paroxetine, Paxil
Differential effects of serotonin reuptake inhibitors on erectile responses, NO-production, and neuronal NO synthase expression in rat corpus cavernosum tissue.

Angulo J, Peiro C, Sanchez-Ferrer CF, Gabancho S, Cuevas P, Gupta S, Saenz de Tejada I.

Fundacion para la Investigacion y el Desarrollo en Andrologia, Department de Investigacion, Hospital Ramon y Cajal, Madrid, Spain.

Increased incidence of impotence is associated with some selective serotonin-reuptake-inhibitors (SSRIs), but the pathophysiological mechanism is unknown. Paroxetine and citalopram are extensively used SSRIs, but only paroxetine has been shown to inhibit nitric oxide synthase (NOS) activity. NO is a key mediator of penile erection. Thus, the aim of this study was to determine the effects of paroxetine and citalopram on erectile function and NO production, in a rat model. Application of cavernosal nerve electrical stimulation produced frequency-related intracavernosal pressure (ICP) increases, which were inhibited by the NOS inhibitor, N(G)-nitro-L-arginine (0.3 mg x kg(-1)). Acute or chronic (2 weeks) paroxetine-treatment (10 mg x kg(-1)) reduced ICP-responses, while citalopram did not. Paroxetine, but not citalopram, significantly reduced nitrite+nitrate plasma levels by 61.4% and inhibited penile neuronal NOS (nNOS) protein expression by 31.2% after chronic treatment. The results show that paroxetine inhibits erectile responses in rats. We propose that this effect is due to reduced NO production and nNOS expression.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11704638&dopt=Abstract paroxetine, Paxil, Paxil CR



paroxetine, Paxil
Long-term costs of treatment for depression: impact of drug selection and guideline adherence.

Crown WH, Treglia M, Meneades L, White A.

MEDSTAT Group, Inc., Cambridge, MA, USA.

OBJECTIVES: This paper examines three processes: SSRI antidepressant choice, adherence to treatment guidelines, and long-term health care expenditures associated with antidepressant treatment for patients with a diagnosis of depression. METHODS: Patient records were abstracted from a medical claims database covering employer-provided health care plans. Treatment episodes required a 6-month antidepressant-free prior period; initial treatment with sertraline, paroxetine or fluoxetine; and data on direct medical costs over the 24 months following the initial prescription. The multivariate model of drug selection, patient adherence to antidepressant use guidelines, and cost was subjected to specification testing to rule out the possibility that nonrandom initial antidepressant selection might lead to sample selection bias. Further tests indicated that the results were free of bias due to a possible correlation between antidepressant selection and use of the medication, or because of the endogeneity of use patterns in the process driving cost. However, there was evidence of unobserved variables correlated with both achieving guideline adherent use and expenditures, which might have led to sample selection bias. RESULTS: Subjects who met the study criteria included 796 initiating therapy with sertraline, 352 with paroxetine, and 882 with fluoxetine. Fluoxetine patients were significantly more likely than sertraline or paroxetine patients to achieve a use pattern that was consistent with guidelines for treating depressive disorder (p < .05). There were no statistically significant differences between the three treatment cohorts in total direct health care expenditures over the 2-year period (p < .05), and depression-related expenditures, other mental health expenditures, and non-mental health care expenditures did not show significant differences across the treatments (p < .05). Natural logged values of antidepressant drug expenditures were predicted to be highest for fluoxetine, followed by sertraline, then paroxetine (p < .01). Predicted log values of mental health expenditures were lower for sertraline relative to fluoxetine. CONCLUSIONS: Fluoxetine patients had the highest likelihood of using antidepressant medication according to treatment guidelines that were developed to assure quality care. This benefit was achieved without incurring greater total health care expenditures.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11705297&dopt=Abstract paroxetine, Paxil, Paxil CR



paroxetine, Paxil
Reduction in serotonin synthesis following acute and chronic treatments with paroxetine, a selective serotonin reuptake inhibitor, in rat brain: an autoradiographic study with alpha-[14C]methyl-L-tryptophan(2).

Yamane F, Okazawa H, Blier P, Diksic M.

Cone Laboratory for Neurosurgical Research, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University St., H3A 2B4, Montreal, Quebec, Canada.

Serotonin (5-HT) synthesis rates were calculated on the basis of the assumption that trapping of alpha-[14C]methyl-L-tryptophan (alpha-[14C]MTrp) is directly related to brain 5-HT synthesis. In the first series of experiments, an acute intraperitoneal injection of paroxetine (10 mg/kg) produced a significant reduction in 5-HT synthesis in brain structures containing serotonergic cell bodies (the dorsal, median, and pallidum raphe nuclei), as well as in most projection areas: the ventral tegmental area, median forebrain bundle, hippocampus CA3 region, and nigrostriatal structures (substantia nigra, lateral and medial caudate nuclei). The reductions in the projection areas were greater (between 25 and 53%) than in those areas containing serotonergic cell bodies (between 18 and 23%). In the cerebral cortex, 5-HT synthesis rates were not modified by acute paroxetine treatment. In a second series of experiments, rats were treated with paroxetine (10 mg/kg/day, s.c., delivered by osmotic minipumps) for 14 days. There was a marked decrease (39-69%) in 5-HT synthesis in every structure examined. In conclusion, the present data suggest that the effects of paroxetine on 5-HT synthesis in the cerebral cortex are different from its effects in the cell body area of the brainstem.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11728384&dopt=Abstract paroxetine, Paxil, Paxil CR



paroxetine, Paxil
Effects of acute treatment with paroxetine, citalopram and venlafaxine in vivo on noradrenaline and serotonin outflow: a microdialysis study in Swiss mice.

David DJ, Bourin M, Jego G, Przybylski C, Jolliet P, Gardier AM.

EA 3544, Lab. Neuropharmacologie, Faculte de Pharmacie, Universite Paris-Sud, Chatenay-Malabry 92296, France.

1. This study investigated whether a single administration of a range of doses (1, 4 and 8 mg kg-1, i.p.) of paroxetine, citalopram or venlafaxine may simultaneously increase extracellular levels of 5-HT ([5-HT]ext) and noradrenaline ([NA]ext) by using in vivo microdialysis in the frontal cortex (FCx) of awake, freely moving Swiss mice. 2. In vivo, paroxetine induced similar increases in cortical [5-HT]ext at the three doses tested, and induced a statistically significant increase in cortical [NA]ext at 4 and 8 mg x kg-1. Citalopram increased neither [5-HT]ext nor [NA]ext at the lowest dose, but increased both neurotransmitter levels at 4 and 8 mg x kg-1. At these doses, citalopram induced greater increases in cortical [5-HT]ext than in [NA]ext. Venlafaxine increased [5-HT]ext and [NA]ext to about 400 and 140% of the respective basal values at 8 mg kg-1. 3. Citalopram and paroxetine have the highest potency to increase cortical [5-HT]ext and [NA]ext, respectively. In addition, the rank of order of efficacy of these antidepressant drugs to increase [5-HT]ext in vivo in the FCx of mice was as follows: venlafaxine>citalopram>paroxetine, while the efficacy to increase cortical [NA]ext in mice of paroxetine and citalopram is similar, and greater than that of venlafaxine. 4. In conclusion, extracellular levels of cortical [NA]ext increase with the highest doses of the very selective SSRI citalopram, as well as with the very potent SSRI paroxetine. Surprisingly, the SNRI venlafaxine increased cortical [5-HT]ext to a greater extent rather than [NA]ext in the range of doses studied in mice.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14530210&dopt=Abstract paroxetine, Paxil, Paxil CR



paroxetine, Paxil
Induction of mania in depression by paroxetine.

Morishita S, Arita S.

Department of Psychiatry, Kawasaki Medical School, Kurashiki, Okayama, Japan. morisita med.kawasaki-m.ac.jp

INTRODUCTION: An investigation of the proportion of patients who have experienced mania with antidepressant treatment and their characteristics would seem to be of clinical use. AIMS: The purpose of this clinical study was to examine the predictors of induction of mania in depression patients as a result of paroxetine treatment. METHOD: A retrospective cohort analysis was carried out among depression patients treated in the Department of Psychiatry, Kawasaki Medical School Hospital, Kurashiki, Japan, in 2000 and 2001. Some 79 patients were identified who were receiving paroxetine to treat depression. A variety of clinical factors including gender, the type of depression, frequency of episodes, family history, age and daily dose were examined as possible predictors of induction of mania by paroxetine. RESULTS: Seven (8.86%) of the 79 paroxetine-treated patients developed mania. A Cox proportional hazards analysis showed the type of depression and the history of family psychiatric illness to be independent predictive factors of the induction of mania by paroxetine treatment. CONCLUSIONS: The rate of mania induction of paroxetine is not substantially different from that found for conventional antidepressants. The type of depression and the history of family psychiatric illness may be considered as predictors of mania induction in depression patients taking paroxetine treatment. Copyright 2003 John Wiley & Sons, Ltd.

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paroxetine, Paxil
Sertralilne, paroxetine and venlafaxine in refugee post traumatic stress disorder with depression symptoms.

Smajkic A, Weine S, Duric-Bijedic Z, Boskailo E, Lewis J, Pavkovic I.

Project on Genocide, Psychiatry and Witnessing, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA.

The authors describe the use of three new antidepressants: Sertralilne, Paroxetine and Venlafaxine in treating Posttraumatic Stress Disorder and symptoms of Depression in adult Bosnian refugees victims of ethnic cleansing. 32 Bosnian refugees with PTSD and symptoms of Depression presenting for treatment of the mental health consequences of surviving ethnic cleansing, participated in a case series study. All subjects completed open trials of Sertraline (15), Paroxetine (12) or Venlafaxine (5), with standard clinical doses. Overall, Sertraline and Paroxetine yielded statistically significant improvement at 6 weeks in the total PTSD symptom severity, in each symptom cluster, in Beck Depression Inventory and in Global Assessment of Functioning. Venlafaxine produced statistically significant improvement at 6 weeks in the total PTSD symptom severity, in each symptom cluster and in Global Assessment of Functioning but did not yield significant improvement in symptoms of depression and had a high rate of side effects.

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paroxetine, Paxil
Is dopamine implicated in the antidepressant-like effects of selective serotonin reuptake inhibitors in the mouse forced swimming test?

Renard CE, Fiocco AJ, Clenet F, Hascoet M, Bourin M.

EA Neurobiologie de l'anxiete et de la depression, Faculte de Medecine, BP 53508, 1 rue Gaston Veil, 44035 Nantes Cedex 01, France.

RATIONALE: Microdialysis, binding and behavioural studies have shown that the dopaminergic system plays a role in antidepressant treatment. OBJECTIVES: The present study determined whether the antidepressant-like effects of selective serotonin reuptake inhibitors measured in the mouse forced swimming test are mediated via dopamine receptors. METHODS: Male Swiss mice were randomly assigned to groups of 24 animals and injected IP with citalopram, fluoxetine, fluvoxamine, sertraline, or paroxetine alone or in combination with the dopamine D(1)agonist SKF 38393, the D(1) antagonist SCH 23390, the D(2) agonist bromocriptine, the D(2) antagonist sulpiride, the D(3) agonist PD 128 907, or the D(3) antagonist nafadotride. RESULTS: The anti-immobility effects of paroxetine, fluvoxamine and citalopram were increased by co-administration of SKF 38393 (0.5 and 2 mg/kg), SCH 23390 (0.06 mg/kg), bromocriptine (0.5 and 2 mg/kg) or PD 128 907 (1 and 2 mg/kg), and were attenuated by SCH 23390 (0.5 mg/kg). The anti-immobility effects of paroxetine and fluvoxamine were also increased with sulpiride (0.5 and 2 mg/kg). The anti-immobility effect of fluoxetine was increased by SKF 38393 (2 mg/kg) and PD 128 907(1 and 2 mg/kg) co-administration. The anti-immobility effect of sertraline (16 mg/kg) was increased by SKF 38393 (0.5 mg/kg), bromocriptine (2 mg/kg) and PD 128 907 (2 mg/kg) and the effect of sertraline (2 mg/kg) was increased by bromocriptine (2 mg/kg). The anti-immobility effect of paroxetine (4 mg/kg) was increased by nafadotride (2 mg/kg). CONCLUSIONS: These data indicate that the antidepressant activity of various SSRIs involves different dopamine receptor subtypes and that the serotoninergic and dopaminergic systems interact with each other.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11797068&dopt=Abstract paroxetine, Paxil, Paxil CR