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)

The current study sought to test the efficacy and safety of the novel selective norepinephrine reuptake inhibitor LY2216684 compared to placebo in patients with major depressive disorder (MDD). Escitalopram was used as a control for assay sensitivity. Adult outpatients with MDD, confirmed at screening by the Mini International Neuropsychiatric Interview, a Self-Rated Quick Inventory of Depressive Symptomatology (QIDS-SR) score of at least 12 and a Clinical Global Impression-Severity Score of at least 4, were randomly assigned to LY2216684 (N=269), placebo (N=138), or escitalopram (N=62). Efficacy, safety, and tolerability outcomes were compared during 8 weeks of double-blind treatment. LY2216684 plasma concentrations were measured. LY2216684 did not show statistically significant improvement from baseline compared to placebo in the primary analysis of the Hamilton depression rating scale (HAM-D(17)) total score. Escitalopram demonstrated significant improvement compared to placebo on the HAM-D(17) total score, suggesting adequate assay sensitivity. Both LY2216684 and escitalopram showed statistically significant improvement from baseline on the patient-rated QIDS-SR total score compared to placebo. Headache, nausea, constipation, dry mouth, and insomnia were the most frequently reported adverse events in the LY2216684 group. A 3-6 beats per minute mean increase from baseline in pulse rate was observed in the LY2216684 group. LY2216684 plasma concentrations increased as the dose increased from 3 mg to 12 mg. The results of this initial investigation of LY2216684's efficacy suggest that it may have antidepressant potential. More definitive data to confirm this is necessary. Its safety profile does not preclude further clinical development.
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PMID:A study of the effects of LY2216684, a selective norepinephrine reuptake inhibitor, in the treatment of major depression. 1990 80

Escitalopram is one of the most popular selective serotonin reuptake inhibitors (SSRIs) in current use as a first-line treatment for depression. Escitalopram is well-tolerated and rarely associated with serious side effects. Endocrine and reproductive side effects of serotonergic antidepressants are uncommon and galactorrhea is very rarely mentioned among SSRI-related side effects. Serotonin-enhancing antidepressants may result in a rise in prolactin levels through suppression of dopamine neurotransmission. In the present study, we report a case of hyperprolactinemic galactorrhea associated with escitalopram. A 36-year-old woman developed galactorrhea after initiation of escitalopram for depression and was found to have an elevated prolactin level. Escitalopram was discontinued with resolution of the patient's galactorrhea and normalization of her prolactin level.
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PMID:A case of galactorrhea associated with excitalopram. 2004 1

The majority of currently marketed drugs contain a mixture of enantiomers; however, recent evidence suggests that individual enantiomers can have pharmacological properties that differ importantly from enantiomer mixtures. Escitalopram, the S-enantiomer of citalopram, displays markedly different pharmacological activity to the R-enantiomer. This review aims to evaluate whether these differences confer any significant clinical advantage for escitalopram over either citalopram or other frequently used antidepressants. Searches were conducted using PubMed and EMBASE (up to January 2009). Abstracts of the retrieved studies were reviewed independently by both authors for inclusion. Only those studies relating to depression or major depressive disorder were included. The search identified over 250 citations, of which 21 studies and 18 pooled or meta-analyses studies were deemed suitable for inclusion. These studies reveal that escitalopram has some efficacy advantage over citalopram and paroxetine, but no consistent advantage over other selective serotonin reuptake inhibitors. Escitalopram has at least comparable efficacy to available serotonin-norepinephrine reuptake inhibitors, venlafaxine XR and duloxetine, and may offer some tolerability advantages over these agents. This review suggests that the mechanistic advantages of escitalopram over citalopram translate into clinical efficacy advantages. Escitalopram may have a favourable benefit-risk ratio compared with citalopram and possibly with several other antidepressant agents.
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PMID:Escitalopram--translating molecular properties into clinical benefit: reviewing the evidence in major depression. 2014 75

The objective of this study was to evaluate the efficacy and tolerability of escitalopram versus serotonin and noradrenaline reuptake inhibitors (SNRIs) as second step treatment (defined operationally as poor response or intolerability to an antidepressant) for major depressive disorder (MDD). Results from all eligible head-to-head clinical trials of MDD (which excluded patients who earlier failed two or more antidepressants) sponsored by Lundbeck or Forest comparing escitalopram and SNRIs (venlafaxine and duloxetine) were pooled. A second step treatment subgroup was identified, defined as patients treated earlier with any antidepressant in the 6-month period before baseline. Data from three clinical trials were included in the analysis; 132 patients were identified in the second step treatment subgroup (66 in each of the escitalopram and SNRI groups). The primary efficacy analysis showed that the patients subsequently treated with escitalopram had significantly lower Montgomery Asberg Depression Rating Scale total scores after 8 weeks compared with those subsequently treated with SNRIs (difference = -6.4, P<0.0001). Escitalopram treatment was also associated with higher clinical response (73 vs. 44%, P=0.0004) and remission rates (62 vs. 41%, P=0.0083) compared with subsequent treatment with SNRIs. Escitalopram showed a better tolerability profile with lower all-cause withdrawals from study (9 vs. 23%, P<0.04) and lower withdrawals because of adverse events (2 vs. 17%, P<0.003). In conclusion, escitalopram is associated with a better efficacy and tolerability profile than SNRIs (duloxetine and venlafaxine) when used as a second step treatment in patients with MDD. These results should be confirmed in prospective randomized clinical trials.
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PMID:Escitalopram versus serotonin noradrenaline reuptake inhibitors as second step treatment for patients with major depressive disorder: a pooled analysis. 2035 64

Antidepressant medication treatment has been associated with improvement in negative symptoms in patients with schizophrenia. In this study, we evaluated the efficacy of escitalopram for the treatment of negative symptoms in patients with schizophrenia. Under double-blind conditions, 40 patients with chronic schizophrenia were randomized to add-on treatment with escitalopram (up to 20mg) or placebo for 10weeks. The primary outcome measures were the scores on the Positive and Negative Syndrome Scale (PANSS)-negative subscale and the Social Functioning Scale (SFS). Secondary outcome measures included the Positive and Negative Syndrome Scale (PANSS)-total and positive scales, the Scale for Assessment of Negative Symptoms (SANS), the Clinical Global Impression Scale (CGI), the Hamilton Depression Rating Scale (HDRS) and the Abnormal Involuntary Movement Scale (AIMS). Of 40 patients, 36 completed the study and another 2 were excluded after 8weeks due to side effects. Thus, 38 patients (19 on both treatment arms) were considered in the efficacy analysis. The reduction in the PANSS negative subscale score was 5% for escitalopram and 10% for placebo (NS). There were no significant inter-group differences in primary and secondary endpoints. Escitalopram was well tolerated, but was not more effective than placebo in the treatment of negative symptoms in patients with chronic schizophrenia. Further work in this field is needed to determine whether some subgroups of patients with negative symptoms may nevertheless respond to antidepressant medications.
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PMID:Escitalopram in the treatment of negative symptoms in patients with chronic schizophrenia: a randomized double-blind placebo-controlled trial. 2047 99

Escitalopram is a selective serotonin reuptake inhibitor (SSRI), and is the second antidepressant to be approved for use in treating major depressive disorder (MDD) in adolescent patients (aged 12-17 years) in the US. In a randomized, double-blind, flexible-dose, multicenter trial, once-daily escitalopram 10-20 mg (n = 154) for 8 weeks was significantly better than placebo (n = 157) in improving the severity of depressive symptoms (as assessed by the change in the Children's Depression Rating Scale-Revised [CDRS-R] total score) in adolescent patients with MDD. Preliminary data from a combined analysis of the double-blind data from this trial and double-blind data from a 16-week, fixed-dose, extension study suggest a significant difference between escitalopram and placebo recipients in the change in CDRS-R total scores after 24 weeks of treatment. In a similarly designed flexible-dose trial in pediatric patients (aged 6-17 years), a significant difference between once-daily escitalopram 10-20 mg (n = 77) and placebo (n = 80) for 8 weeks, as assessed by the change in CDRS-R total score, was not shown in the primary analysis (i.e. patients of all ages). In a pre-specified subgroup of adolescent patients, no significant difference was shown between the escitalopram and the placebo groups when analyzed using the last observation carried forward method, but was shown using the observed case method. Escitalopram 10-20 mg/day showed better efficacy than placebo for some secondary endpoints (e.g. the change in the Clinical Global Impression [CGI]-Severity score, the CGI-Improvement response rate) but not others (e.g. CDRS-R response rate, rate of remission) [corrected].Once-daily escitalopram 10-20 mg for 8 weeks was generally well tolerated in clinical trials in adolescent or pediatric patients with MDD. The incidence of suicidality-related adverse events was generally similar between escitalopram and placebo recipients.
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PMID:Escitalopram: in the treatment of major depressive disorder in adolescent patients. 2048 45

In addition to the large personal challenge that depression and anxiety present, these disorders are associated with a substantial burden of disability and lost productivity, and are responsible for considerable strain on healthcare resources and on society. Escitalopram is recommended as first-line therapy for the treatment of major depressive disorder and severe depression, and is indicated in anxiety disorders. Compared with other antidepressants, escitalopram has equal or superior efficacy, as proven in clinical trial settings, equal or superior real-life effectiveness, established in both clinical and observational studies, and a better tolerability profile. While drug acquisition costs are higher for escitalopram than for generic drugs such as fluoxetine and citalopram, numerous prospective and modeled economic analyses show that associated direct and indirect costs of treatment are lower with escitalopram than with citalopram, fluoxetine, sertraline and venlafaxine. Thus, escitalopram appears to be more economically efficient than many antidepressants currently available. Escitalopram has a prominent role in the treatment of major depressive disorder and anxiety disorders, and may also prove to be important in the treatment of mixed depressive anxiety disorder.
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PMID:Efficacy, effectiveness and efficiency of escitalopram in the treatment of major depressive and anxiety disorders. 2052 19

Cognitive behavioral therapy (CBT) and pharmacotherapy are each efficacious for generalized anxiety disorder (GAD). It is not known, however, whether GAD partial and nonresponders to one treatment modality benefit from the other. This study explored acceptability and efficacy of escitalopram for persons with persistent GAD symptoms after a course of CBT. Twenty-four patients with GAD were treated with CBT and 15 completed at least 12 sessions. Eight completers continued to have clinically significant symptoms and were offered 12 weeks of treatment with escitalopram, and 7 started escitalopram treatment. During CBT, patients evidenced significant improvement in GAD, depression, and quality of life. During escitalopram treatment, patients evidenced trends toward further improvement in GAD, depression, and quality of life. Escitalopram phase completers had initially reported low-to-moderate preferences for medication treatment. Escitalopram may benefit GAD patients with clinically significant symptoms after CBT and merits further study under controlled conditions in a larger sample.
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PMID:Escitalopram for persistent symptoms of generalized anxiety disorder after CBT: a pilot study. 2053 Nov 28

Chronic treatment with antidepressants affects several proteins linked to neuroplasticity, particularly brain derived neurotrophic factor (BDNF): this leads eventually to their therapeutic effects. It is possible that also for putative early therapeutic onset, antidepressants may act by promoting cellular adaptations linked to neuroplasticity. Escitalopram, known to be already effective in preclinical models of depression after 7 days, allowed us to investigate whether two effective treatment regimens (7 and 21 days) may contribute to synaptic plasticity by acting on BDNF signalling. We focused our attention on two regulators of BDNF transcription, CREB and CaRF (calcium responsive factor), and on kinases, CaMKII, ERK1/2 and p38 MAPK, linked to BDNF that play a distinctive role in synaptic plasticity. We evaluated whether the effects of escitalopram on these targets may be different in brain areas involved in the depressive symptomatology (hippocampus, frontal and prefrontal cortex). Here we demonstrate that escitalopram regulates intracellular pathways linked to neuroplasticity at both the time points evaluated in an area-specific manner. While the two escitalopram-treatment regimens failed to affect gene expression in the rat frontal cortex, 7days of treatment with escitalopram activated intracellular pathways linked to BDNF and increased the levels of Pro-BDNF in the rat prefrontal cortex. Moreover, 21 days of treatment with escitalopram decreased CREB/BDNF signalling while increasing p38 levels in the rat hippocampus. Even if further experiments with different antidepressant strategies will be needed, our data suggest that escitalopram efficacy may be mediated by early and late effects on synaptic plasticity in selective brain areas.
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PMID:Time-dependent effects of escitalopram on brain derived neurotrophic factor (BDNF) and neuroplasticity related targets in the central nervous system of rats. 2059 17

The pharmacological treatment of older adults with major depressive disorder presents a variety of challenges, including a relative lack of high quality studies designed to measure the efficacy and safety of antidepressants specific to this patient population. Gaining a clear understanding of how to use antidepressants in elderly patients with depression, especially new and widely used agents, would provide valuable insight to clinicians. The purpose of the current article is to review the pharmacology, efficacy and safety of newer antidepressants (i.e. escitalopram, duloxetine and desvenlafaxine) in the treatment of late-life depression. To accomplish this goal, a MEDLINE and PubMed search (1966 - February 2010) was conducted for relevant articles. Animal and human studies have clearly demonstrated the effects of desvenlafaxine, duloxetine and escitalopram on monoamine reuptake transporters. The serotonergic and noradrenergic actions of desvenlafaxine and duloxetine may provide for a faster onset of antidepressant activity in the elderly, but more definitive data are needed and the clinical effects of the possible faster onset of action need to be elucidated. Duloxetine and escitalopram are extensively metabolized via cytochrome P450 (CYP) enzymes and the decreased hepatic metabolism present in many older adults should be taken into account when prescribing these medications. Duloxetine possesses the greatest likelihood of producing clinically relevant drug-drug interactions because of its inhibition of CYP2D6. All three agents must also be used cautiously in older adults with poor renal function. In terms of clinical efficacy, 14 prospective published trials involving escitalopram (n = 8) and duloxetine (n = 6) in the treatment of older adults with major depressive disorder were identified. No such studies involving desvenlafaxine were found. Of the five randomized, double-blind, controlled trials, 46% and 37% of antidepressant-treated patients were considered responders and remitters, respectively. In contrast to escitalopram, duloxetine-treated patients experienced improvements in depressive symptoms that more consistently differentiated themselves from the symptoms of placebo-treated patients. Escitalopram and duloxetine were generally well tolerated, but 5-20% and 10-27% of patients, respectively, dropped out because of medication-related adverse effects. Adverse effects experienced by older adults were generally similar to those experienced by younger adults, although indirect comparisons suggest that older adults are more likely to experience dry mouth and constipation with duloxetine and escitalopram, while orthostasis may be more common in older adults prescribed desvenlafaxine. Overall, duloxetine and escitalopram represent modestly effective treatments for late-life depression that are generally well tolerated but do produce a variety of adverse effects. Conclusions regarding desvenlafaxine cannot be made at this time because of a lack of geriatric-specific data.
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PMID:Pharmacological and clinical profile of newer antidepressants: implications for the treatment of elderly patients. 2065 91


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