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Journal of the American Academy of... Sep 1999Paroxetine is a selective serotonin reuptake inhibitor with demonstrated efficacy in treating obsessive-compulsive disorder (OCD) in adults. This study evaluates the... (Clinical Trial)
Clinical Trial
OBJECTIVE
Paroxetine is a selective serotonin reuptake inhibitor with demonstrated efficacy in treating obsessive-compulsive disorder (OCD) in adults. This study evaluates the safety and effectiveness of paroxetine in pediatric OCD patients.
METHOD
In a 12-week, open-label trial of paroxetine, 20 OCD outpatients, aged 8 to 17 years, were treated for OCD with daily doses ranging from 10 to 60 mg. Target symptoms were rated at regular intervals with the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), the Children's Global Assessment Scale, the Clinical Global Impression Scale, the Hamilton Anxiety Rating Scale, and the Yale Global Tic Severity Scale.
RESULTS
Paroxetine proved relatively safe in this brief trial with a small sample and appeared to be effective in patients with OCD; mean CY-BOCS scores decreased significantly (z = 3.49, p = .0005) from 30.6 +/- 3.5 to 21.6 +/- 6.8 on medication. The most common side effects (n > or = 2) were hyperactivity/behavioral activation, headache, insomnia, nausea, and anxiety. Paroxetine did not have to be discontinued in any of the patients because of side effects; the most serious side effects included hyperactivity/behavioral activation in 3 younger patients (< 10 years) necessitating dosage reduction but not discontinuation.
CONCLUSIONS
Preliminary evidence suggests that short-term treatment of pediatric OCD outpatients with paroxetine may be relatively safe and effective.
Topics: Adolescent; Child; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Obsessive-Compulsive Disorder; Paroxetine; Selective Serotonin Reuptake Inhibitors; Treatment Outcome
PubMed: 10504818
DOI: 10.1097/00004583-199909000-00024 -
Biological Trace Element Research Feb 2023It is known that serotonin reuptake inhibitors (SSRIs), which are widely used in mood disorders, affect the hypothalamic-pituitary-thyroid axis activity. In this study,...
It is known that serotonin reuptake inhibitors (SSRIs), which are widely used in mood disorders, affect the hypothalamic-pituitary-thyroid axis activity. In this study, we investigated the effect of paroxetine, an SSRI, on thyroid hormone levels in rats. We also examined the role of irisin, a newly discovered potential regulatory hormone for metabolism, on paroxetine-induced changes. A total of 64 Sprague-Dawley female and male rats were randomly divided into four subgroups for each gender and treated as follows: sham-operated control (vehicle), paroxetine (treated with 20 mg/kg paroxetine by oral gavage), irisin (100 ng/kg/day for 28 days with mini-osmotic pumps), and paroxetine + irisin group (n = 8). Serum fasting free triiodothyronine (fT3) and free thyroxine (fT4) levels were measured by automated chemiluminescence method. Serum thyroid-stimulating hormone (TSH) level was determined with enzyme-linked immunosorbent analysis (ELISA). Compared to the sham control group (p < 0.05), the significantly reduced fT4 and TSH serum levels in paroxetine-treated male animals were markedly increased by subcutaneous irisin perfusion. fT3 levels significantly increased in both irisin (4.35 ± 0.17 pq/mL) and paroxetine + irisin groups (4.51 ± 0.19 pq/mL) compared to sham control (3.60 ± 0.23 pq/mL) and paroxetine groups (3.57 ± 0.12 pq/mL) (p < 0.05). It was observed that serum fT3, fT4, and TSH levels decreased in female animals receiving paroxetine compared to the sham control group. Subcutaneous administration of irisin increased these hormone levels. However, these changes were not statistically significant. These results suggested that irisin may play a role in the mechanism underlying the beneficial effects of exercise in preventing SSRI-related side effects by increasing thyroid hormone levels, which were decreased by paroxetine.
Topics: Male; Female; Rats; Animals; Thyroid Gland; Fibronectins; Paroxetine; Thyroxine; Rats, Sprague-Dawley; Thyroid Hormones; Triiodothyronine; Thyrotropin
PubMed: 35322355
DOI: 10.1007/s12011-022-03204-8 -
The Journal of Clinical Psychiatry Oct 1996
Topics: Angioedema; Depressive Disorder; Edema; Female; Humans; Middle Aged; Paroxetine; Selective Serotonin Reuptake Inhibitors; Tongue Diseases
PubMed: 8909336
DOI: No ID Found -
Der Nervenarzt Aug 1997We report on a 22-year-old schizophrenic patient who attempted suicide and suffered an epidural hemorrhage. 16 days after the neurosurgical operation. After several...
We report on a 22-year-old schizophrenic patient who attempted suicide and suffered an epidural hemorrhage. 16 days after the neurosurgical operation. After several weeks of treatment with promethazine, 1 day after intake of paroxetin he partially lost consciousness and developed extrapyramidal symptoms and vegetative disorders. Hyper-Ck-aemia up to 680 U/l was observed. Malignant neuroleptic syndrome (MNS) was diagnosed, which led to withdrawal of paroxetin and promethazine. He was put on dantamacrine and amantadine until the symptoms resolved. To date there have been few reports on MNS under tricyclic antidepressants and selective serotonin inhibitors. The influence of the central serotonergic system on the pathophysiology of MNS is discussed.
Topics: Adult; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Depressive Disorder; Drug Therapy, Combination; Hematoma, Subdural; Humans; Male; Neuroleptic Malignant Syndrome; Neurologic Examination; Paroxetine; Postoperative Complications; Schizophrenia; Schizophrenic Psychology; Suicide, Attempted
PubMed: 9380213
DOI: 10.1007/s001150050178 -
Fabrication of solid lipid nanoparticles-based patches of paroxetine and their permeation behaviour.Artificial Cells, Nanomedicine, and... Dec 2023Paroxetine is not suitable for oral administration due to its extensive first-pass metabolism, thus resulting in less bioavailability. This study aimed to prepare novel...
Paroxetine is not suitable for oral administration due to its extensive first-pass metabolism, thus resulting in less bioavailability. This study aimed to prepare novel paroxetine-loaded solid lipid nanoparticles (SLNs) based sustained-release transdermal patches to overcome these problems by enhancing drug absorption and bioavailability. Nine formulations of paroxetine SLNs were prepared by the hot melt-homogenization method using different concentrations of glycerol monostearate (Kolliwax) and Tween 80. Then these prepared SLNs were incorporated in a matrix type transdermal patch having a matrix of ethyl cellulose and polyvinyl pyrrolidone in 3:2 with polyvinyl alcohol. The SLNs showed a particle size range of 113-230 nm and an entrapment efficiency of 85.14%. The SLNs showed sustained paroxetine release (77.86-95.63% release) up to 48 h. FTIR studies showed no interaction between drug and formulation components. Paroxetine is evenly distributed in an amorphous form in SLNs, as demonstrated by DSC as well as PXRD analysis. SLNs formulated patches showed higher drug permeation through the skin than drug-based transdermal patches., Draize patch test revealed no sign of erythema after applying paroxetine-loaded SLN patches (score 0) as observed with the marketed product. The developed SLNs based transdermal patches showed increased permeability and sustained release behaviour.
Topics: Paroxetine; Liposomes; Administration, Oral; Biological Availability
PubMed: 36855254
DOI: 10.1080/21691401.2023.2179631 -
JAMA Jun 2003Standard therapy for hot flashes has been hormone replacement with estradiol or progestational agents, but recent data suggest that antidepressants inhibiting serotonin... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
CONTEXT
Standard therapy for hot flashes has been hormone replacement with estradiol or progestational agents, but recent data suggest that antidepressants inhibiting serotonin reuptake may also be effective.
OBJECTIVE
To evaluate a selective serotonin reuptake inhibitor (paroxetine controlled release [CR]) in treating the vasomotor symptoms displayed by a general cross-section of menopausal women.
DESIGN AND SETTING
Randomized, double-blind, placebo-controlled, parallel group study conducted across 17 US sites, including urban, suburban, and rural clinics.
PATIENTS
A total of 165 menopausal women aged 18 years or older experiencing at least 2 to 3 daily hot flashes and must have discontinued any hormone replacement therapy for at least 6 weeks. Women were excluded if they had any signs of active cancer or were undergoing chemotherapy or radiation therapy.
INTERVENTION
After a 1-week placebo run-in phase, study participants were randomized to receive placebo or receive 12.5 mg/d or 25.0 mg/d of paroxetine CR (in a 1:1:1 ratio) for 6 weeks.
MAIN OUTCOME MEASURES
Mean change from baseline to week 6 in the daily hot flash composite score (frequency x severity).
RESULTS
Fifty-six participants were randomly assigned to receive placebo and 51 to receive 12.5 mg/d and 58 to receive 25.0 mg/d of paroxetine CR. The mean reductions in the hot flash frequency composite score from baseline to week 6 were statistically significantly greater for those receiving paroxetine CR than for those receiving placebo. By week 6, the mean daily hot flash frequency went from 7.1 to 3.8 (mean reduction, 3.3) for those in the 12.5-mg/d and from 6.4 to 3.2 (mean reduction, 3.2) for those in the 25-mg/d paroxetine CR groups and from 6.6 to 4.8 (mean reduction, 1.8) for those in the placebo group. Mean placebo-adjusted reduction in hot flash composite scores were -4.7 (95% confidence interval, - 8.1 to -1.3; P =.007) comparing 12.5-mg/d paroxetine CR with placebo; and -3.6 (95% confidence interval, -6.8 to -0.4; P =.03) comparing 25.0-mg/d paroxetine CR with placebo. This corresponded to median reductions of 62.2% for those in the 12.5-mg/d and 64.6% for those in the 25.0-mg/d paroxetine CR groups compared with 37.8% for those in the placebo group.
CONCLUSION
Paroxetine CR may be an effective and acceptable alternative to hormone replacement and other therapies in treating menopausal hot flash symptoms.
Topics: Adult; Aged; Delayed-Action Preparations; Double-Blind Method; Female; Health Status Indicators; Hot Flashes; Humans; Logistic Models; Menopause; Middle Aged; Paroxetine; Selective Serotonin Reuptake Inhibitors; Treatment Outcome
PubMed: 12783913
DOI: 10.1001/jama.289.21.2827 -
Organic & Biomolecular Chemistry May 2020The mechanism-based inactivation (MBI) of P450 by paroxetine was investigated by computational analysis. The drug-enzyme interactions were figured out through studying...
The mechanism-based inactivation (MBI) of P450 by paroxetine was investigated by computational analysis. The drug-enzyme interactions were figured out through studying energy profiles of three competing mechanisms. The potency of paroxetine as P450's inhibitor was estimated based on the availability of two active sites for the MBI in the paroxetine structure. The inactivation by the amino site of paroxetine mainly proceeds via the hydrogen atom transfer pathway because of the lower energy demand of its rate determining step. In addition, the low-spin state is the predominant route in the MBI at the methylenedioxo active site as a result of being rebound barrier-free mechanism. Our comparative investigation showed that inactivation at the secondary amine is thermodynamically more favorable because of the lower energy barrier of the dehydration mechanism of the hydroxylated paroxetine complex than its methylenedioxo counterpart. The results of docking analysis coincided with the outputs of DFT calculations since the docking pose with the lowest binding affinity is that for conformation with polar interaction between the amino group of paroxetine and the oxo moiety of P450's active site. Assessment of the molecular dynamics simulations trajectories revealed the favorable interaction of paroxetine with P450.
Topics: Amines; Catalysis; Catalytic Domain; Cytochrome P-450 Enzyme System; Dehydration; Enzyme Activation; Hydroxylation; Molecular Conformation; Molecular Dynamics Simulation; Paroxetine; Protein Binding; Thermodynamics
PubMed: 32301459
DOI: 10.1039/d0ob00529k -
Paroxetine in the treatment of panic disorder. A randomised, double-blind, placebo-controlled study.The British Journal of Psychiatry : the... Sep 1995This study compared the efficacy and tolerability of paroxetine with placebo in the treatment of panic disorder. (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
This study compared the efficacy and tolerability of paroxetine with placebo in the treatment of panic disorder.
METHOD
After three weeks of placebo, patients received 12 weeks of treatment with paroxetine (20, 40, or 60 mg) or placebo, and finally two weeks of placebo. Dosages were adjusted according to efficacy and tolerability. Standardised cognitive therapy was given to all patients. The primary measure of outcome was reduction in the number of panic attacks.
RESULTS
Analysis of the results showed statistically significant differences in favour of paroxetine between the two treatment groups in two out of the three primary measures of outcome, i.e. 50% reduction in total number of panic attacks and number of panic attacks reduced to one or zero over the study period. For the third measure of outcome, the mean change in the total number of attacks from baseline, there was a positive trend in favour of paroxetine. The results of the primary measures of outcome were strongly supported by the results of the secondary efficacy measures of outcome. In addition, paroxetine, at all doses, was very well tolerated.
CONCLUSION
Paroxetine plus cognitive therapy was significantly more effective than placebo plus cognitive therapy in the treatment of panic disorder.
Topics: Adolescent; Adult; Aged; Denmark; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Panic Disorder; Paroxetine; Selective Serotonin Reuptake Inhibitors; Treatment Outcome
PubMed: 7496647
DOI: 10.1192/bjp.167.3.374 -
Journal of the American Academy of... 1994
Topics: Adolescent; Autistic Disorder; Humans; Male; Paroxetine; Self-Injurious Behavior; Treatment Outcome
PubMed: 8083152
DOI: 10.1097/00004583-199407000-00022 -
The Medical Letter on Drugs and... Oct 2013
Topics: Drug Interactions; Female; Hot Flashes; Humans; Menopause; Paroxetine; Selective Serotonin Reuptake Inhibitors
PubMed: 24165707
DOI: No ID Found