Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new paroxetine research articles will be listed here shortly after becoming available to us.
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Medical research on paroxetine
Neurochem Res. 2008 Jun 18;
Cupello A, Albano C, Gatta E, Scarrone S, Villa E, Zona G
The binding of [(3)H]-paroxetine to membrane serotonin transporter (SERT) has been studied in membranes from different sources and subcellular fractions. From rat were membranes from venous blood platelets, brain total cortex, brain microsomes, brain crude and purified synaptosomes. Membranes were obtained from venous blood platelets from human volunteers and from brain cortex tissue from neurosurgery (cerebral lobectomies following craniocerebral injuries). The main finding was that the K (D) of paroxetine binding to the SERT was the same for platelet and nerve ending (synaptosomal) membranes. That parameter was significantly lower in membranes from brain microsomes and cortex total tissue. No species related difference was found, where comparison was possible, between human and rat tissue. The equality of K (D) of paroxetine binding to blood platelet membranes and to membranes from nerve endings appears to encourage the use of such membranes as a model for brain SERT. Binding at two different temperatures for several of the fractions suggests that paroxetine-SERT interaction is entropy-driven.
Management Strategies for Premenstrual Syndrome/Premenstrual Dysphoric Disorder (July/August) (CE).
Ann Pharmacother. 2008 Jun 17;
Jarvis CI, Lynch AM, Morin AK
OBJECTIVE: To evaluate the current nonpharmacologic and pharmacologic treatment options for symptoms of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). DATA SOURCES: Literature was obtained through searches of MEDLINE Ovid (1950-March week 3, 2008) and EMBASE Drugs and Pharmacology (all years), as well as a bibliographic review of articles identified by the searches. Key terms included premenstrual syndrome, premenstrual dysphoric disorder, PMS, PMDD, and treatment. STUDY SELECTION AND DATA EXTRACTION: All pertinent clinical trials, retrospective studies, and case reports in human subjects published in the English language were identified and evaluated for the safety and efficacy of pharmacologic and nonpharmacologic treatments of PMS/PMDD. Data from these studies and information from review articles were included in this review. DATA SYNTHESIS: Selective serotonin-reuptake inhibitors (SSRIs) have been proven safe and effective for the treatment of PMDD and are recommended as first-line agents when pharmacotherapy is warranted. Currently fluoxetine, controlled-release paroxetine, and sertraline are the only Food and Drug Administration-approved agents for this indication. Suppression of ovulation using hormonal therapies is an alternative approach to treating PMDD when SSRIs or second-line psychotropic agents are ineffective; however, adverse effects limit their use. Anxiolytics, spironolactone, and nonsteroidal antiinflammatory drugs can be used as supportive care to relieve symptoms. Despite lack of specific evidence, lifestyle modifications and exercise are first-line recommendations for all women with PMS/PMDD and may be all that is needed to treat mild-to-moderate symptoms. Herbal and vitamin supplementation and complementary and alternative medicine have been evaluated for use in PMS/PMDD and have produced unclear or conflicting results. More controlled clinical trials are needed to determine their safety and efficacy and potential for drug interactions. CONCLUSIONS: Healthcare providers need to be aware of the symptoms of PMS and PMDD and the treatment options available. Treatment selection should be based on individual patient symptoms, concomitant medical history, and need for contraception.
Anal Chem. 2008 Jun 14;
Lajeunesse A, Gagnon C, Sauvé S
A novel analytical method has been developed for the determination of six basic antidepressants (venlafaxine, sertraline, paroxetine, citalopram, amitriptyline, and fluoxetine) and four of their metabolites ( O-desmethylvenlafaxine, desmethylsertraline, nortriptyline, and norfluoxetine) in raw sewage and roughly primary-treated wastewater. For analytical development purposes, two ion exchange solid-phase extraction cartridges were compared. Extracts were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with positive-mode electrospray (+ESI) and selected reaction monitoring transitions. The choice of a basic mobile phase significantly improved the instrumental sensitivity (by up to 14-fold for norfluoxetine) relative to common +ESI acidic mobile phases. In addition to the remarkable gain in sensitivity, negligible matrix effects were also observed in the raw sewage samples. Analyte recoveries ranged from 80 to 103% and effluent detection limits from 0.048 to 0.10 ng/L. Samples collected at the Montreal Wastewater Treatment Plant showed the unequivocal presence of all the target compounds at concentrations of 2-346 ng/L. The target antidepressants were also detected in samples taken from the effluent receiving waters (i.e., the St. Lawrence River) but at lower concentrations (0.41-69 ng/L). The highly sensitive proposed method constitutes one of the best means for monitoring the environmental occurrence of tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and some of their metabolites.
Br J Pharmacol. 2008 Jun 16;
Kreilgaard M, Smith DG, Brennum LT, Sánchez C
Background and purpose:Bridging the gap between preclinical research and clinical trials is vital for drug development. Predicting clinically relevant steady-state drug concentrations (Css) in serum from preclinical animal models may facilitate this transition. Here we used a pharmacokinetic/pharmacodynamic (PK/PD) modelling approach to evaluate the predictive validity of 5-hydroxytryptamine (5-HT; serotonin) transporter (SERT) occupancy and 5-hydroxytryptophan (5-HTP)-potentiated behavioral syndrome induced by 5-HT reuptake inhibitor (SRI) antidepressants in mice.Experimental approach:Serum and whole brain drug concentrations, cortical SERT occupancy and 5-HTP-potentiated behavioral syndrome were measured over 6 h after a single subcutaneous injection of escitalopram, paroxetine or sertraline. [(3)H]2-(2-dimethylaminomethylphenylsulphanyl)-5-methyl-phenylamine ([(3)H]MADAM) was used to assess SERT occupancy. For PK/PD modelling, an effect-compartment model was applied to collapse the hysteresis and predict the steady-state relationship between drug exposure and PD response.Key results:The predicted Css for escitalopram, paroxetine and sertraline at 80% SERT occupancy in mice are 18 ng mL(-1), 18 ng mL(-1) and 24 ng mL(-1), respectively, with corresponding responses in the 5-HTP behavioral model being between 20-40% of the maximum.Conclusions and implications:Therapeutically effective SERT occupancy for SRIs in depressed patients is approximately 80%, and the corresponding plasma Css are 6-21 ng mL(-1), 21-95 ng mL(-1) and 20-48 ng mL(-1) for escitalopram, paroxetine and sertraline, respectively. Thus, PK/PD modelling using SERT occupancy and 5-HTP-potentiated behavioral syndrome as response markers in mice may be a useful tool to predict clinically relevant plasma Css values.British Journal of Pharmacology advance online publication, 16 June 2008; doi:10.1038/bjp.2008.243.
MDR1 gene polymorphism: therapeutic response to paroxetine among patients with major depression.
Prog Neuropsychopharmacol Biol Psychiatry. 2008 Apr 3;
Mihaljevic Peles A, Bozina N, Sagud M, Rojnic Kuzman M, Lovric M
The multidrug resistance transporter, P-glycoprotein (P-gp), encoded by polymorphic MDR1 (ABCB1) gene, is involved in efflux transport of several antidepressants and acts as a barrier to different exogenous noxa in the blood-brain barrier. MDR1 gene belongs to the best understood mediators of drug resistance. Different polymorphisms in MDR1 have been found to be connected with P-gp expression and function. The aims of the study were to investigate the potential influence of MDR1 polymorphisms, exon 26 C3435T and exon 21 G2677T/A, on treatment response to paroxetine (20 mg/day) in patients with major depression. To assess and evaluate therapeutic response to paroxetine, all patients were rated weekly using the HAMD-17 scale. Responders were defined as subjects with a decrease in HAMD scale by >/=50% at week 6 of treatment. The study population included 127 patients with major depression (diagnosed by Structured Clinical Interview for DSM-IV disorders). Our results indicated that MDR1 variants G2677T and C3435T are not associated with therapeutic response to paroxetine in patients with major depressive disorder. The associations between paroxetine and P-glycoprotein still need to be clarified.
[Painful palate and xerostomia after using paroxetine]
Ned Tijdschr Tandheelkd. 2008 May; 115(5): 271-3
Bots CP, van Nieuw Amerongen A, Brand HS
This article presents the case of a 58-year-old woman with diabetes mellitus type 2 who, for one and a half years, had been using paroxetine, a specific serotonin re-uptake inhibitor, to reduce a depression. She complained of xerostomia, dry eyes, and pain of the palate. In the middle of the hard palate a circumscribed, erythemous mucosal lesion was observed. This painful spot had developed, according to the woman, virtually immediately after she had begun to use the medication with paroxetine. The salivary flow rates were reduced when compared with well-known reference values. The diagnosis was hyposalivation. After substitution of paroxetine by lithium, the painful palate and xerogenic complaints disappeared. This case report suggests a causal relationship between, on the one hand, paroxetine and other serotonin re-uptake inhibitors and, on the other, atypical oral pain as well as hyposalivation.
Toxic epidermal necrolysis after paroxetine treatment.
N Z Med J. 2008; 121(1274): 86-9
Ahmed R, Eagleton C
Toxic epidermal necrolysis (TEN) is a rare complication of paroxetine treatment and can be life-threatening. We report a case of paroxetine-induced TEN in an 80-year-old Maori female. She was started on paroxetine 10 mg once daily 6 days prior to hospital admission. The patient then developed extensive vesiculobullous skin eruptions. She was treated with intravenous fluid, corticosteroid, and local dressings and concurrently her paroxetine was stopped. A series of laboratory investigations were carried out and a final diagnosis of TEN was made from skin biopsy. The patient was discharged home after 2 weeks of treatment. Her skin lesions improved gradually.
Practical clinical guidelines for assessing and managing menopausal symptoms after breast cancer.
Ann Oncol. 2008 Jun 16;
Hickey M, Saunders C, Partridge A, Santoro N, Joffe H, Stearns V
BACKGROUND: The purpose of this study was to provide practical, evidence-based guidelines for evaluating and treating common menopausal symptoms following breast cancer. METHODS: Literature review of the causes, assessment and management of menopausal symptoms in breast cancer patients. RESULTS: A number of nonhormonal treatments are effective in treating hot flashes. Whether pharmacological treatment is given will depend on the severity of symptoms and on patient wishes. For severe and frequent hot flashes, the best data support the use of venlafaxine, paroxetine and gabapentin in women with breast cancer. Side-effects are relatively common with all these agents. For vaginal dryness, topical estrogen treatment is the most effective but the safety of estrogens following breast cancer is not established. There are limited data on effective treatments for sexual dysfunction during menopause. CONCLUSION: Menopausal symptoms after breast cancer should be evaluated and managed as warranted using a systematic approach and may benefit from multidisciplinary input.
J Clin Psychiatry. 2008 May 27; e1-e8
Steiner M, Ravindran AV, Lemelledo JM, Carter D, Huang JO, Anonychuk AM, Simpson SD
OBJECTIVE: To evaluate the efficacy and safety of intermittent, luteal phase-only administration of paroxetine (10 mg and 20 mg) in the treatment of premen-strual dysphoric disorder (PMDD). METHOD: In this multicenter trial, female outpatients (aged 18-45 years) from 4 Canadian health centers meeting DSM-IV criteria for PMDD were asked to perform daily ratings of their premenstrual symptoms for 2 consecutive menstrual cycles. Those displaying the symptoms of irritability and/or depressed mood in the luteal phases but not in the follicular phases of their menstrual cycles were randomly assigned to intermittent, luteal phase-only treatment with paroxetine 10 mg or 20 mg or placebo for 4 additional cycles. The primary efficacy endpoint was the percent change from baseline at study endpoint on the visual analog scale irritability score. Treatment differences were tested using analysis of covariance ad hoc. Estimated treatment mean differences and their associated 95% confidence intervals were also calculated. Data were collected from May 1999 to November 2002. RESULTS: Ninety-nine patients were included in the intention-to-treat population. When compared with placebo, patients treated with paroxetine 20 mg attained a significant reduction in irritability (difference in median percent change: -23.9, 95% CI = -51.3 to -6.2, p = .014; difference in mean absolute change: -18.6, 95% CI = -32.5 to -4.6, p = .007). A statistically significant difference was not observed when the patients treated with the lower dose of paroxetine (10 mg) were compared with placebo. Treatment was well tolerated with no unexpected side effects. CONCLUSION: Intermittent administration of paroxetine 20 mg significantly reduced irritability symptoms in patients with PMDD. These results are consistent with previous studies suggesting that PMDD may be treated effectively by luteal phase-only administration of a selective serotonin reuptake inhibitor. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00620581.
J Psychopharmacol. 2008 May 30;
Tint A, Haddad PM, Anderson IM
Abstract Twenty-eight patients treated with selective serotonin reuptake inhibitors/venlafaxine were randomised to a 3-day (short) or 14-day (longer) antidepressant taper and openly assessed after a 5- to 7-day drug-free washout and again after 7-day treatment with a new antidepressant of the treating clinician's choice. A 'discontinuation syndrome' (>/=3 new symptoms on the Discontinuation Emergent Signs and Symptoms checklist) occurred in 46% of patients with a similar frequency in those with short (7/15) versus longer (6/13) taper. Patients initially on short-half life antidepressants had significantly greater increases in discontinuation and depressive symptoms than those stopping fluoxetine. Four patients, all on paroxetine, developed emergent suicidal ideation after taper. These results support the importance of half-life in determining discontinuation symptoms and suggest that there is little advantage to a 2-week taper over a 3-day taper when switching antidepressants. Antidepressant discontinuation in depressed patients can be associated with worsening depression and increased suicidality.