citalopram escitalopram Lexapro
A 5-HT(2C) receptor-mediated interaction between 2,5-dimethoxy-4-methylamphetamine and citalopram in the rat.

Eckler JR, Reissig CJ, Rabin RA, Winter JC.

Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, 102 Farber Hall, Buffalo, NY 14214-3000, USA.

Previous studies conducted in our laboratory have shown that acute administration of the selective serotonin re-uptake inhibitor (SSRI), citalopram, potentiates the stimulus effects of the phenethylamine hallucinogen [-]-2,5-dimethoxy-4-methylamphetamine (DOM) in the rat while neither substituting for the DOM stimulus when administered alone nor altering brain levels of DOM. The present investigation was designed to determine the mechanism by which citalopram acts on DOM-induced stimulus control. To that end, we tested the following hypotheses: (a) citalopram blocks the transport of DOM by the serotonin transporter, (b) citalopram acts via the 5-HT(1A) receptor, and (c) citalopram acts via the 5-HT(2C) receptor. Hypothesis (a) was rejected on the basis of equilibrium saturation studies of [3H]citalopram binding, which revealed no significant affinity of DOM for the 5-HT transporter of rat brain membranes. Hypotheses (b) and (c) were tested in a group of 20 rats in which stimulus control was established with DOM (0.6 mg/kg; 75 min pretreatment time). A two-lever, fixed ratio 10 (FR10), positively reinforced task with saline controls was employed. Hypothesis (b), a role for the 5-HT(1A) receptor, was rejected on the basis of an absence of antagonism of the effects of citalopram on DOM by the selective 5-HT(1A) receptor antagonist, WAY-100635. In contrast, Hypothesis (c), a role for the 5-HT(2C) receptor, gained support from the observation of significant antagonism of the effects of citalopram on DOM by the selective 5-HT(2C) receptor antagonist, SB-242084.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15388280&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Neonatal administration of citalopram delays somatic maturation in rats.

Deiro TC, Manhaes-de-Castro R, Cabral-Filho JE, Souza SL, Freitas-Silva SR, Ferreira LM, Guedes RC, Camara CR, Barros KM.

Departamento de Nutricao, Centro de Ciencias da Saude, Universidade Federal de Pernambuco, Av. Morais Rego 1235, 50670-901 Recife, PE, Brazil.

We investigated the somatic maturation of neonate rats treated during the suckling period with citalopram, a selective serotonin reuptake inhibitor. Groups with 6 male neonates were randomly assigned to different treatments 24 h after birth. Each litter was suckled by one of the dams until the 21st postnatal day. Body weight, head axis and tail length were measured daily from the 1st to the 21st postnatal day. Time of ear unfolding, auditory conduit opening, incisor eruption, and eye opening was determined. Pups received 5 mg (Cit5), 10 mg (Cit10) or 20 mg/kg (Cit20) citalopram sc, or saline (0.9% NaCl, w/v, sc). Compared to saline, body weight was lower (24.04%, P < 0.01) for Cit10 from the 10th to the 21st day and for Cit20 from the 6th to the 21st day (38.19%, P < 0.01). Tail length was reduced in the Cit20 group (15.48%, P < 0.001) from the 8th to the 21st day. A reduction in mediolateral head axis (10.53%, P < 0.05) was observed from the 11th to the 21st day in Cit10 and from the 6th to the 21st day in Cit20 (13.16%, P < 0.001). A reduction in anteroposterior head axis was also observed in the Cit20 group (5.28%, P < 0.05) from the 13th to the 21st day. Conversely, this axis showed accelerated growth from the 12th to the 21st day in the Cit5 group (13.05%, P < 0.05). Auditory conduit opening was delayed in the Cit5 and Cit20 groups and incisor eruption was delayed in all citalopram groups. These findings show that citalopram injected during suckling to rats induces body alterations and suggest that the activity of the serotoninergic system participates in growth mechanisms.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15448871&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
The effect of escitalopram, desipramine, electroconvulsive seizures and lithium on brain-derived neurotrophic factor mRNA and protein expression in the rat brain and the correlation to 5-HT and 5-HIAA levels.

Jacobsen JP, Mork A.

Department of Neurochemistry, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. jprj lundbeck.com

The reported increase in brain-derived neurotrophic factor (BDNF) mRNA expression after antidepressant treatment is a cornerstone of the BDNF hypothesis of antidepressant action. However, if this increase becomes manifest on the BDNF protein level is unknown. In the present study we performed parallel measurements of BDNF mRNA and protein expression in the frontal cortex and hippocampus of the rat after chronic treatment with electroconvulsive seizures (ECS), lithium, desipramine or escitalopram. ECS increased BDNF mRNA and protein in the hippocampus and BDNF protein in the frontal cortex. Desipramine moderately increased BDNF mRNA expression in the dentate gyrus but did not change BDNF protein in neither region. Escitalopram did not affect BDNF mRNA expression, but decreased BDNF protein in the frontal cortex and the hippocampus. Lithium increased BDNF protein levels in the hippocampus and frontal cortex, but overall decreased BDNF mRNA expression. Thus, here we report a striking non-correspondence between changes in BDNF mRNA and protein expression induced by the antidepressant treatments and lithium. Further, increased expression of BDNF mRNA or protein was not a common action of the treatments. We also investigated if treatment-induced modulations of the tissue contents of 5-hydroxytryptamine (5-HT) and its metabolite, 5-hydroxy-indoleacetic acid (5-HIAA), were related to changes in BDNF mRNA or protein expression. No correlation was found. However, all treatments increased 5-HT levels in the hippocampus.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15451381&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
[Second generation SSRIS: human monoamine transporter binding profile of escitalopram and R-fluoxetine]

[Article in French]

Owens JM, Knight DL, Nemeroff CB.

University school of Medicine. Dept of Psychiatry and Behavorial sciences, 1639 Pierce drive, suite 4000 WMRB, Atlanta GA 30322, USA.

BACKGROUND: Single isomers of the selective serotonin reuptake inhibitors citalopram (escitalopram, S-citalopram) and fluoxetine (R-fluoxetine) are currently under development for the treatment of depression and other psychiatric disorders. Previous studies conducted in laboratory animals have revealed that the biological effects on serotonin reuptake for citalopram reside in the S enantiomer. In contrast, both enantiomers of fluoxetine contribute to its biological activity. METHODS: In the present study, the potency and selectivity of escitalopram, R-fluoxetine, and all of the other currently available selective serotonine reuptake ihibitors were compared for binding affinity at the human serotonin, norepinephrine, and dopamine transporters and several select neurotransmitter receptors using radioligand binding assays. RESULTS: Both escitalopram and R-fluoxetine were potent inhibitors of the serotonin transporter (Ki=1,1 and 1,4 nmol/L, respectively). escitalopram was the most serotonin transporter-selective compound tested and was approximately 30 fold more potent than R-citalopram. CONCLUSIONS: As noted previously, paroxetine and sertraline possess moderate affinity (<50 nmol/L) for the human norepinephrine transporter and dopamine transporter, respectively. R-fluoxetine, unlike the other selective serotonin reuptake inhibitors, possesses moderate affinity (Ki=64 nmol/L) for the serotonin 2C receptor. Potential clinical correlates of these unique attributes of escitalopram and R-fluoxetine are discussed. (Biol Psychiatry 2001; 50: 345-350 " 2001 Society of Biological Psychiatry).

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12232544&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
[Clinical efficacy of citalopram in patients with hypertension and concomitant depression]

[Article in Russian]

[No authors listed]

Patients (n=28) with mild to moderate hypertension and depression were given enalapril (20 mg/day). If target blood pressure was not achieved in 10 days hydrochlorothiazide (12.5 mg/day) was added. These patients were randomized into 2 groups in one of which antihypertensive therapy was supplemented with citalopram (20 mg/day) for 6 weeks. Psychological status was assessed by Beck Depression Inventory (BDI) and Spielberger State-Trait Anxiety Inventory (STAI). Total BDI score in citalopram group decreased 51% (-12.2+/-1.5; p<0.001). Complete reduction of symptoms of depression (BDI score <19) occurred in 86% of patients. There was no significant lowering of BDI score in control group. STAI score among citalopram treated patients with concomitant anxiety (STAI score >50) decreased from initial 62.9+/-2.1 to 46.3+/-3.1 by week 6 (p<0.001). Only minor changes of STAI score took place in control group. According to data of 24-hour monitoring lowering of systolic blood pressure time indexes was somewhat more pronounced in citalopram group than in control group (24 hour -49.8 and -34.4%, diurnal -56.6 and -42%, nocturnal -37.9 and -23%, respectively).

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15477790&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Single photon emission computed tomography (SPECT) of anxiety disorders before and after treatment with citalopram.

Carey PD, Warwick J, Niehaus DJ, van der Linden G, van Heerden BB, Harvey BH, Seedat S, Stein DJ.

MRC Unit on Anxiety Disorders, Department of Psychiatry, University of Stellenbosch, Tygerberg, 7505, Cape Town, South Africa. pcarey sun.ac.za

BACKGROUND: Several studies have now examined the effects of selective serotonin reuptake inhibitor (SSRI) treatment on brain function in a variety of anxiety disorders including obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and social anxiety disorder (social phobia) (SAD). Regional changes in cerebral perfusion following SSRI treatment have been shown for all three disorders. The orbitofrontal cortex (OFC) (OCD), caudate (OCD), medial pre-frontal/cingulate (OCD, SAD, PTSD), temporal (OCD, SAD, PTSD) and, thalamic regions (OCD, SAD) are some of those implicated. Some data also suggests that higher perfusion pre-treatment in the anterior cingulate (PTSD), OFC, caudate (OCD) and antero-lateral temporal region (SAD) predicts subsequent treatment response. This paper further examines the notion of overlap in the neurocircuitry of treatment and indeed treatment response across anxiety disorders with SSRI treatment. METHODS: Single photon emission computed tomography (SPECT) using Tc-99 m HMPAO to assess brain perfusion was performed on subjects with OCD, PTSD, and SAD before and after 8 weeks (SAD) and 12 weeks (OCD and PTSD) treatment with the SSRI citalopram. Statistical parametric mapping (SPM) was used to compare scans (pre- vs post-medication, and responders vs non-responders) in the combined group of subjects. RESULTS: Citalopram treatment resulted in significant deactivation (p = 0.001) for the entire group in the superior (t = 4.78) and anterior (t = 4.04) cingulate, right thalamus (t = 4.66) and left hippocampus (t = 3.96). Deactivation (p = 0.001) within the left precentral (t = 4.26), right mid-frontal (t = 4.03), right inferior frontal (t = 3.99), left prefrontal (3.81) and right precuneus (t= 3.85) was more marked in treatment responders. No pattern of baseline activation distinguished responders from non-responders to subsequent pharmacotherapy. CONCLUSIONS: Although each of the anxiety disorders may be mediated by different neurocircuits, there is some overlap in the functional neuro-anatomy of their response to SSRI treatment. The current data are consistent with previous work demonstrating the importance of limbic circuits in this spectrum of disorders. These play a crucial role in cognitive-affective processing, are innervated by serotonergic neurons, and changes in their activity during serotonergic pharmacotherapy seem crucial.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15482603&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
A comparison of the direct costs and cost effectiveness of serotonin reuptake inhibitors and associated adverse drug reactions.

Sullivan PW, Valuck R, Saseen J, MacFall HM.

Pharmaceutical Outcomes Research Program, Department of Clinical Pharmacy, School of Pharmacy, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. Patrick.Sullivan UCHSC.edu

BACKGROUND: The economic burden of depression is known to be high and was estimated to be USD 83.1 billion in 2000. Serotonin reuptake inhibitors (SRIs), including both selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs), have a superior adverse effect and safety profile relative to traditional agents (e.g. TCAs), and as a result have demonstrated superior cost effectiveness. Although efficacy across the SRIs is similar, the incidence of adverse drug reactions (ADRs) within SRIs remains significant and varies by agent. Patients who experience ADRs from SRIs may seek medical care, require additional treatment, and even discontinue treatment altogether, leading to increased utilisation and cost of therapy. OBJECTIVE: This study estimates the direct cost and cost effectiveness, taking into account the impact of treatment-related ADRs, of eight currently marketed SRIs (citalopram, escitalopram, generic fluoxetine, paroxetine, paroxetine controlled release [CR], sertraline, venlafaxine and venlafaxine extended release [XR]) used as initial treatment for depression. METHODS: A decision analytic model with a 6-month treatment goal was used to estimate the direct cost and cost effectiveness of treatment from the managed care/payer perspective. Estimates of SRI-related ADRs, associated treatments and costs were derived from the US FDA-approved prescribing information and published literature. Efficacy was assumed to be similar across all SRIs. Effectiveness was measured using quality-adjusted life years (QALY) based on EuroQol EQ-5D scores derived from the 2000 Medical Expenditure Panel Survey (MEPS). Censored least absolute deviations (CLAD) regression analysis was used to derive age-adjusted estimates of utility for all health states. Univariate and Bayesian second-order multivariate probabilistic sensitivity analyses were conducted to examine the impact of uncertainty in the parameter estimates. RESULTS: The expected direct cost and cost effectiveness of treatment from least to most expensive were: escitalopram (USD 3891; 0.341), citalopram (USD 3938; 0.340), generic fluoxetine (USD 4034; 0.335), venlafaxine XR (USD 4226; 0.336), sertraline (USD 4250; 0.335), generic paroxetine (USD 4385; 0.332), paroxetine CR (USD 4440; 0.332) and venlafaxine (USD 4613; 0.326). Monte Carlo simulation results suggested that escitalopram was the most likely (77%) to be cost effective for a willingness to pay < or = USD 50,000 per QALY, followed by citalopram (22%), generic fluoxetine (0.3%) and all other SRIs (0%). Sensitivity analyses indicated that the results of the study were robust to the assumptions underpinning the model. CONCLUSIONS: SRI-related ADRs have a significant impact on the direct cost and cost effectiveness of treatment. Escitalopram, with the lowest ADR rate of the SRIs, had the lowest expected treatment cost and greatest effectiveness when compared with citalopram, generic fluoxetine, generic paroxetine, paroxetine CR, sertraline, venlafaxine and venlafaxine XR.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15521793&dopt=Abstract citalopram escitalopram Lexapro