citalopram escitalopram Lexapro
Long-term treatment with citalopram in patients with highly recurrent forms of unipolar depression.

Franchini L, Spagnolo C, Rampoldi R, Zanardi R, Smeraldi E.

Department of Neuropsychiatric Sciences, School of Medicine, University of Milan, Universita Vita e Salute, Via Luigi Prinetti, 29, 20127, Milan, Italy. franchini.linda hsr.it

The authors evaluated the efficacy and safety of citalopram in a 28-month study in 48 inpatients with highly recurrent forms of unipolar depression. The patients, who each had at least one depressive episode during the 18 months preceding the index episode, were openly treated with citalopram, 40 mg/day. Thirty-six of the patients had a stable response to citalopram and continued treatment as outpatients for 4 months. No relapses were observed. At the time of recovery, 32/36 subjects received maintenance treatment with citalopram (40 mg) for an additional 24 months. At the end of the study, 11/32 patients experienced a single new recurrence.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11740983&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Citalopram as adjunctive therapy in bipolar depression.

Kupfer DJ, Chengappa KN, Gelenberg AJ, Hirschfeld RM, Goldberg JF, Sachs GS, Grochocinski VJ, Houck PR, Kolar AB.

Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, PA 15213, USA. kupferdj msx.upmc.edu

BACKGROUND: The treatment of bipolar depression remains a major clinical challenge. The effectiveness and safety of adjunctive citalopram were evaluated in DSM-IV-diagnosed bipolar depressed patients in a 5-site study. METHOD: The treatment strategy consisted of an open-label add-on design in which patients received 8 weeks of acute treatment with citalopram adjunctive to their ongoing treatment with mood stabilizers. Ongoing treatment with 1 antipsychotic, 1 anxiolytic, and 1 hypnotic agent was permitted. Responders to the 8-week trial then received 16 weeks of additional treatment with citalopram. RESULTS: Forty-five subjects entered the trial; 12 dropped out before the end of the acute treatment phase. Of the 33 patients who completed the acute treatment phase, 64% (N = 21) were responders and 36% (N = 12) were nonresponders. In the continuation phase of the study, 14 patients achieved sustained remission, 3 patients did not achieve remission before completing 16 weeks of continuation treatment, 2 patients experienced a relapse, and 2 patients dropped out of the study and did not have a chance to remit. In spite of the extensive concomitant medication usage allowed in this study, citalopram treatment was well tolerated and the level of reported adverse events (including headache, nausea, diarrhea, and sexual dysfunction) relatively low. CONCLUSION: The high response rate, the high rate of sustained remission, and the low rate of adverse events strongly support the use of citalopram as a treatment for bipolar I or II depression. These findings should stimulate a controlled double-blind trial to demonstrate even more clearly the usefulness of this drug in the therapeutic regimen for bipolar disorder.

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citalopram escitalopram Lexapro
Enantioselective analysis of citalopram and metabolites in adolescents.

Carlsson B, Olsson G, Reis M, Walinder J, Nordin C, Lundmark J, Scordo MG, Dahl ML, Bengtsson F, Ahlner J.

Division of Clinical Pharmacology, Department of Medicine and Care, Faculty of Health Sciences, Linkoping University, Sweden. bjorn.carlsson.lio.se

Studies of the antidepressant effect and pharmacokinetics of citalopram have been performed in adults, but the effects on children and adolescents have only been studied to a minor extent despite its increasing use in these age groups. The aim of this study was to investigate a group of adolescents treated for depression, with respect to the steady-state plasma concentrations of the enantiomers of citalopram and its demethylated metabolites desmethylcitalopram and didesmethylcitalopram. Moreover, the authors studied the genotypes for the polymorphic cytochrome P450 enzymes CYP2D6 and CYP2C19 in relation to the different enantiomers. The S/R ratios of citalopram and desmethylcitalopram found in this study of 19 adolescents were similar to studies involving older patients. The concentrations of the R-(-)- and S-(+)-enantiomers of citalopram and desmethylcitalopram were also in agreement with values from earlier studies, the R-(-)-enantiomer (distomer) being the major enantiomer. The results indicate that the use of oral contraceptives may have some influence on the metabolism of citalopram. This might be because of an interaction of the contraceptive hormones with the CYP2C19 enzyme.

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citalopram escitalopram Lexapro
Role of 5-HT1A receptors in the mediation of acute citalopram effects: a 8-OH-DPAT challenge study.

Pruus K, Vaarmann A, Rudissaar R, Allikmets L, Matto V.

Department of Pharmacology, University of Tartu, Estonia.

(1) The study was aimed to investigate the effects of the minimal effective doses of acute citalopram (5 mg/kg), (+/-)-8-hydroxydipropylaminotetralin HBr (8-OH-DPAT; 0.1 mg/kg), and their combined treatment on the rat open field and forced swimming behaviour and post-mortem monoamine content. (2) The animals were prospectively divided into the vehicle- and para-chlorophenylalanine (p-CPA)-pretreated (350 mg/kg) groups. (3) Acute citalopram (5 mg/kg), 8-OH-DPAT (0.1 mg/kg), or their combined treatment had no major effect on the rat open field and forced swimming behaviour. (4) The post-mortem catecholamine content in four brain regions studied was unchanged in all treatment groups. (5) The combined 8-OH-DPAT (0.1 mg/kg) and citalopram (5 mg/kg) treatment partially reversed the p-CPA-induced decrease of serotonin (5-HT) and 5-hydroxy-indolacetic acid (5-HIAA) content. (6) The present experiments demonstrate that the 5-HT1A receptors mediate some of the selective serotonin reuptake inhibitor (SSRI)-induced biochemical phenomena.

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citalopram escitalopram Lexapro
In vitro biotransformation of the selective serotonin reuptake inhibitor citalopram, its enantiomers and demethylated metabolites by monoamine oxidase in rat and human brain preparations.

Kosel M, Gnerre C, Voirol P, Amey M, Rochat B, Bouras C, Testa B, Baumann P.

Unite de Biochimie et Psychopharmacologie Clinique, Departement Universitaire de Psychiatrie Adulte, CH-1008 Prilly-Lausanne, Switzerland.

This study was conducted to identify enzyme systems eventually catalysing a local cerebral metabolism of citalopram, a widely used antidepressant of the selective serotonin reuptake inhibitor type. The metabolism of citalopram, of its enantiomers and demethylated metabolites was investigated in rat brain microsomes and in rat and human brain mitochondria. No cytochrome P-450 mediated transformation was observed in rat brain. By analysing H2O2 formation, monoamine oxidase A activity in rat brain mitochondria could be measured. In rat whole brain and in human frontal cortex, putamen, cerebellum and white matter of five brains monoamine oxidase activity was determined by the stereoselective measurement of the production of citalopram propionate. All substrates were metabolised by both forms of MAO, except in rat brain, where monoamine oxidase B activity could not be detected. Apparent Km and Vmax of S-citalopram biotransformation in human frontal cortex by monoamine oxidase B were found to be 266 microM and 6.0 pmol min(-1) mg(-1) protein and by monoamine oxidase A 856 microM and 6.4 pmol min(-1) mg(-1) protein, respectively. These Km values are in the same range as those for serotonin and dopamine metabolism by monoamine oxidases. Thus, the biotransformation of citalopram in the rat and human brain occurs mainly through monoamine oxidases and not, as in the liver, through cytochrome P-450.

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citalopram escitalopram Lexapro
Inhibitory actions of the selective serotonin re-uptake inhibitor citalopram on HERG and ventricular L-type calcium currents.

Witchel HJ, Pabbathi VK, Hofmann G, Paul AA, Hancox JC.

Cardiovascular Research Laboratories and Department of Physiology, School of Medical Sciences, Bristol, UK. harry.witchel bris.ac.uk

Using whole-cell patch clamp recording of heterologous HERG-mediated currents in transfected mammalian cells, we observed that the selective serotonin re-uptake inhibitor citalopram blocks HERG with an IC(50) of 3.97 microM. This is slightly less potent than fluoxetine in our system (IC(50) of 1.50 microM). In isolated guinea pig ventricular cardiomyocytes citalopram inhibited L-type calcium current (I(Ca,L)). The voltage dependence of I(Ca,L) inactivation in the presence of 100 microM citalopram was shifted significantly leftward. As a result, the I(Ca,L) 'window' in citalopram was found to be (a) smaller and (b) leftward-shifted compared to control. The effects of citalopram on both calcium current amplitude and the I(Ca,L) 'window' may help to explain citalopram's good cardiac safety profile, given its propensity to block HERG at excessive dosages.

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citalopram escitalopram Lexapro
Pentylenetetrazol-kindling of seizures selectively decreases [3H]-citalopram binding in the CA-3 area of rat hippocampus.

Szyndler J, Wierzba-Bobrowicz T, Maciejak P, Siemiatkowski M, Rok P, Lehner M, Czlonkowska AI, Bidzinski A, Wislowska A, Zienowicz M, Plaznik A.

Department of Experimental and Clinical Pharmacology, Medical University, 26/28 Krakowskie Przedmiescie Street, 00-927 Warsaw, Poland.

The present study was aimed at determining the changes in the 5-HT transporter activity, in different brain structures after pentylenetetrazol induced kindling of seizures. We examined [3H]-citalopram binding in the rat brain structures, and the neurodegenerative effects in the hippocampal formation using autoradiographic and immunohistochemical methods. A statistically significant and selective reduction in the binding of [3H]-citalopram was found in the CA3 field of the hippocampus (P=0.009), and a similar tendency, close to the significance level, in the dentate gyrus (P=0.05). This effect was accompanied by a loss of neurons and activation of microglia in the hippocampal formation. The present data suggest the important role for CA3- serotonergic innervation in pentylenetetrazol induced kindling of seizures.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12457739&dopt=Abstract citalopram escitalopram Lexapro