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 in the treatment of generalised anxiety disorder

Paroxetine is a selective serotonin re-uptake inhibitor useful in the treatment of a wide range of psychiatric disorders. Generalised anxiety disorder (GAD) is characterised by excessive persistent anxiety and worry about a number of events and activities occurring on more days than not for at least 6 months. GAD is the most common anxiety disorder in primary care settings. Paroxetine was the second antidepressant to receive an FDA indication for the treatment of GAD. In contrast to benzodiazepines, which had been the mainstay of treatment for anxiety disorders for many years, antidepressants, such as paroxetine, are more effective for the psychic symptoms of anxiety, which include worry, tension, irritability and concentration difficulties, and carry a more tolerable and safe side effect profile.     

Paroxetine in the treatment of generalised anxiety disorder

Paroxetine is a selective serotonin re-uptake inhibitor useful in the treatment of a wide range of psychiatric disorders. Generalised anxiety disorder (GAD) is characterised by excessive persistent anxiety and worry about a number of events and activities occurring on more days than not for at least 6 months. GAD is the most common anxiety disorder in primary care settings. Paroxetine was the second antidepressant to receive an FDA indication for the treatment of GAD. In contrast to benzodiazepines, which had been the mainstay of treatment for anxiety disorders for many years, antidepressants, such as paroxetine, are more effective for the psychic symptoms of anxiety, which include worry, tension, irritability and concentration difficulties, and carry a more tolerable and safe side effect profile.     

Increased urinary tribulin output in generalised anxiety disorder

Urinary output of an endogenous monoamine oxidase inhibitor and benzodiazepine receptor binding inhibitor (tribulin) was raised in a group of patients with generalised anxiety disorder compared with controls. Tribulin levels remained relatively constant in individual patients over the 6-week period of observation, mean values remaining high even after reduction of anxiety following non-drug behaviour therapy.     

Pregabalin: in the treatment of generalised anxiety disorder

Pregabalin, the pharmacologically active S-enantiomer of 3-aminomethyl-5-methyl-hexanoic acid, is a structural analogue of GABA, although it is not active at GABA receptors, nor does it acutely alter GABA uptake or degradation.black triangle Pregabalin binds with high affinity to the alpha2-delta subunit protein of voltage-gated calcium channels in CNS tissues and acts as a presynaptic modulator of the excessive release, in hyperexcited neurons, of various excitatory neurotransmitters. Binding of pregabalin to the alpha2-delta subunit appears necessary for its demonstrable anxiolytic, analgesic and anticonvulsant activities in animal models.black triangle Oral pregabalin, typically at dosages of 300-600 mg/day, was superior to placebo and similar to lorazepam 6 mg/day, alprazolam 1.5 mg/day and venlafaxine 75 mg/day in improving anxiety and depressive symptoms in patients with moderate-to-severe generalised anxiety disorder (GAD). Pregabalin had a rapid onset of anxiolytic activity relative to alprazolam and venlafaxine, which was evident after 1 week. Additionally, pregabalin (initial dosage 450 mg/day) was effective for the prevention of relapse of GAD over 34 weeks. Pregabalin was well tolerated during dosage escalation to fixed dosages (maximum 600 mg/day) over 7 days. Dizziness and somnolence, usually of mild to moderate severity, were the most common adverse events.black triangle The drug was not associated with a clinically significant medication withdrawal syndrome during a 1-week taper following 4 or 6 weeks' double-blind treatment.     

Pregabalin for the treatment of generalised anxiety disorder

Pregabalin is a new anxiolytic that has been recently licensed for the treatment of generalised anxiety disorder (GAD) in Europe. Short-term efficacy is based on six positive placebo-controlled studies, all of which showed a significant early separation from placebo in all of the doses used (150-600 mg) at the first week, and the efficacy at the end of the treatment was comparable with the comparators used in four of these studies. Pregabalin was effective in more or less severe GAD, on psychic and somatic symptoms of GAD, and in treating the subsyndromal depressive symptoms of GAD. Efficacy in the elderly was shown in a separate placebo-controlled study. The effect on cognitive function was minimal and notably less than that observed with benzodiazepines. The discontinuation symptoms following abrupt treatment cessation were similar to the rates with serotonin-noradrenaline re-uptake inhibitors and lower than with benzodiazepines with no signals of tolerance or dependence.     

Pregabalin for the treatment of generalised anxiety disorder

Pregabalin is a new anxiolytic that has been recently licensed for the treatment of generalised anxiety disorder (GAD) in Europe. Short-term efficacy is based on six positive placebo-controlled studies, all of which showed a significant early separation from placebo in all of the doses used (150 – 600 mg) at the first week, and the efficacy at the end of the treatment was comparable with the comparators used in four of these studies. Pregabalin was effective in more or less severe GAD, on psychic and somatic symptoms of GAD, and in treating the subsyndromal depressive symptoms of GAD. Efficacy in the elderly was shown in a separate placebo-controlled study. The effect on cognitive function was minimal and notably less than that observed with benzodiazepines. The discontinuation symptoms following abrupt treatment cessation were similar to the rates with serotonin–noradrenaline re-uptake inhibitors and lower than with benzodiazepines with no signals of tolerance or dependence.     

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.     

曲唑酮与帕罗西汀治疗焦虑症病人睡眠障碍的比较

目的 :比较曲唑酮和帕罗西汀对焦虑症病人睡眠障碍的疗效。方法 :4 5例焦虑症病人随机分为 2组。曲唑酮组 2 2例 ,给予曲唑酮 5 0～ 10 0mg·d- 1,qn× 8wk。帕罗西汀组 2 3例 ,给予帕罗西汀2 0～ 4 0mg·d- 1,qn× 8wk。结果 :睡眠障碍因子评分 :在 1wk时 ,曲唑酮组 3.0±s 1.7,帕罗西汀组4 .0± 1.6 ;在 2wk时 ,曲唑酮组 1.3± 1.2 ,帕罗西汀组 2 .3± 1.3(均P <0 .0 5 )。总睡眠时间 :2组比较在 1wk时差异有非常显著意义 (P <0 .0 1) ;在 2wk时差异有显著意义 (P <0 .0 5 )。早醒现象 :2组比较在 2 ,4wk时差异均有显著意义 (P <0 .0 5 )。睡眠增多、嗜睡不良反应分别为 0 / 2 3,6 / 2 2 (P <0 .0 5 )。结论 :曲唑酮比帕罗西汀改善睡眠见效早、作用快、作用强 ,睡眠时间长 ,早醒现象轻     

Citalopram challenge in social anxiety disorder

The aim of the present study was to evaluate neuroendocrine and behavioural responses to a challenge with the selective serotonin (5-HT) reuptake inhibitor citalopram (Cit) in patients with social anxiety disorder (SAD). Cit was given intravenously (20 mg over 30 min) to 18 patients with SAD and 18 matched healthy subjects in a double-blind, placebo-controlled cross-over design. Cit challenge resulted in the increased plasma concentrations of cortisol and prolactin relatively to placebo without significant differences between the patients and controls. The patients had higher ratings of anxiety that were not affected by Cit, and more headaches than controls after Cit. Thus, the neuroendocrine sensitivity to 5-HT stimulation with Cit in patients with SAD was not different from the response in controls indicating lack of major alterations in the function of 5-HT receptors. The increased headache in patients may suggest hypersensitivity of some subtypes of 5-HT receptors in SAD.     

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.     

Escitalopram versus paroxetine for social anxiety disorder: an analysis of efficacy for different symptom dimensions.

BACKGROUND: A previous factor analysis of pooled data demonstrated that the Liebowitz Social Anxiety Scale (LSAS) can be divided into six subscales. This paper examines data from a fixed-dose trial of escitalopram versus paroxetine, in order to determine the differential effects of these agents on symptom dimensions in social anxiety disorder (SAD). METHODS: Data from a 24-week randomised, placebo-controlled, comparative study of fixed doses of escitalopram (5 mg, 10 mg, 20 mg) versus paroxetine (20 mg) in SAD were examined. The six factors identified in a previous factor analysis of baseline data from escitalopram studies on the primary efficacy scale, the LSAS, were used to compute subscale scores. These were analysed using analysis of covariance (ANCOVA), and standardised effect sizes were calculated. RESULTS: The combined escitalopram data and the paroxetine data both demonstrated significant superiority to placebo on each of the 6 LSAS factors at week 24 (OC analysis). Escitalopram doses of 5 mg, 10 mg, and 20 mg were generally more effective than placebo for each of the factors. Escitalopram 20 mg was significantly more effective than paroxetine 20 mg on 5 of the 6 symptom dimensions. CONCLUSION: Factor analysis of the LSAS allows for useful secondary analyses that support and extend the primary efficacy analysis of this instrument. The analysis here indicates that different escitalopram doses are effective across the various symptom dimensions of SAD.     

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.     

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.     

Effect of short-term SSRI treatment on cognitive bias in generalised anxiety disorder

RATIONALE: There is considerable evidence showing that individuals with generalised anxiety disorder (GAD) selectively process threat-related information, e.g. they have a bias to interpret ambiguous information in a threat-related manner. Cognitive theories of anxiety, which provide the basis of cognitive-behaviour therapy, propose that such processing biases play an important role in causing and maintaining anxiety. OBJECTIVES: Given that treatment with selective serotonin re-uptake inhibitors (SSRIs) appears to be effective for GAD, we examined whether it is successful in removing cognitive bias. METHODS: The clinical group included 19 patients with a diagnosis of GAD, and the control group consisted of a non-clinical sample of volunteers, matched for age, gender and years in education. The patients were assessed on measures of interpretative bias (homophone task), anxiety and depression before being prescribed an SSRI (paroxetine or citalopram). After 4 weeks, the cognitive task and mood measures were repeated in the patient group. RESULTS: Prior to treatment, the GAD group showed a significantly greater level of threat-related interpretive bias than controls. Following SSRI treatment, there were significant reductions in both interpretive bias and in anxiety levels in the GAD group. Furthermore, individuals who showed greater clinical improvement (e.g. reflected by reduced anxiety scores) showed a correspondingly greater reduction in their cognitive bias. CONCLUSION: The results suggest that SSRIs are effective in modifying both subjective anxiety levels and threat-related interpretive bias.     

A psychopharmacological treatment algorithm for generalised anxiety disorder (GAD)

Generalised anxiety disorder (GAD) is defined as excessive and uncontrollable worry and anxiety about everyday life situations. It is a chronic disorder, and is associated with substantial somatisation, high rates of comorbid depression and other anxiety disorders, and significant disability. The evidence base for pharmacotherapy and psychotherapy has continued to grow, and a wide range of drug choices for GAD now exists. Current guidelines for GAD generally restrict themselves to presentation of the evidence for various treatments, which, as a result, generally do not offer detailed discussion or recommendation of strategies beyond the first level of treatment, or take into account the individual circumstances of the patient. Thus, there is a lack of algorithm-based treatment guidelines for GAD. Our aim is, therefore, to present an algorithm for the psychopharmacologic management of GAD, intended for all clinicians who treat patients with GAD, where issues of pharmacotherapy are under consideration. We also hope that these GAD algorithms and other guidelines can help to identify high-priority areas that need further study. In this algorithm, we provide a sequenced approach to the pharmacotherapy of GAD, taking into account salient symptomatology and comorbidity, levels of evidence and extent of response. Special issues, including comorbidity, insomnia, suicidality, substance abuse, treatment adherence, pregnancy and lactation, cross-cultural issues, use of medication in the elderly, psychosocial treatment and dosing issues are also addressed.