Paroxetine controlled release

A controlled-release (CR) formulation of the SSRI paroxetine has been developed. This CR formulation delays the release of paroxetine until the tablet has passed through the stomach; the drug is then released over 4-5 hours. In well designed placebo-controlled trials in patients with major depressive disorder (including a study in the elderly), social anxiety disorder or premenstrual dysphoric disorder (PMDD), paroxetine CR was consistently superior to placebo with regards to primary endpoints (i.e. mean Hamilton Rating Scale for Depression total score [major depressive disorder], Liebowitz social anxiety scale total score and Clinical Global Impressions-Global Improvement score [social anxiety disorder] and Visual Analogue Scale-Mood score [PMDD]). The duration of treatment was 12 weeks or, in PMDD, over three menstrual cycles (intermittent or continuous administration). Paroxetine CR also demonstrated efficacy in three well designed studies in patients with panic disorder with or without agoraphobia. Paroxetine CR was generally well tolerated in clinical trials, with an adverse-event profile typical of SSRIs, although recipients of paroxetine CR experienced significantly less nausea than recipients of immediate-release paroxetine in the first week of treatment.     

Paroxetine: an update of its use in psychiatric disorders in adults

Paroxetine is a selective serotonin reuptake inhibitor (SSRI), with antidepressant and anxiolytic activity. In 6- to 24-week well designed trials, oral paroxetine 10 to 50 mg/day was significantly more effective than placebo, at least as effective as tricyclic antidepressants (TCAs) and as effective as other SSRIs and other antidepressants in the treatment of major depressive disorder. Relapse or recurrence over 1 year after the initial response was significantly lower with paroxetine 10 to 50 mg/day than with placebo and similar to that with imipramine 50 to 275 mg/day. The efficacy of paroxetine 10 to 40 mg/day was similar to that of TCAs and fluoxetine 20 to 60 mg/day in 6- to 12-week trials in patients aged > or =60 years with major depression. Paroxetine 10 to 40 mg/day improved depressive symptoms to an extent similar to that of TCAs in patients with comorbid illness, and was more effective than placebo in the treatment of dysthymia and minor depression. Paroxetine 20 to 60 mg/day was more effective than placebo after 8 to 12 weeks' treatment of obsessive-compulsive disorder (OCD), panic disorder, social anxiety disorder (social phobia), generalised anxiety disorder (GAD) and post-traumatic stress disorder (PTSD). Improvement was maintained or relapse was prevented for 24 weeks to 1 year in patients with OCD, panic disorder, social anxiety disorder or GAD. The efficacy of paroxetine was similar to that of other SSRIs in patients with OCD and panic disorder and similar to that of imipramine but greater than that of 2'chlordesmethyldiazepam in patients with GAD. Paroxetine is generally well tolerated in adults, elderly individuals and patients with comorbid illness, with a tolerability profile similar to that of other SSRIs. The most common adverse events with paroxetine were nausea, sexual dysfunction, somnolence, asthenia, headache, constipation, dizziness, sweating, tremor and decreased appetite. In conclusion, paroxetine, in common with other SSRIs, is generally better tolerated than TCAs and is a first-line treatment option for major depressive disorder, dysthymia or minor depression. Like other SSRIs, paroxetine is also an appropriate first-line therapy for OCD, panic disorder, social anxiety disorder, GAD and PTSD. Notably, paroxetine is the only SSRI currently approved for the treatment of social anxiety disorder and GAD, which makes it the only drug of its class indicated for all five anxiety disorders in addition to major depressive disorder. Thus, given the high degree of psychiatric comorbidity of depression and anxiety, paroxetine is an important first-line option for the treatment of major depressive disorder, OCD, panic disorder, social anxiety disorder, GAD and PTSD.     

Spotlight on paroxetine in psychiatric disorders in adults

Paroxetine is a selective serotonin reuptake inhibitor (SSRI), with antidepressant and anxiolytic activity. In 6- to 24-week well designed trials, oral paroxetine 10 to 50 mg/day was significantly more effective than placebo, at least as effective as tricyclic antidepressants (TCAs) and as effective as other SSRIs and other antidepressants in the treatment of major depressive disorder. Relapse or recurrence over 1 year after the initial response was significantly lower with paroxetine 10 to 50 mg/day than with placebo and similar to that with imipramine 50 to 275 mg/day. The efficacy of paroxetine 10 to 40 mg/day was similar to that of TCAs and fluoxetine 20 to 60 mg/day in 6- to 12-week trials in patients aged > or = 60 years with major depression. Paroxetine 10 to 40 mg/day improved depressive symptoms to an extent similar to that of TCAs in patients with comorbid illness, and was more effective than placebo in the treatment of dysthymia and minor depression. Paroxetine 20 to 60 mg/day was more effective than placebo after 8 to 12 weeks' treatment of obsessive-compulsive disorder (OCD), panic disorder, social anxiety disorder (social phobia), generalised anxiety disorder (GAD) and post-traumatic stress disorder (PTSD). Improvement was maintained or relapse was prevented for 24 weeks to 1 year in patients with OCD, panic disorder, social anxiety disorder or GAD. The efficacy of paroxetine was similar to that of other SSRIs in patients with OCD and panic disorder and similar to that of imipramine but greater than that of 2'chlordesmethyldiazepam in patients with GAD. Paroxetine is generally well tolerated in adults, elderly individuals and patients with comorbid illness, with a tolerability profile similar to that of other SSRIs. The most common adverse events with paroxetine were nausea, sexual dysfunction, somnolence, asthenia, headache, constipation, dizziness, sweating, tremor and decreased appetite. In conclusion, paroxetine, in common with other SSRIs, is generally better tolerated than TCAs and is a first-line treatment option for major depressive disorder, dysthymia or minor depression. Like other SSRIs, paroxetine is also an appropriate first-line therapy for OCD, panic disorder, social anxiety disorder, GAD and PTSD. Notably, paroxetine is the only SSRI currently approved for the treatment of social anxiety disorder and GAD, which makes it the only drug of its class indicated for all five anxiety disorders in addition to major depressive disorder. Thus, given the high degree of psychiatric comorbidity of depression and anxiety, paroxetine is an important first-line option for the treatment of major depressive disorder, OCD, panic disorder, social anxiety disorder, GAD and PTSD.     

Efficacy and tolerability of controlled-release paroxetine

Paroxetine controlled-release (CR) was developed with the objective of minimizing the occurrence and severity of selective serotonin reuptake inhibitor (SSRI)-associated adverse events, thereby improving clinical outcomes. Paroxetine CR delays the onset and controls the rate of absorption of medication. Multicenter controlled clinical trials have found lower rates of early-onset, treatment-associated nausea and lower dropout rates from adverse events in depressed patients treated with paroxetine CR compared with those treated with the conventional, immediate-release formulation. At the same time, clinical response and remission rates are favorable. Other studies have demonstrated the efficacy and tolerability of paroxetine CR in geriatric depression, panic disorder, and social anxiety disorder. The CR formulation of paroxetine appears to represent an effective pharmacokinetic approach to minimizing SSRI adverse events and thereby enhancing clinical outcomes.     

Advances in recognition and treatment of social anxiety disorder: a 10-year retrospective

Social anxiety disorder frequently begins in early life and is associated with the subsequent development of comorbid conditions such as depressive and substance use disorders. Social anxiety disorder, particularly the generalized subtype, is characterized by marked impairment in numerous functional domains, including education and social relations. Paroxetine, the first medication to receive an indication in the United States for the treatment of social anxiety disorder, has been shown to be effective in 50% to 60% of patients. The mechanism of action of paroxetine in the treatment of social anxiety disorder is at present unclear. A possible role for early treatment to prevent complications of social anxiety disorder should be explored.     

Paroxetine: a review of its pharmacology, pharmacokinetics and utility in the treatment of a variety of psychiatric disorders

Paroxetine is a selective serotonin re-uptake inhibitor (SSRI). In vitro studies show that it is able to produce a concentration-dependent competitive inhibition of serotonin uptake into brain synaptosomes. This effect can also be demonstrated following in vivo administration of the compound to animals. Paroxetine is almost completely absorbed following oral administration. However, the drug undergoes extensive first pass metabolism. As a result, less than 50% of a single dose of paroxetine reaches the general circulation. Paroxetine is primarily metabolised by the cytochrome P4502D6 isoenzyme. The compound has also been shown to inhibit the activity of this enzyme. As a result, plasma levels of compounds metabolised by the cytochrome P4502D6 isoenzyme can be increased in patients given paroxetine. Paroxetine has been extensively evaluated in clinical studies in depressed patients. The compound shows efficacy superior to placebo, and similar to that obtained with standard tricyclic or tetracyclic agents. Paroxetine also appears to be as efficacious as other SSRIs. The efficacy seen in short-term studies with paroxetine in the treatment of depression is maintained when the drug is given chronically. More recently, paroxetine has been shown to be efficacious in the treatment of panic disorder, obsessive-compulsive disorder, and social anxiety disorder. Nausea, headache and somnolence are the most common adverse events reported by patients given paroxetine. As with other selective serotonin re-uptake inhibitors, a significant percentage of men under therapy with paroxetine report abnormal ejaculation. Paroxetine is well-tolerated by elderly patients, and appears to be associated with few serious adverse events.     

Paroxetine: safety and tolerability issues

Paroxetine is a selective serotonin re-uptake inhibitor (SSRI) available in immediate release and controlled release (CR) formulations. Paroxetine is the most potent inhibitor of serotonin re-uptake among the now available SSRIs. Paroxetine has been approved for the treatment of major depressive disorder (MDD), obsessive–compulsive disorder, panic disorder (PD), generalised anxiety disorder, post traumatic stress disorder (PTSD), and social anxiety disorder (SAD) in adults, whereas paroxetine CR is approved for the treatment of MDD, SAD, PD and premenstrual dysphoric disorder in adults. The overall efficacy of paroxetine seems to be comparable to other SSRIs in the treatment of approved indications, although paroxetine treatment induces more sedation, constipation, sexual dysfunction, discontinuation syndrome and weight gain than other SSRIs. Recent data suggest that paroxetine treatment leads to increased rates of congenital malformations, although this evidence is not conclusive. Paroxetine and paroxetine CR are not indicated for use in the paediatric population and are categorised as Pregnancy Class D. In conclusion, whether the tolerability profile of paroxetine differs substantially from other new antidepressants (including other SSRIs) needs to be determined in adequately powered well-designed randomised controlled comparative clinical trials.     

Paroxetine: safety and tolerability issues

Paroxetine is a selective serotonin re-uptake inhibitor (SSRI) available in immediate release and controlled release (CR) formulations. Paroxetine is the most potent inhibitor of serotonin re-uptake among the now available SSRIs. Paroxetine has been approved for the treatment of major depressive disorder (MDD), obsessive-compulsive disorder, panic disorder (PD), generalised anxiety disorder, post traumatic stress disorder (PTSD), and social anxiety disorder (SAD) in adults, whereas paroxetine CR is approved for the treatment of MDD, SAD, PD and premenstrual dysphoric disorder in adults. The overall efficacy of paroxetine seems to be comparable to other SSRIs in the treatment of approved indications, although paroxetine treatment induces more sedation, constipation, sexual dysfunction, discontinuation syndrome and weight gain than other SSRIs. Recent data suggest that paroxetine treatment leads to increased rates of congenital malformations, although this evidence is not conclusive. Paroxetine and paroxetine CR are not indicated for use in the paediatric population and are categorised as Pregnancy Class D. In conclusion, whether the tolerability profile of paroxetine differs substantially from other new antidepressants (including other SSRIs) needs to be determined in adequately powered well-designed randomised controlled comparative clinical trials.     

An evaluation of paroxetine in generalised social anxiety disorder

It is estimated that social anxiety disorder affects approximately 13.3% individuals within the community at some point in their lifetime and is associated with significant functional impairment. A variety of drug groups have demonstrated efficacy in treating social anxiety disorder, including selective serotonin reuptake inhibitors (SSRIs). Paroxetine is an SSRI approved by the FDA and Health Canada for the treatment of a variety of psychiatric conditions. Paroxetine has been the most studied agent in social anxiety disorder and has been shown to be effective in short-term, fixed- and flexible-dose placebo-controlled trials, as well as in long-term treatment. The pharmacotherapy of social phobia will be reviewed, with a special focus on investigations with paroxetine.     

The selective serotonin reuptake inhibitor paroxetine is effective in more generalized and in less generalized social anxiety disorder

RATIONALE: The DSM-IV includes the specifier "generalized" to refer to social anxiety disorder (social phobia) patients if the fears include "most social situations". The focus on interventions such as the selective serotonin reuptake inhibitors (SSRIs) for generalized social anxiety disorder arguably runs the risk that inadequate treatment will be provided to patients with the non-generalized or discrete subtypes. There are, however, few data to address whether more generalized and less generalized subgroups of social anxiety disorder differ in response to medication. OBJECTIVE: To compare response of more generalized and less generalized social anxiety disorder to pharmacotherapy. METHODS: Data from three randomized placebo-controlled double-blind multicenter trials of the SSRI paroxetine in social anxiety disorder were pooled. Response on the Clinical Global Impression Global Improvement item was analyzed using logistic regression, and change in total Liebowitz Social Anxiety Score was analyzed using analysis of variance, with both models incorporating treatment (paroxetine vs placebo), subgroup (more generalized vs less generalized), demographic, and clinical variables. RESULTS: The prevalence of more generalized social anxiety disorder was higher in females than in males. However, there was no significant difference in terms of age or clinical characteristics (duration of condition, baseline pulse, mean arterial blood pressure). At treatment endpoint there were significant treatment effects (for paroxetine vs placebo), but no significant subgroup effects (for more generalized vs less generalized). CONCLUSIONS: Although the current database is limited insofar as few patients with discrete social anxiety disorder would have been included, it is helpful in addressing the value of medication for patients lying on the spectrum from generalized to non-generalized and discrete social anxiety disorder. Paroxetine was effective in both more generalized and in less generalized social anxiety disorder.     

度洛西汀与帕罗西汀治疗社交焦虑症对照研究

目的比较度洛西汀与帕罗西汀治疗社交焦虑障碍的疗效及不良反应。方法对86例社交焦虑障碍门诊及住院患者,随机分为两组,度洛西汀组和帕罗西汀组各43例,治疗8周,采用汉密尔顿焦虑量表(HAMA)和临床疗效总评量表,病情严重程度量表(CGI-SI)评定临床疗效,用治疗中出现的症状量表(TESS)评定药物不良反应。结果经过8周治疗,度洛西汀组和帕罗西汀组有效率分别为86.05和83.72两组疗效差异无统计学意义(P>0.05),两组不良反应发生率差异无统计学意义(P>0.05)。结论度洛西汀和帕罗西汀对社交焦虑障碍的疗效相当,不良反应较小,值得临床推广。     

帕罗西汀与氯丙咪嗪治疗强迫症的临床对照研究

目的：观察并对比帕罗西汀和氯丙咪嗪治疗强迫症患者的疗效和不良反应。方法：以CCMD-3作为诊断标准,选取强迫症患者100例,随机分为2组,分别用帕罗西汀和氯丙咪嗪治疗8周。应用Yale-Brown强迫量表（Y-BOCS）、汉密顿抑郁量表（HAMD）、汉密顿焦虑量表（HAMA）及临床4级标准评定疗效,用副反应量表（TESS）评定不良反应。在治疗前及治疗后4、8周末,分别评定临床疗效、以上量表的分数及不良反应。结果：帕罗西汀与氯丙咪嗪两组患者疗效的差异无显著性（P〉0.05）;帕罗西汀不良反应明显少于氯丙咪嗪（P〈0.01）,而且耐受性好。结论：帕罗西汀治疗强迫症的疗效与氯丙咪嗪相当,但帕罗西汀具有日剂量小、给药简单方便、不良反应比氯丙咪嗪少而轻等优点     

A meta-analysis of the efficacy and tolerability of paroxetine versus tricyclic antidepressants in the treatment of major depression

This meta-analysis examined efficacy and tolerability data from 39 randomized, double-blind, parallel-group studies comparing paroxetine (n = 1924) with clomipramine (n = 141) or other tricyclic antidepressants (TCAs; n = 1693) in the treatment of major depression. Paroxetine had comparable antidepressant efficacy to TCAs, including clomipramine, as assessed by response rates based on a < or = 50% reduction in Hamilton Rating Scale for Depression (HAMD) total score (58-66%) and a HAMD total score < or = 8 (38-48%) at endpoint, and absolute improvements in HAMD total score (mean change 12.3-14.5). Absolute improvements in HAMD anxiety factor scores were similar between paroxetine and clomipramine (mean change 2.3 versus 2.4, P = 0.566), but paroxetine was statistically significantly more effective on this measure than other TCAs (mean change 2.3 versus 2.1, P = 0.028). The proportion of patients who experienced adverse events with > 1% incidence was statistically significantly lower with paroxetine than with clomipramine (64% versus 77%, P = 0.02) or other TCAs (64% versus 71%, P < 0.001). The incidence of patient withdrawals due to adverse events was also statistically significantly lower with paroxetine than with clomipramine (17% versus 27%, P = 0.014), but an advantage seen for paroxetine over other TCAs (17% versus 20%, P = 0.130) did not reach statistical significance. These findings demonstrate that paroxetine has comparable efficacy to and better tolerability than TCAs, including clomipramine, and is therefore an appropriate treatment strategy for depression, particularly in the common clinical situation where concomitant anxiety symptoms are present.     

In vivo neuroimaging correlates of the efficacy of paroxetine in the treatment of mood and anxiety disorders

The advent of neuroimaging technology has brought with it a deeper understanding of brain function and structure in health and psychiatric illness. This article overviews pertinent findings from neuroimaging studies in mood and anxiety disorders. Paroxetine is a particularly well-studied psychopharmacologic agent in this regard. The findings of neuroimaging studies of paroxetine will be placed into perspective for a better understanding of the interaction of this selective serotonin reuptake inhibitor (SSRI) with the serotonergic and noradrenergic systems in the brain that mediate clinical efficacy. When considered in the context of a burgeoning literature on neuroimaging research of the pathophysiology of mood and anxiety disorders, the findings of paroxetine studies suggest a neurobiological explanation for the mechanisms whereby chronic administration of paroxetine affects neural systems involved in the pathophysiology of major depression and several anxiety disorders such as obsessive-compulsive disorder, posttraumatic stress disorder, and social anxiety disorder.     

The efficacy of selective serotonin reuptake inhibitors in adult social anxiety disorder: a meta-analysis of double-blind, placebo-controlled trials

Social anxiety disorder is associated with impairment in social and occupational functioning, significant personal distress and a possible economic burden, resulting in a reduction in quality of life. To understand better the efficacy of selective serotonin reuptake inhibitors in social anxiety disorder, randomized, double-blind, placebo-controlled trials were evaluated. Pubmed and PsychINFO electronic databases were searched for social anxiety disorder, social phobia, selective serotonin reuptake inhibitors, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline. Fifteen published, randomized, double-blind, placebo-controlled trials of selective serotonin reuptake inhibitors in social anxiety disorder were identified. Design, subject number, drug and dose, trial length, rating instruments, and baseline and end point data were extracted and then verified independently by a second investigator. Effect sizes were calculated from mean changes in drug and placebo groups in the Liebowitz Social Anxiety Scale and the Sheehan Disability Scale, as well as from other scales where available. For the binary data of the Clinical Global Impression of Change scores, Theta log-odds ratios (the effect-size measure appropriate for binary data) were calculated from proportion changes. Effect sizes for the Liebowitz Social Anxiety Scale ranged from -0.029 to 1.214. Effect sizes for the Sheehan Disability Scale ranged from 0.203 to 0.480 for work, 0.237 to 0.786 for social function, and 0.118 to 0.445 for family function. The Theta log-odds ratios for Clinical Global Impression of Change scores ranged from 0.644 to 3.267. Consistent with previous studies, selective serotonin reuptake inhibitors appear more effective than placebo for social anxiety disorder, with improvement extending into social and occupational function.     

Paroxetine in the treatment of post-traumatic stress disorder: pooled analysis of placebo-controlled studies

Post-traumatic stress disorder (PTSD) is increasingly understood to be a medical disorder characterised by particular psychobiological dysfunctions that respond to specific treatments. Paroxetine is a selective serotonin re-uptake inhibitor that has been found effective in the treatment of major depression as well as a range of anxiety disorders. This paper reviews data on the use of paroxetine for the treatment of adult PTSD. There have been three 12-week, placebo-controlled studies of paroxetine in PTSD. As these followed a partly similar design, a pooled analysis of the studies is possible and is reported here. Paroxetine is effective in the short-term treatment of PTSD, resulting in significantly better response and remission rates than placebo, improving sleep disturbance and reducing each of the symptom clusters of PTSD, as well as the disability associated with this condition. The medication is effective in both male and female PTSD patients and whether or not there are comorbid disorders such as depression.     

Paroxetine in the treatment of post-traumatic stress disorder: pooled analysis of placebo-controlled studies

Post-traumatic stress disorder (PTSD) is increasingly understood to be a medical disorder characterised by particular psychobiological dysfunctions that respond to specific treatments. Paroxetine is a selective serotonin re-uptake inhibitor that has been found effective in the treatment of major depression as well as a range of anxiety disorders. This paper reviews data on the use of paroxetine for the treatment of adult PTSD. There have been three 12-week, placebo-controlled studies of paroxetine in PTSD. As these followed a partly similar design, a pooled analysis of the studies is possible and is reported here. Paroxetine is effective in the short-term treatment of PTSD, resulting in significantly better response and remission rates than placebo, improving sleep disturbance and reducing each of the symptom clusters of PTSD, as well as the disability associated with this condition. The medication is effective in both male and female PTSD patients and whether or not there are comorbid disorders such as depression.     

Efficacy of the novel anxiolytic pregabalin in social anxiety disorder: a placebo-controlled, multicenter study

Pregabalin is a novel compound in development for the treatment of anxiety disorders. The safety and efficacy of pregabalin for the treatment of social anxiety disorder was evaluated in a double-blind, multicenter clinical trial in which 135 patients were randomized to 10 weeks of double-blind treatment with either pregabalin 150 mg/d. pregabalin 600 mg/d, or placebo. The primary efficacy parameter was change from baseline to end point in the Liebowitz Social Anxiety Scale (LSAS) total score. Safety was assessed through clinical and laboratory monitoring, and recording spontaneously reported adverse events. Ninety-four patients (70%) completed the 11-week double-blind treatment phase. LSAS total score was significantly decreased by pregabalin 600 mg/d treatment compared with placebo (P = 0.024, analysis of covariance). Significant differences (P < or = 0.05) between pregabalin 600 mg/d and placebo were seen on several secondary measures including the LSAS subscales of total fear, total avoidance, social fear, and social avoidance, and the Brief Social Phobia Scale fear subscale. Pregabalin 150 mg/d was not significantly better than placebo on any measures. Somnolence and dizziness were the most frequently occurring adverse events among patients receiving pregabalin 600 mg/d. In conclusion, pregabalin 600 mg/d was an effective and well-tolerated treatment of social anxiety disorder.     

A double-blind, placebo-controlled study of a flexible dose of venlafaxine ER in adult outpatients with generalized social anxiety disorder

Venlafaxine extended release (ER) is a dual serotonin-norepinephrine reuptake inhibitor previously shown to be effective in the treatment of major depressive disorder and generalized anxiety disorder. This placebo-controlled, multicenter, randomized, double-blind trial examined the efficacy and safety of venlafaxine ER in outpatients with generalized social anxiety disorder. Two hundred seventy-two outpatients were randomly assigned to receive either a flexible dose of venlafaxine ER (75 to 225 mg/d) or placebo for 12 weeks. Venlafaxine ER was statistically significantly more effective than placebo as demonstrated by the Liebowitz Social Anxiety Scale total scores at weeks 4 to 12. Scores of both the Clinical Global Impression-Severity and Clinical Global Impression-Improvement scales showed that venlafaxine ER was significantly more effective than placebo at weeks 4 to 12. In addition, more venlafaxine ER-treated patients achieved CGI-Improvement scores of 1 or 2 than placebo-treated patients at weeks 4 to 12, demonstrating a greater percentage of responders to venlafaxine ER treatment. Assessment using the fear/anxiety and avoidance subscales of the Liebowitz Social Anxiety Scale and the Social Phobia Inventory Scale also showed venlafaxine ER to be more effective than placebo at weeks 4 to 12 and 6 to 12, respectively. The Sheehan Disability Inventory showed that patients in the venlafaxine ER-treated group had significantly better outcomes in social life at weeks 4 and 12, and in work at week 12. Adverse events were similar to those reported in studies of venlafaxine ER in depression and generalized anxiety disorder. Venlafaxine ER was safe, well tolerated, and efficacious in the short-term treatment of generalized social anxiety disorder.