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.     

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.     

Treatment of depression with comorbid anxiety disorders: differential efficacy of paroxetine versus moclobemide

To compare the efficacy and tolerability of moclobemide versus paroxetine for the treatment of depression with comorbid anxiety disorders. Outpatients fulfilling DSM-III-R criteria for major depression or dysthymia and for a co-occurring comorbid anxiety disorder (panic disorder, generalized anxiety disorder or obsessive-compulsive disorder) after a 1-week run-in phase were randomly assigned to open-label moclobemide (300-600 mg/day) or paroxetine (20-40 mg/day) for 4 months. Primary criterion for response was a 50% score reduction from baseline on Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale scores. Mean changes in Clinical Global Impressions Severity of Illness and Improvement Scales (CGI-I) were also used to evaluate treatment response. Of the 123 patients included in the study, 65 were randomly assigned to moclobemide and 58 to paroxetine. At study end, the two treatment groups did not differ significantly in terms of proportion of responders. Treatment group differences emerged when comorbid anxiety diagnoses were considered. In patients with comorbid panic disorder, paroxetine was superior to moclobemide in improving both anxiety and depression (five patients out of 18 in the moclobemide group and nine out of 14 in the paroxetine group were rated as responders according to CGI-I, P = 0.04). Neither medication was superior in treating comorbid generalized anxiety disorder. These findings indicate that both moclobemide and paroxetine are effective for treatment of depression with comorbid anxiety disorders. However, in the subgroup with comorbid panic disorder, paroxetine is more effective than moclobemide in reducing both depressive and anxiety symptoms.     

Obsessive-compulsive disorder: implications of the efficacy of an SSRI, paroxetine

Obsessive-compulsive disorder (OCD) is an anxiety disorder that commonly presents comorbidly with other psychiatric disorders. The underlying neurobiology of OCD is associated with circuits involving the basal ganglia, thalamus, and the frontal cortex. Randomized, placebo-controlled trials indicate acute and long-term efficacy of potent selective serotonin reuptake inhibitors (SSRIs), such as paroxetine. There is suggestive evidence that higher doses of paroxetine than those used in major depression are needed for benefit in OCD. Because of their safety and beneficial adverse-event profile, the SSRIs have become the leading choice in the pharmacological management of OCD.     

A meta-analysis of pharmacotherapy for social anxiety disorder: an examination of efficacy,moderators, and mediators

Introduction: Social anxiety disorder (SAD) is among the most prevalent mental disorders, associated with impaired functioning and poor quality of life. Pharmacotherapy is the most widely utilized treatment option. The current study provides an updated meta-analytic review of the efficacy of pharmacotherapy and examines moderators and mediators of treatment efficacy.

Areas Covered: A comprehensive search of the current literature yielded 52 randomized, pill placebo-controlled trials of pharmacotherapy for adults diagnosed with SAD. Data on potential mediators of treatment outcome were collected, as well as data necessary to calculate pooled correlation matrices to compute indirect effects.

Expert Opinion: The overall effect size of pharmacotherapy for SAD is small to medium (Hedges’ g = 0.41). Effect sizes were not moderated by age, sex, length of treatment, initial severity, risk of study bias, or publication year. Furthermore, reductions in symptoms mediated pharmacotherapy’s effect on quality of life. Support was found for reverse mediation. Future directions may include sustained efforts to examine treatment mechanisms of pharmacotherapy using rigorous longitudinal methodology to better establish temporal precedence.     

Defining an appropriate management strategy for social anxiety disorder

Social anxiety disorder is a chronic and disabling, yet treatable, condition. Effective treatment should alleviate the core domains of fear, anxiety and physiological symptoms, as well as reduce overall disability and improve social functioning. Response to treatment can, therefore, be assessed at a global level where overall improvement is considered, and at the level of individual symptoms. In considering the way in which response to treatment can be measured, this review also identifies several factors that may worsen the prognosis of social anxiety disorder. Clinical studies of monoamine oxidase inhibitors, selective serotonin reuptake inhibitors (SSRIs), and benzodiazepines for the treatment of social anxiety disorder are presented and discussed. The accumulation of evidence supports the use of SSRIs as first line therapy for social anxiety disorder, and the majority of data come from well controlled studies of paroxetine. In line with the recommendations of the International Consensus Group on Depression and Anxiety, a strategy for the management of social anxiety disorder is provided.     

Tiagabine for social anxiety disorder

Tiagabine, a selective gamma-aminobutyric acid (GABA) reuptake inhibitor was evaluated for the treatment of patients with social anxiety disorder (SAD). Adults with SAD received open-label tiagabine 4-16 mg per day for 12 weeks. Intent-to-treat data are available for 54 patients with improvement demonstrated in Liebowitz Social Anxiety Scale, Clinician Global Impression-Severity (CGI-S) and -Improvement (CGI-I), Social Phobia Inventory, and Sheehan Disability Scale scores. In all, 40.7% (22/54) of the intent to treat sample and 63.0% (17/27) of the completer sample were considered CGI responders (CGI-I score of one or two). Tiagabine was generally well tolerated. Results of this pilot study suggest that tiagabine may be an option for the treatment of patients with SAD. Larger, controlled studies are required to fully elucidate the potential of tiagabine for the treatment of SAD.     

帕罗西汀联合阿普唑仑治疗广泛性焦虑症的疗效观察

目的探讨帕罗西汀联合阿普唑仑治疗广泛性焦虑症患者的疗效,关注其对焦虑和抑郁评分的影响,以期为临床工作提供帮助。方法收集本院诊治的广泛性焦虑症的患者80例,随机分为观察组（40例）与对照组（40例）,对照组单纯应用帕罗西汀治疗,观察组应用帕罗西汀联合阿普唑仑治疗,观察治疗对患者焦虑和抑郁评分的影响。结果观察组在治疗2、4、8周后对焦虑和抑郁的改善情况明显优于对照组,两组差异有统计学意义（P〈0.05）。结论帕罗西汀联合阿普唑仑治疗广泛性焦虑症患者的疗效明显,对焦虑和抑郁改善的效果理想,临床中可以积极应用。     

Neurobehavioral effects of interferon-alpha in cancer patients: phenomenology and paroxetine responsiveness of symptom dimensions.

We have previously shown that the risk of major depression in patients with malignant melanoma undergoing interferon-alpha (IFN-alpha) therapy can be reduced by pretreatment with the antidepressant, paroxetine. Using dimensional analyses, the present study assessed the expression and treatment responsiveness of specific clusters of neuropsychiatric symptoms over the first three months of IFN-alpha therapy. Forty patients with malignant melanoma eligible for IFN-alpha treatment were randomly assigned to receive either paroxetine or placebo in a double-blind design. Neuropsychiatric assessments were conducted at regular intervals during the first twelve weeks of IFN-alpha therapy and included the 21-item Hamilton Depression Rating Scale, the 14-item Hamilton Anxiety Rating Scale and the Neurotoxicity Rating Scale. Neurovegetative and somatic symptoms including anorexia, fatigue and pain appeared within two weeks of IFN-alpha therapy in a large proportion of patients. In contrast, symptoms of depressed mood, anxiety and cognitive dysfunction appeared later during IFN-alpha treatment and more specifically in patients who met DSM-IV criteria for major depression. Symptoms of depression, anxiety, cognitive dysfunction and pain were more responsive, whereas symptoms of fatigue and anorexia were less responsive, to paroxetine treatment. These data demonstrate distinct phenomenology and treatment responsiveness of symptom dimensions induced by IFN-alpha, and suggest that different mechanisms mediate the various behavioral manifestations of cytokine-induced "sickness behavior."     

帕罗西汀联合放松疗法在焦虑症中的应用效果观察

目的 探讨帕罗西汀辅以放松疗法治疗焦虑症的临床效果.方法 回顾性分析80例焦虑症患者的临床资料,其中40例患者采用帕罗西汀辅以放松疗法治疗为研究组,40例患者采用帕罗西汀治疗为对照组.比较两组患者治疗第1、2、6周末的焦虑量表评分结果.结果 治疗后研究组患者第1、2、6周末的HAMA评分显著低于对照组（P＜0.01）.用药第6周,研究组帕罗西汀的平均剂量显著少于对照组（P＜0.05）.两组不良反应比较差异无统计学意义（P＞0.05）.结论 帕罗西汀辅以放松疗法治疗焦虑征能够显著提高临床效果,减少药物使用剂量,值得临床推广应用.     

Escitalopram versus placebo in the treatment of dysthymic disorder

Numerous studies have assessed the acute efficacy of antidepressants, including selective serotonin reuptake inhibitors, in treating dysthymic disorder; however, escitalopram, the S-enantiomer of citalopram, has not been studied. Thirty-six outpatients with Structured Clinical Interview for DSM-III-R-diagnosed dysthymic disorder, aged 23-65 years (mean±SD=44.7±11 years), were randomly assigned to double-blind escitalopram (maximum dose 20?mg/day) versus placebo for 12 weeks. Inclusion criteria included age 18-65 years and Hamilton Depression Rating Scale (HDRS) score≥12. We hypothesized that escitalopram would be superior to placebo in the HDRS-24 item total score at week 12. We also hypothesized the superiority of escitalopram over placebo for secondary measures, including the percentage of participants classified as responders and remitters, as well as social functioning (Social Adjustment Scale), clinical global impression-improvement, Global Assessment of Functioning Scale. Participants' baseline HDRS-24 averaged 23.4±5.9. Final HDRS-24 scores at last observation carried forward did not differ significantly between escitalopram-treated (mean±SD=10.88±5.83) and placebo-treated individuals (mean±SD=16.4±6.34) (F=2.82, degrees of freedom=1,32, P=0.10). Significant differences favoring active medication were found on the Social Adjustment Scale and the Clinical Global Impression Severity and Global Assessment of Functioning Scale, but not in the percentages of responders or remitters. A larger study sample or higher escitalopram dose may show more significant placebo-medication differences.     

Pharmacotherapy of social anxiety disorder

INTRODUCTION: Social anxiety disorder (SAD) is one of the most common psychiatric disorders, with a lifetime prevalence of 5-12%. Fears of scrutiny and embarrassment in social and public situations are accompanied by anxiety symptoms, avoidance behavior, and impairment in social and work functioning. Several classes of medication, as well as cognitive-behavioral therapies, have evidence for efficacy in the treatment of SAD, but only a minority of individuals with the disorder receives treatment. AREAS COVERED: This review focuses on the evidence-based treatment of SAD with medications including serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, other antidepressants, benzodiazepines, alpha-delta calcium-channel agents, and beta-adrenergic blockers. It discusses clinical considerations in the selection and monitoring of treatments, including issues of safety, duration of treatment, comorbidity, and integration of medication with psychotherapeutic treatment. For this review, a PubMed literature search was conducted during July, 2010. EXPERT OPINION: Medications in several classes have been demonstrated efficacious in the treatment of SAD. Treatment selection and implementation require attention to clinical diagnosis, patient education, and appropriate monitoring.     

Drugs in development for social anxiety disorder: more to social anxiety than meets the SSRI

Individuals with social phobia (SP) fear and avoid a wide variety of social and performance situations in which they are exposed to unfamiliar persons or to possible scrutiny by others. The lifetime prevalence of SP is estimated to be as high as 13%. It is frequently co-morbid with and usually precedes the onset of other psychiatric illnesses and is associated with significant occupational and social impairment, including academic and vocational underachievement. Fortunately, there are effective treatments for this common and debilitating condition. There is currently considerable evidence for the efficacy of pharmacotherapy and especially the monoamine oxidase inhibitors (MAOIs) and selective serotonin re-uptake inhibitors (SSRIs) in the treatment of this disorder. However, SSRIs are generally preferred as the first-line treatment of choice due to the advantages of SSRIs over MAOIs in terms of safety and tolerability. Despite encouraging results, current treatments most often produce partial symptomatic improvement, rather than high end-state functioning. While current first line treatments for social phobia target the serotonergic system, it is important to remember that different social fears are likely to have different developmental roots and may be based on quite different neurobiological systems. In this article we provide a review of current pharmacotherapeutic options for SP, current knowledge of the neurobiology of SP, and a review of new and promising directions in pharmacological research. It is increasingly clear that serotonin (5-HT) is unlikely to be the whole story in SP and that other brain chemical systems, especially the dopaminergic, noradrenaline-corticotropin releasing hormone and gamma-aminobutyric acid (GABA) dependent systems, most probably have an important role to play in a substantial percentage of cases. A number of new and novel agents, including the substance P antagonists, GABA agonists and CRF antagonists show considerable promise in the treatment of SP. However, in order to enhance the understanding of the neurobiology and treatment response of SP, we need to develop more sophisticated theory-driven typologies of SP.     

Drugs in development for social anxiety disorder: more to social anxiety than meets the SSRI

Individuals with social phobia (SP) fear and avoid a wide variety of social and performance situations in which they are exposed to unfamiliar persons or to possible scrutiny by others. The lifetime prevalence of SP is estimated to be as high as 13%. It is frequently co-morbid with and usually precedes the onset of other psychiatric illnesses and is associated with significant occupational and social impairment, including academic and vocational underachievement. Fortunately, there are effective treatments for this common and debilitating condition. There is currently considerable evidence for the efficacy of pharmacotherapy and especially the monoamine oxidase inhibitors (MAOIs) and selective serotonin re-uptake inhibitors (SSRIs) in the treatment of this disorder. However, SSRIs are generally preferred as the first-line treatment of choice due to the advantages of SSRIs over MAOIs in terms of safety and tolerability. Despite encouraging results, current treatments most often produce partial symptomatic improvement, rather than high end-state functioning. While current first line treatments for social phobia target the serotonergic system, it is important to remember that different social fears are likely to have different developmental roots and may be based on quite different neurobiological systems. In this article we provide a review of current pharmacotherapeutic options for SP, current knowledge of the neurobiology of SP, and a review of new and promising directions in pharmacological research. It is increasingly clear that serotonin (5-HT) is unlikely to be the whole story in SP and that other brain chemical systems, especially the dopaminergic, noradrenaline-corticotropin releasing hormone and γ-aminobutyric acid (GABA) dependent systems, most probably have an important role to play in a substantial percentage of cases. A number of new and novel agents, including the substance P antagonists, GABA agonists and CRF antagonists show considerable promise in the treatment of SP. However, in order to enhance the understanding of the neurobiology and treatment response of SP, we need to develop more sophisticated theory-driven typologies of SP.     

电针与帕罗西汀治疗惊恐障碍的临床疗效

目的 比较电针疗法与帕罗西汀片治疗惊恐障碍的疗效和安全性。方法 将59例随机分为电针组(30例)和帕罗西汀组(29例),疗程为4周。在治疗前及治疗1、2、4、8周时采用焦虑自评量表(SAS)、汉密尔顿抑郁量表(HAMA)、疗效指数(CGI-EI)、Barthel指数(BI)量表评定疗效和不良反应。结果 电针组总有效率为86.66%,帕罗西汀组为82.76%,两组疗效差异无统计学意义;疗效指数及起效时间两组间有显著差异,电针组起效时间短、不良反应少。结论 两种方法治疗惊恐障碍疗效相当,但电针疗法起效时间短、疗效指数高、不良反应少。     

Pregabalin for the treatment of social anxiety disorder

Introduction: Social anxiety disorder (SAD) is one of the most common psychiatric disorders, causing a reduction of in the quality of life by impairing functioning in social situations. The lifetime prevalence of SAD is estimated to be 12%. Selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs) are considered first-line drugs for SAD. However, new effective therapeutic options are still needed. Pregabalin is a novel anxiolytic, which seems to be a promising therapy for SAD.

Areas covered: This review presents the results of three randomized controlled trials (RCTs) comparing the efficacy and safety of pregabalin with placebo in patients with generalized SAD. The authors also discuss the long-term safety and tolerability data from an extension study.

Expert opinion: The results of the RCTs have demonstrated efficacy and safety with pregabalin at doses of 600 mg or 450 mg/d for treating generalized SAD. Thus, pregabalin may be an effective therapeutic option, especially for patients who cannot tolerate the adverse effects or who demonstrate a lack of efficacy with SSRIs or SNRIs. In addition to being an alternative therapy to SSRIs or SNRIs, it may also have value as an add-on therapy, either to augment pharmacotherapy or in addition to cognitive-behavioral therapy.     

Efficacy of Venlafaxine ER in patients with social anxiety disorder: a double-blind, placebo-controlled, parallel-group comparison with paroxetine

This study evaluated the anxiolytic efficacy, safety and tolerability of a flexible dose of venlafaxine extended release (ER) compared with placebo and paroxetine in the short-term treatment of generalized social anxiety disorder (SAD). Adult outpatients with generalized SAD (n = 434) were randomized to receive capsules of venlafaxine ER 75 mg to 225 mg/day, paroxetine 20 mg to 50 mg/day, or placebo for 12 weeks. The primary efficacy variable was the Liebowitz social anxiety scale total score. Secondary efficacy variables included the patient-rated social phobia inventory and the proportion of responders in each group (a responder was defined as having a clinical global impression-improvement score of 1 or 2). Treatment with venlafaxine ER was associated with significantly greater improvement than treatment with placebo for all primary and secondary efficacy variables (p < 0.05). No significant differences in primary or secondary efficacy variables were observed between the venlafaxine ER and paroxetine groups. The week 12 response rates were 69%, 66% and 36% for the venlafaxine ER, paroxetine and placebo groups, respectively. Both active treatments were generally well tolerated and were associated with a similar incidence of adverse events. This study shows that venlafaxine ER is an effective, safe and well-tolerated drug treatment for SAD.     

社交焦虑障碍的药物治疗

社交焦虑障碍是常见的焦虑障碍之一.目前临床常用治疗药物主要有选择性5-羟色胺再摄取抑制剂(SSRI)、选择性5-羟色胺和去甲肾上腺素再摄取抑制剂(SSNRI)及苯二氮(艹卓)类药物等.本文综述药物治疗近况.