxetine) followed by 10 months of open antidepressant medication treatment (augmentation, switch strategies) was conducted in an outpatient research clinic. 121 adults aged 60 years or older with major depressive disorder (MDD) or persistent depressive disorder and a 24-item Hamilton Rating Scale for Depression (HRSD) ≥16 were enrolled. Primary measures assessed serially over 12 months include response (50% reduction from baseline HRSD score), remission (HRSD score <10), and frailty (non/intermediate frail [0-2 deficits] vs frail [≥3 deficits]); latent class analysis was used to classify longitudinal frailty trajectories. A 2-class model best fit the data, identifying a consistently low frailty risk (63% of the sample) and consistently high frailty risk (37% of the sample) trajectory. Response and remission rates (ps ≤ .002) for adults in the high-risk frailty class were at least 21 percentage points worse than those in the low-risk class over 12 months. Furthermore, subsequent frailty was associated with previous frailty (ps ≤ .01) but not previous response or remission (ps ≥ .10). Antidepressant medication is poorly effective for MDD occurring in the context of frailty in older adults. Furthermore, even when an antidepressant response is achieved, this response does little to improve their frailty. These data suggest that standard psychiatric assessment of depressed older adults should include frailty measures and that novel therapeutic strategies to address comorbid frailty and depression are needed.

The Effect of Synbiotic as an Adjuvant Therapy to Fluoxetine in Moderate Depression: A Randomized Multicenter Trial

Background: Depression is a serious and burdensome disorder in modern societies, with lifetime prevalence of about 16%. Disturbed immune responses in the gut and immune-privileged sites including the central nervous system might occur subsequent to dysbiosis of gut microbiome. In this study we aimed at assessing the efficacy of 6 weeks synbiotic supplementation in the treatment of moderate depression in a double-blind, placebo-controlled, multi-center, and randomized trial. Methods: A total of 40 adult outpatients, who met the diagnostic and statistical manual of mental disorders fifth edition for moderate depression, were recruited based on the structured interview for DSMV. Recruited patients had a Hamilton rating scale for depression (HAM-D) score of 17 to 23 at baseline. All patients received fluoxetine (20 mg/d) for 4 weeks. Then, either a synbiotic capsule (plus fluoxetine) or placebo (plus fluoxetine) was added to the therapy for 6 weeks. Results: The mean age of the participants in the synbiotic treated group was 34.45 years and it was 35.50 years in the placebo group. Following the adjustment of ANCOVA models for gender, age, and BMI at baseline, there was a greater reduction in HAM-D score in synbiotic treated patients (Mean ± SD = -19.25 ± 1.71) compared to placebo taking group (Mean ± SD = -17.75 ± 2.05; P = 0.024). At the end of the 10th week of the intervention and after applying ANCOVA adjusted for the mentioned variables as well as baseline HAM-D score, it was found that the synbiotic group had a significantly decreased HAM-D score compared to the placebo (3.65 vs. 4.80, P = 0.013). Conclusions: The results of the current study revealed the efficacy of synbiotic as an adjuvant therapy in moderate depression.

The effect of fecal microbiota transplantation on psychiatric symptoms among patients with irritable bowel syndrome, functional diarrhea and functional constipation: An open-label observational study

BackgroundsThe intestinal microbiota is considered as a potential common underpinning pathophysiology of Functional Gastrointestinal Disorders (FGIDs) and psychiatric disorders such as depression and anxiety. Fecal Microbiota Transplantation (FMT) has been reported to have therapeutic effects on diseases related to dysbiosis, but few studies have evaluated its effect on psychiatric symptoms. MethodsWe followed 17 patients with either Irritable Bowel Syndrome (IBS), Functional Diarrhea (FDr) or Functional Constipation (FC) who underwent FMT for the treatment of gastrointestinal symptoms and observation of psychiatric symptoms. Changes in Hamilton Rating Scale for Depression (HAM-D) and subscale of sleep-related items, Hamilton Rating Scale for Anxiety (HAM-A) and Quick Inventory for Depressive Symptoms (QIDS) between baseline and 4 weeks after FMT, and relationship with the intestinal microbiota were measured. ResultsAt baseline, 12 out of 17 patients were rated with HAM-D ≥ 8. Significant improvement in HAM-D total and sleep subscale score, HAM-A and QIDS were observed (p = 0.007, p = 0.007, p = 0.01, p = 0.007, respectively). Baseline Shannon index indicated that microbiota showed lower diversity in patients with HAM-D ≥ 8 compared to those of healthy donors and patients with HAM-D < 8. There was a significant correlation between baseline Shannon index and HAM-D score, and a correlation between Shannon index change and HAM-D improvement after FMT. LimitationsThe small sample size with no control group. ConclusionsOur results suggest that depression and anxiety symptoms may be improved by FMT regardless of gastrointestinal symptom change in patients with IBS, FDr and FC, and the increase of microbiota diversity may help to improve patient's mood.

High-Dose, Unilateral ECT Found as Effective as Bilateral ECT

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessHigh-Dose, Unilateral ECT Found as Effective as Bilateral ECTMark MoranMark MoranSearch for more papers by this authorPublished Online:11 Mar 2016https://doi.org/10.1176/appi.pn.2016.3b8AbstractThe study appears as the Food and Drug Administration is considering reclassifying ECT from a “high-risk” to a “low-risk” medical device, a change that APA supports.Twice-weekly high-dose unilateral electroconvulsive therapy (ECT) appears to be no less effective than bitemporal ECT for depression and may be preferable because of its better cognitive side-effect profile, according to a report in the February 19 AJP in Advance.Maria Semkovska, Ph.D., of the Department of Psychiatry at Trinity College Dublin and colleagues reported on the results of EFFECT-Dep (Enhancing the Effectiveness of Electroconvulsive Therapy in Severe Depression). The trial was a randomized, “non-inferiority” trial with a six-month follow-up to determine whether high-dose unilateral ECT was inferior to the more standard bitemporal ECT for severe depression in routine practice over six months. One-hundred and thirty-eight participants were randomly assigned to bitemporal or high-dose unilateral ECT. Participants were inpatients recruited between May 2008 and October 2012 from St. Patrick’s Mental Health Services, an independent nonprofit organization that provides national services and runs Ireland’s largest ECT clinic“Seizure threshold”—the minimum charge required to induce the generalized seizure needed for therapeutic effect—was established by dose titration at the first session, and subsequent treatments were 1.5 times this threshold for bitemporal ECT and six times this threshold for unilateral ECT. In line with regular practice, the number of ECT sessions was determined by referring clinicians in consultation with patients, with up to 12 sessions in accordance with recommendations of the Irish Mental Health Commission The primary outcome was change in the 24-item Hamilton Rating Scale for Depression (HAM-D) score after the ECT course. A pre-specified range of a four-point difference in either direction was established as the range within which the treatment would be considered “non-inferior.”Secondary depression outcomes included HAM-D scores at the three- and six-month follow-ups, end-of-treatment remission and response status, and relapse status for remitters during the six-month follow-up. Remission was defined as 60 percent or greater decrease from the baseline HAM-D score and a score of 10 or less for two consecutive weeks; response was defined as a 60 percent or more decrease from the baseline HAM-D score and a score of 16 or less; and relapse was defined as a HAM-D score of 16 or more for two consecutive weeks.The researchers found that high-dose unilateral ECT was not inferior to bitemporal ECT on HAM-D scores, with a mean difference of 1.08 points in favor of unilateral ECT (within the range of “non-inferiority”). There were no significant differences for response and remission or six-month relapse status. Recovery of orientation was quicker following unilateral ECT, and bitemporal ECT was associated with a lower percent recall of autobiographical information.The study appears as the Food and Drug Administration (FDA) is proposing to reclassify ECT from a Class III (high-risk) medical device to Class II (low-risk), a change APA supports. Comments on the proposal were due March 28.Semkovska and colleagues say the AJP study has important clinical implications. “In terms of harms/benefits ratio, high-dose unilateral ECT was non-inferior to bitemporal ECT but showed a better cognitive profile, especially for preserving retrograde personal memories and fewer subjective cognitive side effects,” they wrote.“While there is much interest in other modifications to maintain effectiveness but reduce side effects (such as ultra-brief pulse-width ECT), these require further refinement and characterization for optimization. Our findings justify considering high-dose unilateral ECT as the preferred ECT option for treating depression and may help improve acceptability and availability of this effective treatment.” ■“Bitemporal Versus High-Dose Unilateral Twice-Weekly Electroconvulsive Therapy for Depression (EFFECT-Dep): A Pragmatic, Randomized, Non-Inferiority Trial” can be accessed here. ISSUES NewArchived

Association analysis of imbalanced interhemispheric functional coordination and early therapeutic efficacy in major depressive disorder: Evidence from resting state fMRI

IntroductionEmerging evidences indicate that the alteration of interhemispheric functional coordination may be involved in the pathogenesis of major depressive disorder (MDD). In present study, we aim to explore the potential marker by using the voxel-mirrored homotopic connectivity (VMHC) approach, which may be contributing to predict the clinical prognosis in MDD.MethodsEighty-two MDD patients and 50 normal control (NC) subjects participated in this study. We divided the MDD group into unremitted and remitted group according to the reduction rate of Hamilton Rating Scale for Depression (HAMD) within 2 weeks.ResultsThe study detected significantly decreased VMHC in bilateral precuneus (pCu), inferior temporal gyrus (ITG) and increased VMHC in middle frontal gyrus (MFG) and caudate nucleus when compared remitted depression (RD) group to unremitted depression (URD) group. Meanwhile, when compared with NC group, the URD group presented reduced VMHC in bilateral cerebellum anterior lobe, thalamus and postcentral gyrus. Furthermore, the VHMC in media frontal gyrus, postcentral gyrus and precentral gyrus were significantly decreased in RD group. Correlation analysis suggested that reduced VMHC in bilateral pCu was negatively correlated with the baseline HAMD score of URD (r = −0.325, P = 0.041). Receiver operating characteristic (ROC) curve indicated that three regional VMHC changes could identify depressed patient with poorer treatment response: ITG [area under curve (AUC) = 0.699, P = 0.002, 95% CI = 0.586–0.812], MFG (AUC = 0.692, P = 0.003, 95% CI = 0.580–0.805), pCu (AUC = 0.714, P = 0.001, 95% CI = 0.603–0.825).ConclusionThe current study combined with previous evidence indicates that the subdued intrinsic interhemispheric functional connectivity might represents a novel neural trait involved in the pathophysiology of MDD.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Third-wave cognitive therapy versus mentalisation-based treatment for major depressive disorder: a randomised clinical trial

ObjectiveTo compare the benefits and harms of third-wave cognitive therapy versus mentalisation-based therapy in a small sample of depressed participants.SettingThe trial was conducted at an outpatient psychiatric clinic for non-psychotic...

Treatment response and cognitive impairment in major depression: Association with C-reactive protein

Levels of inflammatory markers have been found to be significantly associated with major depressive disorder (MDD) and cognitive impairment. The aim of this study was to investigate whether the level of C-reactive protein (CRP) is correlated with depressive mood and cognitive impairment in MDD patients. In 149 subjects with MDD, the 21-item Hamilton Rating Scale for Depression (HAM-D), Continuous Performance Test (CPT), Finger-Tapping Test (FTT), and Wisconsin Card-Sorting Test (WCST) were administered before and after antidepressant treatment. Besides, the level of CRP was measured. After 6weeks of treatment, the total HAM-D scores decreased significantly. In addition, the subjects' performance in the masked CPT and the WCST with completed categories significantly improved (p<0.001 and p=0.027, respectively) after the reliable change indices were corrected for practice effects. The CRP levels had increased significantly after six weeks of treatment after adjustment for age and gender (p<0.001). In addition, the CRP levels remained significantly high after six weeks of treatment in patients with a higher baseline level (r=0.657, p<0.001). Although the association between baseline CRP level and HAM-D score was not significant, the baseline CRP level was significantly correlated with treatment response at week 2 (r=0.327, p=0.020). The baseline CRP level was also negatively correlated with performance in the FTT before treatment (r=-0.580, p=0.006). Moreover, the baseline CRP level was significantly correlated with performance in the FTT (r=-0.501, p=0.021) and WCST with completed categories (r=-0.521, p=0.015) at week 6. The cognitive function of patients with high baseline CRP levels might remain impaired even if their mood symptoms improve after antidepressant treatment. Whether adjunctive anti-inflammatory medication may help to preserve cognitive function merits further investigation.

Onset of Clinical Effects and Plasma Concentration of Fluvoxamine in Japanese Patients

It is widely accepted that selective serotonin reuptake inhibitors (SSRIs) require 2 to 4 weeks of administration before improvements in emotional symptoms of depression are seen. We evaluated whether early monitoring of Hamilton Rating Scale for Depression (HAMD) scores in patients treated with the SSRI fluvoxamine could predict antidepressant response, and also assessed the relationship between the onset of clinical response following the start of fluvoxamine administration and its plasma concentration. Twelve depressed patients (baseline HAMD score ≥15) received an initial dose of fluvoxamine (50 mg/d) followed by an optimized maintenance dose according to their clinical symptoms after 7 d. HAMD scores and plasma drug concentrations were determined at 7 and 28 d after the first administration. There were 7 responders and 5 non-responders on day 28, as evaluated by HAMD scores. The HAMD score for the responders was significantly lower than that for the non-responders on day 7 (mean±S.D., 11.6±6.1 vs. 26.6±6.5, p=0.006). Thus, the reduction in HAMD score on day 7 was clearly divided between responders and non-responders. On day 28, the plasma concentration of fluvoxamine in responders was lower than that in non-responders (14.2±10.5 ng/ml vs. 44.2±28.1 ng/ml, p=0.051). Furthermore, receiver operating characteristic curve analysis conducted on day 28 revealed an upper concentration threshold of 28.2 ng/ml (p=0.042), with none in the responder group above that level. Our results suggest that HAMD score after the first week of treatment with fluvoxamine and the upper threshold of plasma drug concentration could predict whether a patient is a non-responder.

MAOA gene polymorphisms and response to mirtazapine in major depression

Polymorphisms in the monoamine oxidase A (MAOA) gene may influence treatment outcomes in major depression disorder (MDD). To investigate the association of MAOA genetic polymorphisms and response to mirtazapine in patients with MDD. Fifty-eight adult patients in Taiwan who met the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) diagnostic criteria for MDD were given mirtazapine for 7 weeks and evaluated on days 0, 7, 14, 21, 49 using the 24-item Hamilton Rating Scale for Depression (HRSD). Remission was defined as a final HRSD <or= 10 and a 50% reduction in baseline HRSD score. Patients provided venous blood for DNA testing. The patients' response to mirtazapine treatment was compared between those who had the long-form polymorphism in the MAOA gene promoter and the short-form polymorphism. The total HRSD scores after mirtazapine treatment were significantly lower than baseline (p < 0.001). There were 10 cases (38.5%) in short from and 6 (18.8%) in long from group touched the remission stage. Patients with the short-form group had a greater response to mirtazapine (p < 0.001) than those with the long-form polymorphism after controlling for age, sex, and apolipoprotein E genetic (APOE) polymorphism. The genetic polymorphisms in the MAOA promoter region may be associated with treatment response to mirtazapine.

Prevalence and Clinical Correlates of Medical Comorbidities in Patients With Bipolar I Disorder

We studied the relationship between number of medical comorbidities in patients with bipolar I disorder and their demographic and clinical characteristics. Data were from 174 patients in the acute phase of the Pittsburgh Maintenance Therapies in Bipolar Disorder (MTBD) study, a randomized controlled trial comparing Interpersonal and Social Rhythm Therapy to an intensive clinical management approach for individuals with a lifetime diagnosis of bipolar I disorder or schizoaffective disorder, manic type, according to Research Diagnostic Criteria, who were receiving adjunctive protocol-driven pharmacotherapy. Patients entered the MTBD study from 1991 to 2000. We examined the acute-phase Hamilton Rating Scale for Depression (HAM-D) and Bech-Rafaelsen Mania Scale scores, demographics, clinical history, and medical comorbidities. Patients with a high number of medical comorbidities had longer duration of both lifetime depression (p = .02) and lifetime inpatient depression treatment (p = .04), had higher baseline HAM-D score (p = .01), and were more likely to be treated for a depressed clinical state during the acute phase of the MTBD study (p = .05). Moreover, higher severity of baseline medical comorbidities predicted slower decreases in HAM-D score among depressed (p = .004) and mixed/cycling (p = .003) patients even after controlling for baseline HAM-D score. Medical illness is correlated with several indicators of poorer prognosis and outcome in bipolar I disorder. Not only do preventing and treating medical comorbidities in bipolar patients decrease the morbidity and mortality related to physical illness, but they could also enhance psychological well-being and possibly improve the course of bipolar illness. Identification of characteristics in bipolar I patients that are correlated to increased risk for medical comorbidities is a fundamental step in understanding the nature of the relationship between bipolar disorder and medical illness.

Traitement des épisodes dépressifs sévères : escitalopram est plus efficace que citalopram

Escitalopram is a highly selective serotonin reuptake inhibitor (SSRI). It is the therapeutically active S-enantiomer of citalopram. It has been shown, compared with placebo, to be an effective and well-tolerated treatment for major depressive disorders (MDD) in both primary and specialist care settings. A recent meta-analysis has found that escitalopram-treated patients showed significant higher response rates and increased mean change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total scores at weeks 1 and 8 compared with citalopram-treated patients. Each of these active drugs shares similar safety profiles. Although the efficacy of newer antidepressants has been well established for the treatment of mild-to-moderate depression, there are very few studies concerning severe depression.To determine if escitalopram is more effective than citalopram in patients with severe depression.Data were pooled from three different clinical trials, each similar in design and inclusion/exclusion criteria, primary endpoints and assessment schedules. This analysis was exhaustive because it included all trials in which the maximum dose for escitalopram (20 mg) could be administered. According to the cut-off point taken to define severe depression based on the MADRS total score ( 30), 506 patients were considered as severely depressed patients and so included in this analysis. Among them, 169 received escitalopram, 171 received citalopram and 166 received the placebo. The primary efficacy parameter was the mean change from baseline to end of treatment in MADRS total score between escitalopram and citalopram groups, based on last-observation-carried-forward method. The change from baseline to endpoint of the Hamilton rating scale for Depression (HAM-D) and the Clinical Global Impression of Improvement and Severity (CGI-I and CGI-S) were also analysed as secondary criteria. Clinical response was defined by at least a 50% reduction in baseline MADRS total score or by at least a 60% reduction in baseline HAM-D score or by a score of 1 (very much improved) on the CGI scale, and remission by a MADRS total score pound 12.Results showed that the mean change from baseline in the MADRS total score was significantly higher in the escitalopram group compared with the citalopram group (- 17.3 vs - 13.8 respectively, p=0.003). This significant difference was observed as early as week 1 (p=0.01). Response rates were significantly higher for escitalopram than for citalopram (56% vs 41% respectively, p=0.007). A borderline significant difference was found for remission rate in the observed-cases analysis (43% vs 33% respectively, p=0.07). Analyses of the HAM-D, CGI-I and CGI-S scores revealed consistent results.This study shows that the new SSRI escitalopram has better efficacy in the treatment of severe depression than citalopram, its racemic parent. Mean differences between treatments groups were in favour of escitalopram for all scales. The benefits of escitalopram compared with citalopram, as demonstrated by both magnitude of effect and time of onset, are superior to the benefits of citalopram, an antidepressant drug with proven efficacy. This evidence clearly supports the use of escitalopram as a legitimate first-line treatment for MDD.

Testosterone Replacement Therapy for Hypogonadal Men With Major Depressive Disorder

Symptoms of male hypogonadism include low libido, fatigue, and dysphoria and are alleviated with testosterone replacement. The prevalence of major depressive disorder (MDD) in hypogonadal men is not known, nor is the antidepressant efficacy of testosterone replacement in depressed, hypogonadal men. A 6-week double-blind, placebo-controlled clinical trial was conducted in 32 men with DSM-IV MDD and a low testosterone level, defined as total serum testosterone < or = 350 ng/dL. Patients were randomly assigned to receive weekly 1-mL intramuscular injections of either testosterone enanthate, 200 mg, or sesame seed oil (placebo). The primary outcome measure was the 24-item Hamilton Rating Scale for Depression (HAM-D). Thirty patients were randomly assigned to an intervention; 13 received testosterone, and 17 received placebo. Mean +/- SD age was 52+/-10 years, mean testosterone level was 266.1+/-50.6 ng/dL, and mean baseline HAM-D score was 21+/-8. All patients who received testosterone achieved normalization of their testosterone levels. The HAM-D scores decreased in both testosterone and placebo groups, and there were no significant between-group differences: reduction in group mean HAM-D score from baseline to endpoint was 10.1 in patients who received testosterone and 10.5 in those who received placebo. Response rate, defined as a 50% or greater reduction in HAM-D score, was 38.5% (5/13) for patients who received testosterone and 41.2% (7/17) for patients who received placebo. Patients receiving testosterone had a marginal but statistically significant improvement in sexual function (p = .02). In this clinical trial with depressed, hypogonadal men, antidepressant effects of testosterone replacement could not be differentiated from those of placebo.

Escitalopram: A consistently effective antidepressant

La prise en charge thérapeutique des patients atteints de dépression sévère reste encore un challenge pour les médecins. Par rapport à la forme légère ou modérée, la dépression sévère se caractérise souvent par une durée plus longue, une co-morbidité supérieure, une plus faible probabilité de rémission spontanée et un taux de rechute plus important. Par ailleurs, si l’efficacité des nouveaux antidépresseurs est bien établie dans la dépression légère à modérée, beaucoup moins d’études ont été réalisées dans la dépression sévère. Probablement parce que la dépression sévère n’est pas perçue comme une entité à part, mais comme un continuum dans la clinique de cette pathologie, et aussi peut-être en raison d’une absence de consensus clair sur la définition même de cette sévérité. Après avoir utilisé les définitions basées sur la clinique et sur le mode de prise en charge, les auteurs semblent désormais privilégier l’utilisation des échelles cliniques avec un seuil spécifique pour cette définition. En utilisant l’échelle MADRS (Montgomery-Åsberg Depression Rating Scale) et la valeur seuil de 30 pour définir la sévérité de la dépression, nous avons réalisé une analyse poolée avec les données des trois essais cliniques comparant l’efficacité du escitalopram à celle du citalopram. Les résultats montrent de façon constante une meilleure efficacité du escitalopram par rapport au citalopram, dans cette indication particulière qu’est la dépression sévère.Escitalopram is a highly selective serotonin reuptake inhibitor (SSRI). It is the therapeutically active S-enantiomer of citalopram. It has been shown, compared with placebo, to be an effective and well-tolerated treatment for major depressive disorders (MDD) in both primary and specialist care settings. A recent meta-analysis has found that escitalopram-treated patients showed significant higher response rates and increased mean change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total scores at weeks 1 and 8 compared with citalopram-treated patients. Each of these active drugs shares similar safety profiles. Although the efficacy of newer antidepressants has been well established for the treatment of mild-to-moderate depression, there are very few studies concerning severe depression.To determine if escitalopram is more effective than citalopram in patients with severe depression.Data were pooled from three different clinical trials, each similar in design and inclusion/exclusion criteria, primary endpoints and assessment schedules. This analysis was exhaustive because it included all trials in which the maximum dose for escitalopram (20 mg) could be administered. According to the cut-off point taken to define severe depression based on the MADRS total score ( 30), 506 patients were considered as severely depressed patients and so included in this analysis. Among them, 169 received escitalopram, 171 received citalopram and 166 received the placebo. The primary efficacy parameter was the mean change from baseline to end of treatment in MADRS total score between escitalopram and citalopram groups, based on last-observation-carried-forward method. The change from baseline to endpoint of the Hamilton rating scale for Depression (HAM-D) and the Clinical Global Impression of Improvement and Severity (CGI-I and CGI-S) were also analysed as secondary criteria. Clinical response was defined by at least a 50 % reduction in baseline MADRS total score or by at least a 60 % reduction in baseline HAM-D score or by a score of 1 (very much improved) on the CGI scale, and remission by a MADRS total score £ 12. Results - Results showed that the mean change from baseline in the MADRS total score was significantly higher in the escitalopram group compared with the citalopram group (− 17.3 vs − 13.8 respectively, p = 0.003). This significant difference was observed as early as week 1 (p = 0.01). Response rates were significantly higher for escitalopram than for citalopram (56 % vs 41 % respectively, p = 0.007). A borderline significant difference was found for remission rate in the observed-cases analysis (43 % vs 33 % respectively, p = 0.07). Analyses of the HAM-D, CGI-I and CGI-S scores revealed consistent results.This study shows that the new SSRI escitalopram has better efficacy in the treatment of severe depression than citalopram, its racemic parent. Mean differences between treatments groups were in favour of escitalopram for all scales. The benefits of escitalopram compared with citalopram, as demonstrated by both magnitude of effect and time of onset, are superior to the benefits of citalopram, an antidepressant drug with proven efficacy. This evidence clearly supports the use of escitalopram as a legitimate first-line treatment for MDD.