Paroxetine labeling

TABLE 2. Effects of repeated systemic administration of MDMA on the regional decreases in [ H]paroxetine-labeled serotonin uptake sites... 

Battaglia, G. Yeh, S.Y. O Heam, E. Molliver. M.E. Kuhar, M.J. and De Souza, E.B. 3,4-Methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) preferentially destroy serotonin terminals in rat brain Quantification of neurodegeneration by measurement of H-paroxetine-labeled serotonin uptake sites. 

Loss of [3H]-paroxetine-labeled SERT binding sites in forebrain regions 20 mg/kg, 4 days s.c., twice daily, 2 weeks Battaglia et al.67... 

An open-label study of paroxetine and fluoxetine (Alonso et al, 1997) in depressed Hispanic (Mexican descent, n = 13) and non-Hispanic females (n = 13) showed no differences in response rates. At variance with the tricyclic data, Hispanic subjects complained of fewer side effects (2.2 2.0 vs. 5.1 2.5 p < 0.005), but twice as many terminated participation prior to study completion due to non-compliance, intolerable side effects or pregnancy. 

Since the introduction of the first approved SSRI, fluoxetine (1) in 1987 [9], a number of SSRIs have been developed for the treatment of depression [2], Currently, the five most commonly prescribed SSRIs are fluoxetine, escitalopram (2, S-enantiomer of citalopram), sertraline (3), paroxetine (4) and fluvoxamine (5). Recent effort in the clinical development of new SSRIs has focused on the treatment of premature ejaculation (PE) by taking advantage of the ejaculation-delaying side effects of SSRIs [10]. Although SSRIs have been prescribed off-label to treat this condition, an SSRI with rapid onset of action and rapid clearance could be preferred for on-demand treatment of PE [11,12]. Dapoxetine (LY210448, 6), an... 

Benjamin J, Ben-Zion IZ, Karbofsky E, Dannon P (2000) Double-blind placebo-controlled pilot study of paroxetine for specific phobia. Psychopharmacology (Berl) 149 194-196 Berlant J, van Kammen DP (2002) Open-label topiramate as primary or adjunctive therapy in chronic civilian posttraumatic stress disorder a preliminary report. J Clin Psychiatry 63 15-20... 

In a 4-month open-label study of 15 adults with severe and profound mental retardation (seven with PDD), paroxetine at doses of 20 to 50 mg daily was significantly effective for symptoms of aggression at 1-month, but not at 4-month follow-up (Davanzo et al., 1998). The investigators hypothesized that adaptive changes may have occurred in 5-HT receptor density, availability of 5-HT, or in 5-HT transporter sensitivity. 

Several preliminary lines of research have started to suggest that antidepressants, once considered ineffective in generalized anxiety disorder, may be very efficacious [Gorman and Kent 1999]. In particular, venlafaxine has been effective in treating generalized anxiety disorder in both open-label and double-blind trials, and imipramine and paroxetine were as effective as a benzodiazepine in the long-term treatment of generalized anxiety disorder. 

A 12-week open-label study of paroxetine in 19 civilians with PTSD found this agent to be efficacious for PTSD. The results also showed that people who had been exposed to any kind of childhood trauma were less likely to respond to therapy (276). 

Since the study by Emsiie and colleagues, there has also been a positive, double-blind, placebo-controlled study with paroxetine (120), and sertraline has also shown promise in an open-label trial in adolescents with major depression (121). 

Several placebo-controlled studies have demonstrated the effectiveness of SSRIs in the treatment of social phobia, particularly paroxetine [147-150], However, due to its adverse impact on sleep, the SSRIs may not be the first choice for social phobia with sleep complaints. Serotonin/norepinephrine re-uptake inhibitors (SNRI), such as venlafaxine [151], have also been reported to be effective for social phobia in several open label studies. However, no placebo-controlled trial has been conducted... 

Rosenthal M (2003) Tiagabine for the treatment of generalized anxiety disorder a randomized, open-label, clinical trial with paroxetine as a positive control. J Clin Psychiatry 64 1245-1249... 

Even worse, GSK made sure that Study 329 was eventually published in a whitewashed form in the prestigious Journal of the American Academy of Child and Adolescent Psychiatry (Keller et ah, 2001). The title left no doubt about the scientific nature of the study Efficacy of Paroxetine in the Treatment of Adolescent Major Depression A Randomized, Controlled Trial. The conclusion to the lengthy analysis, a mere one sentence long, left no doubt about what the reader was supposed to learn Paroxetine is generally well tolerated and effective for major depression in adolescents. That one sentence, so prominently displayed as the last line of the abstract, was a drug company public relations triumph, one bound to vastly increase the off-label prescription to children of their ineffective, dangerous drug. 

Fluoxetine and other selective serotonin reuptake inhibitors (SSRIs) have been associated with increasing suicidal ideation in some populations of patients. Recent studies have led the British Department of Health to warn physicians against using paroxetine off label. Fluoxetine was specifically exempted from this recommendation. Long-term studies of patients with depression who were treated with fluoxetine have shown it to be fairly well tolerated. Primary adverse effects include nausea (23%), headache (21%), and insomnia (20%). 

Alonso et al. (1997) conducted an open-label study of SSRIs in the treatment of depression in 13 Hispanic (Mexican descent) and 13 non-Hispanic female patients. Patients met DSM-III criteria for depression and were treated for 6 weeks with either fluoxetine or paroxetine. Improvement was similar in both groups, but side effects were reported significantly more often by the non-Hispanics. As in many of the clinical studies involving Hispanic populations, the sample size was extremely small. A preponderance of PMs could have been sampled in the non-Hispanic group, which could account for the increased incidence of side effects. As mentioned earlier, the poor-metabolism rate among Caucasians is 5%-10% (Agundez et al. 1994). 

SAD can present in children of preschool to elementary school age. If the disorder is not treated, it can persist into adulthood and increase the risk of depression and substance abuse. CBT and social skills training are effective nonpharmacological therapies in children. Pharmacological evidence is limited to case studies or open-label trials. SSRIs are considered first-line therapy because of tolerability and effectiveness. Fluoxetine, fluvoxamine, sertraline, and paroxetine were effective in children with SAD. Headache, nausea, drowsiness, insomnia, jitteriness, and stomach aches were reported in children receiving SSRIs. 

However when high micromolar concentrations (200 micro M) of 5-HT or of 5-HT uptake inhibitors were used in determining the dissociation half life of H-imipramine, H-paroxetine and H-dtalopram dissociating from human platelet membrane preparations it appears that not only the dissociation half life was prolonged but also that the prolongation was different for each of the three labeled uptake inhibitors [24]. This led to the conclusion that the three labeled ligands each bind to a different domain on the 5-HT transporter. 

Because serotonin may have a role in regulating sympathetic nervous system activity (25,82,83), selective serotonin-reuptake inhibitors have been proposed as a potential therapy and open-label studies have found that these agents may reduce recurrent NCS (25,84). In a randomized placebo-controlled trial, 82% of patients who were randomly assigned to receive paroxetine were free of syncope for 25 months, compared with 53% of the placebo group (p < 0.001) (85). 

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