citalopram escitalopram Lexapro
A pharmacoeconomic evaluation of escitalopram, a new selective serotonin reuptake inhibitor Comparison of cost-effectiveness between escitalopram, citalopram, fluoxetine,and venlafaxine for the treatment of depression in Norway.

Francois C, Toumi M, Aakhus AM, Hansen K.

International Department of Health-Economics, Epidemiology and Pricing, Lundbeck A/S,Paris, France.

This study compared the cost-effectiveness of escitalopram to that of citalopram,fluoxetine, and venlafaxine in the treatment of depression in Norway.A two-path decision analytic model with a 6-month horizon was used.Patients start at the primary path and are referred to specialist care in the secondary care path. Model inputs included drugspecific probabilities from comparative trial data, literature, and a panel of experts.The main outcome measure is success (remission), and costs of treatment (total and drug costs).Treatment with escitalopram yielded lower expected cost and greater effectiveness than citalopram,fluoxetine, and venlafaxine. The expected success rate was 64.2% with escitalopram,58.7% with citalopram, 58.7% with fluoxetine, and 62.1% with venlafaxine.Average expected total costs per patient were similar with escitalopram (19,661 Norwegian crowns) and venlafaxine (20,989) and somewhat higher with citalopram (22,379) and fluoxetine (22,558).Budgetary impact estimates a decrease in total health care budget of 72 million crowns.Escitalopram is therefore the most cost-effective alternative and its use would significantly reduce health care costs for the treatment of depression in Norway.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15609164&dopt=Abstract citalopram escitalopram Lexapro



citalopram escitalopram Lexapro
Serotonergic influence on the potentiation of D-amphetamine and apomorphine-induced rotational behavior by the alpha(2)-adrenoceptor antagonist 2-methoxy idazoxan in hemiparkinsonian rats.

Srinivasan J, Schmidt WJ.

Zoological Institute, Neuropharmacology, University of Tuebingen, Tuebingen, Germany.

The alpha(2)-adrenoceptor antagonists potentiate both ipsilateral and contralateral rotations induced by amphetamine and apomorphine respectively in hemiparkinsonian rats. The present study investigated the role of serotonergic transmission in this potentiation in unilaterally 6-hydroxydopamine nigral lesioned rats. D-amphetamine (0.5 mg/kg, i.p.) produced ipsilateral rotations, which were decreased by the dopamine receptor antagonist haloperidol (0.2 mg/kg, i.p.) and the alpha(1)-receptor antagonist prazosin (1 mg/kg, i.p.). The selective alpha(2)-antagonist 2-methoxy idazoxan (0.2 mg/kg, i.p.) potentiated the amphetamine-induced ipsilateral rotations, that were attenuated by haloperidol and prazosin. The selective serotonin re-uptake inhibitor citalopram (10 mg/kg, i.p.) and selective serotonin synthesis inhibitor p-chlorophenylalanine (150 mg/kg, i.p., 3 days) decreased and increased the observed potentiation respectively. Apomorphine (0.2 mg/kg, s.c.) produced contralateral rotations, which were decreased by haloperidol but not by prazosin. 2-methoxy idazoxan potentiated these rotations which were attenuated by haloperidol but not by prazosin. Citalopram and p-chlorophenylalanine increased and decreased the observed potentiation respectively. Citalopram and p-chlorophenylalanine had no effect by per se on D-amphetamine and apomorphine-induced rotations. 2-methoxy idazoxan alone increased both ipsilateral and contralateral spontaneous rotations. Taken together, these findings indicate that an increase in noradrenergic tone by 2-methoxy idazoxan potentiates both D-amphetamine-induced ipsilateral and apomorphine induced contralateral rotations. alpha(1)-Antagonism attenuates D-amphetamine induced ipsilateral rotations and its potentiation by 2-methoxy idazoxan but not apomorphine rotations or its potentiation. Increasing and decreasing the serotonergic transmission decreases and increases D-amphetamine potentiation, whereas increases and decreases apomorphine potentiation respectively. The possible mechanisms for these findings are discussed.

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citalopram escitalopram Lexapro
Chronic administration of citalopram in olfactory bulbectomy rats restores brain 5-HT synthesis rates: an autoradiographic study.

Hasegawa S, Watanabe A, Nguyen KQ, Debonnel G, Diksic M.

Cone Neurosurgical Research Laboratory, Department of Neurology and Neurosurgery, Montreal Neurological Institute, Montreal, Quebec, Canada.

RATIONALE: The olfactory bulbectomized (OBX) rat model is widely accepted as an animal model of depression with a proposed serotonergic imbalance in the brain. OBJECTIVE: To study the effects of chronic administration of citalopram on serotonin (5-HT) synthesis rates. METHOD: Serotonin synthesis was evaluated using the alpha-[(14)C]methyl-L: -tryptophan (alpha-MTrp) autoradiographic method in OBX rats. Citalopram was administered continuously (10 mg kg(-1) day(-1)) for 14 days using a subcutaneous osmotic minipump. RESULTS: The OBX rats treated with citalopram (OBX-CTP) have the same 5-HT synthesis rates as the sham-operated rats treated with citalopram (Sham-CTP). The OBX-CTP rats, relative to the OBX rats treated with saline (OBX-SAL), showed a reduction in the majority of the terminal brain structures, suggesting a normalization of 5-HT synthesis in the OBX-CTP rats following treatment. The OBX-SAL rats have significantly greater synthesis than the Sham-SAL rats in a majority of the terminal structures, but lower rates in the dorsal raphe. A few structures in the OBX-CTP group have lower synthesis than in the Sham-SAL group (e.g., dorsal raphe, hippocampus, amygdala). The data suggest that receptors in some brain areas are likely still responsive to the elevated levels of the extracellular 5-HT produced by citalopram. CONCLUSION: There is no significant global or individual structure difference in the synthesis between the Sham-CTP and OBX-CTP groups. The similarity in the synthesis between the OBX-CTP, Sham-CTP and Sham-SAL groups is likely a result of changes in the sensitivity of the receptors through which 5-HT synthesis is controlled. Because of some of the differences in the synthesis between the Sham-CTP and Sham-SAL groups, the data suggest that receptors throughout the brain are not fully desensitized.

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citalopram escitalopram Lexapro
Randomized double-blind comparison of serotonergic (Citalopram) versus noradrenergic (Reboxetine) reuptake inhibitors in outpatients with somatoform, DSM-IV-TR pain disorder.

Aragona M, Bancheri L, Perinelli D, Tarsitani L, Pizzimenti A, Conte A, Inghilleri M.

Department of Psychiatry, University of Rome La Sapienza, V.le Universita 30 00185 Rome, Italy.

OBJECTIVES: Whether the effect of tricyclic antidepressants on Pain Disorder arises from their noradrenergic or serotonergic actions or both remains unclear. We compared the selective serotonin reuptake inhibitor (SSRI) citalopram and the noradrenergic reuptake inhibitor (NARI) reboxetine in outpatients with Pain Disorder. We also distinguished the drugs' analgesic and antidepressant effects. METHODS: In this 8-week, randomized double-blind study, 35 patients with a DSM-IV-TR diagnosis of Pain Disorder were randomly assigned to receive either citalopram 40 mg/day (N=17 patients) or reboxetine 8 mg/day (N=18). The Present Pain Intensity (PPI) scale and the Total Pain Rating Index (tPRI) of the McGill Pain Questionnaire were used to measure the effect on pain symptoms. Changes in the Zung Self-Rating Depression Scale (Zung-D) scores were evaluated to monitor a possible antidepressant effect. For all patients who had at least one assessment, an intent-to-treat analysis was performed. RESULTS: No significant differences were found in the demographic variables or clinical characteristics of the two treatment groups. In the citalopram group, PPI and tPRI scores measured at baseline decreased after treatment (tPRI: 41.9 vs. 30.0, p=.004; PPI: 3.5 vs. 2.8, p=.045) whereas in the reboxetine group differences were not statistically significant (tPRI: 35.2 vs. 31.5; PPI: 3.7 vs. 3.1). The Zung-D showed no significant changes between baseline and endpoint assessment in either group. CONCLUSIONS: Our study suggests that the SSRI citalopram may have a moderate analgesic effect in patients with Pain Disorder, and that this analgesic activity appears to be not correlated to changes in depressive scores. If confirmed in a larger sample, this evidence suggests that patients who are intolerant or resistant to tricyclic antidepressants, may be treated with SSRIs.

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citalopram escitalopram Lexapro
Transplacental transfer of citalopram, fluoxetine and their primary demethylated metabolites in isolated perfused human placenta.

Heikkine T, Ekblad U, Laine K.

Department of Pharmacology and Clinical Pharmacology, University of Turku, Finland.

OBJECTIVE: To investigate the transplacental transfer and the effects of protein binding on the transfer of citalopram, desmethylcitalopram, fluoxetine and desmethylfluoxetine in the isolated perfused human placenta model. DESIGN: Prospective observational study. METHODS: Fifteen term human placentas were obtained immediately after delivery with maternal consent and a 2-hour non-recirculating perfusion cycle of a single placental cotyledon was set up. Citalopram (1230 nmol/L) and desmethylcitalopram (600 nmol/L) or fluoxetine (1455 nmol/L) and desmethylfluoxetine (1525 nmol/L) were added to the maternal reservoir and their appearance to the fetal circulation was followed by repeated measurements. To investigate the effect of protein binding on the transfer of citalopram and fluoxetine, nine additional perfusions were performed without albumin in the perfusion medium. Citalopram and desmethylcitalopram concentrations were measured by reversed-phase high performance liquid chromatography. Fluoxetine and desmethylfluoxetine concentrations was measured by gas chromatography and antipyrine (used as a reference compound) concentrations spectrophotometrically. RESULTS: The mean (SD) steady-state transplacental transfer (TPT(SS)%) for citalopram, desmethylcitalopram, fluoxetine and desmethylfluoxetine was 9.1%, 5.6% (P = 0.017 compared with citalopram), 8.7% and 9.1%, respectively, calculated as the ratio between the steady-state concentrations in fetal venous and maternal arterial sides. The TPT(SS)%s of citalopram, desmethylcitalopram, fluoxetine and desmethylfluoxetine were 86%, 50%, 88% and 91% of that of freely diffusable antipyrine. The absence of albumin significantly reduced the transfer of citalopram and fluoxetine (TPT(SS)% 1.1% and 4.8%, respectively) but not the transfer of antipyrine. CONCLUSION: Citalopram, fluoxetine and desmethylfluoxetine all cross the human placenta, and may, therefore, affect the perinatal outcome of infants exposed to these drugs during pregnancy. The transfer of desmethylcitalopram was significantly lower, which in the clinical setting may suggest lower fetal exposure of serotonin re-uptake inhibition by citalopram compared with fluoxetine. The presence of albumin was necessary for the transplacental transfer of both citalopram and fluoxetine.

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citalopram escitalopram Lexapro
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.

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citalopram escitalopram Lexapro
Escitalopram in the treatment of social anxiety disorder: analysis of efficacy for different clinical subgroups and symptom dimensions.

Stein DJ, Kasper S, Andersen EW, Nil R, Lader M.

MRC Unit on Anxiety Disorders, University of Stellenbosch, Cape Town, South Africa. djs2 sun.ac.za

Escitalopram has demonstrated efficacy for the acute treatment of social anxiety disorder (SAD) in two placebo-controlled trials and for long-term treatment in a relapse-prevention study. Social anxiety disorder is a heterogeneous disorder. This study questions whether this new selective serotonin reuptake inhibitor is effective across different subgroups of patients. Data from two randomised, placebo-controlled, 12-week escitalopram SAD trials were pooled. General linear models were used to determine the efficacy of escitalopram in different patient subgroups. Furthermore, a factor analysis of the primary efficacy scale, the Liebowitz Social Anxiety Scale (LSAS), was undertaken, and a determination made of whether treatment effects were similar for the different symptom dimensions. Escitalopram was effective in both younger and older patients, in male and female patients, and in patients with more and less severe social anxiety symptoms. The LSAS factor analysis showed six factors, which were differentially associated with different areas of disability. Escitalopram was significantly superior to placebo for all six symptom dimensions. The treatment effects of escitalopram were independent of gender, symptom severity and chronicity, and comorbid depressive symptoms. A six-factor model of social anxiety symptoms is supported by the distinctive association between these symptom dimensions and different areas of disability, but did not predict differential response to escitalopram. (c) 2005 Wiley-Liss, Inc.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15643634&dopt=Abstract citalopram escitalopram Lexapro