OBJECTIVETo study the pharmacokinetics of paroxetine tablet in Chinese healthy volunteers.

METHODSTwenty healthy subjects received a single oral dose of 40 mg paroxetine tablet. The plasma concentrations of paroxetine were determined using high-performance liquid chromatography (HPLC) and the measurements were analyzed with 3P97 program.

RESULTSThe plasma concentration curve of paroxetine following a single oral dose administration conformed to the two-compartment open model. The main pharmacokinetics parameters of paroxetine were: C(max)64.74-/+18.43 ng/ml, T(max)5.64-/+1.84 h, t(1/2) 20.03-/+5.33 h, AUC(0-120) 976.47-/+309.49 ng.h/ml, and AUC(0-inf) 1086.75-/+376.54 ng.h/ml.

CONCLUSIONThe pharmacokinetics of paroxetine in human body conforms to the two-compartment open model.

Administration, Oral ; Adult ; Chromatography, High Pressure Liquid ; Humans ; Paroxetine ; administration & dosage ; pharmacokinetics ; Serotonin Uptake Inhibitors ; administration & dosage ; pharmacokinetics ; Tablets ; Young Adult

OBJECTIVETo investigate the effect of antidepressant on irritable bowel syndrome (IBS).

METHODSA self-control and follow-up study on subclinical dosage of antidepressants therapy (fluoxetine 10 mg/d, paroxetine 10 mg/d or doxepin 45 mg/d) for 9-12 wks in 46 patients with refractory IBS symptoms according to Rome II criteria was performed, the clinical outcomes were evaluated by scales changes of symptom-related-anxiety, severity index of symptom, and quality of life specific of IBS, as well as general psychiatric health by SCL-90 during treatment and follow-up periods.

RESULTSAll 46 cases completed therapy and first follow-up unit (12 wks after treatment) (FFU), at the end of FFU, clinical symptoms in all patients were improved (P < 0.01). Comparison of the scores of symptom-related-anxiety, index of symptom, and quality of life specific of IBS at the end of FFU with that at basal level, indexes of the severity (3.4 +/- 1.5 vs 1.8 +/- 0.84) and frequency (3.8 +/- 1.60 vs 2.0 +/- 0.76) of symptoms were subsided significantly (P < 0.01, respectively); the scores of symptom-anxiety questionnaire including body anxiety (16.04 +/- 1.65 vs 10.83 +/- 1.64, P < 0.001), cognitive anxiety (18.78 +/- 2.12 vs 11.17 +/- 1.89, P < 0.001), fear (15.80 +/- 1.76 vs 10.78 +/- 1.85, P < 0.001) and avoiding (15.47 +/- 1.53 vs 10.16 +/- 1.59, P < 0.001) were also subsided significantly. In the meantime, IBS-QoL improved significantly (P < 0.05), dysphoria, body image, interference with activity, health worry, social reaction and overall scores were improved significantly (P < 0.01, respectively). The status of general psychiatric health was also improved significantly (P < 0.01).

CONCLUSIONSTreatment of refractory IBS with subclinical dosage antidepressant is rational and effective, However a further study on its mechanisms is suggested.

Adult ; Antidepressive Agents ; administration & dosage ; Doxepin ; administration & dosage ; Female ; Fluoxetine ; administration & dosage ; Follow-Up Studies ; Humans ; Irritable Bowel Syndrome ; drug therapy ; Male ; Middle Aged ; Paroxetine ; administration & dosage ; Quality of Life

OBJECTIVETo observe the curative effect of acupuncture following principle of relieving depression and regulating mentality (RDRM) in treating patients with melancholia, and compare it with that of Western medicinal treatment.

METHODSPatients in the observed group were treated with needling and electroacupuncture (EA), and those in the control group orally taken Fluoxetine or Paroxetine. The curative effect, Hamilton Depression Scale scores (HAMD), effect initiating time and sustaining time were observed and compared.

RESULTSThe total effective rate was 87.5% and 79.1% in the observed group and the control group respectively, showing insignificant difference between them (P > 0.05), but comparison of the initiating time and sustaining time between the two groups did show significant different (P < 0.01).

CONCLUSIONAcupuncture with following RDRM principle has definite effect in treating melancholia, which is comparable to Western medicinal treatment, and shows a superiority to the latter in effect initiating and sustaining time.

Acupuncture Therapy ; methods ; Adult ; Aged ; Antidepressive Agents, Second-Generation ; administration & dosage ; therapeutic use ; Depressive Disorder ; psychology ; therapy ; Electroacupuncture ; Female ; Fluoxetine ; administration & dosage ; therapeutic use ; Humans ; Male ; Middle Aged ; Paroxetine ; administration & dosage ; therapeutic use ; Treatment Outcome

Citalopram and paroxetine are selective serotonin reuptake inhibitors and also have antinociceptive effects. We investigated the antiallodynic and antihyperalgesic effects of intrathecally administered morphine, citalopram, paroxetine, and combinations thereof, in a rat model in which peripheral inflammation was induced by complete Freund's adjuvant (CFA). Drugs were intrathecally administered via direct lumbar puncture. Mechanical allodynia was measured using a Dynamic Plantar Aesthesiometer. Thermal hyperalgesia and cold allodynia were determined by measuring latency of paw withdrawal in response to radiant heat and cold water. Behavioral tests were run before and 15, 30, 45, and 60 min after intrathecal injection. Intraplantar injection of CFA produced mechanical allodynia, thermal hyperalgesia, and cold allodynia. Intrathecally administered morphine (0.3 or 1 microg) had antiallodynic or antihyperalgesic effects (24.0%-71.9% elevation). The effects of morphine were significantly increased when a combination of citalopram (100 microg) and paroxetine (100 microg) was added (35.2%-95.1% elevation). This rise was reversed by naloxone and methysergide. The effects of citalopram and paroxetine were also reversed by naloxone and methysergide. We suggest that the mu opioid receptor and serotonin receptors play major roles in production of the antiallodynic and antihyperalgesic effects of morphine, citalopram, paroxetine, and combinations thereof, in animals experiencing inflammatory pain.
Analgesics, Opioid/administration & dosage/*pharmacology ; Animals ; Behavior, Animal/drug effects ; Citalopram/administration & dosage/pharmacology ; Disease Models, Animal ; Hyperalgesia/etiology ; Inflammation/*chemically induced/pathology ; Injections, Spinal ; Male ; Morphine/administration & dosage/*pharmacology ; Pain/*prevention & control ; Pain Measurement ; Pain Threshold/drug effects ; Paroxetine/administration & dosage/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Serotonin/*chemistry/metabolism ; Serotonin Uptake Inhibitors/administration & dosage/*pharmacology ; Temperature ; Time Factors

Recently Korean Food and Drug Administration approved Hypericum perforatum preparations (St. John's wort) as an over-the-counter drug. The authors reported a case of Hypericum perforatum induced mania in a patient with major depressive disorder and reviewed. A seventy-five years old female patient was diagnosed as major depression 5 years ago, and had been admitted in the psychiatric ward twice and had received regular outpatient treatment. Since October 1998, she took paroxetine 20 mg, and bromazepam 1.5 mg constantly. But all of a sudden, she stopped taking the drugs on June 20th 2000, and took Hypericum perforatum 300 mg three times daily. Ten days after, she became abruptly talkative, irritable, hyperactive, and euphoric. She was diagnosed as Hypericum perforatum-induced mania. Manic symptoms came down after several days by discontinuation of taking Hypericum perforatum. Since then she has been got a continuous treatment with paroxetine 20 mg, and she is in full remission state now. Hypericum perforatum is one of herb extracts, which is known to have the antidepressant effect like traditional and newer antidepressants. The side effects of Hypericum perforatum are gastrointestinal disturbance, allergy reaction, fatigue, photosensitivity. And more serious side effect is drug-drug interaction due to it's inducing effect of cytochrome P450 and P-glycoprotein. It is possible to switch from depression to manic episode as was in this case. Although it was approved as an over-the-counter drug in Korea, the use of Hypericum perforatum need to be thoroughly examined to prevent misused if not fully understood.
Antidepressive Agents ; Bipolar Disorder* ; Bromazepam ; Cytochrome P-450 Enzyme System ; Depression* ; Depressive Disorder, Major ; Fatigue ; Female ; Humans ; Hypericum* ; Hypersensitivity ; Korea ; Outpatients ; P-Glycoprotein ; Paroxetine ; United States Food and Drug Administration

PURPOSE: Nonresponse to any selective serotonin reuptake inhibitor (SSRI) treatment is rare. In this study, we aimed to investigate ejaculation delay nonresponse to paroxetine treatment in men with lifelong premature ejaculation (PE) who were also known to be nonresponders to other SSRIs. MATERIALS AND METHODS: Five males with lifelong PE who were known nonresponders to paroxetine and other serotonergic antidepressants and eight males with lifelong PE who were specifically recruited were included. Blood sampling occurred 1 month and 1 day before the start of treatment and at the end of three consecutive series of 4 weeks of daily treatment with 10-, 20-, and 30-mg paroxetine, respectively. Blood samples for measurement of leptin and paroxetine were taken at 8:30 AM, 9:30 AM, 10:30 AM, and 11:30 AM, respectively. At 9:00 AM, one tablet of 10-, 20-, or 30-mg paroxetine was taken during the first, second, and third month, respectively. Intravaginal ejaculatory latency time (IELT) was measured with a stopwatch. The main outcome measures were the fold increase in the geometric mean IELT, serum leptin and paroxetine concentrations, body mass index (BMI), 5-HT1A receptor C-1019G polymorphism, and CYP2D6 mutations. RESULTS: Between the 7 paroxetine responders and 6 nonresponders, the fold increase in the geometric mean IELT was significantly different after daily 10-mg (p=0.003), 20-mg (p=0.002), and 30-mg paroxetine (p=0.026) and ranged from 2.0 to 8.8 and from 1.1 to 1.7, respectively. BMI at baseline and at the end of the study was not significantly different between responders and nonresponders. Serum leptin levels at baseline were similar in responders and nonresponders and did not change during treatment. The serum paroxetine concentration increased with increasing dosage and was not significantly different between responders and nonresponders. There was no association between the fold increase in the geometric mean IELT and serum paroxetine levels during the three treatment periods nor between leptin levels during the treatment periods and serum paroxetine levels. For the 5-HT1A receptor C-1019G variation, all responders had the CC genotype and all nonresponders had the GC genotype, respectively. CONCLUSIONS: Complete absence of paroxetine-induced ejaculation delay is presumably related to pharmacodynamic factors and perhaps to 5-HT1A receptor gene polymorphism.
Adolescent ; Adult ; Aged ; Body Mass Index ; Cytochrome P-450 CYP2D6/genetics ; Humans ; Leptin/blood ; Male ; Middle Aged ; Mutation ; Paroxetine/*administration & dosage/blood ; Polymorphism, Genetic ; Premature Ejaculation/*drug therapy/genetics ; Receptor, Serotonin, 5-HT1A/genetics ; Risk Factors ; Serotonin Uptake Inhibitors/*administration & dosage ; Time Factors ; Treatment Outcome ; Young Adult

PURPOSE: Nonresponse to any selective serotonin reuptake inhibitor (SSRI) treatment is rare. In this study, we aimed to investigate ejaculation delay nonresponse to paroxetine treatment in men with lifelong premature ejaculation (PE) who were also known to be nonresponders to other SSRIs. MATERIALS AND METHODS: Five males with lifelong PE who were known nonresponders to paroxetine and other serotonergic antidepressants and eight males with lifelong PE who were specifically recruited were included. Blood sampling occurred 1 month and 1 day before the start of treatment and at the end of three consecutive series of 4 weeks of daily treatment with 10-, 20-, and 30-mg paroxetine, respectively. Blood samples for measurement of leptin and paroxetine were taken at 8:30 AM, 9:30 AM, 10:30 AM, and 11:30 AM, respectively. At 9:00 AM, one tablet of 10-, 20-, or 30-mg paroxetine was taken during the first, second, and third month, respectively. Intravaginal ejaculatory latency time (IELT) was measured with a stopwatch. The main outcome measures were the fold increase in the geometric mean IELT, serum leptin and paroxetine concentrations, body mass index (BMI), 5-HT1A receptor C-1019G polymorphism, and CYP2D6 mutations. RESULTS: Between the 7 paroxetine responders and 6 nonresponders, the fold increase in the geometric mean IELT was significantly different after daily 10-mg (p=0.003), 20-mg (p=0.002), and 30-mg paroxetine (p=0.026) and ranged from 2.0 to 8.8 and from 1.1 to 1.7, respectively. BMI at baseline and at the end of the study was not significantly different between responders and nonresponders. Serum leptin levels at baseline were similar in responders and nonresponders and did not change during treatment. The serum paroxetine concentration increased with increasing dosage and was not significantly different between responders and nonresponders. There was no association between the fold increase in the geometric mean IELT and serum paroxetine levels during the three treatment periods nor between leptin levels during the treatment periods and serum paroxetine levels. For the 5-HT1A receptor C-1019G variation, all responders had the CC genotype and all nonresponders had the GC genotype, respectively. CONCLUSIONS: Complete absence of paroxetine-induced ejaculation delay is presumably related to pharmacodynamic factors and perhaps to 5-HT1A receptor gene polymorphism.
Adolescent ; Adult ; Aged ; Body Mass Index ; Cytochrome P-450 CYP2D6/genetics ; Humans ; Leptin/blood ; Male ; Middle Aged ; Mutation ; Paroxetine/*administration & dosage/blood ; Polymorphism, Genetic ; Premature Ejaculation/*drug therapy/genetics ; Receptor, Serotonin, 5-HT1A/genetics ; Risk Factors ; Serotonin Uptake Inhibitors/*administration & dosage ; Time Factors ; Treatment Outcome ; Young Adult

While regional cerebral blood flow (rCBF) studies on adults involving the caudate, prefrontal, orbitofrontal, and cingulated areas have been reported, no such published data on children exist. In this study, we aimed to determine the significance of pre- and post-treatment regional cerebral blood flow (rCBF) differences in children with obsessive compulsive disorder (OCD) and compared them with healthy controls. Eighteen drug-free obsessive compulsive children, aged 11 to 15, without comorbid states except for anxiety disorders - participated in this study. The control group consisted of 12 children, aged 11 to 15, with no medical or psychiatric illnesses. Using SPECT (Single Photon Emission Computerized Tomography) scans with Technetium-99m-HMPAO-hexamethly propyleneamine oxime (Tc99mHMPAO), the rCBF was calculated in 15 regions of the control group according to a standard protocol, while in the study group, it was measured at baseline and after 12 weeks of treatment with a fixed dose of paroxetine (20 mg qd). We compared the resulting pre- and post-treatment CBF values for the control group and study group. The right and left caudates, right and left dorsolateral prefrontals, and cingulate had significantly higher rCBF in children with obsessive compulsive disorder than in the control group. These areas, in addition to the right anteromedial temporal, showed significant rCBF reduction after treatment with paroxetine. The mean percentage of change in obsession scores during the treatment correlated significantly with the baseline and post- treatment rCBF level of the right caudate, post-treatment left caudate, and baseline left caudate. Our findings on children are consistent with adult studies and support the theory of a cortical-striatal-thalamic-cortical loop disturbance in OCD.
Adolescent ; Cerebrovascular Circulation/*drug effects ; Child ; Depressive Disorder/drug therapy/physiopathology/radionuclide imaging ; Female ; Human ; Male ; Obsessive-Compulsive Disorder/*drug therapy/*physiopathology/radionuclide imaging ; Paroxetine/*administration & dosage ; Serotonin Uptake Inhibitors/*administration & dosage ; Technetium Tc 99m Exametazime/diagnostic use ; Tomography, Emission-Computed, Single-Photon