Paroxetine

Selective serotonin reuptake inhibitors may be less efficacious than tricyclic antidepressants in the treatment of severe depression in older patients. The authors compared the 12-week clinical outcome of older depressed patients treated with nortriptyline or paroxetine in a double-blind randomized comparison in 116 psychiatric inpatients and outpatients (mean age: 72+/-8 years) who presented with a major depressive episode or melancholic depression. Discontinuation and response rates were compared in patients who began or who completed treatment. The discontinuation rate due to side effects was significantly higher with nortriptyline than with paroxetine (33% vs. 16%). There were no significant differences between the rates of response in the Intent-to-Treat analysis (nortriptyline: 57% vs. paroxetine: 55% ), or the Completer analysis (nortriptyline: 78% vs. paroxetine: 84%). Although paroxetine appears to be better tolerated than nortriptyline, the efficacy of these two drugs does...

Anxiety disorders have a lifetime prevalence which exceeds 15% in the general population and particularly Generalized Anxiety Disorder (GAD) (lifetime prevalence of 5.1%) accounts for second most frequent psychiatric disorder in the primary care setting. Methodology: The present 12 weeks' study was a prospective, randomized clinical study in 60 subjects. Aim of the study is to compare the efficacy between two drugs using HAM-A, HADS, CGI scales. Results: In Paroxetine group there was only very little clinical difference in HAM-A and HADS reduction than Ashwagandha group however the difference did not reach statistical significance. Similarly, reduction in CGI scores did not reach statistical significance. Conclusion: Ashwagandha (Withania Somnifera) when compared was as much efficacious as Paroxetine but had better side effect profile hence could be given in patients not tolerating the side effect of Selective serotonin reuptake inhibitors (SSRIs) or can be given in mild to moderate anxiety as an initial drug.

In this case study from litigation, we show how ghostwriting of clinical trial results can contribute to the manipulation of data to favor the study medication. Study 329 for paroxetine pediatric use was negative for efficacy and positive for harm. Yet the ghostwritten publication from this study concluded that paroxetine provided evidence of efficacy and safety and continues to be influential. Despite the role of named authors in revisions of the manuscript, the sponsor company remained in control of the message.

Anxiety disorders have a lifetime prevalence which exceeds 15% in the general population and particularly Generalized Anxiety Disorder (GAD) (lifetime prevalence of 5.1%) accounts for second most frequent psychiatric disorder in the primary care setting. Methodology: The present 12 weeks' study was a prospective, randomized clinical study in 60 subjects. Aim of the study is to compare the efficacy between two drugs using HAM-A, HADS, CGI scales. Results: In Paroxetine group there was only very little clinical difference in HAM-A and HADS reduction than Ashwagandha group however the difference did not reach statistical significance. Similarly, reduction in CGI scores did not reach statistical significance. Conclusion: Ashwagandha (Withania Somnifera) when compared was as much efficacious as Paroxetine but had better side effect profile hence could be given in patients not tolerating the side effect of Selective serotonin reuptake inhibitors (SSRIs) or can be given in mild to moderate anxiety as an initial drug.

Neuroimaging studies of individuals with posttraumatic stress disorder (PTSD) have revealed altered patterns of activity in medial prefrontal brain regions, including the anterior cingulate cortex (ACC), an area implicated in affect regulation. Selective serotonin reuptake inhibitors (SSRIs) have been shown to effectively treat PTSD symptoms, but there remains a lack of functional neuroimaging research examining the effects of psychopharmacological treatment on brain function in PTSD. The purpose of this pilot study was to assess the effects of the SSRI paroxetine on neural responses to traumatic memories in a small sample of patients with PTSD, as measured with PET imaging; we hypothesized that paroxetine treatment would be associated with increased regional cerebral blood flow (rCBF) in the medial prefrontal cortex. Thirteen participants with PTSD were given controlled-release paroxetine (paroxetine CR) or placebo in a randomized, double-blind fashion for 12 weeks. Participants underwent brain imaging using positron emission tomography (PET) before and at the end of treatment in conjunction with exposure to neutral scripts and personalized trauma scripts. Participants treated with paroxetine CR and placebo both exhibited significantly increased rCBF in the ACC during trauma versus neutral script presentations; however, we noted an increase in function in the orbitofrontal cortex (OFC) in paroxetine-treated (but not placebo-treated) participants. Participants in both groups showed decreases in overall PTSD symptomatology following treatment; paroxetine-treated participants showed a slightly greater percentage decrease in symptoms. These preliminary findings indicate that increased ACC function represents a nonspecific response to treatment, whereas increased OFC function is specifically associated with paroxetine treatment in PTSD. These pilot data reveal putative mechanisms for SSRI treatment in PTSD and substantiate the need for large-scale placebo-controlled studies investigating these effects.► Paroxetine, but not placebo, treatment is associated with increased OFC activation. ► Paroxetine and placebo treatments are both associated with increased activation in the ACC. ► SSRI treatment may act more specifically on orbitofrontal circuits that modulate fear extinction. ► These pilot data reveal putative mechanisms for SSRI treatment in PTSD. ► Our findings substantiate the need for further imaging studies of SSRI treatment in PTSD.

The problem of ghostwriting in corporate-sponsored clinical trials is of concern to medicine, bioethics, and government agencies. We present a study of the ghostwritten archival report of an industry-sponsored trial comparing antidepressant treatments for bipolar depression: GlaxoSmithKline (GSK) paroxetine study 352. This analysis is based upon publicly available evidence presented in a complaint of research misconduct filed with the Office of Research Integrity of the Department of Health and Human Services. We performed a deconstruction of the published study to show how primary and secondary outcome analyses were conflated, turning a 'negative' clinical trial into a 'positive' study - with conclusions and recommendations that could adversely affect patient health. The paroxetine 352 study was a randomized, double-blind, placebo-controlled, 19-site trial comparing paroxetine and imipramine in 117 patients with bipolar type I major depressive episode which was unre...

The increase of extracellular 5-HT in brain terminal regions produced by the acute administration of 5-HT reuptake inhibitors (SSRI's) is hampered by the activation of somatodendritic 5-HT(1A) autoreceptors in the raphe nuclei. The present in vivo electrophysiological studies were undertaken, in the rat, to assess the effects of the coadministration of venlafaxine, a dual 5-HT/NE reuptake inhibitor, and (-)pindolol on pre- and postsynaptic 5-HT(1A) receptor function. The acute administration of venlafaxine and of the SSRI paroxetine (5 mg/kg, i.v.) induced a suppression of the firing activity of dorsal hippocampus CA(3) pyramidal neurons. This effect of venlafaxine was markedly potentiated by a pretreatment with (-)pindolol (15 mg/kg, i.p.) but not by the selective beta-adrenoceptor antagonist metoprolol (15 mg/kg, i.p.). That this effect of venlafaxine was mediated by an activation of postsynaptic 5-HT(1A) receptors was suggested by its complete reversal by the 5-HT(1A) antagon...

Purpose: To compare the efficacy and safety of dapoxetine, paroxetine, and placebo for the oral pharmaco-therapy of premature ejaculation. Materials and Methods: Three hundred forty potent men with premature ejaculation were recruited to this study. Patients were randomly assigned to receive 60 mg dapox-etine (group 1, n = 115), or 20 mg paroxetine (group 2, n = 113) or placebo (group 3, n = 112) orally daily during a 12-week period for each agent. The efficacy of the 3 treatments was assessed every 2 weeks during treatment and at the end of study using responses to International Index of Erectile Function (IIEF), intravaginal ejaculatory latency time (IELT) evaluation, mean intercourse satisfaction domain, mean weekly coitus episodes and adverse drug effects. Results: At the end of the 12-week treatment with dapox-etine, paroxetine, and placebo, the mean IELT was increased from 38, 31 and 34 seconds to 179, 370 and 55 seconds, respectively (P = 0.01 in group 1 and P = 0.001 in group 2). Baseline mean intercourse satisfaction domain values of International Index of Erectile Function of 10, 11, and 11 reached 14, 17 and 12 at the end of the 12-week treatment in groups 1, 2, and 3 respectively (P = 0.03 in groups 1, 2). The mean weekly intercourse episodes increased from pretreatment values of 1.4, 1.3, and 1.3 to 2.2, 2.5 and 1.4, for dapoxetine, paroxetine and placebo, respectively (P = 0.04 in groups 1, 2). The incidence of adverse effects with dapoxetine and paroxetine was significantly higher (P = 0.04 in groups 1, 2) compared to that of placebo. Conclusions: Paroxetine appears to provide significantly better results in terms of IELT and intercourse satisfaction versus dapoxetine. Each treatment was well tolerated.

Recent studies have suggested that the activation of mammalian target of rapamycin (mTOR) signaling may be related to antidepressant action. Therefore, the present study evaluated whether antidepressant drugs would exert differential effects on mTOR signaling in the rat hippocampus under conditions of chronic restraint stress. Male Sprague-Dawley rats were subjected to restraint stress for 6 h/days for 21 days with either escitalopram (10 mg/kg) or paroxetine (10 mg/kg) administered after the chronic stress procedure. Western blot analyses were used to assess changes in the levels of phospho-Ser(2448)-mTOR, phospho-Thr(37/46)-4E-BP-1, phospho-Thr(389)-p70S6 K, phospho-Ser(422)-eIF4B, phospho-Ser(240/244)-S6, phospho-Ser(473)-Akt, and phospho-Thr(202)/Tyr(204)-ERK in the hippocampus. Chronic restraint stress significantly decreased the levels of phospho-mTOR complex 1 (mTORC1), phospho-4E-BP-1, phospho-p70S6 K, phospho-eIF4B, phospho-S6, phospho-Akt, and phospho-ERK (p < 0.05); th...

This article reviews the state-of-the-art research in posttraumatic stress disorder (PTSD) from several perspectives: (1) Sex differences: PTSD is more frequent among women, who tend to have different types of precipitating traumas and higher rates of comorbid panic disorder ...

Many subjects with depression and with brain lesions can poorly control their emotions with fits of weeping and tearfulness; neurological patients present outbursts of laughter as well. This condition is called Emotional Lability (EL). The antidepressant drugs of the family of selective serotonine reuptake inhibitors (SSRI) improve EL within a few days in both depressive and neurological disorders. EL can be present in healthy subjects as well, in whom it is considered as normal, although often embarrassing. Two healthy subjects with EL, were treated with 20 mgs of Paroxetine or placebo for cycles of 5 days. Moreover the effect was observed of either Paroxetine or Fluoxetine on the emotion control of three patients with mood disorders both when they were depressed and after recovering from the depression. In all subjects, after few days of treatment, EL disappeared, and their emotion control and behaviour were both modified. (1) In healthy subjects EL is often embarrassing; the poss...