citalopram Celexa
Effects of the androgen antagonist flutamide and the serotonin reuptake inhibitor citalopram in bulimia nervosa: a placebo-controlled pilot study.

Sundblad C, Landen M, Eriksson T, Bergman L, Eriksson E.

Department of Pharmacology, Goteborg University, Goteborg, Sweden.

Prompted by previous studies suggesting that bulimia nervosa in women may be associated with elevated serum levels of testosterone, we have evaluated the possible effect of androgen antagonism in this condition. To this end, women meeting the DSM-IV criteria of bulimia nervosa, purging type, were treated in a one-center study with the androgen receptor antagonist flutamide (n = 9), the serotonin reuptake inhibitor citalopram (n = 15), flutamide plus citalopram (n = 10), or placebo (n = 12) for 3 months using a double-blind design. Self-rated global assessment of symptom intensity suggests all active treatments to be superior to placebo. The reduction in binge eating compared with baseline was statistically significant in both groups given flutamide but not in the groups given citalopram only or placebo. A moderate and reversible increase in serum transaminase levels led to discontinuation in two subjects in the flutamide group. It is concluded that blockade of androgen receptors may reduce some of the symptoms of bulimia nervosa in women.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15643104&dopt=Abstract citalopram Celexa



citalopram Celexa
Chronic treatment with citalopram does not affect the expression of alpha(1)-adrenergic receptor (alpha(1)-ar) subtypes.

Kreiner G, Bielawski A, Zelek-Molik A, Kowalska M, Nalepa I.

Laboratory of Intracellular Signaling, Department of Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Krakow, Poland. nfnalepa cyf-kr.edu.pl.

We previously reported that chronic treatment with imipramine and electroconvulsive shock up-regulate the density and alpha(1A)-adrenergic receptor (alpha(1A)-AR) mRNA level in the rat prefrontal cortex, while the expression of the alpha(1B) subtype was unchanged. The present study examined whether repeatedly given citalopram, a selective serotonin reuptake inhibitor, induces any changes in the expression of alpha(1A) and alpha(1B) aubtypes of alpha(1)-AR. The receptors density was assessed in the rat cerebral cortex by [(3)H]prazosin binding while the expression of alpha(1A) and alpha(1B) receptors' mRNA was measured in the rat prefrontal cortex by Northern blot analysis or competitive reverse transcription and polymerase chain reaction (RT-PCR), respectively. We did not find any changes in alpha(1A)- and alpha(1B)-AR density or mRNA expression in the investigated rat brain structures of citalopram-treated rats. Thus, it seems that up-regulation of alpha(1A)-AR subtype is characteristic only of those antidepressant agents in which a noradrenergic component is involved in their pharmacological mechanism of action.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15662097&dopt=Abstract citalopram Celexa



citalopram Celexa
Brainstem levels of transcription factor AP-2 in rat are changed after treatment with phenelzine, but not with citalopram.

Berggard C, Damberg M, Oreland L.

Department of Neuroscience, Unit of Pharmacology, Uppsala University, PO Box 593 BMC, SE-751 24, Uppsala, Sweden. cecilia.berggard neuro.uu.se.

BACKGROUND: Before therapeutic effect is obtained after treatment with antidepressant drugs, like serotonin selective reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAO-Is) there is an initial lag-period of a few weeks. Neuronal adaptations on a molecular level are supposed to be involved in the initiation of the antidepressant effect. Transcription factor AP-2 is essential for neuronal development and many genes involved in the brainstem monoaminergic systems have binding sites for AP-2 in their regulatory regions. The genotype of the AP-2beta isoform has been associated with e.g. anxiety-related personality traits and with platelet MAO activity. In addition, previous studies have shown that the levels of AP-2alpha and AP-2beta in rat whole brain were decreased after 10 days of treatment with citalopram (SSRI) and imipramine (TCA), and were increased with phenelzine (MAO-I). RESULTS: In the present study, we report that treatment with citalopram for 1, 7 or 21 days did not have effect on the AP-2 levels in rat brainstem. However, after treatment with phenelzine for 1, 7 or 21 days the levels of AP-2alpha and AP-2beta had increased after 7 days, but had returned to control levels at day 21. CONCLUSION: The decrease in AP-2 levels in rat whole brain previously seen after treatment with citalopram does not seem to be localised to the brainstem, it may rather occur in the monoaminergic terminal projection areas. The present data suggest that the increase in AP-2 levels previously seen in rat whole brain after subchronic treatment with phenelzine is located in the brainstem. It cannot, however, be excluded that other brain regions are involved.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15663788&dopt=Abstract citalopram Celexa



citalopram Celexa
Citalopram and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized, 9-month, placebo-controlled, double-blind study.

Suvanto-Luukkonen E, Koivunen R, Sundstrom H, Bloigu R, Karjalainen E, Haiva-Mallinen L, Tapanainen JS.

Department of Obstetrics and Gynecology, Oulu University Hospital, PL 24, 90029 OYS, Oulu, Finland. Eila.Suvanto-Luukkonen oulu.fi

OBJECTIVE: Nonhormonal treatment of postmenopausal symptoms is a subject of great interest today. The results of studies on selective serotonin reuptake inhibitors (SSRIs) are promising, but long-term results do not exist. The objective of this study was to evaluate the efficacy of citalopram and fluoxetine in the treatment of physical and psychological menopausal symptoms and their effects on psychosocial and sexual well being in symptomatic postmenopausal women. DESIGN: One hundred fifty healthy women suffering from menopausal symptoms were recruited to this placebo-controlled double-blind study with a follow-up period of 9 months. They were randomized into three groups receiving placebo, fluoxetine, or citalopram. The initial dose was 10 mg of both fluoxetine and citalopram, and it was increased to 20 mg at 1 month and to 30 mg at the 6-month visit. The main outcome measures were hot flushes and Kupperman index. The RAND-36 Quality of Life questionnaire, Beck's Depression Scale, and the McCoy Female Sexuality Questionnaire were used at every control visit. RESULTS: There were no statistically significant differences between the groups in respect to number of hot flushes, Kupperman index, or Beck's Depression Scale, although there was a tendency in all these parameters in favor of SSRIs versus placebo. Insomnia improved significantly in the citalopram group versus placebo. Discontinuation rates at nine months were 40% in the placebo group, 34% in the fluoxetine group and 34% in the citalopram group. CONCLUSIONS: Compared with placebo, citalopram and fluoxetine have little effect on hot flushes and cannot therefore be recommended for the treatment of menopausal symptoms, if vasomotor symptoms are the main complaint. Whether the improvement of insomnia by means of citalopram affects the quality of sleep needs further investigation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15668596&dopt=Abstract citalopram Celexa



citalopram Celexa
Serotonin modulation of cerebral blood flow measured with positron emission tomography (PET) in humans.

Geday J, Hermansen F, Rosenberg R, Smith DF.

PET Center, Aarhus University Hospital, Aarhus, Denmark.

To develop a method to measure the dynamic response of the serotonin system in vivo, the effects of intravenously administered citalopram (the most selective of the serotonin reuptake inhibitors) or clomipramine on cerebral blood flow (CBF) were evaluated. CBF was measured with positron emission tomography (PET) in 27 normal subjects scanned under baseline conditions and, on the same day, after an intravenous (IV) infusion of placebo, citalopram, or clomipramine using a randomized, double-blind design. The main effects of the drugs on blood flow occurred in the thalamus, hypothalamus, and cingulate cortex. Compared to placebo, clomipramine reduced blood flow in the mediodorsal and ventral lateral nuclei of the thalamus, whereas citalopram reduced blood flow in the pulvinar nucleus and the hypothalamus. Compared to clomipramine, citalopram decreased blood flow in the cingulate cortex. The findings support previous reports showing acute central effects of citalopram and clomipramine on regional serotonergic functions measured by PET. Acute side effects may, however, require that care is taken in the selection of experimental designs for future PET studies using IV administration of these antidepressants. Synapse 55:224-229, 2005. (c) 2005 Wiley-Liss, Inc.

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citalopram Celexa
Specific serotonergic reuptake inhibition impairs vigilance performance acutely and after subchronic treatment.

Riedel WJ, Eikmans K, Heldens A, Schmitt JA.

Experimental Psychopharmacology Unit, Brain and Behaviour Institute, Faculty of Psychology, Universiteit Maastricht, The Netherlands. w.riedel psychology.unimaas.nl

Subchronic treatment with the selective serotonergic reuptake inhibitors (SSRIs) fluoxetine, venlafaxine and paroxetine, but not sertraline, were previously shown to specifically impair vigilance performance. The current study was designed to compare the vigilance effects of subchronic treatment with the SSRIs sertraline and citalopram in healthy volunteers, according to a placebo-controlled, double-blind, three-way cross-over design. Twenty-four healthy subjects, aged 30-50 years, of whom 21 completed the study, underwent three treatment periods of 2 weeks in which they received sertraline (50 mg on days 1-8, 100 mg on days 8-15), citalopram (20 mg on days 1-8, 40 mg on days 8-15) and placebo. Treatment periods were separated by 14 days washout periods. Vigilance performance was assessed through a 45-min Mackworth Clock Test at days 1, 8 and 15 of each treatment period. It was found that citalopram impaired vigilance performance acutely after the first 20 mg dose and subchronically after 40 mg daily doses. By contrast, no vigilance impairment was found during sertraline treatment. Sertraline is the only SSRI studied so far with no detrimental effects on vigilance. This may be due to the affinity of sertraline for the dopamine reuptake site. Because citalopram is the most specific SSRI showing this effect, it is concluded that the SSRI-induced decrement of vigilance performance is specifically associated with serotonergic reuptake inhibition.

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citalopram Celexa
The safety of newer antidepressants in pregnancy and breastfeeding.

Gentile S.

Department of Mental Health ASL Salerno 1, District n. 4, Cava de' Tirreni (Salerno), Italy.

The pregnancy and postpartum periods are considered to be relatively high risk times for depressive episodes in women, particularly for those with pre-existing psychiatric illnesses. Therefore, it may be necessary to start or continue the pharmacological treatment of depression during these two timeframes. Hence, the aim of this review is to examine the effects on the fetus and infant of exposure, through the placenta and maternal milk, to the following drugs: fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram, mirtazapine, venlafaxine, reboxetine and bupropion.The teratogenic risks, perinatal toxicity and effects on the neurobehavioural development of newborns associated with exposure through the placenta or maternal milk to these medications need to be carefully assessed before starting psychopharmacological treatment in pregnant or lactating women. In spite of the limitations of some of the studies reviewed, the older selective serotonin-reuptake inhibitors (SSRIs) [as we await further data regarding escitalopram] and venlafaxine seem to be devoid of teratogenic risks. By contrast, the data concerning possible consequences related to exposure to SSRIs via the placenta and breastmilk on neonatal adaptation and long-term neurocognitive infant's development are still controversial. Nevertheless, a number of reports have shown that an association between placental exposure to SSRIs and adverse but self-limiting effects on neonatal adaptation may exist. In addition, the information on both teratogenic and functional teratogenic risks associated with exposure to bupropion, mirtazapine and reboxetine is incomplete or absent; at present, these compounds should not be used as first-line agents in the pharmacological treatment of depression in pregnancy and breastfeeding.Untreated depression is not without its own risks since mothers affected by depression have a negative impact on the emotional development of their children and major depression, especially when complicated by a delusional component, may lead to the mother attempting suicide and infanticide. Consequently, clinicians need to help mothers weigh the risks of prenatal exposure to drugs for their babies against the potential risks of untreated depression and abrupt discontinuation of pharmacological treatment. Given these situations, we suggest that choosing to administer psychopharmacological treatment in pregnant or breastfeeding women with depression will result primarily from a careful evaluation of their psychopathological condition; currently, the degree of severity of maternal disease appears to represent the most relevant parameter to take this clinical decision.

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citalopram Celexa
Synthesis and characterization of EADAM: a selective radioligand for mapping the brain serotonin transporters by positron emission tomography.

Jarkas N, McConathy J, Votaw JR, Voll RJ, Malveaux E, Camp VM, Williams L, Goodman RR, Kilts CD, Goodman MM.

Department of Radiology, Division of Radiological Sciences, Emory University, Atlanta, GA 30322, USA.

[(11)C]N,N-Dimethyl-2-(2'-amino-4'-ethylphenylthio)benzylamine ([(11)C]EADAM) was synthesized in the development of a serotonin transporter (SERT) imaging ligand for positron emission tomography (PET). The methods of ligand synthesis, results of in vitro characterization, (11)C labeling and in vivo micro-PET imaging studies of [(11)C]EADAM in cynomolgus monkey brain are described. (11)C was introduced into N,N-dimethyl-2-(2'-amino-4'-ethylphenylthio)benzylamine () by alkylation of N-methyl-2-(2'-amino-4'-ethylphenylthio)benzylamine () in 32% radiochemical yield (end of bombardment [EOB], decay-corrected from [(11)C]methyl iodide). Competition binding assays in cells stably expressing the transfected human dopamine transporter (DAT), SERT and norepinephrine transporter (NET) labeled with [(3)H]WIN 35428 or [(125)I]RTI-55, [(3)H]citalopram and [(3)H]nisoxetine, respectively, indicated the following order of SERT affinity: ADAM>EADAM>>fluvoxamine. The affinity of EADAM for DAT and NET was 500- and >1000-fold lower, respectively, than for SERT. Micro-PET brain imaging studies in a cynomolgus monkey demonstrated high [(11)C]EADAM uptake in the striatum, thalamus and brainstem. [(11)C]EADAM uptake in these brain regions peaked in less than 60 min following administration of [(11)C]EADAM. The tissue-to-cerebellum ratios of the striatum, thalamus and brainstem were 1.67, 1.71 and 1.63, respectively, at 120 min postinjection of [(11)C]EADAM. Analysis of monkey arterial plasma samples using high-pressure liquid chromatography determined there was no detectable formation of lipophilic radiolabeled metabolites capable of entering the brain. In a displacement experiment with citalopram in a cynomolgus monkey, radioactivity in the striatum, thalamus and brainstem was displaced 20-60 min after administration of citalopram. In a blocking experiment with citalopram in a cynomolgus monkey, radioactivity in the striatum, thalamus and brainstem was significantly reduced. These results support the candidacy of [(11)C]EADAM as a radioligand for visualizing brain SERT using PET.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15691664&dopt=Abstract citalopram Celexa