UMLS:C0011570 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Escitalopram is a selective serotonin reuptake inhibitor (SSRI); it is the therapeutically active S-enantiomer of the racemic mixture, citalopram. This review aimed to compare the efficacy and tolerability of escitalopram versus citalopram and several other SSRIs (citalopram, fluoxetine, paroxetine, sertraline), and a selective reuptake inhibitor of noradrenaline and serotonin, venlafaxine XR, for treatment of DSM IV (Diagnostic and Statistical Manual of mental disorders - fourth edition) major depressive disorder, based on the studies evaluated by the Commission de la Transparence de la R6publique Frangaise, and data from a pooled analysis presented in 2005 at the 158th annual congress of the American Psychiatric Association. Change from baseline to end-point on total MADRS (Montgomery-Asberg Depression Rating Scale--10 items, score range: 0-60) was the primary efficacy parameter; changes on HAM-D17 (Hamilton rating scale for depression--17 items), CGI-S and CGI-I (Clinical global Impression-Severity and-Improvement), and response rates (> or = 50% MADRS score reduction) and remissions (< 12 MADRS score) were the secondary efficacy parameters. Tolerability assessment was based on the numbers and rates of adverse events observed with treatment, and the DESS (Discontinuation Emergent Signs and Symptoms-43 items) scale was used for assessment of adverse events observed with treatment withdrawal. Analyses were based on intention to treat using the LOCF (last observation carried forward) method. Efficacy of escitalopram appeared to be at least equivalent to that of the active comparators in all cases. The difference between active compounds was more marked when depressive symptoms were more severe. From the point of view of tolerability, frequency of adverse effects occurring on treatment and the frequency of treatment discontinuations due to adverse effects were comparable with both escitalopram and the active comparators; however, the comparisons were mostly favourable to escitalopram, though differences were generally not statistically significant. In both studies of escitalopram versus venlafaxine XR, treatment discontinuations due to adverse events were less frequent on escitalopram than on venlafaxine XR (7.5% vs 11.2%, and 4.1% vs 16.0% respectively). With regard to adverse events associated with the withdrawal period, the signs and symptoms occurring on treatment discontinuation assessed after 1 week using the DESS scale were less frequent on escitalopram than on venlafaxine XR at 8 weeks and paroxetine at 24 weeks. Concerning suicide risk, a review of clinical trials involving 2277 patients on escitalopram and 1814 patients on placebo showed that this risk was minimal, and similar in both groups; moreover, no evidence was found suggesting that escitalopram might promote suicidal behaviour compared with placebo. These results suggest that escitalopram is suitable to be considered as a first-line drug treatment for major depressive disorder.
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PMID:[Escitalopram for treatment of major depressive disorder in adults]. 1638 16

The present study aimed at investigating depression specificity and escitalopram medication efficacy in 33 patients with panic attacks (PA). Depression according to BDI was found in 96,4% patients with PA. Most important clinical peculiarities of depression in PA patients were asthenia, somatic preoccupation and anxiety in combinations with mild or severe depressed mood and mild lack of satisfaction. Development and severity of depression were significantly associated with duration and frequency of PA. Escitalopram was prescribed in a dosage of 10 mg/day for 2-months. The drug was shown to have high efficacy in the treatment of depression, high preventive activity for PA as well as good tolerability with rare and mild side effects. The conclusion was made that morbidity of depression and PA and depression specificity in patients with PA may be explained by the common pathophysiological mechanisms. Serotonin dysfunction may be the most important mechanism.
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PMID:[Depressive disorders in panic attack patients and their correction with escitalopram]. 1639 1

In order to study the gene-environment interaction as well as investigate prophylactic/ameliorative effects of early intervention on development of adult life psychopathology, we superimposed maternal separation on an animal model of depression the Flinders Sensitive Line (FSL) rats and their controls the Flinders Resistant Line (FRL) rats and studied behavior following treatment with escitalopram. Animals were maternally separated for 180 min/day from postnatal day 2 (PND 2) to 14. The control groups were left undisturbed. Treatment with escitalopram or vehicle admixed to food pellets was commenced on PND 43 and continued until PND 73. The Porsolt swim test was carried out on PND 65. Baseline FRL/FSL differences in body weight and swim duration, considered to be an inverse index of depression, were found (p's<0.001). In the FSL, maternal separation further decreased swim duration (p<0.001) while the FRL strain was unaffected. Escitalopram had no effect in FRL, but increased swim duration in both maternally non-separated and separated FSL (p<0.05 and p=0.001; respectively). These results confirm the strain differences between the FSL and FRL and demonstrate that the long-term effects of early life adverse experience will to a significant degree depend on the genetic make-up of an individual. Finally, antidepressant treatment reversed behavioral abnormalities caused by genetic and environmental factors. This study highlights the importance of genetic factors in susceptibility to early life adverse events, and demonstrates the efficiency of early antidepressant treatment in reversing behavioral abnormalities, both those caused by genetic factors and by environmental factors.
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PMID:Adult life behavioral consequences of early maternal separation are alleviated by escitalopram treatment in a rat model of depression. 1641 67

Escitalopram (ESC) is a new selective serotonin reuptake inhibitor (SSRI) used in the treatment of depression. There are limited data regarding accidental and intentional ESC exposure. We conducted a retrospective chart review of isolated ESC ingestions reported to our regional poison center during 2003-2004. Twenty-eight patients met inclusion criteria. The average patient age was 28.1 years (range 2-75 years) and the average amount of ESC ingested was 62.5 mg (range 5-300 mg from 19 cases). The most common formulation ingested was the 20-mg tablet. There were eight accidental ingestions and 20 intentional overdoses. Six of the eight accidental ingestions were observed at home with follow-up in 24 h, and no adverse outcomes were reported. The other two accidental overdoses were observed in the Emergency Department (ED) and discharged home with no adverse events reported. Nineteen of the intentional overdoses were observed in the ED for approximately 4-6 h and discharged home or to an inpatient psychiatry ward. One of the intentional overdose patients was admitted for persistent lethargy, but had a good outcome. ESC toxicity can theoretically be life threatening, but no patients in our series had adverse sequealae after accidental or intentional overdose.
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PMID:Outcomes after supratherapeutic escitalopram ingestions. 1643 30

Intravenous (iv) administration of an antidepressant is a common practice in some European countries, particularly in France, Spain, and Italy in the initial treatment phase of hospitalised, severe depressed patients. After a beneficial response is observed, patients are switched to an oral formulation. The approved treatment period of the iv form of citalopram is limited to 8-10 days. The high bioavailability of citalopram permits the use of identical iv and oral doses. Citalopram is a racemate, consisting of a 1:1 mixture of the S- and R-enantiomers. The therapeutically active component is the S-enantiomer (escitalopram). Pharmacokinetic single dose administration studies in healthy subjects have demonstrated that daily oral administration of 20 mg of escitalopram or 40 mg citalopram results in similar plasma concentrations of the S-enantiomer of citalopram. This open-label multicentre French prospective study investigated the tolerability and efficacy of oral escitalopram 10 and 20 mg/day, administered for a 6-week period as continuation treatment of citalopram (20 mg or 40 mg daily) intravenous (iv), in patients with Major Depressive Disorder. A total of 171 patients were enrolled, of whom 147 (85%) completed the study. The mean MADRS score at inclusion (last citalopram dose) was 31.6 +/- 9.9. The total MADRS score decreased after 3 days of oral treatment with escitalopram. Escitalopram demonstrated a continuous effect in treating depressive symptoms throughout the study. The decrease in MADRS mean total score from baseline was statistically significant to each visit (day 3, 15; p < 0.0001). At final visit (J42), the decrease was - 18.9 +/- 11.7 (p < 0.0001) and the MADRS mean total score was 12.7 +/- 9.3. There were no differences seen in the patient response comparing gender, age, and the single or recurrent episodes. The changes of Clinical Global Impression scores (CGI-S, CGI-I, PGE-Patient Global Evaluation) were also indicative of an improvement of the patients' depression. The CGI-I and PGE scores were significantly correlated indicating good agreement between investigator and patient in rating the degree of improvement. At the end of the study, 67% of patients were classified as responders (decrease of MADRS score from baseline > or = 50%), and the majority of them were considered remitters (final MADRS score < or = 12). Overall, the switch from intravenous citalopram to oral escitalopram was well tolerated in the study population. In all, 57 patients (33%) reported at least one adverse event (AE) during the study (21 patients in the 10 mg group and 36 patients in the 20 mg group); of these, 7 patients (4%) withdrew from the study. The most frequently reported AEs were suggestive of residual symptoms of depression (anxiety, 9%; insomnia, 5% of patients). In conclusion, in this study oral escitalopram (10 mg or 20 mg) was well tolerated as continuation treatment after switching from intravenous citalopram (20 mg or 40 mg). From the efficacy and safety data of this study, it can be concluded that the switch from citalopram iv to oral escitalopram (10 and 20 mg/day) is effective in decreasing depressive symptoms, and could be safely proposed in patients with major depressive disorder.
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PMID:[Safety and efficacy of oral escitalopram as continuation treatment of intravenous citalopram, in patients with major depressive disorder--the navigade switch study]. 1691 Jun 29

Most patients with depression have symptoms of anxiety associated with their illness. Our aim in this study was to investigate the efficacy of escitalopram, a proven antidepressant, on symptoms of anxiety in patients with major depressive disorder (MDD). Data from five placebo-controlled escitalopram studies in MDD were analyzed. Three of the studies also included a comparison with citalopram. In all studies, anxiety was assessed using the Inner Tension item (item 3) of the Montgomery-Asberg Depression Rating Scale (MADRS). In three studies, anxiety symptoms were also specifically assessed, either continuously over time or at baseline and end point, by using the Hamilton Rating Scale for Anxiety (HAM-A), the Anxious Mood item of the HAM-A (item 1), the Psychic Anxiety subscale of the HAM-A (items 1-6 and 14), the Anxiety Psychic item (item 10) of the Hamilton Rating Scale for Depression (HAM-D-24), and the Anxiety/Somatization subfactor (items 10-13, 15, and 17) of the HAM-D-24. Escitalopram was significantly superior to placebo in all comparisons. Citalopram was also consistently better than placebo in all comparisons, except in the HAM-D-24 Anxiety/Somatization subfactor. In some comparisons with placebo, escitalopram showed a significantly earlier onset of action or an earlier separation. Escitalopram was significantly more effective compared to placebo in treating both anxiety symptoms and the entire depression in the total depressive population, as well as in depressive patients with a high degree of anxiety.
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PMID:Escitalopram in the treatment of anxiety symptoms associated with depression. 1693 93

This open, multicenter, prospective study in France assessed the efficacy and tolerability of escitalopram in patients with depression, with or without comorbid anxiety. Escitalopram was administered over a 12-week treatment period to 790 depressed patients, including 482 patients with at least one concomitant anxiety disorder. The study was completed by 649 patients. At baseline, the mean Montgomery-Asberg Depression Rating Scale (MADRS) total score was 31.5 and decreased to 12.4 at end point (last observation carried forward [LOCF]). The MADRS score decreased by 20.5 points in patients with no anxiety disorder and by 18.3 points in patients with at least one concomitant anxiety disorder. The mean Hamilton Anxiety Rating Scale (HAM-A) total score at baseline was 25.6, which decreased to 10.8 at end point (LOCF). The HAM-A score decreased by 13.8 points in patients with no anxiety disorder and by 15.5 points in patients with at least one anxiety disorder. Adverse events were reported by 246 patients (31%). The most frequent adverse events were nausea in 65 patients (8%) and headache in 38 patients (5%); 61 patients (8%) discontinued treatment due to adverse events. Escitalopram was well tolerated and efficacious in reducing symptoms of depression in patients with or without comorbid anxiety over a 12-week treatment period.
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PMID:A prospective study of escitalopram in the treatment of major depressive episodes in the presence or absence of anxiety. 1704 22

Escitalopram, the S-enantiomer of citalopram and the most selective of the selective serotonin reuptake inhibitor (SSRI) has been shown to be efficacious in the treatment of major depression in white populations. Our aim in this study was to investigate the efficacy and tolerability of escitalopram in Chinese patients with moderate to severe major depression. Patients who met DSM-IV criteria for a major depressive episode were enrolled in this multicenter, randomized, double-blind, fixed-dose comparison trial. Patients were given escitalopram 10 mg/day or fluoxetine 20 mg/day for 8 weeks. All patients were assessed with the 17-item Hamilton Depression Rating Scale (HAM-D-17) and the Montgomery-Asberg Depression Rating Scale (MADRS). Tolerability was assessed on the basis of adverse effects (measured with a locally developed checklist), regular biochemical tests, and electrocardiograph (ECG) assessments. Two hundred forty patients were enrolled and randomized to escitalopram (123 patients) or fluoxetine (117 patients). The HAM-D-17 total scores of both groups decreased significantly from baseline, but there was no significant difference at week 8 between the two groups (15.8 for escitalopram and 14.7 for fluoxetine; P >.05). There were no significant differences in response rates at all visits after treatment based on either HAM-D-17 or MADRS. A post hoc analysis indicated that escitalopram was superior to fluoxetine on two items of the HAM-D-17: "depressed mood" (P =.023) and "work and interest" (P =.024). The adverse events reported in the escitalopram and fluoxetine groups were comparable, and most were mild to moderate. Both drugs showed good compliance profiles. Escitalopram 10 mg/day is at least as efficacious as fluoxetine 20 mg/day and well tolerated in Chinese patients with major depression, with possible superiority in some core symptoms such as "depressed mood" and "work and interest."
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PMID:Escitalopram in major depressive disorder: a multicenter, randomized, double-blind, fixed-dose, parallel trial in a Chinese population. 1714 53

Clinical trials have shown better efficacy of escitalopram over citalopram, and review-based economic models the cost-effectiveness of escitalopram vs. citalopram (brand and generic). No head-to-head clinical trial has, however, evaluated the cost-effectiveness of both drugs so far. The aim of this study was to assess the relative cost-effectiveness of escitalopram compared with citalopram in patients with major depressive disorder. An economic evaluation was conducted alongside a double-blind randomized clinical trial conducted by general practitioners and psychiatrists comparing fixed doses of escitalopram (20 mg/day) or citalopram (40 mg/day) over 8 weeks in ambulatory care patients with major depressive disorder (baseline Montgomery-Asberg Depression Rating Scale score > or =30). Resources use was recorded using a standardized form recording use of healthcare services and days of sick leave for the 2-month prestudy period and for the 8-week study period. Statistically significant improvements were observed in patients treated with escitalopram. Mean per-patient costs for the escitalopram group, compared with the citalopram group, were 41% lower (96 euro vs. 163 euro; P<0.05) from a healthcare perspective. Differences were mostly related to lower hospitalization costs for escitalopram compared with citalopram recipients, assuming a parity price between escitalopram and citalopram. Bootstrapped distributions of the cost-effectiveness ratios also showed better effectiveness and lower costs for escitalopram compared with citalopram. Escitalopram is significantly more effective than citalopram, and is associated with lower healthcare costs. This prospective economic analysis demonstrated that escitalopram is a cost-effective first-line treatment option for major depressive disorder.
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PMID:Cost-effectiveness of escitalopram vs. citalopram in major depressive disorder. 1729 11

Escitalopram is the (S)-enantiomer of the racemic selective serotonin reuptake inhibitor antidepressant citalopram. Clinical studies have shown that escitalopram is effective and well tolerated in the treatment of depression and anxiety disorders. Following oral administration, escitalopram is rapidly absorbed and reaches maximum plasma concentrations in approximately 3-4 hours after either single- or multiple-dose administration. The absorption of escitalopram is not affected by food. The elimination half-life of escitalopram is about 27-33 hours and is consistent with once-daily administration. Steady-state concentrations are achieved within 7-10 days of administration. Escitalopram has low protein binding (56%) and is not likely to cause interactions with highly protein-bound drugs. It is widely distributed throughout tissues, with an apparent volume of distribution during the terminal phase after oral administration (V(z)/F) of about 1100L. Unmetabolised escitalopram is the major compound in plasma. S-demethylcitalopram (S-DCT), the principal metabolite, is present at approximately one-third the level of escitalopram; however, S-DCT is a weak inhibitor of serotonin reuptake and does not contribute appreciably to the therapeutic activity of escitalopram. The didemethyl metabolite of escitalopram (S-DDCT) is typically present at or below quantifiable concentrations. Escitalopram and S-DCT exhibit linear and dose-proportional pharmacokinetics following single or multiple doses in the 10-30 mg/day dose range. Adolescents, elderly individuals and patients with hepatic impairment do not have clinically relevant differences in pharmacokinetics compared with healthy young adults, implying that adjustment of the dosage is not necessary in these patient groups. Escitalopram is metabolised by the cytochrome P450 (CYP) isoenzymes CYP2C19, CYP2D6 and CYP3A4. However, ritonavir, a potent inhibitor of CYP3A4, does not affect the pharmacokinetics of escitalopram. Coadministration of escitalopram 20mg following steady-state administration of cimetidine or omeprazole led to a 72% and 51% increase, respectively, in escitalopram exposure compared with administration alone. These changes were not considered clinically relevant. In vitro studies have shown that escitalopram has negligible inhibitory effects on CYP isoenzymes and P-glycoprotein, suggesting that escitalopram is unlikely to cause clinically significant drug-drug interactions. The favourable pharmacokinetic profile of escitalopram suggests clinical utility in a broad range of patients.
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PMID:The clinical pharmacokinetics of escitalopram. 1737 80

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