Disease relevance of Escitalopram

• Quetiapine-induced weight gain and escitalopram [1].
• A case of hyponatremia associated with escitalopram [2].
• The overall discontinuation rate, excluding relapses, was 13.2% for patients treated with escitalopram and 8.3% for patients treated with placebo [3].
• Combination therapy of lamotrigine and escitalopram may cause myoclonus [4].
• Headache and abdominal pain were the only adverse events in >10% of patients in the escitalopram group [5].

Psychiatry related information on Escitalopram

• AIMS: To assess the efficacy of different doses of escitalopram in generalised anxiety disorder [6].
• Escitalopram in the treatment of panic disorder: a randomized, double-blind, placebo-controlled trial [7].
• An open trial of adjunctive escitalopram in bipolar depression [8].
• Open-label trial of escitalopram in the treatment of posttraumatic stress disorder [9].
• Escitalopram did not affect driving, psychomotor performance, or subjective mood throughout treatment [10].

High impact information on Escitalopram

• Second-generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine [11].
• However, ritonavir, a potent inhibitor of CYP3A4, does not affect the pharmacokinetics of escitalopram [12].
• 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 [12].
• Clinical studies have shown that escitalopram is effective and well tolerated in the treatment of depression and anxiety disorders [12].
• The clinical pharmacokinetics of escitalopram [12].

Chemical compound and disease context of Escitalopram

• Its S-enantiomer escitalopram, which may have faster onset and greater magnitude of effect than citalopram in other conditions, has not yet been investigated in PTSD [9].
• Escitalopram and paroxetine in the treatment of generalised anxiety disorder: randomised, placebo-controlled, double-blind study [6].
• The mean number of discontinuation emergent signs and symptoms in the venlafaxine XR group (mean: 5.0) was significantly (P<0.001) higher than for the escitalopram group (mean: 2.4) [13].
• With the understanding that serotonergic drugs might curb compulsive hair pulling, we conducted a preliminary investigation examining the effectiveness of escitalopram, a potent and selective serotonin uptake inhibitor, in the treatment of trichotillomania [14].
• Oculogyric dystonic reaction to escitalopram with features of anaphylaxis including response to epinephrine [15].

Biological context of Escitalopram

• A preliminary study of luteal phase versus symptom-onset dosing with escitalopram for premenstrual dysphoric disorder [16].
• Escitalopram has low protein binding (56%) and is not likely to cause interactions with highly protein-bound drugs [12].
• METHOD: Twenty-seven women meeting DSM-IV criteria for PMDD were randomly assigned in a double-blind manner to luteal phase (N = 13) or symptom-onset (N = 14) dosing of escitalopram (10-20 mg/day) for 3 consecutive menstrual cycles [16].
• Escitalopram showed insignificant activity at other monoamine transporters and 144 other binding sites [17].
• CONCLUSION: The study shows that escitalopram is safe for use during breastfeeding [18].

Anatomical context of Escitalopram

• Chronic treatment with escitalopram reversed the CMS-induced decrease in cytogenesis in the dentate gyrus of the ventral hippocampal formation, but in recovered animals only [19].
• They were randomly assigned to receive venlafaxine, sertraline, or escitalopram in combination with a 2-week period of sham or active 15-Hz rTMS on the left dorso-lateral prefrontal cortex [20].
• The novel radioligand [(123)I]ADAM and single photon emission computer tomography (SPECT) were used to measure midbrain SERT occupancies for different doses of escitalopram and citalopram [21].
• In conclusion, the present in-vitro and in-vivo studies show that R-citalopram counteracts the activity of escitalopram and paroxetine, but not fluoxetine, by acting at the allosteric binding site of the 5-HT transporter, either located in the dorsal raphe nucleus or post-synaptically in the ventral hippocampus [22].
• Transformation of escitalopram (S-CT), the pharmacologically active S-enantiometer of citalopram, to S-desmethyl-CT (S-DCT), and of S-DCT to S-didesmethyl-CT (S-DDCT), was studied in human liver microsomes and in expressed cytochromes (CYPs) [23].

Associations of Escitalopram with other chemical compounds

• A total of 15 healthy subjects were tested on three occasions receiving either oral citalopram (20 mg), escitalopram (10 mg), or placebo in a double-blind, randomized, crossover design [24].
• Single-dose pharmacokinetics of metoprolol were measured before and after 17 days of treatment with escitalopram 20 mg/d, duloxetine 60 mg/d, or sertraline 100 mg/d in young healthy male and female participants [25].
• The aim of the present study was to find out whether acute oral administration of the SSRI, citalopram, increases salivary cortisol in healthy volunteers and whether the increase produced by an equivalent dose of its active isomer, escitalopram, is greater [24].
• R-citalopram functionally antagonises escitalopram in vivo and in vitro: evidence for kinetic interaction at the serotonin transporter [26].
• Both the increase in basal corticosterone and decrease in glucocorticoid receptor immunoreactivity were reversed by escitalopram pretreatment [27].
• Risperidone reverses escitalopram-induced inhibition of norepinephrine neuronal activity by a mechanism involving serotonin-2A receptors [28].

Gene context of Escitalopram

• RESULTS: Escitalopram inhibited 5-HTT functions approximately 2 times more potently than citalopram and at least 40 times more potently than R-citalopram [17].
• CYP2C19 activity is a better predictor of escitalopram clearance than is Child-Pugh classification [29].
• OBJECTIVE: This study assessed mood and neuropsychological function in a population of middle-aged women with major depressive disorder treated with escitalopram [30].
• This study is the first to directly compare the relative effects of duloxetine, escitalopram, and sertraline on the functional activity of the drug-metabolizing cytochrome P450 2D6 enzyme as assessed by changes in the pharmacokinetics of the cytochrome P450 2D6 model substrate drug, metoprolol [25].
• CONCLUSION: Escitalopram is a very selective 5-HT reuptake inhibitor [17].

Analytical, diagnostic and therapeutic context of Escitalopram

• Following oral administration, escitalopram is rapidly absorbed and reaches maximum plasma concentrations in approximately 3-4 hours after either single- or multiple-dose administration [12].
• Randomized controlled trials of escitalopram in bipolar depression are warranted [8].
• In vivo imaging of serotonin transporter occupancy by means of SPECT and [(123)I]ADAM in healthy subjects administered different doses of escitalopram or citalopram [21].
• In some experiments escitalopram and R-citalopram were infused into the frontal cortex by reverse microdialysis [31].
• Escitalopram, the active enantiomer of the selective serotonin reuptake inhibitor (SSRI) citalopram, has effects in animal models for the detection of antidepressant and anxiolytic effect and in patients with major depressive and anxiety disorders [32].

References