paroxetine, Paxil
Differential period of onset of action of fluvoxamine, paroxetine and milnacipran for depression.

Morishita S, Arita S.

Department of Psychiatry, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, Japan. morisita med.kawasaki-m.ac.jp

INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) and dual serotonin and noradrenaline reuptake inhibitors (SNRIs) are the most commonly prescribed class of antidepressants, yet it is not known whether one is superior to another. AIMS: The purpose of this clinical practice was to compare the periods of onset of action of fluvoxamine, paroxetine and milnacipran. METHODS: A retrospective cohort analysis was carried out among out-patients with depression treated in the Department of Psychiatry, Kawasaki Medical School Hospital, Kurashiki, Japan, in 2000 and 2001. A total of 206 patients receiving fluvoxamine, paroxetine and milnacipran were identified. RESULTS: The cumulative percentage of responders receiving milnacipran reached over 80% after 4 weeks, but it did reach this level for fluvoxamine or paroxetine until after 6 weeks. CONCLUSIONS: The differential period of onset of action should help guide clinicians in determining a suitable duration of antidepressants for depression. Copyright 2003 John Wiley & Sons, Ltd.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12923828&dopt=Abstract paroxetine, Paxil, Paxil CR



paroxetine, Paxil
Excretion of paroxetine into breast milk.

Ohman R, Hagg S, Carleborg L, Spigset O.

Department of Psychiatry, Ostersund Hospital, Sweden.

BACKGROUND: The study was carried out to quantify the excretion of the selective serotonin reuptake inhibitor paroxetine in breast milk. METHOD: In 6 lactating women, the concentrations of paroxetine in breast milk and serum were studied at the times for assumed minimum (24 hours after dose intake) and maximum (4-7 hours after dose intake) drug levels in milk. Moreover, a seventh subject was studied with frequent and regular sampling throughout a dose interval of 24 hours at 2 different dose levels. RESULTS: The mean milk/serum concentration ratios in the first 6 subjects ranged from 0.39 to 1.11 (overall mean +/- SD = 0.69 +/- 0.29), and the mean estimated dose to the infants ranged from 0.7% to 2.9% (overall mean +/- SD = 1.4% +/- 0.79%) of the weight-adjusted maternal dose. Based on area-under-the-curve data from the seventh subject, the milk/serum concentration ratio was 0.69 at a dose of 20 mg/day and 0.72 at a dose of 40 mg/day; the estimated relative doses to the infant were 1.0% and 2.0%, respectively. The mean increase in milk paroxetine concentrations from assumed minimum to assumed maximum was 61% (range, 4%-172%; p < .01). The mean paroxetine concentration in hindmilk was 78% higher than in foremilk (range, 16%-169%; p < .01), an increase that was parallel to the increase in milk triglyceride levels (r = 0.83, p = .005). No adverse drug reactions or unusual behaviors were reported in the infants. CONCLUSION: The study indicates that the relative dose to a suckling infant for paroxetine is lower than that reported for fluoxetine and citalopram and higher than that reported for sertraline and fluvoxamine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10485633&dopt=Abstract paroxetine, Paxil, Paxil CR



paroxetine, Paxil
Economic appraisal of citalopram in the management of single-episode depression.

Sclar DA, Skaer TL, Robison LM, Galin RS.

Pharmacoeconomics and Pharmacoepidemiology Research Unit, College of Pharmacy, Washington State University, Pullman 99164-6510, USA. sclar mail.wsu.edu

A retrospective intent-to-treat analysis (N = 1,339) was conducted to discern the natural course of antidepressant use and direct health service expenditures for the treatment of single-episode depression (DSM-IV code 296.20) among patients initiating antidepressant pharmacotherapy with either a tricyclic antidepressant (TCA) (amitriptyline, N = 237) or a selective serotonin reuptake inhibitor (SSRI) (citalopram, N = 71; fluoxetine, N = 411; paroxetine, N = 334; or sertraline, N = 286). Data were derived from the computer archive of a network-model health maintenance organization for the period of January 1, 1996, through April 30, 1999. Comparisons at the end of the 6-month post-period (180 days) were undertaken between cohorts initiating antidepressant pharmacotherapy with citalopram and each SSRI or TCA. Consistent with the intent-to-treat design, all accrued health service expenditures were assigned to the pharmacotherapeutic option initially prescribed. Multivariate models were adjusted for patient's age, gender, number of concomitant disease state processes, use of health services in the 6-month time frame (180 days) before initiating antidepressant pharmacotherapy, specialty of physician recording a diagnosis of single-episode depression, and the presence or absence of a previous diagnosis of single-episode depression and receipt of antidepressant pharmacotherapy. Patients initiating antidepressant pharmacotherapy with citalopram were far more likely to (1) have been diagnosed by a psychiatrist (37%; p < or = 0.05); (2) continue with the original pharmacotherapeutic option (79%) compared with patients originally prescribed amitriptyline (51%; chi2 = 17.29, df = 1, p < or = 0.05) or sertraline (65%; chi2 = 36.91, df = 1, p < or = 0.05); no significant difference was found compared with patients initiating antidepressant pharmacotherapy with paroxetine (72%; p = not significant [NS]) or fluoxetine (83%; p = NS); (3) obtain 90 days or more of antidepressant pharmacotherapy (86%) compared with those prescribed amitriptyline (69%; chi2 = 8.09, df = 1, p < or = 0.05); no significant difference was found compared with sertraline (77%), paroxetine (81%), or fluoxetine (84%); and (4) obtain 6 months (180 days) of antidepressant pharmacotherapy (68%) compared with those prescribed amitriptyline (39%; chi2 = 18.26, df = 1, p < or = 0.05) or sertraline (51%; chi2 = 6.02, df = 1, p < or = 0.05); no significant difference was found compared with paroxetine (56%) or fluoxetine (59%). Receipt of amitriptyline or sertraline as initial medication was associated with a per capita increase (p < or = 0.05) in health service utilization (17% and 9%, respectively) relative to citalopram. No significant difference (p > 0.05) in health service utilization was discerned between citalopram and either fluoxetine or paroxetine. Multivariate models adjusted for nonrandom assignment to the initial pharmacotherapeutic option confirmed these findings. Further research over a longer time course is warranted.

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paroxetine, Paxil
Course and cost of treatment for depression with fluoxetine, paroxetine, and sertraline.

Russell JM, Berndt ER, Miceli R, Colucci S, Grudzinski AN.

University of Texas Medical Branch, Galveston 77555-0191, USA. jrussell utmb.edu

OBJECTIVE: To compare depression-related treatment costs and total healthcare costs for patients diagnosed with depression and treated with either sertraline, paroxetine, or fluoxetine. PATIENTS AND METHODS: Claims records from a national database of patients diagnosed with depression who began treatment with an SSRI in 1995, following an antidepressant medication-free period of at least 6 months, were included. Treatment course and associated depression-related treatment and total healthcare costs during the subsequent 12-month treatment period were examined using univariate and multivariate methods. RESULTS: Nine-hundred five (905) patients taking sertraline, 492 on paroxetine, and 945 on fluoxetine met inclusion criteria. The groups were similar and representative with respect to gender and age. Mean dose over the 12-month treatment period increased 24%, indicating significant titration in all cohorts. Patients treated with paroxetine had shorter treatment duration (157.0 days) than did patients treated with fluoxetine (192.6 days) or sertraline (166.9 days, P < 0.001). Patients receiving index treatment with paroxetine were most likely to switch to another SSRI (21.3%); those taking sertraline were second most likely to switch (16.1%); and those on fluoxetine were least likely (12.4%, P = 0.001). Mean costs for depression-related outpatient visits and hospitalizations were similar. Mean antidepressant prescription costs differed, being $586, $419, and $446 for fluoxetine, paroxetine and sertraline cohorts, respectively (P < 0.001). In this sample, the fluoxetine cohort did not have lower nonpharmaceutical healthcare costs to offset higher pharmaceutical acquisition costs. Conclusions from median and multivariate analyses were robust to these findings. CONCLUSIONS: During this study period when fluoxetine, paroxetine, and sertraline were all well-established agents, similar depression-related treatment courses and cost characteristics among all 3 drugs were observed.

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paroxetine, Paxil
Treatment of premature ejaculation with paroxetine hydrochloride.

McMahon CG, Touma K.

Australian Centre for Sexual Health, St. Luke's Hospital, Sydney.

AIMS OF THIS STUDY: To evaluate the efficacy of chronic and 'on demand' administration of paroxetine hydrochloride in the drug treatment of premature ejaculation (PE). MATERIALS AND METHODS: Ninety-four normally potent men, aged 18-61 y (mean 39 y) with premature ejaculation were treated between January 1996 and March 1997, with oral paroxetine hydrochloride, a selective serotonin re-uptake inhibitor (SSRI). All men were either married or in a stable relationship. Sixty-four out of ninety-four men (Group A) were initially treated with paroxetine hydrochloride 20 mg administered once daily. Those men who responded with improved ejaculatory control within four weeks, were then treated with 'on-demand' paroxetine hydrochloride (20 mg) administered 3-4 h prior to planned intercourse. The remaining 33 out of 94 men (Group B) were initially treated with 'on-demand' paroxetine hydrochloride 20 mg administered 3-4 h prior to planned intercourse. RESULTS: The mean pre-treatment ejaculatory latency time (ELT) of both group A and B was 0.4 min (range 0-1 min) in 205 intercourses at a frequency of 0.4 intercourses per week. In group A after four weeks of daily administration of paroxetine, the mean ELT was 4.5 min (range 1-anejac.) in 761 intercourses at a frequency of 2.4 intercourses per week. Fifty-three out of sixty-one men in group A regarded their ejaculatory control as improved and were then treated with 'on-demand' paroxetine, achieving an ELT of 3.9 min (range 0-10) in 608 intercourses at a frequency of 2.6 intercourses per week. Thirty-six men in this group of 53 regarded that they had maintained improved ejaculatory control with a mean ELT of 5.5 min (range 2-20 min) after a further four weeks of treatment (P < 0.001). The remaining 17 men reported a recurrence of poor ejaculatory control with a mean ELT of 0.7 min (range 0-2 min). In group B with initial 'on-demand' paroxetine after a mean of 4.5 weeks of treatment, the mean ELT was 1.5 min (range 0-5 min) in 298 intercourses at a frequency of 2.2 intercourses per week. Adverse effects were only recorded in men taking daily paroxetine and included anejaculation in 5 out of 61, inhibited orgasm in 3 out of 61 and reduced libido on 3 out of 61. Erectile dysfunction was not reported and 'on demand' paroxetine was not associated with any adverse effects. CONCLUSIONS: Paroxetine hydrochloride appears to be a useful agent in the pharmacological treatment of premature ejaculation when administered on a chronic, an 'on-demand' basis following chronic treatment or initial 'on demand' basis.

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paroxetine, Paxil
Binding of [(3)H]lysergic acid diethylamide to serotonin 5-HT(2A) receptors and of [(3)H]paroxetine to serotonin uptake sites in platelets from healthy children, adolescents and adults.

Sigurdh J, Spigset O, Allard P, Mjorndal T, Hagglof B.

Department of Child and Adolescent Psychiatry, Norrland University Hospital, Umea, Sweden.

Possible age effects on binding of [(3)H]lysergic acid diethylamide ([(3)H]LSD) to serotonin 5-HT(2A) receptors and of [(3)H]paroxetine to serotonin uptake sites were studied in platelets from healthy children (11-12 years of age), adolescents (16-17 years of age) and adults. Significant overall age effects were found both for the number of binding sites (B(max)) for [(3)H]LSD binding (p < 0.001), the affinity constant (K(d)) for [(3)H]LSD binding (p < 0.001), B(max) for [(3)H]paroxetine binding (p < 0.001) and K(d) for [(3)H] paroxetine binding (p = 0.006). In general, there was a decrease in B(max) with increasing age, which predominantly occurred between the ages 11-12 years and 16-17 years for the 5-HT(2A) receptor, and after 16-17 years of age for the serotonin uptake site. These developmental changes might have an impact on the effect of treatment with serotonergic drugs in children and adolescents. When the platelet serotonin variables investigated are employed in studies in children or adolescents, age matching or, alternatively, introduction of age control in the statistical analysis should be performed.

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paroxetine, Paxil
Behavioral changes in developing mice after prenatal exposure to paroxetine (Paxil)

Coleman FH, Christensen HD, Gonzalez CL, Rayburn WF.

Department of Obstetrics and Gynecology, The University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.

OBJECTIVE: The aim of this study was to conduct in a randomized, placebo-controlled manner behavioral testing on mice offspring exposed prenatally to the selective serotonin reuptake inhibitor paroxetine. STUDY DESIGN: Forty-one CD-1 mice consumed paroxetine (Paxil, n = 21) or a placebo (n = 20) for 2 weeks before conception and throughout gestation. The daily dose of paroxetine used, 30 mg x kg(-1) x d(-1), is known to achieve concentrations in the rat serum equivalent to the upper therapeutic level in human beings and to achieve concentrations in the fetal rat brain equivalent to those in the adult mouse. Behavioral testing consisted of multiple tasks during early development, followed by motor, anxiety, reproduction, and depression tasks in the juvenile and adult periods. RESULTS: Offspring in the 2 treatment groups showed no statistical differences in many early development tasks (geotaxis, homing, social play) or in locomotor and exploratory activities throughout development. Performances during a depression task (forced swim), anxiety tasks (elevated plus maze as juveniles and adults), and reproduction revealed no treatment differences. Offspring exposed prenatally to paroxetine had a 15% to 25% increase in separation vocalization (P <.04) and a significant increase in male aggression during cage changing (P <.03). CONCLUSION: Prenatal exposure to a clinically relevant dose of paroxetine in mice produced no major behavioral alterations but did heighten performance on select anxiety testing in infant offspring and on aggressive behavior in adult males.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10561639&dopt=Abstract paroxetine, Paxil, Paxil CR