Paroxetine In Patients Research Articles

Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine

Objective To investigate the efficacy of hypericum extract WS 5570 (St John's wort) compared with paroxetine in patients with moderate to severe major depression.Design Randomised double blind, double dummy, reference...

P.4.039 An association between 5-HTTLPR and the severity, clinical effect of paroxetine in patients with panic disorder

P.4.039 An association between 5-HTTLPR and the severity, clinical effect of paroxetine in patients with panic disorder

A prospective randomized single-blind, multicenter trial comparing the efficacy and safety of paroxetine with and without quetiapine therapy in depression associated with anxiety

OBJECTIVETo evaluate quetiapine as an adjunct to paroxetine in patients with comorbid depression and anxiety.METHODProspective, multicenter, single-blind trial of patients with DSM-IV major depression and associated anxiety, who were randomized to an 8-week treatment with paroxetine alone (n=54) or paroxetine+quetiapine (n=58). Quetiapine was dosed to 200 mg/day and paroxetine to 60 mg/day, as required.RESULTSDecrease in HAM-A scores was significantly greater in the combined therapy group than with paroxetine alone at weeks 2, 4, 6 and LOCF (P<0.008). Decrease in HAM-D scores was significantly greater in the combined therapy group than with paroxetine alone throughout the study period (P<0.008). Regarding adverse events, it was found that increases in anxiety and insomnia were more prevalent in the paroxetine only group, while increased appetite was more prevalent when quetiapine was added (P<0.05).CONCLUSIONQuetiapine added to paroxetine is well tolerated and may speed up and improve response in patients with comorbid depression and anxiety.

Mirtazapine acts more rapidly than paroxetine in patients with depression,

Mirtazapine acts more rapidly than paroxetine in patients with depression,

Occupancy of brain serotonin transporters during treatment with paroxetine in patients with social phobia: a positron emission tomography study with 11C McN 5652.

Although selective serotonin reuptake inhibitors (SSRIs) are widely used in the treatment of anxiety and depressive disorders, the occupancy of the serotonin reuptake transporter (SERT) achieved in humans at typical clinical doses by these agents remains poorly characterized. The purpose of this study was to determine the occupancy of the SERT achieved in vivo by the SSRI paroxetine in social phobia patients at typical antianxiety doses. Measures of SERT availability were obtained with positron emission tomography and the SERT radiotracer [(11)C](+)-McN 5652 in five patients with social phobia before and during treatment with paroxetine at usual therapeutic doses (20-40 mg per day). Occupancy of the SERT by paroxetine was high in all subjects and in all regions measured after 3-6 months of continuous treatment. The results of this study in an anxiety disorder sample are consistent with previously reported results in a depressed sample and suggest that paroxetine at therapeutic doses achieves very high occupancy levels of the SERT.

Randomised controlled study of sleep after nefazodone or paroxetine treatment in out-patients with depression

Sleep effects of antidepressants are important clinically and for elucidating mechanism of action: selective serotonin reuptake inhibitors disturb sleep and 5-HT(2) receptor-blocking compounds may enhance sleep quality. To compare the objective and subjective effects on sleep of paroxetine and nefazodone in patients with moderate to severe depression. Forty patients with depression were randomised to take paroxetine 20-40 mg/day or nefazodone 400-600 mg/day for 8 weeks. Objective and subjective quality of sleep and depression measures were assessed throughout. Nefazodone significantly increased objective sleep efficiency and total sleep time, and improved subjective sleep on days 3 and 10. Paroxetine decreased sleep efficiency early in treatment and some sleep disruption remained at week 8. Paroxetine but not nefazodone produced marked suppression of rapid eye movement (REM) sleep. Nefazodone improves sleep in early treatment compared with paroxetine in patients with moderate to severe depression. These effects are seen within the first 2 weeks of treatment and diminish thereafter.

Tolerability of combined treatment with lithium and paroxetine in patients with bipolar disorder and depression.

Patients with bipolar disorder are often prescribed lithium in combination with a selective serotonin reuptake inhibitor. Doubts still remain, however, about the safety of the combination, particularly with regard to the risk of developing a serotonin syndrome. The authors retrospectively evaluated the safety of the combination of lithium and paroxetine when the two medications were sequentially prescribed in patients with bipolar disorder. The authors examined a sample of 17 patients with bipolar disorder who were treated with lithium during a depressive episode and who required paroxetine as an adjunctive antidepressant to ongoing lithium treatment. Averaging across all subjects, no statistically significant increase was found for any of the somatic symptoms that were assessed before and after paroxetine was added to ongoing lithium therapy. Examining the clinical records of each patient in detail; however, four patients who developed significant adverse events, possibly related to an emerging serotonin syndrome were identified. Clinicians should be aware of the possible development of a serotonin syndrome among patients in whom paroxetine is added to ongoing lithium treatment.

PMH12: PREVALENCE OF COMORBID ANXIETY AND DEPRESSION AMONG PATIENTS PRESCRIBED SSRI MONOTHERAPY

OBJECTIVE: To examine the distribution of mental health conditions comorbid to depression, especially anxiety, among patients treated for 1–6 months or 7–12 months with an SSRI. METHODS: The study comprised a retrospective review of integrated medical and pharmacy claims from a national managed care organization. Continuously enrolled patients between the ages of 18 and 65 years were identified from the 1.9M claims underlying six IPA model plans for 1997–1998. Patients placed on SSRI therapy following a 4 month period without drugs were stratified according to underlying mental health conditions and length of SSRI monotherapy. RESULTS: Overall, between 47% and 52% of patients placed on SSRI monotherapy had a history of depression; an additional 5–12% had histories of anxiety without depression. Greater proportions of patients for whom paroxetine was prescribed rather than either fluoxetine or sertraline had anxiety comorbid to depression in the year prior to initiating drug therapy(11.5%, 6.5%, 7.9%, respectively)(Chi-square <.001). The 40 or more percent of patients without depression or anxiety in their histories—12 months preceding initiation of drug therapy and month of initiation—but treated with SSRIs often had diagnoses for other mental health conditions, specifically neurotic disorders, affective psychoses, nondependent abuse of drugs and adjustment reaction. These diagnoses patterns persisted when patients were subset according to persistence of therapy, i.e., SSRI therapy for greater or fewer than 6 months. CONCLUSIONS: These results support the common belief that physicians differentially prescribe SSRIs according to comorbid symptoms. Observed differences in the prevalence of diagnoses across SSRI therapies are consistent with differences in the range of approved indications across drugs and preferential prescribing of paroxetine for patients with comorbid anxiety disorders.

Fluoxetine: a review of its therapeutic potential in the treatment of depression associated with physical illness.

Fluoxetine is a potent and selective inhibitor of neuronal serotonin (5-hydroxytryptamine) reuptake. Fluoxetine reduces food, energy and carbohydrate intake and increases resting energy expenditure, which may account for the moderate and transient bodyweight loss observed with its use. Glucose tolerance and/or hypoglycaemia in patients with type 2 diabetes mellitus improve with fluoxetine therapy. The ability of fluoxetine to inhibit cytochrome P450 (CYP) isoenzymes (CYP2D6, CYP2C and CYP3A4), is potentially important for patients with physical illness who may be taking multiple concomitant medications. Fluoxetine was more effective than placebo in 2 double-blind, randomised trials, and according to limited data appears to be equally effective compared with other SSRIs and tricyclic antidepressants (TCAs), in the treatment of depression in patients with HIV/AIDS. The efficacy of fluoxetine is also superior to that of placebo in the treatment of depression in patients with diabetes mellitus and stroke as shown in double-blind randomised trials, although its efficacy relative to that of nortriptyline in stroke is uncertain. Fluoxetine had similar efficacy to that of desipramine in patients with cancer, with improved Hamilton Depression Rating Scale and quality-of-life scores from baseline; however, the drug was not more effective than placebo in a double-blind randomised trial. Medically healthy individuals tolerate fluoxetine well. Like other SSRIs, fluoxetine lacks the anticholinergic, cardiovascular, sedative and weight-increasing properties of TCAs, and is safer in overdose than TCAs and monoamine oxidase inhibitors. Rates of sexual dysfunction and suicidal ideation with fluoxetine appear similar to those seen with other SSRIs. Fluoxetine has shown superior efficacy compared with placebo in the treatment of depression in patients with HIV/AIDS, diabetes mellitus or stroke; however, it has not significantly improved depressive symptoms versus placebo in patients with cancer. The efficacy of fluoxetine appears similar to that of desipramine in patients with stroke, cancer or HIV, and is similar to that of sertraline or paroxetine in patients with HIV/AIDS; comparisons with nortriptyline give equivocal results. The potential for drug interactions with fluoxetine use should be carefully considered because most patients with comorbid physical illness will be receiving multiple comedications. Although fluoxetine has proved effective as an antidepressant in this population in several clinical trials, its drug interaction profile and long half-life are a potential limitation, and these properties should be carefully considered in relation to the status of each patient.

Fluoxetine versus sertraline and paroxetine in major depression: tolerability and efficacy in anxious depression

Background: Major depression with high levels of anxiety (anxious depression) is a common subtype of depression associated with greater psychosocial impairment and poorer response to antidepressant treatment. It is unclear whether in this population there are differences in efficacy or tolerability across selective serotonin reuptake inhibitors. For this reason, using head-to-head acute treatment comparison, we compared efficacy and tolerability of fluoxetine, sertraline, and paroxetine among depressed patients with high levels of anxiety. Methods: Patients ( N=108) with DSM-IV major depression and high levels of anxiety (a HAM-D-Anxiety/Somatization Factor score ≥7) were randomized to fluoxetine, sertraline, or paroxetine treatment in a double-blind fashion. Changes in overall depression and anxiety were assessed. Results: Patients demonstrated similar baseline-to-endpoint improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores. Patients also demonstrated similar change-over-time improvement in HAM-D-17 and HAM-D-Anxiety/Somatization Factor scores, except at week one where fluoxetine- and sertraline-treated patients had statistically significantly greater improvement than paroxetine-treated patients in the HAM-D-Anxiety/Somatization Factor score. There were no significant differences across treatments in percentages of patients with substantial emergence, any worsening, or improvement at endpoint in individual HAM-D Items 9 (agitation), 10 (psychic anxiety), and 11 (somatic anxiety). Overall, all treatments were well tolerated. Conclusion: These data showed no significant differences in efficacy and tolerability of fluoxetine, sertraline, and paroxetine in patients with high levels of baseline anxiety symptoms during the acute treatment of major depression. Each treatment was similarly effective in improving depression in this subtype of patients with anxious depression.

Therapeutic advances: Paroxetine for the treatment of social anxiety disorder

Data from early studies of selective serotonin reuptake inhibitors have shown that these agents are effective in the treatment of social anxiety disorder (social phobia). This review highlights the outcomes of three large clinical trials of paroxetine in patients with social anxiety disorder. In two of the studies, patients received a flexible dose of paroxetine (20-50 mg/day) or placebo; the third trial was a fixed-dose study, in which patients received paroxetine 20, 40, or 60 mg/day, or placebo. A total of 861 subjects were randomized to treatment for 12 weeks, in centers across the U.S.A., Canada, Europe, and South Africa. The primary outcome measures were the Clinical Global Impressions (CGI) Global Improvement item and Liebowitz Social Anxiety Scale (LSAS) Total Score. In each of the studies, 45-66% of patients receiving paroxetine were rated as responders (very much or much improved on the CGI scale). Paroxetine treatment improved symptoms of social anxiety, as measured by the LSAS, compared with placebo. Differences between paroxetine and placebo groups were statistically significant and were clinically relevant within each study. In general, paroxetine was well tolerated. Paroxetine is effective for the treatment of social anxiety disorder. Based on the findings from these studies, a starting dose of 20 mg/day is recommended. The range of efficacy appears to be 20-50 mg/day for most patients.

Efficacy and tolerability of paroxetine in patients with fibromyalgia syndrome: a single-blind study

The efficacy and tolerability of paroxetine, a selective serotonin reuptake inhibitor, were evaluated in a 12-week, single-blind, randomized study. Forty outpatients with fibromyalgia syndrome (FMS) were allocated to receive paroxetine 20 mg once daily for 3 months (group A; n = 20) or placebo once daily for 3 months (group B; n = 20). The investigator's overall assessment of paroxetine's efficacy was much improved or improved in 68% of group A patients, slightly improved in 24%, and no change in 8%. Group A patients' overall assessment of paroxetine's efficacy was much improved or improved in 40%, slightly improved in 48%, and no change in 12%. The investigator's and group B patients' overall assessments of the placebo's efficacy were no change in 96% and 82% and slightly improved in 4% and 18%, respectively. The investigator's overall assessment of tolerability was very good or good in 82% of group A patients and very good or good in 98% of group B patients. The patients' overall assessment of tolerability was very good or good in 70% in group A and in 18% in group B. Based on the findings, paroxetine appeared to be effective and well tolerated in our group of patients with FMS. Key words: fibromyalgia, selective serotonin re-uptake inhibitors, paroxetine, efficacy, tolerability.

3H]Paroxetine binding to human peripheral lymphocyte membranes of patients with major depression before and after treatment with fluoxetine

Serotonin has been involved in major depression and is also related to central and peripheral mechanisms of neuroimmunomodulation. Recently, the uptake of [ 3H]serotonin into human peripheral blood lymphocytes has been reported. We determined the density of serotonin uptake sites by the binding of [ 3H]paroxetine to blood peripheral lymphocyte membrane preparations of controls and of patients with major depression before and after treatment with fluoxetine for six weeks. The severity of depression was assessed by the use of Hamilton Rating Scale for Depression and of Beck Depression Inventory. There was a reduction in the number of sites for [ 3H]paroxetine in patients before administration of the antidepressant respecting controls, and a recovery after the treatment. Affinity was unchanged. No correlation was obtained between the severity of symptoms determined by Hamilton Rating Scale for Depression or by Beck Depression Inventory, and the number of binding sites for [ 3H]paroxetine. The levels of the plasma serotonin metabolite, 5-hydroxyindoleacetic acid, did not differ between the three groups of subjects, but serotonin was lower in patients after treatment respecting controls and in patients before treatment. The significant correlation between specific binding of [ 3H]paroxetine and plasma serotonin levels in controls was not present in the patients. Lymphocyte serotonin transporter is decreased in major depressed patients and is modulated by antidepressant treatment. In addition of counting with a peripheral marker in depression, the study of serotonin system in lymphocytes might contribute to understand the bi-directional interaction between the nervous and the immune systems.

Pindolol appears to enhance the effect of paroxetine in patients with major depression,

Pindolol appears to enhance the effect of paroxetine in patients with major depression,

Paroxetine

Paroxetine

Pharmacotherapy of obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is a chronic and often incapacitating disorder that is frequently complicated by mood and additional anxiety diagnoses. Although appropriate pharmacotherapy is often of great benefit, full remission is rare. Separate multi-center, placebo-controlled trials of clomipramine, paroxetine, fluoxetine, sertraline and fluvoxamine, respectively, have established the unparalleled efficacy and safety of the serotonin reuptake inhibitors (SRIs) in the treatment of OCD. Direct comparisons of SRIs suggest similar efficacy, but reduced tolerability for clomipramine in comparison to fluoxetine, fluvoxamine, sertraline and paroxetine in patients with OCD. Although 60-80% of OCD patients will respond to SRI treatment, partial symptom reduction (mean improvement, 25-40% from baseline) remains the rule. Controlled trials of adjuvant lithium, buspirone, thyroid hormone or clonazepam added to ongoing SRI therapy have failed to demonstrate substantial further antiobsessive effects. The presence of comorbid conditions, specific OCD symptom content and various other clinical features have been investigated as potential predictors of medication response in patients with OCD, but consistent factors have not yet been identified. Clinical experience and preliminary data does suggest that a lack of response to one or more SRIs does not preclude response to another SRI. An overview of the pharmacotherapy of OCD, including first-line medication(s) and the comparative efficacy and pharmacological features of the different SRIs will be presented in this review, as well as potential strategies for OCD patients who fail to respond to conventional pharmacotherapeutic interventions.

Comparison of Paroxetine and Maprotiline in Minor Depression

Whilst the efficacy of paroxetine has been demonstrated in MDD, its clinical utility in minor depression has not been established. This study assesses the antidepressant efficacy of paroxetine in patients meeting RDC criteria for minor depression. All patients scored 13 points on the 17-item Hamilton Depression Rating Scale (HAMD) at baseline. After a 3 day washout period, patients were randomised to receive paroxetine 20–40mg/day or maprotiline 100-150mg/day, dose being titrated according to clinical response after 3 weeks treatment at the lower doses. Assessments conducted at baseline (day 0) and at weekly intervals for 6 weeks included the 17-item HAMD, the Montgomery-Asberg Depression Rating Scale (MADRS), and the physicians Clinical Global Impression (CGI). 245 patients (126 paroxetine and 119 maprotiline) were evaluable on an intent to treat basis. The two groups were well matched on all major demographic variables. For the changes from baseline on the HAMD total, the paroxetine group had significantly greater mean reductions at weeks 3-6 and end-point (p≤ 0.04). This result was reinforced by the numbers of patients achieving a 50% reduction in HAMD total at weeks 4 to 6: week 4 - 79% paroxetine, 67% maprotiline; week 6: −91% paroxetine, 80% maprotiline. The robustness of these findings was further underscored by similar results for the MADRS and the CGI. These results indicate the superior efficacy of paroxetine compared to maprotiline in minor depression.

Pharmacokinetics of paroxetine in patients with cirrhosis

In a 14-day multiple-dose study the pharmacokinetics of paroxetine was investigated in 12 patients with alcoholic cirrhosis and in 6 subjects without liver disease. The dose of 20-30 mg paroxetine daily was adjusted to the reduction in liver function, as assessed by the galactose elimination capacity. Accordingly, all but two of the cirrhotic patients received 20 mg, while all six control subjects received 30 mg. Dose-corrected, trough drug concentration at steady state (CSSmin) and dose-corrected AUC24h were significantly higher in the patients with liver diseases than in the control subjects [3.4 vs 1.5 ng.ml-1 per mg paroxetine and 89 vs 43 h (ng).ml-1 per mg paroxetine]. The elimination t1/2 was prolonged [83 vs 36 h], but the difference was not statistically significant, and the cirrhotic patients were still able to clear almost all the paroxetine by metabolism. All but two patients with cirrhosis experienced nausea during the first two or three days after the first dose, while none of the controls had this symptom. The study showed slower elimination of paroxetine and consequently higher plasma levels in patients with cirrhosis, suggesting that in the latter the dose of paroxetine should be in the lower end of the therapeutic range.

The pharmacokinetics of paroxetine in patients with liver cirrhosis

The pharmacokinetics of paroxetine in patients with liver cirrhosis

Tricyclic antidepressants--blood level measurements and clinical outcome: an APA Task Force report. Task Force on the Use of Laboratory Tests in Psychiatry

The Task Force examines the present status of studies investigating the relationship between blood plasma concentrations of tricyclic antidepressants and clinical outcome. It discusses some of the discrepancies that have developed among various antidepressant drugs and evaluates the clinical implications of the current status of blood level monitoring. The Task Force concludes that plasma level measurements of imipramine, desmethylimipramine, and nortriptyline are unequivocally clinically useful in certain situations, that these measurements are helpful in many situations, and that plasma level measurements are likely to grow in usefulness.