Effect of age and gender on citalopram and desmethylcitalopram steady-state plasma concentrations in adults and elderly depressed patients

Lima, Cabral; Baumann, Pierre; Brawand-Amey, Marlyse; Brogli, Christian; Jacquet, Sylvie; Cochard, Nathalie; Powell-Golay, Kerry; Eap, Chin B.

doi:10.1016/j.pnpbp.2005.06.001

Cited by 25 publications

(14 citation statements)

References 15 publications

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“…This might arise from our narrow age interquartile range (36–56 years) and the absence of extremes ages comparing to other studies, compromising our power to detect an effect of age. An influence of sex on the pharmacokinetics of rac‐ citalopram is controversial in the literature . A recent study showed that sex seems to affect only the disposition of the R‐enantiomer, which could explain the absence of sex effect in our study .…”

Section: Discussioncontrasting

confidence: 48%

Escitalopram population pharmacokinetics in people living with human immunodeficiency virus and in the psychiatric population: Drug–drug interactions and probability of target attainment

Courlet

Guidi

Glatard

et al. 2019

Brit J Clinical Pharma

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Aims The aims of this study were to characterize escitalopram pharmacokinetic profile, to identify factors influencing drug exposure, notably drug–drug interactions with antiretrovirals, and to simulate expected exposure under standard dosage regimen. Methods A population pharmacokinetic analysis was performed using NONMEM. A total of 159 plasma concentration measurements were obtained from 39 human immunodeficiency virus (HIV)‐infected and 71 uninfected psychiatric patients. The influence of age, weight, sex, HIV and psychiatric cohorts, racemic citalopram treatment, and comedications on oral clearance was examined. Simulations served to calculate the percentage of patients expected to be under‐ or over‐exposed, considering established therapeutic targets (15–80 ng/mL). Results A 1‐compartment model with first‐order absorption and elimination described the data adequately. The average escitalopram clearance and volume of distribution were 23.1 L/h (interindividual variability 51%), and 920 L, respectively. Escitalopram disposition did not differ between HIV‐infected and uninfected patients, and was not affected by antiretroviral treatments. Coadministration of at least 1 proton‐pump inhibitor (CYP2C19 inhibitor) modestly influenced escitalopram elimination (clearance decreased by 19%), with limited clinical relevance. Model‐based simulations showed that, under a standard regimen of 10 mg once daily, a significant proportion of patients (56%) might be under‐exposed. Conclusion The variability in escitalopram disposition is large and poorly explained by demographic, clinical and environmental covariates, thus suggesting a role for dosage individualization based on therapeutic drug monitoring in case of poor clinical response. Escitalopram disposition is modestly impacted by comedications and therefore no a priori dosage adjustments are needed in patients receiving antiretroviral treatments, including boosted regimens.

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Section: Discussioncontrasting

confidence: 48%

Escitalopram population pharmacokinetics in people living with human immunodeficiency virus and in the psychiatric population: Drug–drug interactions and probability of target attainment

Courlet

Guidi

Glatard

et al. 2019

Brit J Clinical Pharma

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“…Because the main outcome was the effect of citalopram pre-treatment on endotoxin-induced symptoms, the data for these two subjects were excluded from final analyses. In the remaining eight subjects (3 women, 5 men) the trough citalopram plasma level was 24.7 ± 5.0 ng/ml, which is lower than that (42 ± 17 ng/ml) achieved in outpatients treated with 20 mg/day (de Mendonca Lima et al 2005), indicating that steady-state levels were not fully reached. Endotoxin administration caused an increase in heart rate from 63 ± 14 to 89 ± 14 bpm and from 63 ± 12 to 91 ± 10 bpm in the Pbo-End and Cit-End conditions, respectively.…”

Section: Resultsmentioning

confidence: 61%

Citalopram reduces endotoxin-induced fatigue

Hannestad

DellaGioia

Ortiz

et al. 2011

Brain, Behavior, and Immunity

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Increased levels of inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-6 (IL-6) may play a role in depression. Mild depressive-like symptoms can be induced in humans through activation of the innate immune system with endotoxin. Whether preventive treatment with antidepressants can reduce endotoxin-induced symptoms has never been tested. In a double-blind, randomized, placebo-controlled, cross-over study, we administered intravenous low-dose endotoxin (0.8 ng/kg) or placebo to 11 healthy subjects who had received oral pre-treatment with citalopram (10 mg twice a day) or placebo for five days. The Montgomery-Åsberg Depression Rating Scale, the State and Trait Anxiety Inventory, and a visual analog scale were used to measure depressive and anxiety symptoms and social anhedonia. Serum levels of TNF and IL-6 were measured with immunoassays. Compared to placebo, endotoxin administration increased serum levels of TNF and IL-6, and caused mild depressive-like symptoms, in particular lassitude and social anhedonia. While citalopram pre-treatment had no effect on the innate immune response to endotoxin, it reduced the endotoxin-induced MADRS total score by 50%, with a moderate effect size (Cohen’s d=0.5). Most of the MADRS total score was due to the Lassitude item, and citalopram pre-treatment specifically reduced endotoxin-induced lassitude with a large effect size (Cohen’s d=0.9). These results suggest that subchronic pre-treatment with the serotonin-reuptake inhibitor citalopram blunts mood symptoms induced by acute immune system activation with endotoxin without inhibiting the peripheral immune response.

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“…Furthermore, our measured citalopram levels at week 12 (mean [SD], 55.7 [49.3] ng/mL) exceed those reported for adults receiving 20 mg/d for depression. 33 Therefore, underdosing is an unlikely explanation for our results.…”

Section: Commentmentioning

confidence: 75%

Lack of Efficacy of Citalopram in Children With Autism Spectrum Disorders and High Levels of Repetitive Behavior

King

Hollander²,

Sikich³

et al. 2009

Arch Gen Psychiatry

436

297

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Context Selective serotonin reuptake inhibitors are widely prescribed for children with autism spectrum disorders. Objectives To determine the efficacy and safety of citalopram hydrobromide therapy for repetitive behavior in children with autism spectrum disorders. Design National Institutes of Health–sponsored randomized controlled trial. Setting Six academic centers, including Mount Sinai School of Medicine, North Shore–Long Island Jewish Health System, University of North Carolina at Chapel Hill, University of California at Los Angeles, Yale University, and Dartmouth Medical School. Participants One hundred forty-nine volunteers 5 to 17 years old (mean [SD] age, 9.4 [3.1] years) were randomized to receive citalopram (n = 73) or placebo (n = 76). Participants had autistic spectrum disorders, Asperger disorder, or pervasive developmental disorder, not otherwise specified; had illness severity ratings of at least moderate on the Clinical Global Impressions, Severity of Illness Scale; and scored at least moderate on compulsive behaviors measured with the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders. Interventions Twelve weeks of citalopram hydrobromide (10 mg/5 mL) or placebo. The mean (SD) maximum dosage of citalopram hydrobromide was 16.5 (6.5) mg/d by mouth (maximum, 20 mg/d). Main Outcome Measures Positive response was defined by a score of much improved or very much improved on the Clinical Global Impressions, Improvement subscale. An important secondary outcome was the score on the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders. Adverse events were systematically elicited using the Safety Monitoring Uniform Report Form. Results There was no significant difference in the rate of positive response on the Clinical Global Impressions, Improvement subscale between the citalopram-treated group (32.9%) and the placebo group (34.2%) (relative risk, 0.96; 95% confidence interval, 0.61-1.51; P> .99). There was no difference in score reduction on the Children's Yale-Brown Obsessive Compulsive Scales modified for pervasive developmental disorders from baseline (mean [SD], −2.0 [3.4] points for the citalopram-treated group and −1.9 [2.5] points for the placebo group; P=.81). Citalopram use was significantly more likely to be associated with adverse events, particularly increased energy level, impulsiveness, decreased concentration, hyperactivity, stereotypy, diarrhea, insomnia, and dry skin or pruritus. Conclusion Results of this trial do not support the use of citalopram for the treatment of repetitive behavior in children and adolescents with autism spectrum disorders. Trial Registration clinicaltrials.gov Identifier: NCT00086645

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Effect of age and gender on citalopram and desmethylcitalopram steady-state plasma concentrations in adults and elderly depressed patients

Cited by 25 publications

References 15 publications

Escitalopram population pharmacokinetics in people living with human immunodeficiency virus and in the psychiatric population: Drug–drug interactions and probability of target attainment

Escitalopram population pharmacokinetics in people living with human immunodeficiency virus and in the psychiatric population: Drug–drug interactions and probability of target attainment

Citalopram reduces endotoxin-induced fatigue

Lack of Efficacy of Citalopram in Children With Autism Spectrum Disorders and High Levels of Repetitive Behavior

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