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Paroxetine
Terms modified by Paroxetine Selected AbstractsA controlled trial of paroxetine for chronic PTSD, dissociation, and interpersonal problems in mostly minority adults,DEPRESSION AND ANXIETY, Issue 2 2007Randall D. Marshall M.D. Abstract This study evaluated the efficacy of paroxetine for symptoms and associated features of chronic posttraumatic stress disorder (PTSD), interpersonal problems, and dissociative symptoms in an urban population of mostly minority adults. Adult outpatients with a primary DSM-IV diagnosis of chronic PTSD received 1 week of single-blind placebo (N = 70). Those not rated as significantly improved were then randomly assigned to placebo (N = 27) or paroxetine (N = 25) for 10 weeks, with a flexible dosage design (maximum 60,mg by week 7). Significantly more patients treated with paroxetine were rated as responders (14/21, 66.7%) on the Clinical Global Impression,Improvement Scale (CGI-I) compared to patients treated with placebo (6/22, 27.3%). Mixed effects models showed greater reductions on the Clinician-Administered PTSD Scale (CAPS) total score (primary plus associated features of PTSD) in the paroxetine versus placebo groups. Paroxetine was also superior to placebo on reduction of dissociative symptoms [Dissociative Experiences Scale (DES) score] and reduction in self-reported interpersonal problems [Inventory of Interpersonal Problems (IIP) score]. In a 12-week maintenance phase, paroxetine response continued to improve, but placebo response did not. Paroxetine was well tolerated and superior to placebo in ameliorating the symptoms of chronic PTSD, associated features of PTSD, dissociative symptoms, and interpersonal problems in the first trial conducted primarily in minority adults. Depression and Anxiety 24:77,84, 2007. Published 2006 Wiley-Liss, Inc. [source] A randomized, placebo-controlled trial of paroxetine in nursing home residents with non-major depressionDEPRESSION AND ANXIETY, Issue 3 2002Adam B. Burrows M.D. Abstract Depression is common across a broad spectrum of severity among nursing home residents. Previous research has demonstrated the effectiveness of antidepressants in nursing home residents with major depression, but it is not known whether antidepressants are helpful in residents with less severe forms of depression. We conducted a randomized double-blind placebo-controlled 8-week trial comparing paroxetine and placebo in very old nursing home residents with non-major depression. The main outcome measure was the primary nurse's Clinical Impression of Change (CGI-C). Additional outcome measures were improvement on the interview-derived Hamilton Depression Rating Scale (HDRS) and Cornell Scale for Depression (CS) scores. Twenty-four subjects with a mean age of 87.9 were enrolled and twenty subjects completed the trial. Placebo response was high, and when all subjects were considered, there were no differences in improvement between the paroxetine and placebo groups. Two subjects that received paroxetine developed delirium, and subjects that received paroxetine were more likely to experience a decrease in Mini Mental State Exam scores (P = .03). There were no differences in serum anticholinergic activity between groups. In a subgroup analysis of 15 subjects with higher baseline HDRS and CS scores, there was a trend toward greater improvement in the paroxetine group in an outcome measure that combined the CGI-C and interview-based measures (P = .06). Paroxetine is not clearly superior to placebo in this small study of very old nursing home residents with non-major depression, and there is a risk of adverse cognitive effects. Because of the high placebo response and the trend towards improvement in the more severely ill patients, it is possible that a larger study would have demonstrated a significant therapeutic effect for paroxetine as compared with placebo. The study also illustrates the discordance between patient and caregiver ratings, and the difficulties in studying very elderly patients with mood disorders. Depression and Anxiety 15:102,110, 2002. © 2002 Wiley-Liss, Inc. [source] A Convenient Synthesis of (,)-ParoxetineEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 15 2004László Czibula Abstract A convenient synthesis of the antidepressant paroxetine starting from 1-benzyl-4-piperidone (2) is reported. A stereoselective reduction resulted in cis -piperidine-3-methanol [(+)- 6]. The reaction between cis -piperidine-3-methanol mesylate (7) and sesamol led to benzyl-protected trans -paroxetine (9) through an inversion reaction of the stereogenic center at position 3. The latter compound was deprotected by hydrogenolysis. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] A placebo controlled investigation into the effects of paroxetine and mirtazapine on measures related to car driving performanceHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2003F. Ridout Abstract Objective To assess the effects of paroxetine and mirtazapine on psychometric performance related to car driving, including an on-the-road test of BRT. Method In a 4-way, double blind randomised crossover study, 12 healthy volunteers received paroxetine 20,mg mane, mirtazapine 15,mg/30,mg nocte (comparator), mirtazapine 15,mg mane/15,mg b.i.d.(verum) and placebo over a 5 day period with a washout period of 7 days between treatments. Psychometric assessments included ,on-the-road' BRT (BRT), CFF (CFF), CRT (CRT) and subjective measures of sedation and sleep parameters. Results Paroxetine had no significant effect on BRT compared with placebo. Although subjective ratings of sleep quality and sedation were impaired, there were significant improvements in both CFF and the recognition reaction component of CRT with paroxetine. Mirtazapine 15,mg/30,mg nocte impaired laboratory performance and some subjective tests. Mirtazapine 15 mg mane/15,mg b.i.d. improved sleep, but significantly impaired all other measures. Conclusion Paroxetine 20,mg/day has no psychomotor or behavioural toxicity and has no negative impact on BRT. Further research into the chronic and sub-chronic effects of mirtazapine is needed to establish the clinical significance of these results. Copyright © 2003 John Wiley & Sons, Ltd. [source] Use of paroxetine for the treatment of depression and anxiety disorders in the elderly: a reviewHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 3 2003*Article first published online: 11 DEC 200, Michel Bourin Abstract Paroxetine is a potent selective serotonin reuptake inhibitor (SSRI) with indications for the treatment of depression, obsessive, compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post-traumatic stress disorder, premenstrual dysphoric disorder and chronic headache. There is wide interindividual variation in the pharmacokinetics of paroxetine in adults as well as in the elderly with higher plasma concentrations and slower elimination noted in the latter. Elimination is also reduced in severe renal and hepatic impairment, however, serious adverse events are extremely rare even in overdose. A Pub Med search was used to collect information on the efficacy and tolerability in elderly patients. There are few studies of depression in the elderly and only one study in the old,old. In anxiety disorders including general anxiety disorder, panic disorder, obsessive,compulsive disorder and social anxiety, there are no studies at all in the elderly. However, the safety of the drug allows its prescription in the elderly. In summary, paroxetine is well tolerated in the treatment of depression in those between the ages of 65 and 75, although few studies have examined its use in those of 75 and older. Copyright © 2002 John Wiley & Sons, Ltd. [source] Mirtazapine and paroxetine: a drug-drug interaction study in healthy subjectsHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2001F. J. L. Ruwe Abstract Paroxetine inhibits cytochrome P450 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. [source] Maintenance Treatment for Old-Age Depression Preserves Health-Related Quality of Life: A Randomized, Controlled Trial of Paroxetine and Interpersonal PsychotherapyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 9 2007Alexandre Y. Dombrovski MD OBJECTIVES: To determine whether maintenance antidepressant pharmacotherapy and interpersonal psychotherapy sustain gains in health-related quality of life (HR-QOL) achieved during short-term treatment in older patients with depression. DESIGN: After open combined treatment with paroxetine and interpersonal psychotherapy, responders were randomly assigned to a two (paroxetine vs placebo) by two (monthly interpersonal psychotherapy vs clinical management) double-blind, placebo-controlled maintenance trial. HR-QOL outcomes were assessed over 1 year. SETTING: University-based clinic. PATIENTS: Of the referred sample of 363 persons aged 70 and older with major depression, 210 gave consent, and 195 started acute treatment; 116 met criteria for recovery, entered maintenance treatment, and were included in this analysis. INTERVENTIONS: Paroxetine; monthly manual-based interpersonal psychotherapy. MEASUREMENTS: Overall HR-QOL as measured using the Quality of Well-Being Scale (QWB) and six specific HR-QOL domains derived from the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) subscales. RESULTS: All domains of HR-QOL except physical functioning improved with successful acute and continuation treatment. After controlling for any effects of psychotherapy, pharmacotherapy was superior to placebo in preserving overall well-being (P=.04, effect size (r)=0.23), social functioning (P=.02, r=0.27), and role limitations due to emotional problems (P=.007, r=0.30). Interpersonal psychotherapy (controlling for the effects of pharmacotherapy) did not preserve HR-QOL better than supportive clinical management. CONCLUSION: Maintenance antidepressant pharmacotherapy is superior to placebo in preserving improvements in overall well-being achieved with treatment response in late-life depression. No such benefit was seen with interpersonal psychotherapy. [source] Effects of Acute Alcohol Intoxication and Paroxetine on Aggression in MenALCOHOLISM, Issue 4 2009Michael S. McCloskey Background:, The purpose of this study was to examine the role of the serotonin (5-HT) system in alcohol-related aggression. Methods:, Specifically, we experimentally examined the effects of 5-HT augmentation on alcohol-related aggression in men (n = 56). After consuming either alcohol (mean blood alcohol concentration of 0.10%) or a placebo (no alcohol) drink, and taking either 20 mg of paroxetine (Paxil®) or a placebo pill, participants were provided the opportunity to administer electric shock to a (faux) opponent during a task disguised as a reaction-time game. Aggression was defined as the intensity of shock chosen and the frequency with which an extreme (clearly painful) shock was chosen. We predicted that 5-HT augmentation would be associated with lower aggressive behavior overall, and also reduce the aggression facilitating effects of acute alcohol intoxication. Results:, The results indicated that alcohol intoxication increased aggression, particularly under low provocation. Paroxetine decreased aggression, particularly during high provocation. These effects, however, occurred independently of each other. Conclusions:, The effect of alcohol on extreme aggression was moderated by previous aggression history, with more aggressive individuals showing greater alcohol-related increases in extreme aggression. [source] ORIGINAL RESEARCH,EJACULATORY DISORDERS: Evaluation of Tramadol on Demand Vs.THE JOURNAL OF SEXUAL MEDICINE, Issue 8 2010Daily Paroxetine as a Long-Term Treatment of Lifelong Premature Ejaculation ABSTRACT Introduction., Premature ejaculation (PE) is the most common male sexual dysfunction with many lines of treatment that show conflicting results. Paroxetine and tramadol were both reported to be effective in treatment of PE. Aim., To investigate the effectiveness of long-term daily paroxetine vs. on-demand tramadol HCl in treatment of PE. Main Outcome Measures., Intravaginal ejaculatory latency time (IELT) and Arabic Index of PE (AIPE) were used to assess the efficacy of investigated drugs. Methods., Thirty-five cases with lifelong PE were enrolled in this study. Baseline recording of IELT using a stop watch and AIPE was done. Patients were randomized to take tramadol HCl on-demand or daily paroxetine. Reassessment was done after 6 and 12 weeks. A wash-out period for 2 weeks was given before cross-over to the other medication. Assessment of the effect of the second medication after 6 and 12 weeks was done. Results., Tramadol and paroxetine increased IELT significantly after 6 weeks by seven- and 11-folds, respectively, compared with baseline. After 12 weeks, a decline of IELT to fivefolds was recorded with tramadol whereas further increase of IELT to 22-folds was recorded with paroxetine compared with baseline (P < 0.05). Tramadol improved AIPE score significantly after 6 weeks but not after 12 weeks vs. baseline, whereas paroxetine increased the AIPE score after 6 and 12 weeks vs. baseline (P < 0.05). Conclusions., Daily paroxetine is more effective than on-demand tramadol for treatment of lifelong PE. Tramadol is not recommended as a long-term treatment of lifelong PE. Alghobary M, El-Bayoumy Y, Mostafa Y, E-HM Mahmoud, and Amr M. Evaluation of tramadol on demand vs. daily paroxetine as a long-term treatment of lifelong premature ejaculation. J Sex Med 2010;7:2860,2867. [source] Paroxetine and fluoxetine in pregnancy: a prospective, multicentre, controlled, observational studyBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 5 2008Orna Diav-Citrin WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , In recent years there has been concern regarding the possibility that selective serotonin reuptake inhibitors (SSRIs) cause an increased rate of congenital cardiovascular anomalies. , As of today, there is still debate in the literature as to the possible effects of paroxetine and fluoxetine on the embryonic cardiovascular system. WHAT THIS STUDY ADDS , Based on prospective data from three Teratogen Information Services, we have demonstrated an increased rate of congenital cardiovascular anomalies among the offspring of fluoxetine- and paroxetine-treated mothers. AIMS Recent studies have suggested a possible association between maternal use of selective serotonin reuptake inhibitors (SSRIs) in early pregnancy and cardiovascular anomalies. The aim of the present study was to evaluate the teratogenic risk of paroxetine and fluoxetine. METHODS This multicentre, prospective, controlled study evaluated the rate of major congenital anomalies after first-trimester gestational exposure to paroxetine, fluoxetine or nonteratogens. RESULTS We followed up 410 paroxetine, 314 fluoxetine first-trimester exposed pregnancies and 1467 controls. After exclusion of genetic and cytogenetic anomalies, there was a higher rate of major anomalies in the SSRI groups compared with the controls [paroxetine 18/348 (5.2%), fluoxetine 12/253 (4.7%) and controls 34/1359 (2.5%)]. The main risk applied to cardiovascular anomalies [paroxetine 7/348 (2.0%), crude odds ratio (OR) 3.47, 95% confidence interval (CI) 1.13, 10.58; fluoxetine 7/253 (2.8%), crude OR, 4.81 95% CI 1.56, 14.71; and controls 8/1359 (0.6%)]. On logistic regression analysis only cigarette smoking of ,10 cigarettes day,1 and fluoxetine exposure were significant variables for cardiovascular anomalies. The adjusted ORs for paroxetine and fluoxetine were 2.66 (95% CI 0.80, 8.90) and 4.47 (95% CI 1.31, 15.27), respectively. CONCLUSION This study suggests a possible association between cardiovascular anomalies and first-trimester exposure to fluoxetine. [source] ChemInform Abstract: Ring Expansion: Formal Total Synthesis of (-)-Paroxetine.CHEMINFORM, Issue 5 2002Janine Cossy Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Efficacy and safety of two treatment algorithms in bipolar depression consisting of a combination of lithium, lamotrigine or placebo and paroxetineACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2010M. L. M. Van Der Loos van der Loos MLM, Mulder P, Hartong EGThM, Blom MBJ, Vergouwen AC, van Noorden MS, Timmermans MA, Vieta E, Nolen WA, for the LamLit Study Group. Efficacy and safety of two treatment algorithms in bipolar depression consisting of a combination of lithium, lamotrigine or placebo and paroxetine. Objective:, In a previous paper, we reported about the efficacy of the addition of lamotrigine to lithium in patients with bipolar depression. In the second phase of this study paroxetine was added to ongoing treatment in non-responders. Method:, Bipolar depressed patients (n = 124) treated with lithium were randomized to addition of lamotrigine or placebo. In non-responders after 8 weeks, paroxetine 20 mg was added for another 8 weeks to ongoing treatment. Results:, After 8 weeks the improvement in patients treated with lamotrigine vs. patients treated with placebo was significant. After addition of paroxetine this difference disappeared as a result of greater further improvement in the non-responders to placebo. Conclusion:, Addition of lamotrigine to lithium was found effective in bipolar depressed patients. Further addition of paroxetine in non-responders to lithium plus lamotrigine did not appear to provide additional benefit, while it appeared to do so in non-responders to lithium plus placebo. [source] A controlled trial of paroxetine for chronic PTSD, dissociation, and interpersonal problems in mostly minority adults,DEPRESSION AND ANXIETY, Issue 2 2007Randall D. Marshall M.D. Abstract This study evaluated the efficacy of paroxetine for symptoms and associated features of chronic posttraumatic stress disorder (PTSD), interpersonal problems, and dissociative symptoms in an urban population of mostly minority adults. Adult outpatients with a primary DSM-IV diagnosis of chronic PTSD received 1 week of single-blind placebo (N = 70). Those not rated as significantly improved were then randomly assigned to placebo (N = 27) or paroxetine (N = 25) for 10 weeks, with a flexible dosage design (maximum 60,mg by week 7). Significantly more patients treated with paroxetine were rated as responders (14/21, 66.7%) on the Clinical Global Impression,Improvement Scale (CGI-I) compared to patients treated with placebo (6/22, 27.3%). Mixed effects models showed greater reductions on the Clinician-Administered PTSD Scale (CAPS) total score (primary plus associated features of PTSD) in the paroxetine versus placebo groups. Paroxetine was also superior to placebo on reduction of dissociative symptoms [Dissociative Experiences Scale (DES) score] and reduction in self-reported interpersonal problems [Inventory of Interpersonal Problems (IIP) score]. In a 12-week maintenance phase, paroxetine response continued to improve, but placebo response did not. Paroxetine was well tolerated and superior to placebo in ameliorating the symptoms of chronic PTSD, associated features of PTSD, dissociative symptoms, and interpersonal problems in the first trial conducted primarily in minority adults. Depression and Anxiety 24:77,84, 2007. Published 2006 Wiley-Liss, Inc. [source] A double-blind study of the efficacy of venlafaxine extended-release, paroxetine, and placebo in the treatment of panic disorderDEPRESSION AND ANXIETY, Issue 1 2007Mark H. Pollack M.D. Abstract To date, no large-scale, controlled trial comparing a serotonin,norepinephrine reuptake inhibitor and selective serotonin reuptake inhibitor with placebo for the treatment of panic disorder has been reported. This double-blind study compares the efficacy of venlafaxine extended-release (ER) and paroxetine with placebo. A total of 664 nondepressed adult outpatients who met DSM-IV criteria for panic disorder (with or without agoraphobia) were randomly assigned to 12 weeks of treatment with placebo or fixed-dose venlafaxine ER (75,mg/day or 150,mg/day), or paroxetine 40,mg/day. The primary measure was the percentage of patients free from full-symptom panic attacks, assessed with the Panic and Anticipatory Anxiety Scale (PAAS). Secondary measures included the Panic Disorder Severity Scale, Clinical Global Impressions,Severity (CGI-S) and ,Improvement (CGI-I) scales; response (CGI-I rating of very much improved or much improved), remission (CGI-S rating of not at all ill or borderline ill and no PAAS full-symptom panic attacks); and measures of depression, anxiety, phobic fear and avoidance, anticipatory anxiety, functioning, and quality of life. Intent-to-treat, last observation carried forward analysis showed that mean improvement on most measures was greater with venlafaxine ER or paroxetine than with placebo. No significant differences were observed between active treatment groups. Panic-free rates at end point with active treatment ranged from 54% to 61%, compared with 35% for placebo. Approximately 75% of patients given active treatment were responders, and nearly 45% achieved remission. The placebo response rate was slightly above 55%, with remission near 25%. Adverse events were mild or moderate and similar between active treatment groups. Venlafaxine ER and paroxetine were effective and well tolerated in the treatment of panic disorder. Depression and Anxiety 24:1,14, 2007. © 2006 Wiley-Liss, Inc. [source] A randomized, placebo-controlled trial of paroxetine in nursing home residents with non-major depressionDEPRESSION AND ANXIETY, Issue 3 2002Adam B. Burrows M.D. Abstract Depression is common across a broad spectrum of severity among nursing home residents. Previous research has demonstrated the effectiveness of antidepressants in nursing home residents with major depression, but it is not known whether antidepressants are helpful in residents with less severe forms of depression. We conducted a randomized double-blind placebo-controlled 8-week trial comparing paroxetine and placebo in very old nursing home residents with non-major depression. The main outcome measure was the primary nurse's Clinical Impression of Change (CGI-C). Additional outcome measures were improvement on the interview-derived Hamilton Depression Rating Scale (HDRS) and Cornell Scale for Depression (CS) scores. Twenty-four subjects with a mean age of 87.9 were enrolled and twenty subjects completed the trial. Placebo response was high, and when all subjects were considered, there were no differences in improvement between the paroxetine and placebo groups. Two subjects that received paroxetine developed delirium, and subjects that received paroxetine were more likely to experience a decrease in Mini Mental State Exam scores (P = .03). There were no differences in serum anticholinergic activity between groups. In a subgroup analysis of 15 subjects with higher baseline HDRS and CS scores, there was a trend toward greater improvement in the paroxetine group in an outcome measure that combined the CGI-C and interview-based measures (P = .06). Paroxetine is not clearly superior to placebo in this small study of very old nursing home residents with non-major depression, and there is a risk of adverse cognitive effects. Because of the high placebo response and the trend towards improvement in the more severely ill patients, it is possible that a larger study would have demonstrated a significant therapeutic effect for paroxetine as compared with placebo. The study also illustrates the discordance between patient and caregiver ratings, and the difficulties in studying very elderly patients with mood disorders. Depression and Anxiety 15:102,110, 2002. © 2002 Wiley-Liss, Inc. [source] A randomized controlled study of paroxetine and cognitive-behavioural therapy for late-life panic disorderACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2010G.-J. Hendriks Hendriks G-J, Keijsers GPJ, Kampman M, Oude Voshaar RC, Verbraak MJPM, Broekman TG, Hoogduin CAL. A randomized controlled study of paroxetine and cognitive-behavioural therapy for late-life panic disorder. Objective:, To examine the effectiveness of paroxetine and cognitive-behavioural therapy (CBT) in elderly patients suffering from panic disorder with or without agoraphobia (PD(A)). Method:, Forty-nine patients aged 60+ years with confirmed PD(A) were randomly assigned to 40 mg paroxetine, individual CBT, or to a 14-week waiting list. Outcomes, with avoidance behaviour and agoraphobic cognitions being the primary measures, were assessed at baseline and at weeks 8, 14 (conclusion CBT/waiting list), and at week 26 (treated patients only) and analysed using mixed models. Results:, All outcome measures showed that the patients having received CBT and those treated with paroxetine had significantly better improvement compared with those in the waiting-list condition. With one patient (1/20, 5%) in the CBT and three (3/14, 17.6%) in the paroxetine condition dropping out, attrition rates were low. Conclusion:, Patients with late-life panic disorder respond well to both paroxetine and CBT. Although promising, the outcomes warrant replication in larger study groups. [source] Toward a better understanding of the pathophysiology of OCD SSRI responders: QEEG source localizationACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2007T. G. Bolwig Objective:, To demonstrate the utility of three-dimensional source localization of the scalp-recorded electroencephalogram (EEG) for the identification of the most probable underlying brain dysfunction in patients with obsessive,compulsive disorder (OCD). Method:, Eyes-closed resting EEG data was recorded from the scalp locations of the International 10/20 System. Variable resolution electromagnetic tomography (VARETA) was applied to artifact-free EEG data. This mathematical algorithm estimates the source generators of EEG recorded from the scalp. Results:, An excess in the alpha range was found with sources in the corpus striatum, in the orbito-frontal and temporo-frontal regions in untreated OCD patients. This abnormality was seen to decrease following successful treatment with paroxetine. Conclusion:, The VARETA findings of an activation/deactivation pattern in cortical and subcortical structures in paroxetine-responsive patients are in good accordance with data obtained in previously published positron emission tomography studies related to current hypotheses of a thalamo-striatal-frontal feedback loop being relevant for understanding the pathophysiology of OCD. [source] Dose,response relationship of selective serotonin reuptake inhibitors treatment-emergent hypomania in depressive disordersACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2001R. Ramasubbu Objective:,The notion that antidepressant treatment-associated hypomania or mania being pharmacologically induced has been challenged. To determine whether selective serotonin reuptake inhibitors (SSRI) induced hypomania is secondary to medication effects, we examined the dose,response relationship of SSRI-induced hypomania in two patients with depressive disorder. Method:,Case study. Result:,Hypomanic symptoms emerged during treatment with sertraline at the dose of 300 mg per day in a 45-year-old male with major depression. Paroxetine treatment at the dose of 80 mg per day induced hypomania in a 37-year-old female with dysthymia and trichitillomania. These patients have no family or personal history of bipolar disorder. Hypomania resolved when sertraline was decreased to 200 mg per day and paroxetine to 40 mg per day. No hypomanic switch was observed during 18,24 months follow-up. Conclusion:,In the absence of risk factors for manic switch, SSRI-induced hypomania may be dose-dependent medication effects. [source] Advances in the enantioseparation of second-generation antidepressant drugs by electrodriven methodsELECTROPHORESIS, Issue 1 2006Roberto Mandrioli Abstract Stereochemistry is steadily increasing in importance in the development of new drugs, and the availability of pure enantiomer drugs can make therapy safer and more efficacious. In particular, almost all second-generation antidepressant drugs possess one or more chiral centres; however, only some of them are administered as single enantiomers. A fundamental part of the quality control of pharmaceutical formulations is the determination of enantiomeric excess and enantiomeric purity; this is also important for the therapeutic drug monitoring of depressed patients. For this purpose, efficient and reliable analytical methods are needed and electrodriven techniques (most of all CE, CEC and MEKC) are very efficient and inexpensive candidates for the role. In this review, the enantioselective electrodriven methods available for the analysis of second-generation antidepressant are presented and discussed. In particular, the following pharmacological classes of antidepressants will be considered: selective serotonin reuptake inhibitors (fluoxetine, citalopram, paroxetine, sertraline); norepinephrine reuptake inhibitors (reboxetine); serotonin and norepinephrine reuptake inhibitors (venlafaxine, milnacipran, duloxetine); and noradrenergic and specific serotonergic antidepressants (mirtazapine). [source] Antidepressants and their metabolites in municipal wastewater, and downstream exposure in an urban watershedENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2010Chris D. Metcalfe Abstract Antidepressants are a widely prescribed group of pharmaceuticals that can be biotransformed in humans to biologically active metabolites. In the present study, the distribution of six antidepressants (venlafaxine, bupropion, fluoxetine, sertraline, citalopram, and paroxetine) and five of their metabolites was determined in a municipal wastewater treatment plant (WWTP) and at sites downstream of two WWTPs in the Grand River watershed in southern Ontario, Canada. Fathead minnows (Pimephales promelas) caged in the Grand River downstream of a WWTP were also evaluated for accumulated antidepressants. Finally, drinking water was analyzed from a treatment plant that takes its water from the Grand River 17 km downstream of a WWTP. In municipal wastewater, the antidepressant compounds present in the highest concentrations (i.e., >0.5 µg/L) were venlafaxine and its two demethylation products, O - and N -desmethyl venlafaxine. Removal rates of the target analytes in a WWTP were approximately 40%. These compounds persisted in river water samples collected at sites up to several kilometers downstream of discharges from WWTPs. Venlafaxine, citalopram, and sertraline, and demethylated metabolites were detected in fathead minnows caged 10 m below the discharge from a WWTP, but concentrations were all <7 µg/kg wet weight. Venlafaxine and bupropion were detected at very low (<0.005 µg/L) concentrations in untreated drinking water, but these compounds were not detected in treated drinking water. The present study illustrates that data are needed on the distribution in the aquatic environment of both the parent compound and the biologically active metabolites of pharmaceuticals. Environ. Toxicol. Chem. 2010;29:79,89. © 2009 SETAC [source] Mixture and single-substance toxicity of selective serotonin reuptake inhibitors toward algae and crustaceansENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2007Anne Munch Christensen Abstract Selective serotonin reuptake inhibitors (SSRIs) are used as antidepressant medications, primarily in the treatment of clinical depression. They are among the pharmaceuticals most often prescribed in the industrialized countries. Selective serotonin reuptake inhibitors are compounds with an identical mechanism of action in mammals (inhibit reuptake of serotonin), and they have been found in different aqueous as well as biological samples collected in the environment. In the present study, we tested the toxicities of five SSRIs (citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline) as single substances and of citalopram, fluoxetine, and sertraline in binary mixtures in two standardized bioassays. Test organisms were the freshwater algae Pseudokirchneriella subcapitata and the freshwater crustacean Daphnia magna. In algae, test median effect concentrations (EC50s) ranged from 0.027 to 1.6 mg/L, and in daphnids, test EC50s ranged from 0.92 to 20 mg/L, with sertraline being one of the most toxic compounds. The test design and statistical analysis of results from mixture tests were based on isobole analysis. It was demonstrated that the mixture toxicity of the SSRIs in the two bioassays is predictable by the model of concentration addition. Therefore, in risk assessment based on chemical analysis of environmental samples, it is important to include the effect of all SSRIs that are present at low concentrations, and the model of concentration addition may be used to predict the combined effect of the mixture of SSRIs. [source] Acute and chronic toxicity of five selective serotonin reuptake inhibitors in Ceriodaphnia dubiaENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 9 2004Theodore B. Henry Abstract Contamination of surface waters by pharmaceutical chemicals has raised concern among environmental scientists because of the potential for negative effects on aquatic organisms. Of particular importance are pharmaceutical compounds that affect the nervous or endocrine systems because effects on aquatic organisms are possible at low environmental concentrations. Selective serotonin reuptake inhibitors (SSRIs) are drugs used to treat clinical depression in humans, and have been detected in low concentrations in surface waters. In this investigation, the acute and chronic toxicity of five SSRIs (fluoxetine, Prozac®; fluvoxamine, Luvox®; paroxetine, Paxil®; citalopram, Celexa®; and sertraline, Zoloft®) were evaluated in the daphnid Ceriodaphnia dubia. For each SSRI, the 48-h median lethal concentration (LC50) was determined in three static tests with neonate C. dubia, and chronic (8-d) tests were conducted to determine no-observable-effect concentrations (NOEC) and lowest-observable-effect concentrations (LOEC) for reproduction endpoints. The 48-h LC50 for the SSRIs ranged from 0.12 to 3.90 mg/L and the order of toxicity of the compounds was (lowest to highest): Citalopram, fluvoxamine, paroxetine, fluoxetine, sertraline. Mortality data for the 8-d chronic tests were similar to the 48-h acute data. The SSRIs negatively affected C. dubia reproduction by reducing the number of neonates per female, and for some SSRIs, by reducing the number of broods per female. For sertraline, the most toxic SSRI, the LOEC for the number of neonates per female was 0.045 mg/L and the NOEC was 0.009 mg/L. Results indicate that SSRIs can impact survival and reproduction of C. dubia; however, only at concentrations that are considerably higher than those expected in the environment. [source] Fenfluramine Blocks Low-Mg2+ -Induced Epileptiform Activity in Rat Entorhinal CortexEPILEPSIA, Issue 8 2000K. Gentsch Summary: Purpose: The entorhinal cortex (EC) represents the main input structure to the hippocampus and seems to be critically involved in temporal lobe epilepsy. Considering that the EC receives a strong serotonergic projection from the raphe nuclei and expresses a high density of serotonin (5-HT) receptors, the effect of the 5-HT,releasing drug fenfluramine (FFA) on epileptiform activity generated in the EC was investigated in an in vitro model of epilepsy. Methods: The experiments were performed on 43 horizontal slices containing the EC, the subiculum, and the hippocampal formation obtained from 230,250 g adult Wistar rats. Using extracellular recording techniques, we investigated the effect of bath-applied FFA (200 ,mol/L to 1 mmol/L) on epileptiform activity induced by omitting MgSO4 from the artificial cerebrospinal fluid. Results: We demonstrate that FFA reversibly blocks epileptiform activity in the EC. Surprisingly, in the presence of the 5-HT uptake blocker paroxetine, the FFA-induced effect was diminished. Coapplication of the 5-HTIA receptor antagonist WAY 100635 prevented the FFA-induced anticonvulsive effect, suggesting that (a) the FFA-induced suppression of epileptiform activity is mediated by the release of 5-HT from synaptic terminals within the EC rather than by an unspecific effect of FFA and (b) released 5-HT most likely blocks the activity by activation of 5-HTIA receptors. Conclusion: FFA, which is primarily used because of its anorectic activity, might get an additional therapeutic value in the treatment of temporal lobe epilepsy with parahippocampal involvement. [source] Efficacy screening trials of paroxetine, pentoxifylline, riluzole, pramipexole and venlafaxine in cocaine dependenceADDICTION, Issue 2005Domenic A. Ciraulo ABSTRACT Aims The two studies presented here were conducted to assess the efficacy of paroxetine, pentoxifylline, riluzole, venlafaxine and pramipexole as medications for the treatment of cocaine dependence. Design A multi-arm, modified blinded, placebo-controlled design was used. Setting The studies were conducted at the Boston VA Healthcare System and the Boston University School of Medicine Medication Development Research Unit (MDRU). Participants Participants met criteria for cocaine dependence during a 2-week screening period. Intervention Following random assignment to one of the treatment groups, subjects received active medication or placebo for 8 weeks in combination with cognitive behavioral counseling. In the first study the efficacy of the antidepressant paroxetine (20 mg daily), the phosphodiesterase inhibitor pentoxifylline (1200 mg daily) and the glutamate release inhibitor riluzole (100 mg daily) was assessed. The antidepressant venlafaxine (150 mg daily) and the dopamine agonist pramipexole (1.5 mg daily) were evaluated in the second study. Measurements Urine benzoylecgonine (BE) concentrations, self-report of cocaine use and global impression scores served as primary outcome measures. Secondary measures included assessments of cocaine craving and psychiatric functioning. Adverse events were monitored during the treatment period. Findings None of the active medications produced greater reductions in urine BE concentrations over the treatment period than did placebo. There were trends for BE levels to become reduced in the pentoxifylline group during the first 4 weeks of treatment and for Addiction Severity Index (ASI) drug composite scores to be lower in the pentoxyfylline group at end-point compared to the placebo group. Significant within-group reductions in reported cocaine use and craving were found for all treatment groups, but none of the active medications were superior to placebo on these measures. The accuracy of self-reported cocaine use declined over the study period. Overall, the active medications were well tolerated. Conclusions This study does not support the use of paroxetine, pentoxifylline, riluzole, venlafaxine or pramipexole for the treatment of cocaine dependence. However, these results need to be interpreted with caution because of the small size and lack of homogeneity of the experimental groups. [source] MDMA self-administration in rats: acquisition, progressive ratio responding and serotonin transporter bindingEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2007Susan Schenk Abstract 3,4-Methylenedioxymethamphetamine (MDMA) self-administration has been shown in animals with extensive drug histories, but only a small number of studies have examined high rates of responding maintained by MDMA in previously drug-naďve animals. In the present study, influence of dose (0.25 or 1.0 mg/kg/infusion) on the acquisition of MDMA self-administration was measured during daily 6-h sessions. Dose,effect data were obtained for MDMA (0.25,1.0 mg/kg/infusion) self-administration under a progressive ratio (PR) schedule of reinforcement. The effect of experimenter- or self-administered MDMA on [3H] paroxetine binding in several brain regions was measured. Acquisition of MDMA self-administration was highly variable and not different for 0.25 or 1.0 mg/kg/infusion progressed with approximately 60% of the rats acquiring reliable self-administration during the 15-day test period. The percentage of rats that acquired MDMA self-administration was lower than the percentage of rats that acquired cocaine (0.5 mg/kg/infusion) self-administration, and cocaine self-administration was acquired with a shorter latency. Responding maintained by MDMA was dose dependent, and breakpoints under a PR schedule increased with dose. Radioligand binding and autoradiography demonstrated lower densities of serotonin transporter sites (SERT) in MDMA self-administering rats as compared with controls across brain regions. The reduction in SERT densities was comparable in magnitude to rats treated with experimenter-administered doses of MDMA. These data support the idea that MDMA is a drug with high abuse liability, and long-term self-administration may lead to long-lasting deficits in serotonin neurotransmission. [source] A Convenient Synthesis of (,)-ParoxetineEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 15 2004László Czibula Abstract A convenient synthesis of the antidepressant paroxetine starting from 1-benzyl-4-piperidone (2) is reported. A stereoselective reduction resulted in cis -piperidine-3-methanol [(+)- 6]. The reaction between cis -piperidine-3-methanol mesylate (7) and sesamol led to benzyl-protected trans -paroxetine (9) through an inversion reaction of the stereogenic center at position 3. The latter compound was deprotected by hydrogenolysis. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] Metabolic drug interactions with new psychotropic agentsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2003Edoardo Spina Abstract New psychotropic drugs introduced in clinical practice in recent years include new antidepressants, such as selective serotonin reuptake inhibitors (SSRI) and ,third generation' antidepressants, and atypical antipsychotics, i.e. clozapine, risperidone, olanzapine, quetiapine, ziprasidone and amisulpride. These agents are extensively metabolized in the liver by cytochrome P450 (CYP) enzymes and are therefore susceptible to metabolically based drug interactions with other psychotropic medications or with compounds used for the treatment of concomitant somatic illnesses. New antidepressants differ in their potential for metabolic drug interactions. Fluoxetine and paroxetine are potent inhibitors of CYP2D6, fluvoxamine markedly inhibits CYP1A2 and CYP2C19, while nefazodone is a potent inhibitor of CYP3A4. These antidepressants may be involved in clinically significant interactions when coadministered with substrates of these isoforms, especially those with a narrow therapeutic index. Other new antidepressants including sertraline, citalopram, venlafaxine, mirtazapine and reboxetine are weak in vitro inhibitors of the different CYP isoforms and appear to have less propensity for important metabolic interactions. The new atypical antipsychotics do not affect significantly the activity of CYP isoenzymes and are not expected to impair the elimination of other medications. Conversely, coadministration of inhibitors or inducers of the CYP isoenzymes involved in metabolism of the various antipsychotic compounds may alter their plasma concentrations, possibly leading to clinically significant effects. The potential for metabolically based drug interactions of any new psychotropic agent may be anticipated on the basis of knowledge about the CYP enzymes responsible for its metabolism and about its effect on the activity of these enzymes. This information is essential for rational prescribing and may guide selection of an appropriate compound which is less likely to interact with already taken medication(s). [source] Treating Chronic Tension-type Headache Not Responding to Amitriptyline Hydrochloride With Paroxetine Hydrochloride: A Pilot EvaluationHEADACHE, Issue 9 2003Kenneth A. Holroyd PhD Context.,In some individuals, chronic tension-type headache fails to respond to tricyclic antidepressant medications that often serve as first-line therapy. Objective.,To evaluate the clinical efficacy of paroxetine hydrochloride for chronic tension-type headache not responding to amitriptyline hydrochloride. Design and Setting.,Open-label trial of paroxetine conducted at 2 outpatient sites in Ohio. Participants and Intervention.,Thirty-one adults (mean age, 37 years; 20 women) with chronic tension-type headache (mean, 25 headache days per month) who had failed to respond (less than 30% improvement) to treatment with either amitriptyline (n = 13) or matched placebo (n = 18). All participants were treated with paroxetine (up to 40 mg per day) in a 9-month protocol. Outcome Measures.,Monthly headache index calculated as the mean of pain ratings (0 to 10 scale) recorded by participants in a diary 4 times per day, number of days per month with at least moderate pain (pain rating of 5 or greater), and analgesic medication use. Results.,In patients who had not responded to amitriptyline, paroxetine failed to reduce chronic tension-type headaches or analgesic medication use. In patients who had not responded to placebo, paroxetine produced modest reductions in chronic tension-type headaches and analgesic use. Conclusions.,We found no evidence that chronic tension-type headaches that failed to respond to tricyclic antidepressant therapy with amitriptyline improved when subsequently treated with paroxetine. More support was found for the efficacy of paroxetine in patients with chronic tension-type headaches who had failed to respond to placebo. [source] Effectiveness and tolerability of paroxetine controlled release (CR) in the treatment of major depressive disorder: an open-label, prospective, multi-center trial in KoreaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2007Chi-Un Pae Abstract Objectives This study evaluated the effectiveness and tolerability of paroxetine controlled release (CR) for the treatment of Korean patients with major depressive disorder (MDD) in a naturalistic treatment setting. Methods One hundred and ninety patients with MDD were enrolled in this study. The Hamilton Depression Rating Scale-17 item (HAMD-17) and Clinical Global Impression-Severity (CGI-S) scores were measured at the baseline (day 0) and at weeks 1, 2, 4, and 8 (endpoint). The primary measure of effectiveness was a change in the mean HAMD-17 scores from the baseline to the endpoint. The secondary effectiveness measures included a decrease in the HAMD-17 scores of 50% or more at the endpoint compared with the baseline and a change in the mean CGI-S scores from the baseline to the endpoint. Remission was defined as a HAMD-17 score,,,7 at the endpoint. Results The HAMD-17 scores decreased by 56.5% (observed difference, OD,=,,13.3) (t,=,26.63, p,<,0.0001) from the baseline. The CGI-S scores also decreased by 50.0% (OD,=,,2.3) (t,=,24.47, p,<,0.0001). The response and remission rate at the endpoint was 64.2 and 48.4%, respectively. The adverse events were tolerable. No unexpected or serious side effects were observed. Conclusions Despite the methodological limitations, this study demonstrated that paroxetine CR is effective and tolerable for treating patients with MDD in an East Asian population. Copyright © 2007 John Wiley & Sons, Ltd. [source] A placebo controlled investigation into the effects of paroxetine and mirtazapine on measures related to car driving performanceHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2003F. Ridout Abstract Objective To assess the effects of paroxetine and mirtazapine on psychometric performance related to car driving, including an on-the-road test of BRT. Method In a 4-way, double blind randomised crossover study, 12 healthy volunteers received paroxetine 20,mg mane, mirtazapine 15,mg/30,mg nocte (comparator), mirtazapine 15,mg mane/15,mg b.i.d.(verum) and placebo over a 5 day period with a washout period of 7 days between treatments. Psychometric assessments included ,on-the-road' BRT (BRT), CFF (CFF), CRT (CRT) and subjective measures of sedation and sleep parameters. Results Paroxetine had no significant effect on BRT compared with placebo. Although subjective ratings of sleep quality and sedation were impaired, there were significant improvements in both CFF and the recognition reaction component of CRT with paroxetine. Mirtazapine 15,mg/30,mg nocte impaired laboratory performance and some subjective tests. Mirtazapine 15 mg mane/15,mg b.i.d. improved sleep, but significantly impaired all other measures. Conclusion Paroxetine 20,mg/day has no psychomotor or behavioural toxicity and has no negative impact on BRT. Further research into the chronic and sub-chronic effects of mirtazapine is needed to establish the clinical significance of these results. Copyright © 2003 John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||||||||||||||