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Paroxetine and fluoxetine in pregnancy: a prospective, multicentre, controlled, observational study.British Journal of Clinical Pharmacology Nov 2008Recent studies have suggested a possible association between maternal use of selective serotonin reuptake inhibitors (SSRIs) in early pregnancy and cardiovascular... (Comparative Study)
Comparative Study
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 >or=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.
Topics: Abnormalities, Drug-Induced; Abortion, Induced; Adult; Antidepressive Agents, Second-Generation; Birth Weight; Case-Control Studies; Confidence Intervals; Drug Administration Schedule; Female; Fluoxetine; Gestational Age; Heart Defects, Congenital; Humans; Infant, Newborn; Maternal Age; Odds Ratio; Paroxetine; Pregnancy; Pregnancy Trimester, First; Prospective Studies; Risk; Selective Serotonin Reuptake Inhibitors
PubMed: 18754846
DOI: 10.1111/j.1365-2125.2008.03261.x -
BMC Medicine Aug 2005Inclusion of unpublished data on the effects of antidepressants on children has suggested unfavourable risk-benefit profiles for some of the drugs. Recent meta-analyses... (Review)
Review
BACKGROUND
Inclusion of unpublished data on the effects of antidepressants on children has suggested unfavourable risk-benefit profiles for some of the drugs. Recent meta-analyses of studies on adults have indicated similar effects. We obtained unpublished data for paroxetine that have so far not been included in these analyses.
METHODS
The documentation for drug registration contained 16 studies in which paroxetine had been randomised against placebo. We registered the number of suicides, suicide attempts and ideation. We corrected for duration of medication and placebo treatment and used a standard Bayesian statistical approach with varying priors.
RESULTS
There were 7 suicide attempts in patients on the drug and 1 in a patient on placebo. We found that the probability of increased intensity of suicide attempts per year in adults taking paroxetine was 0.90 with a "pessimistic" prior, and somewhat less with two more neutral priors.
CONCLUSION
Our findings support the results of recent meta-analyses. Patients and doctors should be warned that the increased suicidal activity observed in children and adolescents taking certain antidepressant drugs may also be present in adults.
Topics: Adult; Bayes Theorem; Depression; Humans; Paroxetine; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Suicide, Attempted
PubMed: 16115311
DOI: 10.1186/1741-7015-3-14 -
Psychopharmacology Mar 2016Sexual side effects are commonly associated with selective serotonin reuptake inhibitor (SSRI) treatment. Some evidence suggest that activation of 5-HT1A receptors...
RATIONALE
Sexual side effects are commonly associated with selective serotonin reuptake inhibitor (SSRI) treatment. Some evidence suggest that activation of 5-HT1A receptors attenuates SSRI-induced sexual dysfunction.
OBJECTIVE
This study in male rats compared the effects of vilazodone, an antidepressant with SSRI and 5-HT1A receptor partial agonist activity, with other prototypical SSRIs (citalopram and paroxetine) on sexual behaviors and 5-HT receptors (5-HT1A and 5-HT2A) and transporter (5-HTT) levels in select forebrain regions of the limbic system using quantitative autoradiography.
METHODS
Rats received vilazodone (1, 3, and 10 mg/kg), citalopram (10 and 30 mg/kg), or paroxetine (10 mg/kg) treatment for 14 days. Sexual behaviors (frequency and latency of mounts, intromissions, and ejaculations) were measured in the presence of an estrous female rat on days 1 (acute), 7 (subchronic), and 14 (chronic).
RESULTS
Vilazodone-treated rats exhibited no sexual dysfunction compared with controls; in contrast, the citalopram- and paroxetine-treated rats exhibited impaired copulatory and ejaculatory behaviors after subchronic and chronic treatments. Chronic vilazodone treatment markedly decreased 5-HT1A receptor levels in cortical and hippocampal regions, while the SSRIs increased levels of this receptor in similar regions. All chronic treatments reduced 5-HTT levels across the forebrain; however, the magnitude of the decrease was considerably smaller for vilazodone than for the SSRIs.
CONCLUSIONS
The current studies showed that chronic treatment with vilazodone, in contrast to citalopram and paroxetine, was not associated with diminished sexual behaviors in male rats, which may be related to the differential effects of vilazodone on 5-HT1A receptor and 5-HTT levels relative to conventional SSRIs.
Topics: Animals; Antidepressive Agents; Brain; Citalopram; Male; Paroxetine; Rats; Receptors, Serotonin; Serotonin Plasma Membrane Transport Proteins; Selective Serotonin Reuptake Inhibitors; Sexual Behavior; Vilazodone Hydrochloride
PubMed: 26758283
DOI: 10.1007/s00213-015-4198-1 -
Journal of Cardiovascular Pharmacology... Dec 2010to assess the impact of paroxetine coadministration on the stereoselective pharmacokinetic (PK) properties of carvedilol. (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY OBJECTIVE
to assess the impact of paroxetine coadministration on the stereoselective pharmacokinetic (PK) properties of carvedilol.
DESIGN
prospective, randomized, 2-phase crossover.
SETTING
the University of Michigan General Clinical Research Unit and Michigan Clinical Research Unit.
PARTICIPANTS
twelve healthy volunteers aged 18 to 45 years, male and female, receiving no treatment with prescription or nonprescription medications.
INTERVENTIONS
participants received single dose oral carvedilol (12.5 mg) with and without coadministration of immediate-release paroxetine (10 mg orally twice daily), in random order. Blood samples were collected at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, and 24 hours post-carvedilol dose for determination of R and S carvedilol plasma enantiomer concentrations by high pressure liquid chromatography.
MEASUREMENTS AND MAIN RESULTS
pharmacokinetic (PK) parameters were calculated for each enantiomer by noncompartmental methods and compared between study phases by analysis of variance (ANOVA) controlling for study phase order and subject, with Tukey's studentized range test post hoc. Area under the concentration-time curve (AUC) increased significantly with paroxetine coadministration, approximately 2.5-fold and 1.9-fold for the R and S enantiomers, respectively. R/S AUC ratio increased significantly, from approximately 2.3 to 3.0. Individual increases in enantiomeric AUCs with paroxetine coadministration ranged from 0% to 571% and changes in R/S ratio ranged from -8% to 108%. Heart rate, P-R interval, and blood pressure were monitored and no clinically significant changes in carvedilol effects were noted.
CONCLUSION
this study demonstrated a PK drug-drug interaction between paroxetine and carvedilol, with considerable interparticipant variability in carvedilol PK parameters and magnitude of drug interaction. Stereoselectivity of carvedilol metabolism is preserved with paroxetine coadministration, and R/S AUC ratio generally widens. Although this drug interaction could potentially increase adrenergic antagonism and have significant clinical effects in patients, these effects were not seen in our healthy volunteer participants.
Topics: Adult; Antihypertensive Agents; Area Under Curve; Blood Pressure; Carbazoles; Carvedilol; Cross-Over Studies; Drug Interactions; Female; Heart Rate; Humans; Male; Middle Aged; Paroxetine; Propanolamines; Selective Serotonin Reuptake Inhibitors; Stereoisomerism
PubMed: 20705902
DOI: 10.1177/1074248410372926 -
Psychiatry Research Jul 2021Paroxetine and sertraline are the only FDA approved drugs for treatment of posttraumatic stress disorder (PTSD). Although both drugs show better outcomes than placebo,... (Randomized Controlled Trial)
Randomized Controlled Trial
Paroxetine and sertraline are the only FDA approved drugs for treatment of posttraumatic stress disorder (PTSD). Although both drugs show better outcomes than placebo, not all patients benefit from treatment. We examined predictors and latent classes of SSRI treatment response in patients with PTSD. Symptom severity was measured over a 12-week period in 390 patients suffering from PTSD treated with open-label sertraline or paroxetine and a double-blinded placebo. First, growth curve modeling (GCM) was used to examine population-level predictors of treatment response. Second, growth mixture modeling (GMM) was used to group patients into latent classes based on their treatment response trajectories over time and to investigate predictors of latent class membership. Gender, childhood sexual trauma, and sexual assault as index trauma moderated the population-level treatment response using GCM. GMM identified three classes: fast responders, responders with low pretreatment symptom severity and responders with high pretreatment symptom severity. Class membership was predicted based on time since index trauma, severity of depression, and severity of anxiety. The study shows that higher severity of comorbid disorders does not result in an inferior response to treatment and suggests that patients with longer time since index trauma might particularly benefit from treatment with sertraline or paroxetine.
Topics: Anxiety; Anxiety Disorders; Child; Double-Blind Method; Humans; Paroxetine; Selective Serotonin Reuptake Inhibitors; Stress Disorders, Post-Traumatic
PubMed: 33975171
DOI: 10.1016/j.psychres.2021.113964 -
The International Journal of Risk &... Sep 2016This is an analysis of the unpublished continuation phase of Study 329, the primary objective of which was to compare the efficacy and safety of paroxetine and... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This is an analysis of the unpublished continuation phase of Study 329, the primary objective of which was to compare the efficacy and safety of paroxetine and imipramine with placebo in the treatment of adolescents with unipolar major depression. The objectives of the continuation phase were to assess safety and relapse rates in the longer term. The objective of this publication, under the Restoring Invisible and Abandoned Trials (RIAT) initiative, was to see whether access to and analysis of the previously unpublished dataset from the continuation phase of this randomized controlled trial would have clinically relevant implications for evidence-based medicine.
METHODS
The study was an eight-week double-blind randomized placebo-controlled trial with a six month continuation phase. The setting was 12 North American academic psychiatry centres, from 20 April 1994 to 15 February 1998. 275 adolescents with major depression were originally enrolled in Study 329, with 190 completing the eight-week acute phase. Of these, 119 patients (43%) entered the six-month continuation phase (paroxetine n = 49; imipramine n = 39; placebo n = 31), in which participants were continued on their current treatment, blinded. As per the protocol, we have looked at rates of relapse (based on Hamilton Depression Scale scores) across both acute and continuation phases, and generated a safety profile for paroxetine and imipramine compared with placebo for up to six months.ANOVA testing (generalized linear model) using a model including effects of site, treatment and site x treatment interaction was applied. Otherwise we used only descriptive statistics.
RESULTS
Of patients entering the continuation phase, 15 of 49 for paroxetine (31%), 12 of 39 for imipramine (31%) and 12 of 31 for placebo (39%) completed as responders. Across the study, 25 patients on paroxetine relapsed (41% of those showing an initial response), 15 on imipramine (26%), and 10 on placebo (21%). In the continuation and taper phases combined there were 211 adverse events in the paroxetine group, 147 on imipramine and 100 on placebo. The taper phase had a higher proportion of severe adverse events per week of exposure than the acute phase, with the continuation phase having the fewest events.
CONCLUSIONS
The continuation phase did not offer support for longer-term efficacy of either paroxetine or imipramine. Relapse and adverse events on both active drugs open up the risks of a prescribing cascade. The previously largely unrecognised hazards of the taper phase have implications for prescribing practice and need further exploration.
Topics: Adolescent; Antidepressive Agents, Second-Generation; Child; Depressive Disorder, Major; Double-Blind Method; Female; Humans; Imipramine; Male; Paroxetine; Psychiatric Status Rating Scales; Recurrence
PubMed: 27662279
DOI: 10.3233/JRS-160728 -
Acta Pharmacologica Sinica Jun 2014Clinical evidence shows that co-administration of pravastatin and paroxetine deregulates glucose homeostasis in diabetic patients. The aim of this study was to verify...
AIM
Clinical evidence shows that co-administration of pravastatin and paroxetine deregulates glucose homeostasis in diabetic patients. The aim of this study was to verify this phenomenon in diabetic rats and to elucidate the underlying mechanisms.
METHODS
Diabetes mellitus was induced in male SD rats by a high-fat diet combined with a low-dose streptozotocin injection. The rats were orally administered paroxetine (10 mg/kg) and pravastatin (10 mg/d) or both the drugs daily for 28 d. The pharmacokinetics of paroxetine and pravastatin were examined on d 1 and d 28. Biochemical parameters including serum insulin, glucose and lipids were monitored during the treatments. An insulin-secreting cell line (INS-1) was used for measuring insulin secretion.
RESULTS
In diabetic rats, co-administration of paroxetine and pravastatin markedly increased the concentrations of both the drugs compared with administration of each drug alone. Furthermore, co-administration severely impaired glucose homeostasis in diabetic rats, as demonstrated by significantly increased serum glucose level, decreased serum and pancreatic insulin levels, and decreased pancreatic Insulin-2 mRNA and tryptophan hydroxylase-1 (Tph-1) mRNA levels. Treatment of INS-1 cells with paroxetine (5 and 10 μmol/L) significantly inhibited insulin secretion, decreased the intracellular insulin, 5-HT, Insulin-2 mRNA and Tph-1 mRNA levels. Treatment of the cells with pravastatin (10 μmol/L) significantly stimulated insulin secretion, which was weakened by co-treatment with paroxetine.
CONCLUSION
Paroxetine inhibits insulin secretion at least via decreasing intracellular 5-HT and insulin biosynthesis. The deregulation of glucose homeostasis by co-administration of paroxetine and pravastatin in diabetic rats can be attributed to enhanced paroxetine exposure.
Topics: Animals; Anticholesteremic Agents; Antidepressive Agents, Second-Generation; Blood Glucose; Cell Line; Depression; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Drug Interactions; Hypercholesterolemia; Insulin; Male; Paroxetine; Pravastatin; Rats; Rats, Sprague-Dawley; Serotonin
PubMed: 24902787
DOI: 10.1038/aps.2014.24 -
Psychiatria Danubina Sep 2015We aimed to evaluate serum ghrelin (GHR) levels and lipid profile in panic disorder (PD), with and without agoraphobia, and to compare these parameters before and after...
BACKGROUND
We aimed to evaluate serum ghrelin (GHR) levels and lipid profile in panic disorder (PD), with and without agoraphobia, and to compare these parameters before and after treatment.
SUBJECTS AND METHODS
The GHR and lipid profiles were measured in blood samples taken from 31 PD patients with agoraphobia, 22 PD patients without agoraphobia, and 53 control group subjects. 23 of the 53 patients who were prescribed 20 to 40 mg/day paroxetine had continued treatment. The 23 patients who had continued treatment were measured again at the end of twelve weeks.
RESULTS
The GHR and triglyceride (TRG), total cholesterol (Total-C), low-density lipoproteins (LDL-C), and very low-density lipoproteins (VLDL-C) levels were higher in the PD with agoraphobia group than the PD without agoraphobia and control groups. The 23 patients that had continued their treatment were re-evaluated, and the serum GHR, Total-C levels, and BMI after treatment were significantly decreased, compared to the values before treatment.
CONCLUSIONS
There may be a pathophysiological relationship between the GHR and lipid profiles that interact with each other in PD. In fact, this relationship was more marked in PD with agoraphobia than in PD without agoraphobia.
Topics: Agoraphobia; Ghrelin; Humans; Lipids; Panic Disorder; Paroxetine
PubMed: 26400133
DOI: No ID Found -
Psychopharmacology Bulletin Feb 2019The impact of menopause is a consequence of social, physical and mental changes; hormonal changes play an important role in inducing an increased risk of developing...
BACKGROUND
The impact of menopause is a consequence of social, physical and mental changes; hormonal changes play an important role in inducing an increased risk of developing depressive symptoms. It is essential to treat mood and vasomotor symptoms and to prevent their onset to promote an improvement in the quality of life, both in terms of clinical and psychological conditions.
OBJECTIVE
This observational study aims to compare paroxetine and vortioxetine in a sample of patients affected by postmenopausal depression attending the Anxiety and Depression Clinic in terms of: efficacy in determining clinical remission (HDRS ≤ 7) and tolerability; improvement of autonomic and cognitive symptoms.
METHODS
39 female outpatients with a diagnosis of Postmenopausal Depression (according to DSM-5 criteria) were evaluated as the routine clinical practice through the following scales: Hamilton Depression Rating Scale (HDRS); Menopause Rating Scale (MRS); Montreal Cognitive Assessment (MoCA); Antidepressant Side-Effect Checklist (ASEC); data from/of baseline, after 8 weeks and 12 weeks were recorded.
RESULTS
Both antidepressants resulted to be effective in clinical remission (HDRS ≤ 7) without statistical differences between the two groups (p = 0.3), although paroxetine showed a faster remission than vortioxetine (p = 0.01). Autonomic symptoms showed a higher improvement in the vortioxetine group (p = 0.002). Paroxetine group referred insomnia and sexual problems while patients taking vortioxetine referred diarrhoea and palpitations. Data show a superiority of cognitive performance in the Paroxetine group (p = 0.005), contrary to what stated in literature.
CONCLUSIONS
Data are related to a small sample retrospectively assessed trough a 6-month observation period. Thus, the preliminary results need further research to be confirmed.
Topics: Antidepressive Agents; Depression; Double-Blind Method; Female; Humans; Middle Aged; Paroxetine; Postmenopause; Psychiatric Status Rating Scales; Retrospective Studies; Vortioxetine
PubMed: 30858637
DOI: No ID Found -
Scientific Reports Jan 2018Parasitic helminths infect over 1 billion people worldwide, while current treatments rely on a limited arsenal of drugs. To expedite drug discovery, we screened a...
Parasitic helminths infect over 1 billion people worldwide, while current treatments rely on a limited arsenal of drugs. To expedite drug discovery, we screened a small-molecule library of compounds with histories of use in human clinical trials for anthelmintic activity against the soil nematode Caenorhabditis elegans. From this screen, we found that the neuromodulatory drugs sertraline, paroxetine, and chlorpromazine kill C. elegans at multiple life stages including embryos, developing larvae and gravid adults. These drugs act rapidly to inhibit C. elegans feeding within minutes of exposure. Sertraline, paroxetine, and chlorpromazine also decrease motility of adult Trichuris muris whipworms, prevent hatching and development of Ancylostoma caninum hookworms and kill Schistosoma mansoni flatworms, three widely divergent parasitic helminth species. C. elegans mutants with resistance to known anthelmintic drugs such as ivermectin are equally or more susceptible to these three drugs, suggesting that they may act on novel targets to kill worms. Sertraline, paroxetine, and chlorpromazine have long histories of use clinically as antidepressant or antipsychotic medicines. They may represent new classes of anthelmintic drug that could be used in combination with existing front-line drugs to boost effectiveness of anti-parasite treatment as well as offset the development of parasite drug resistance.
Topics: Ancylostoma; Animals; Anthelmintics; Caenorhabditis elegans; Chlorpromazine; Drug Discovery; Drug Repositioning; Drug Resistance; Paroxetine; Schistosoma mansoni; Sertraline
PubMed: 29343694
DOI: 10.1038/s41598-017-18457-w