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: 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.     

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.     

Clinical experience with paroxetine in social anxiety disorder

Paroxetine is a selective serotonin reuptake inhibitor (SSRI) with proven efficacy in the treatment of depression, panic disorder and obsessive-compulsive disorder. Evidence that paroxetine may be effective in social anxiety disorder (social phobia) first arose from open-label studies. More recently, three multicentre, randomized, placebo-controlled trials have been performed, each lasting 12 weeks, to assess the efficacy and tolerability of paroxetine in the treatment of social anxiety disorder, and these studies are reviewed here. The data from all three studies consistently demonstrated that paroxetine was effective in reducing both the symptoms of anxiety and the disability and impairment of social anxiety disorder. Paroxetine performed significantly better than placebo on all primary (Liebowitz Social Anxiety Scale, Clinical Global Impression) and secondary (Social Avoidance and Distress Scale, Sheehan Disability Scale) outcome measures. Adverse events were restricted to those already known to be associated with SSRIs, no serious adverse events associated with medication were experienced, and the numbers withdrawing from the studies were not significantly different in the paroxetine and control groups. Taken together, these studies confirm that paroxetine is an effective and well tolerated treatment for patients with social anxiety disorder.     

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.     

The relationship between adverse events during selective serotonin reuptake inhibitor treatment for major depressive disorder and nonremission in the suicide assessment methodology study

Little is known about the association between antidepressant treatment-emergent adverse events and symptom nonremission in major depressive disorder. The objective of the current analysis was to determine whether particular baseline symptoms or treatment-emergent symptoms (adverse events) during the first 2 weeks are associated with nonremission after 8 weeks of treatment with a selective serotonin reuptake inhibitor (SSRI).Outpatients clinically diagnosed with nonpsychotic major depressive disorder were recruited from 6 primary and 9 psychiatric care sites. Participants (n = 206) were treated with an SSRI antidepressant (citalopram [20-40 mg/d], escitalopram [10-20 mg/d], fluoxetine [20-40 mg/d], paroxetine [20-40 mg/d], paroxetine CR [25-37.5 mg/d], or sertraline [50-150 mg/d]) for 8 weeks. Remission was defined as having a score of 5 or less on the 16-item Quick Inventory of Depressive Symptomatology-Clinician-Rated at week 8, or using last observation carried forward. Adverse events were identified using the 55-item Systematic Assessment for Treatment Emergent Events-Systematic Inquiry completed by participants at baseline and week 2.Findings indicated that the emergence of adverse events of weakness/fatigue, strange feeling, and trouble catching breath/hyperventilation at week 2 were independently associated with lack of remission even after controlling for the potential confounders of baseline depressive severity, anxious symptoms, antidepressant medication, chronic depression, race, burden of general medical comorbidity, and time in study. Hearing/seeing things appeared to have a protective effect. In conclusion, during SSRI treatment, the adverse events of weakness/fatigue, feeling strange, and trouble catching breath/hyperventilation are associated with nonremission, possibly due to lower adherence, early attrition, difficulty increasing the dose, and reduced efficacy.     

Neuropharmacology of paroxetine

Paroxetine is a potent and selective serotonin reuptake inhibitor (SSRI) with some neuropharmacologic properties unique among this class of compounds. The findings of early in vitro studies demonstrated the potency of paroxetine at inhibiting 5-HT uptake in rat synaptosomes. Paroxetine also has been shown to be a potent and selective inhibitor of the human serotonin transporter (SERT) and has recently been demonstrated to have moderate affinity for the norepinephrine transporter (NET). Because of the affinity and in vitro selectivity of this SSRI, tritiated paroxetine is now widely used as a marker for SERT in laboratory settings, and its use has advanced our understanding of neurotransmitter function in the brain and periphery. The in vivo pharmacologic properties of paroxetine are well characterized, especially following acute administration. However, the pharmacologic effects of chronically administered paroxetine remain an active area of study. Paroxetine administration in laboratory animals has been shown to be associated with decreased SERT density and function, maintenance of normal firing rates and release of 5-HT, and increased activation of postsynaptic 5-HT receptors. Using a novel ex vivo assay, we have demonstrated that paroxetine exhibits dose-related inhibition of the NET in patients treated for depression. At usual clinical doses (ie, 20 mg/d), paroxetine is a potent and selective inhibitor of the SERT; however, at higher doses (ie, 40 mg/d), paroxetine can exhibit marked NET inhibition. The application of these findings of in vivo NET inhibition by paroxetine in the treatment of mood and anxiety disorders will be informed by further clinical studies.     

Paroxetine treatment of major depressive disorder

Major depression is recognized as a common, often chronic and recurrent illness that is associated with significant disability and comorbidity. The treatment of patients with major depressive disorder has advanced tremendously in the past decade as a result of the availability of effective and well-tolerated antidepressants. Paroxetine is a widely studied selective serotonin reuptake inhibitor (SSRI) with evidence for efficacy and safety that is supported by a large body of published literature. Evidence for the efficacy and tolerability of anew controlled-release formulation of paroxetine also has been published. Findings from paroxetine clinical studies have added considerably to our knowledge and understanding of the treatment of major depressive disorder, particularly with regard to duration of treatment, the need for treating to full remission and with full doses, and treatment of patients with concurrent symptoms of anxiety.     

Evaluating the economic consequences of early antidepressant treatment discontinuation: a comparison between controlled-release and immediate-release paroxetine

INTRODUCTION: Early antidepressant discontinuation has been linked to significant clinical and economic consequences. Clinical practice guidelines suggest that treatment should last for at least 3 to 9 months into the continuation phase; however, 30% of patients discontinue therapy within 30 days, and over 40% discontinue therapy within 90 days of initiation, primarily due to adverse events. Clinical trials have shown that controlled-release (CR) paroxetine has a favorable tolerability profile when compared to immediate-release (IR) paroxetine, which may result in lower discontinuation rates and improved economic outcomes. This is the first study to directly compare treatment discontinuation rates and health care expenditures of a CR selective serotonin reuptake inhibitors with its IR counterpart. METHODS: This matched retrospective study used claims from a national managed care database to assess differences in discontinuation rates and health care expenditures between paroxetine CR and IR for treating depression and/or anxiety. Discontinuation was assessed by survival analysis, and health care expenditure was assessed using average monthly medical and pharmacy charges. RESULTS: There were 1275 paroxetine CR patients and 2550 paroxetine IR patients matched in the analysis. At 90 days, 62% of paroxetine CR patients continued therapy versus 56% of paroxetine IR patients. At 180 days, 51% of paroxetine CR patients continued therapy versus 42% of paroxetine IR patients. When evaluating all medical charges, paroxetine CR patients incurred US 119 dollars less per month than paroxetine IR patients (P = 0.054). CONCLUSIONS: Patients receiving paroxetine CR remained on therapy longer than patients on paroxetine IR, which resulted in lower total monthly medical costs for patients receiving paroxetine CR. Differences in costs were primarily driven by reduction in hospitalization expenditures.     

帕罗西汀与小剂量奥氮平治疗老年抑郁症的临床疗效

目的 探讨帕罗西汀与小剂量奥氮平治疗老年抑郁症的临床疗效.方法 选取无锡市精神卫生中心2018年9月-2019年9月收治的老年抑郁症患者100例,按照奇偶法分为奥氮平组和帕罗西汀组,每组50例.帕罗西汀组予以帕罗西汀治疗,奥氮平组在帕罗西汀组基础上予以小剂量奥氮平治疗.2组均治疗8周.比较2组治疗前后抑郁自评量表(SD...     

帕罗西汀与丙米嗪治疗脑卒中后抑郁比较

目的 :比较帕罗西汀与丙米嗪治疗脑卒中后抑郁的疗效及不良反应。方法 :12 1例病人随机分 2组 ,帕罗西汀组 6 1例 (男性 35例 ,女性 2 6例 ;年龄 6 2a±s 10a) ,给帕罗西汀首剂 10mg ,以后 2 0mg ,po ,qd ;6wk为一个疗程。丙米嗪组 6 0例 (男性 33例 ,女性 2 7例 ;年龄 6 3a± 11a) ,给丙米嗪d 1～ 2 2 5mg ,d 3～ 5 5 0mg ,d 6起 75mg ,po ,bid ;6wk为一个疗程。结果 :帕罗西汀组有效率 84 % ,丙米嗪组有效率 82 % ,2组Ridit分析P >0 .0 5。丙米嗪组不良反应较多。结论 :帕罗西汀可用于治疗脑卒中后抑郁     

Paroxetine: new indication. In social phobia: minimal assessment

Social phobia is generally defined as an intense and persistent fear of one or several social situations, with important repercussions for occupational activity or social life. Cognitive psychotherapy and antidepressants have partial efficacy. There is no reference drug therapy. In France, paroxetine is the first drug to be granted a licence for patients with social phobia. Clinical evaluation consists of data from four placebo-controlled trials lasting only 12 to 24 weeks. Treatment with paroxetine was associated with a significant improvement in standard social-phobia scores, although most patients remained symptomatic. Paroxetine is the best assessed selective serotonin reuptake inhibitor in this setting. However, long-term data are lacking, and the disorder is chronic. Paroxetine has not been compared with cognitive therapy. About one-third of patients in clinical trials stopped taking paroxetine, mainly because of adverse events. Gastrointestinal upset, sleep disturbance and ejaculatory problems are frequent. Paroxetine also has the potential to interact with other drugs. In practice, paroxetine may help some patients, provided they are aware of its limitations. The long-term effects of paroxetine in this setting remain unknown.     

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.     

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.     

帕罗西汀与阿米替林治疗躯体化障碍的疗效比较

目的比较帕罗西汀与阿米替林治疗躯体化障碍的疗效和不良反应。方法81例躯体化障碍患者随机分成2组,分别用帕罗西汀与阿米替林治疗8 wk。用症状自评量表(SCL-90)中的躯体化、抑郁和焦虑3个因子总分评定症状变化,用不同减分率评定疗效。用不良反应量表(TESS)评定药物不良反应。结果帕罗西汀组痊愈率为61.90%,总有效率为90.48%;阿米替林的痊愈率为43.59%,总有效率为71.79%,2组疗效比较差异有统计学意义(P<0.05)。2组TESS测评,各时点组间比较,差异有统计学或高度统计学意义(P<0.05或P<0.01)。结论帕罗西汀治疗躯体化障碍疗效确切,不良反应较小。     

Sertraline and obsessive compulsive disorder: new indication. Limited assessment

(1) Sertraline, a selective serotonin reuptake inhibitor (SSRI), is now licensed in France for the treatment of obsessive-compulsive disorder in adults. (2) In this indication the clinical file is of acceptable methodological quality, but it is incomplete: sertraline has not been compared with the other two serotonin reuptake inhibitors approved in obsessive-compulsive disorder, namely fluoxetine and paroxetine. (3) Three placebo-controlled trials have demonstrated the efficacy of sertraline in obsessive-compulsive disorder. (4) In a trial versus clomipramine, sertraline was no more effective in patients able to tolerate the drug, but the rate of treatment withdrawals for adverse events was higher on clomipramine.     

Paroxetine treatment of mood disorders in women: premenstrual dysphoric disorder and hot flashes

With the relatively recent introduction of the selective serotonin reuptake inhibitor (SSRI) class of antidepressants, increased attention has been focused on the use of antidepressants in the treatment of mood disorders across the female life cycle. Evidence for the efficacy of antidepressants in the treatment of premenstrual dysphoric disorder (PMDD) and hot flashes associated with menopause and breast cancer has emerged. The clinical trials experience with paroxetine and the controlled-release (CR) formulation of paroxetine is reviewed.