Paxil scientific update |
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Addiction. 2005 Mar;100 Suppl 1:12-22.
Ciraulo DA, Sarid-Segal O, Knapp CM, Ciraulo AM, Locastro J, Bloch DA, Montgomery MA, Leiderman DB, Elkashef A.
Division of Psychiatry, Boston University School of Medicine and VA Boston Healthcare System Medication Development Research Unit (MDRU), Boston, MA, USA.
Efficacy screening trials of paroxetine, pentoxifylline, riluzole, pramipexole and venlafaxine in cocaine dependence.
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.
Breast Cancer Res Treat. 2005 Feb;89(3):243-9.
Roscoe JA, Morrow GR, Hickok JT, Mustian KM, Griggs JJ, Matteson SE, Bushunow P, Qazi R, Smith B.
University of Rochester Cancer Center, 601 Elmwood Avenue, Box 704, Rochester, New York, 14642, USA,
Effect of paroxetine hydrochloride (Paxil((R))) on fatigue and depression in breast cancer patients receiving chemotherapy.
Background. Fatigue can significantly interfere with a cancer patient's ability to fulfill daily responsibilities and enjoy life. It commonly co-exists with depression in patients undergoing chemotherapy, suggesting that administration of an antidepressant that alleviates symptoms of depression could also reduce fatigue.Methods. We report on a double-blind clinical trial of 94 female breast cancer patients receiving at least four cycles of chemotherapy randomly assigned to receive either 20 mg of the selective serotonin re-uptake inhibitor (SSRI) paroxetine (Paxil(R), SmithKline Beecham Pharmaceuticals) or an identical-appearing placebo. Patients began their study medication seven days following their first on-study treatment and continued until seven days following their fourth on-study treatment. Seven days after each treatment, participants completed questionnaires measuring fatigue (Multidimensional Assessment of Fatigue, Profile of Mood States-Fatigue/Inertia subscale and Fatigue Symptom Checklist) and depression (Profile of Mood States-Depression subscale [POMS-DD] and Center for Epidemiologic Studies-Depression [CES-D]).Results. Repeated-measures ANOVAs, after controlling for baseline measures, showed that paroxetine was more effective than placebo in reducing depression during chemotherapy as measured by the CES-D (p=0.006) and the POMS-DD (p=0.07) but not in reducing fatigue (all measures, ps > 0.27).Conclusions. Although depression was significantly reduced in the 44 patients receiving paroxetine compared to the 50 patients receiving placebo, indicating that a biologically active dose was used, no significant differences between groups on any of the measures of fatigued were observed. Results suggest that modulation of serotonin may not be a primary mechanism of fatigue related to cancer treatment.
Rev Bras Psiquiatr. 2005 Mar;27(1):18-24. Epub 2005 Apr 18.
Schmitt R, Gazalle FK, Lima MS, Cunha A, Souza J, Kapczinski F.
University Hospital, Federal University, RS, Brazil.
The efficacy of antidepressants for generalized anxiety disorder: a systematic review and meta-analysis.
OBJECTIVE: To investigate the efficacy and acceptability of antidepressants in the treatment of generalized anxiety disorder. METHODS: All randomized controlled trials assessing the use of antidepressants in generalized anxiety disorder up to may 2002 were included. Non randomized trials and those that included patients with both generalized anxiety disorder and another Axis I co-morbidity were excluded. Relative risks, weighted mean difference and number needed to treat were estimated. People who died or dropped out were regarded as having had no improvement. RESULTS: Antidepressants (imipramine, venlafaxine and paroxetine) were found to be superior to placebo in treating generalized anxiety disorder. The calculated number needed to treat for antidepressants in generalized anxiety disorder was 5.15. Dropout rates did not differ between antidepressants and placebo. CONCLUSION: The available evidence suggests that antidepressants would probably be a reasonable treatment for generalized anxiety disorder patients in the clinical context.
J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Jun 5;820(1):33-9. Epub 2005 Apr 11.
Juan H, Zhiling Z, Huande L.
Clinical Pharmaceutical Research Institute, Second Xiangya Hospital, Central South University, Changsha 410011, PR China.
Simultaneous determination of fluoxetine, citalopram, paroxetine, venlafaxine in plasma by high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-MS/ESI).
Fluoxetine, citalopram, paroxetine and venlafaxine have been widely used in the treatment of depression. However, no study has been conducted to determine the four drugs simultaneously by high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-MS/ESI). OBJECTIVE:: To establish a new, rapid and sensitive HPLC-MS/ESI method for simultaneous determination and screening in human plasma of the four most commonly prescribed nontricyclic antidepressants: fluoxetine, citalopram, paroxetine and venlafaxine. METHODS:: The analytes in plasma were extracted by solid-phase-extraction column after samples had been alkalinized. The HPLC separation of the analytes was performed on a MACHEREY-NAGEL C(18) (250mmx4.6mm, 5mum, Germany) column, using water (formic acid 0.6 per thousand, ammonium acetate: 30mmol/l)-acetonitrile (35:65, v/v) as mobile phase, with a flow-rate of 0.85ml/min. The compounds were ionized in the electrospray ionization (ESI) ion source of the mass spectrometer and were detected in the selected ion recording (SIR) mode. RESULTS:: The calibration curves were linear in the 5.0-1000.0ng/ml range for all compounds, all of them with coefficients of determination above 0.9900. The average extraction recoveries for all the four analytes were above 73.2%. The methodology recoveries were higher than 95.0%. The limits of detection (LODs) were 0.5, 0.3, 0.3 and 0.1ng/ml for fluoxetine, citalopram, paroxetine and venlafaxine, respectively. The intra- and inter-day variation coefficients were less than 15.0%. CONCLUSION:: The method is accurate, sensitive and simple for routine therapeutic drug monitoring (TDM) as well as toxicologic screening, and for the study of the pharmacokinetics and metabolism of the four drugs.
Psychopharmacology (Berl). 2005 Apr 28
Chen Z, Tetzlaff J, Sripathirathan K, Carrasco GA, Shankaran M, Van De Kar LD, Muma NA, Battaglia G.
Department of Pharmacology and Center for Serotonin Disorders Research, Stritch School of Medicine, Loyola University of Chicago, 2160 South First Avenue, Maywood, IL, 60153, USA.
Paroxetine is effective in desensitizing 5-HT1A receptor function in adult offspring exposed prenatally to cocaine.
RATIONALE: Desensitization of postsynaptic 5-HT(1A) receptors may be responsible for the therapeutic effectiveness of serotonin selective uptake inhibitors (SSRIs). As prenatal cocaine exposure produces long-term deficits in 5-HT neurons in offspring, it may alter the ability of postsynaptic 5-HT(1A) receptors to be desensitized by chronic paroxetine. OBJECTIVES: The aim of the study is to determine (1) prenatal cocaine-induced changes in 5-HT(1A) receptor function and (2) the effectiveness of chronic treatment with paroxetine to produce 5-HT(1A) receptor desensitization in adult offspring exposed to cocaine in utero. METHODS: Pregnant rats received saline or (-)cocaine (15 mg/kg, s.c.) twice daily from gestational days 13 through 20. Adult male offspring from each of prenatal groups were treated with saline or paroxetine (10 mg/kg/day; i.p.) for 14 days. Eighteen hours post-treatment, rats were challenged with saline or the 5-HT(1A) receptor agonist (+)8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.04 or 0.2 mg/kg, s.c.). Plasma oxytocin, adrenocorticotropic hormone (ACTH), corticosterone, renin and prolactin were determined. RESULTS: Prenatal cocaine exposure did not alter 5-HT(1A) receptor-mediated neuroendocrine responses. Paroxetine treatment desensitized 5-HT(1A) receptor-mediated increases in oxytocin, ACTH and corticosterone to a comparable extent in all offspring and reduced the E(max) for ACTH only in prenatal cocaine-exposed offspring. Cortical [(3)H]-8-OH-DPAT- or [(3)H]-WAY100635-labeled 5-HT(1A) receptors were unaltered by prenatal cocaine or subsequent paroxetine treatment. CONCLUSIONS: Postsynaptic 5-HT(1A) receptor function is unaltered by prenatal cocaine exposure and paroxetine can effectively desensitize 5-HT(1A) receptor function in adult cocaine-exposed offspring. These data suggest that paroxetine may be clinically effective in treating mood disorders in adults exposed in utero to cocaine.
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Drug category:Antidepressants
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