paroxetine, Paxil
[Paroxetine treatment for children and adolescents with anxiety disorders]

[Article in Spanish]

Blasco-Fontecilla H, Madoz-Gurpide A, San Sebastian Cabases J, Calvo Ablanedo R, Krauskopf Poblete V.

Unidad de Psiquiatria Infantil, Servicio de Psiquiatria, Hospital Ramon y Cajal, Universidad de Alcala, Madrid, Spain. hmblasco yahoo.es

BACKGROUND: Paroxetine has become an effectiveness treatment in anxiety disorders in adults. Despite the fact that this is an especially prevalent psychiatrist disorder in children and adolescents, there are very few studies in this population. This study examines the effectiveness of paroxetine in children and adolescents with anxiety disorders.METHODOLOGY: Fifteen children and adolescents with ICD-criteria for anxiety disorder were selected. Anxiety measurement was taken with STAI scale and was filled out before treatment and 6 months later (mean). We have used descriptive parameters and t Student test for the analysis of dependent samples. Statistic work was done with SPSS 8.0. RESULTS: On first testing, the mean score for State Factor was 41.8 (ds: 5.9) and on second after treatment- it was 24.66 (ds: 9.8). Trait Factor was 43.53 (ds: 8.27) on first testing and 25 (ds: 8.91) on second. These differences in mean scores for both State and Trait factors were significant (alpha=0.05, p= 0.000). CONCLUSIONS: Our results support the hypothesis of clinical improvement at Anxiety Disorders in children and adolescent using Paroxetine. It seems logical to continue the study increasing sample size and evaluation time.

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paroxetine, Paxil
Aging, estradiol and time of day differentially affect serotonin transporter binding in the central nervous system of female rats.

Krajnak K, Rosewell KL, Duncan MJ, Wise PM.

Department of Biology, West Virginia University, Morgantown, WV 26505, USA. mqk1 cdc.gov

Estrogen-related changes in serotonergic neuronal transmission, including changes in the number of serotonin transporter (SERT) binding sites, have been cited as a possible cause for changes in mood, memory and sleep that occur during the menopausal transition. However, both aging and estradiol regulate SERT binding sites in the brain. The goal of this experiment was to determine how aging and estrogen interact to regulate SERT levels in the forebrain of young and reproductively senescent female Sprague-Dawley rats using [3H]paroxetine. The density of specific [3H]paroxetine binding in various brain regions was compared in young (2-4 months) and reproductively senescent (10-12 months) female rats at three times of day. In most brain regions examined, estrogen and aging independently increased the number of [3H]paroxetine binding sites. The only region that displayed a reduction in [3H]paroxetine binding with age was the suprachiasmatic nucleus (SCN). Time of day influenced [3H]paroxetine binding in the SCN and the paraventricular thalamus (PVT), two regions known to be involved in the regulation of circadian rhythms. Aging and/or estrogen also altered the pattern of binding in these regions. Thus, based on the results of this study, we conclude that aging and estrogen both act to regulate SERT binding sites in the forebrain of female rats, and that this regulation is region specific.

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paroxetine, Paxil
High-performance liquid chromatography-mass spectrometry method for the determination of paroxetine in human plasma.

Zhu Z, Neirinck L.

Pharmascience, Suite 100, 6111 Royalmount Ave, Montreal, Quebec, Canada H4P 2T4. zzhupharmascience.com

A rapid and specific liquid chromatographic mass spectrometric (LC-MS-MS) method has been developed for the determination of paroxetine in human plasma. The procedure involves a liquid-liquid extraction of paroxetine and fluoxetine (internal standard) with cyclohexane-ethyl acetate. The standard curve was linear over a working range of 0.2-50 ng/ml. The lower limit of quantitation was 0.2 ng/ml. No endogenous compounds were found to interfere with the analysis. The absolute recovery was 70.8% for paroxetine and 84.1% for the internal standard. The accuracy of inter-assay and intra-assay accuracy was in the ranges -4.8 to -0.5% and -3.4 to 4.8%, respectively. This method proved to be suitable for bioequivalence studies by being simple, selective and reproducible. Copyright 2002 Elsevier Science B.V.

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paroxetine, Paxil
Mirtazapine and paroxetine: a drug-drug interaction study in healthy subjects.

Ruwe FJ, Smulders RA, Kleijn HJ, Hartmans HL, Sitsen JM.

Clinical Development Department, NV Organon, PO Box 20, 5340 BH Oss, The Netherlands.

Paroxetine inhibits cytochrome P(450) 2D6, which is involved in the metabolism of mirtazapine. The possible drug-drug interaction between two pharmacologically distinct antidepressants, mirtazapine and paroxetine, has been investigated in a randomized, three-way crossover study in 24 healthy male and female subjects. After a titration phase of 3 days, each subject received single daily doses of 30 mg mirtazapine, 40 mg paroxetine or the combination for 6 days. Assessments included serial blood sampling for pharmacokinetics at steady state, cognitive testing using the test battery of CDR Ltd, a visual analogue mood rating scale (Bond and Lader) and the Leeds Sleep Evaluation Questionnaire. Paroxetine inhibits the metabolism of mirtazapine, as shown by increases of approximately 17% and 25% of the 24 h AUC's of mirtazapine and its demethyl metabolite, respectively. Mirtazapine did not alter the pharmacokinetics of paroxetine. The combined administration of mirtazapine and paroxetine probably does not alter cognitive functioning or result in major changes on the visual analogue mood rating scale and Sleep Evaluation Questionnaire, compared with the administration of either drug alone. The incidence of adverse events was lower during combined administration of mirtazapine and paroxetine than during administration of either drug alone. Fatigue, dizziness, headache, nausea, anxiety and somnolence were the most common adverse events during combined administration. These data suggest that the combination of mirtazapine and paroxetine is unlikely to lead to clinically relevant drug-drug interactions and can be used without dose adjustment of either drug. The combination may even be better tolerated than either drug alone. Copyright 2001 John Wiley & Sons, Ltd.

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paroxetine, Paxil
Tianeptine and paroxetine in major depressive disorder, with a special focus on the anxious component in depression: an international, 6-week double-blind study dagger.

Lepine JP, Altamura C, Ansseau M, Gutierrez JL, Bitter I, Lader M, Waintraub L.

Service de Psychiatrie, Hopital Fernand Widal, 200, rue du Faubourg St Denis, 75745 Paris Cedex 10, France.

Tianeptine (37.5 mg/day) and paroxetine (20 mg/day) were compared in a population of depressive patients without past or current history of co-morbid anxiety and/or important anxiolytic treatment. In a 6-week, double blind trial, the special focus was on anxious symptoms.Both drugs showed good efficacy on depressive symptomatology, assessed with MADRS and HDRS, but no difference was detected between tianeptine and paroxetine, for any assessment criterion. Despite the choice of selected depressive patients, without any co-morbid anxious disorder, anxiety scale scores at inclusion (HAMA and BAS) were appreciable but correlated poorly with depressive scores. Both tianeptine and paroxetine improved the apparent anxious component in depression. Tolerability of both drugs was good, although significantly better with tianeptine.Thus tianeptine and paroxetine are effective and safe treatments for major depression and may also act directly on the anxious component of the psychopathology. Copyright 2001 John Wiley & Sons, Ltd.

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paroxetine, Paxil
Perinatal outcome following third trimester exposure to paroxetine.

Costei AM, Kozer E, Ho T, Ito S, Koren G.

the Motherisk program, Division of Clinical Pharmacology/Toxicology, the Hospital for Sick Children, Toronto, Ontario, Canada.

BACKGROUND: Paroxetine hydrochloride is commonly used for maternal depression, panic disorder, and obsessive-compulsive disorder. The drug readily crosses the human placenta. Although it does not appear to increase teratogenic risk, there have been case reports of neonatal withdrawal. Symptoms were described soon after birth and lasted up to 1 month. OBJECTIVE: To investigate whether there is a clinically important discontinuation syndrome in neonates exposed to paroxetine in utero. METHODS: Prospective, controlled cohort study. PATIENTS: Fifty-five pregnant women counseled prospectively by the Motherisk program in Toronto, Ontario, regarding third-trimester exposure to paroxetine and their infants were included in the study group. Pregnant women who discontinued paroxetine before the third trimester or those receiving other drugs known to cause withdrawal-type symptoms, such as opioids or benzodiazepines, were excluded. A comparison group of 27 women using paroxetine during the first or second trimester and 27 women using nonteratogenic drugs were matched for maternal age, gravity, parity, social drug use, and nonteratogenic drug use. RESULTS: Of the 55 neonates exposed to paroxetine in late gestation, 12 had complications necessitating intensive treatment and prolonged hospitalization. The most prevalent clinical picture was respiratory distress (n = 9), followed by hypoglycemia (n = 2), and jaundice (n = 1). The symptoms disappeared within 1 to 2 weeks. In the comparison group, only 3 infants experienced complications (P =.03). In logistic regression, only third-trimester exposure to paroxetine was associated with neonatal distress (odds ratio, 9.53; 95% confidence interval, 1.14-79.3). CONCLUSION: When used near term, paroxetine is associated with a high rate of neonatal complications, possibly caused by its common discontinuation syndrome.

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paroxetine, Paxil
Comparison of the anticholinergic effects of the serotonergic antidepressants, paroxetine, fluvoxamine and clomipramine.

Fujishiro J, Imanishi T, Onozawa K, Tsushima M.

Pharmaceutical Research Center, Meiji Seika Kaisha Ltd., 760 Morooka-cho, Kohoku, Yokohama 222-8567, Japan.

Paroxetine, a selective serotonin reuptake inhibitor, shows relatively high affinity for muscarinic acetylcholine receptors compared to other selective serotonin reuptake inhibitors. To determine whether paroxetine has anticholinergic effects in vivo, we examined the effects of paroxetine on oxotremorine-induced tremor, spontaneous defecation and passive avoidance performance using mice and compared the results with those using fluvoxamine, another selective serotonin reuptake inhibitor, and clomipramine, a tricyclic antidepressant with serotonin selectivity. The potency of antidepressant activity as determined in the tail suspension test was paroxetine>fluvoxamine>clomipramine. Paroxetine and clomipramine inhibited oxotremorine-induced tremor, reduced spontaneous defecation and impaired passive avoidance performance, while fluvoxamine did not have similar effects. A comparison of ED(50) values showed that the ratio of anticholinergic effect to antidepressant activity was fluvoxamine, >3.2; paroxetine, 2.1-2.6; clomipramine, <0.8. These results suggest that paroxetine may induce fewer adverse anticholinergic effects than clomipramine, but more than fluvoxamine.

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