Pharmacotherapy of social anxiety disorder.

Over the last few years, a number of medications have demonstrated their efficacy in the acute treatment of social anxiety disorder. At present, selective serotonin reuptake inhibitors probably constitute the first line treatment, based on their safety, tolerability, and efficacy in the treatment of social anxiety disorder and common comorbid conditions. Data from single trials suggest that clonazepam, bromazepam, and gabapentin may have efficacy similar to the serotonin reuptake inhibitors, but further studies are needed to confirm these findings. The monoamine oxidase inhibitor phenelzine appears to be at least as efficacious as these other agents, but should be reserved for cases that fail to respond to these safer medications. Among the reversible inhibitors of monoamine oxidase A, brofaromine may also be an effective drug, while moclobemide appears to be less potent.Future research directions should include delineating ways to achieve remission (as opposed to response); developing strategies for augmenting partial responders and treating nonresponders to first line approaches; studying the long-term response to medication and prevention of relapse when medication is discontinued; clarifying ways to integrate psychosocial and pharmacological treatment approaches; developing predictors of which patients do best with which treatments; and the treatment of social anxiety disorder in children and adolescents.     

Relative effects of CBT and pharmacotherapy in depression versus anxiety: is medication somewhat better for depression,and CBT somewhat better for anxiety?

Background: Little is known about whether cognitive behavioral therapy (CBT) or pharmacotherapy is relatively more advantageous for depressive versus anxiety disorders. Methods: We conducted a meta‐analysis wherein we searched electronic databases and references to select randomized controlled studies comparing CBT and pharmacotherapy, with or without placebo, in adults with major depressive or anxiety disorders. The primary effect size was calculated from disorder‐specific outcome measures as the difference between CBT and pharmacotherapy outcomes (i.e., positive effect size favors CBT; negative effect size favors pharmacotherapy). Results: Twenty‐one anxiety ( N = 1,266) and twenty‐one depression ( N = 2,027) studies comparing medication to CBT were included. Including all anxiety disorders, the overall effect size was.25 (95% CI: ?0.02, 0.55, P =.07). Effects for panic disorder significantly favored CBT over medications (.50, 95% CI: 0.02, 0.98). Obsessive–compulsive disorder showed similar effects‐sizes, though not statistically significant (.49, 95% CI: ?0.11, 1.09). Medications showed a nonsignificant advantage for social anxiety disorder (?.22, 95% CI: ?0.50, 0.06). The overall effect size for depression studies was.05 (95% CI: ?0.09, 0.19), with no advantage for medications or CBT. Pooling anxiety disorder and depression studies, the omnibus comparison of the relative difference between anxiety and depression in effectiveness for CBT versus pharmacotherapy pointed to a nonsignificant advantage for CBT in anxiety versus depression ( B =.14, 95% CI: ?0.14, 0.43). Conclusions: On balance, the evidence presented here indicates that there are at most very modest differences in effects of CBT versus pharmacotherapy in the treatment of anxiety versus depressive disorders. There seems to be larger differences between the anxiety disorders in terms of their relative responsiveness to pharmacotherapy versus CBT. Depression and Anxiety, 2011. © 2011 Wiley‐Liss, Inc.     

Predictors of response to pharmacotherapy in social anxiety disorder: an analysis of 3 placebo-controlled paroxetine trials

BACKGROUND: There is increasing evidence that patients with social anxiety disorder (social phobia) respond to treatment with selective serotonin reuptake inhibitors (SSRIs). Response rates to SSRIs in social anxiety disorder have ranged from at least 50% in controlled trials to up to 80% in open trials. To date, however, there has been little information available about predictors of response to treatment in this disorder. METHOD: Data from 3 placebo-controlled multicenter trials of paroxetine in DSM-IV social anxiety disorder (N = 829) were analyzed using logistic regression to determine predictors of response. Demographic (age, sex), physiologic (baseline heart rate, baseline mean arterial pressure), clinical (baseline social anxiety symptom severity, baseline disability, duration of illness), and trial variables (paroxetine dose, treatment duration) were included. RESULTS: Only duration of treatment was a statistically significant predictor of treatment response. Further analysis demonstrated that, in paroxetine-treated patients in particular, many nonresponders at week 8 (46/166; 27.7%) were responders at week 12. CONCLUSION: These data demonstrate that paroxetine is a reasonable choice of treatment in a broad spectrum of patients with social anxiety disorder. An optimal trial of medication should continue beyond 8 weeks.     

Relative effects of cognitive and behavioral therapies on generalized anxiety disorder,social anxiety disorder and panic disorder: A meta-analysis

Although cognitive and behavioral therapies are effective in the treatment of anxiety disorders, it is not clear what the relative effects of these treatments are. We conducted a meta-analysis of trials comparing cognitive and behavioral therapies with a control condition, in patients with social anxiety disorder (SAD), generalized anxiety disorder (GAD) and panic disorder. We included 42 studies in which generic measures of anxiety were used (BAI, HAMA, STAI-State and Trait). Only the effects of treatment for panic disorder as measured on the BAI (13.33 points; 95% CI: 10.58–16.07) were significantly (p = 0.001) larger than the effect sizes on GAD (6.06 points; 95% CI: 3.96–8.16) and SAD (5.92 points; 95% CI: 4.64–7.20). The effects remained significant after adjusting for baseline severity and other major characteristics of the trials. The results should be considered with caution because of the small number of studies in many subgroups and the high risk of bias in most studies.     

Results of a naturalistic longitudinal study of benzodiazepine and SSRI use in the treatment of generalized anxiety disorder and social phobia

The past decade has brought major new developments in the psychopharmacologic management of generalized anxiety disorder and social phobia. We examined medication-prescribing patterns for the treatment of these anxiety disorders for 12 years to assess changes in patients' anti-anxiety psychotropic medication usage during that period of evolving practice guidelines. We examined psychotropic medication use in 305 patients with generalized anxiety disorder and 232 with social phobia enrolled in the Harvard/Brown Anxiety Disorders Research Project (HARP), a prospective, longitudinal study of anxiety disorders. Psychotropic treatment patterns seem to have remained relatively stable over 12 years with benzodiazepines the medications most commonly used for both generalized anxiety disorder and social phobia. Comparatively, selective serotonin reuptake inhibitor (SSRI) and venlafaxine usage as stand-alone medications for these disorders remained low throughout the follow-up period. At the 12-year follow-up, 24% of patients with generalized anxiety disorder and 30% of patients with social phobia were utilizing neither an SSRI/selective norepinephrine reuptake inhibitor (SNRI) nor a benzodiazepine. Treatment recommendations for use of SSRIs and venlafaxine in the management of generalized anxiety disorder and social phobia initially promulgated in 1998 had a modest impact on changes in psychopharmacologic practice 4-5 years later. Difficulties in the implementation of treatment guidelines are discussed.     

Antidepressants in social anxiety disorder

Social anxiety disorder (SAD) is a marked and persistent fear of doing almost everything in front of people due to concerns about being judge by others. An up-to-date review is needed in order to reach a practical judgement of all psychopharmacological data. Case reports, open and double-blind trials with SAD were described and commented upon from a clinical point of view. The MEDLINE system was searched from 1975 to 2001. The references from the selected papers were also used as a source. MAOIs (fenelzine, tranylcypromine), reversible monoamino oxidase-A inhibitors (moclobemide, brofaromine), SSRIs (paroxetine, sertraline, fluoxetine, fluvoxamine) and some other antidepressants (venlafaxine, nefazodone) have proven effective in several studies with various methodologies. The MAOIs have more serious adverse effects and the SSRIs have the best tolerance. SSRIs are efficacious and the first choice of treatment.     

阿戈美拉汀治疗首发抑郁障碍效果和安全性的Meta分析

目的系统评价阿戈美拉汀治疗首发抑郁障碍患者的效果和安全性,以期为抑郁障碍的药物治疗提供参考。方法检索PubMed、Web of Science、中国学术期刊全文数据库(CNKI)、维普数据库(VIP)、万方数据库中关于阿戈美拉汀治疗首发抑郁障碍患者的临床随机对照研究,提取阿戈美拉汀与SSRIs/SNRIs类抗抑郁药物在治疗首发抑郁障碍的效果和安全性的数据,采用RevMan 5. 3进行Meta分析。结果共纳入12篇文章,其中中文10篇,英文2篇。Meta分析结果显示,治疗后阿戈美拉汀组与对照组HAMD-17评分差异有统计学意义(SMD=-1. 31,95%CI:-1. 55～-1. 07,Z=10. 77,P0. 01)。由于研究间异质性较大(I2=83%,P0. 01),根据对照组所采用抗抑郁药种类进行亚组分析,分别以氟西汀(SMD=-1. 22,95%CI:-1. 66～-0. 77,Z=5. 30,P0. 01)、度洛西汀(SMD=-0. 88,95%CI:-1. 26～-0. 50,Z=4. 49,P0. 01)为对照的研究治疗后HAMD-17评分与阿戈美拉汀组差异均有统计学意义。关于副作用的Meta分析显示,阿戈美拉汀组与对照组之间差异有统计学意义(RR=0. 63,95%CI:0. 49～0. 80,Z=3. 73,P0. 01)。结论阿戈美拉汀治疗首发抑郁障碍的疗效优于SSRIs/SNRIs类抗抑郁药物或与其疗效相当,副作用小于SSRIs/SNRIs类抗抑郁药物。     

Effectiveness of mood stabilizers and antipsychotics in the maintenance phase of bipolar disorder: a systematic review of randomized controlled trials

BACKGROUND: Bipolar disorder (BD) is a leading cause of disability. Systematic reviews of randomized trials for the treatment of the maintenance phase of BD are lacking. OBJECTIVES: To determine the efficacy and tolerability of mood stabilizers and antipsychotics in the maintenance treatment of BD. METHODS: We systematically reviewed randomized controlled trials of licensed medications for the treatment of any phase of BD. We included randomized controlled trials comparing a medication to placebo or another medication. Comprehensive searches of electronic databases were conducted to March 2005. Outcomes investigated were relapse due to mania, depression or any mood episode, and withdrawal due to any reason or due to an adverse event. Data were combined through meta-analysis. RESULTS: Fourteen studies (n = 2,526) met the inclusion criteria. Lithium, lamotrigine, olanzapine and valproate semisodium each demonstrated evidence to support long-term use. Compared with placebo, all medications were more effective at preventing relapse because of any mood episode. Hazard ratios (HR) were 0.68 [95% confidence interval (CI) = 0.53-0.86] for lithium, 0.68 (95% CI = 0.55-0.85) for lamotrigine, and 0.82 (95% CI = 0.57-1.20) for valproate semisodium; for olanzapine, the risk ratio (RR) was 0.58 (95% CI = 0.49-0.69). Lithium and olanzapine significantly reduced manic relapses (HR = 0.53; 95% CI = 0.35-0.79 and RR = 0.37; 95% CI = 0.24-0.57, respectively). Lamotrigine and valproate semisodium significantly reduced depressive relapses (HR = 0.65; 95% CI = 0.46-0.91 and RR = 0.40; 95% CI = 0.20-0.82, respectively). Lithium significantly reduced manic relapses compared with lamotrigine (HR = 0.56; 95% CI = 0.34-0.92) and olanzapine significantly reduced manic relapses compared with lithium (RR = 1.69; 95% CI = 1.12-2.55). Withdrawal due to an adverse event was approximately twice as likely with lithium compared with valproate semisodium (RR = 1.81; 95% CI = 1.08-3.03) and lamotrigine (RR = 2.20; 95% CI = 1.31-3.70). There were few data for carbamazepine or medications given as adjunct therapy. CONCLUSIONS: Mood stabilizers have differing profiles of efficacy and tolerability, suggesting complementary roles in long-term maintenance treatment.     

The efficacy of light therapy in the treatment of mood disorders: a review and meta-analysis of the evidence

OBJECTIVE: The purpose of this study was to assess the evidence base for the efficacy of light therapy in treating mood disorders. METHOD: The authors systematically searched PubMed (January 1975 to July 2003) to identify randomized, controlled trials of light therapy for mood disorders that fulfilled predefined criteria. These articles were abstracted, and data were synthesized by disease and intervention category. RESULTS: Only 13% of the studies met the inclusion criteria. Meta-analyses revealed that a significant reduction in depression symptom severity was associated with bright light treatment (eight studies, having an effect size of 0.84 and 95% confidence interval [CI] of 0.60 to 1.08) and dawn simulation in seasonal affective disorder (five studies; effect size=0.73, 95% CI=0.37 to 1.08) and with bright light treatment in nonseasonal depression (three studies; effect size=0.53, 95% CI=0.18 to 0.89). Bright light as an adjunct to antidepressant pharmacotherapy for nonseasonal depression was not effective (five studies; effect size=-0.01, 95% CI=-0.36 to 0.34). CONCLUSIONS: Many reports of the efficacy of light therapy are not based on rigorous study designs. This analysis of randomized, controlled trials suggests that bright light treatment and dawn simulation for seasonal affective disorder and bright light for nonseasonal depression are efficacious, with effect sizes equivalent to those in most antidepressant pharmacotherapy trials. Adopting standard approaches to light therapy's specific issues (e.g., defining parameters of active versus placebo conditions) and incorporating rigorous designs (e.g., adequate group sizes, randomized assignment) are necessary to evaluate light therapy for mood disorders.     

The role of duloxetine in the treatment of anxiety disorders

Anxiety disorders (ADs) are the most common type of psychiatric disorders, with a mean incidence of 18.1% and a lifetime prevalence of 28.8%. Pharmacologic options studied for treating ADs may include benzodiazepines, tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRIs), noradrenergic and specific serotonergic drug (NaSSA) and dual-reuptake inhibitors of serotonin and norepinephrine (SNRIs). In this context, the development of SNRIs (venlafaxine and duloxetine) has been particularly useful. As a dual-acting intervention that targets two neurotransmitter systems, these medications would appePar promising for the treatment of ADs. The purpose of this review was to elucidate current facts and views about the role of duloxetine in the treatment of ADs. In February 2007, duloxetine was approved by FDA for the treatment of generalized anxiety disorder (GAD). The results of trials evaluating the use duloxetine in the treatment of GAD are supportive on its efficacy even if further studies on long-term use are needed. Apart from some interesting case reports, no large studies are, to date, present in literature about duloxetine and other ADs such as panic disorder, social anxiety disorder, obsessive-compulsive disorder and post-traumatic stress disorder. Therefore, the clinical efficacy and the relative good tolerability of duloxetine may be further investigated to widen the therapeutic spectrum of ADs.     

Selective serotonin reuptake inhibitor treatment for generalized anxiety disorder: a double-blind, prospective comparison between paroxetine and sertraline

OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) appear to be an effective class of medications for the treatment of generalized anxiety disorder. Within the SSRI class, however, there have been no comparative treatment studies for this disorder. Therefore, in the present study, we compared the efficacy and tolerability of 2 SSRIs, paroxetine and sertraline, in the treatment of generalized anxiety disorder. METHOD: In this parallel-group, double-blind, flexible-dose study, 55 patients with primary generalized anxiety disorder (DSM-IV criteria) were randomly assigned to receive either paroxetine or sertraline treatment for 8 weeks. Primary efficacy measures were the mean changes in Hamilton Rating Scale for Anxiety (HAM-A) scores as well as responder and remission rates based on the Clinical Global Impressions scale. Secondary efficacy measures consisted of the Indiana University Generalized Anxiety Measurement Scale and self-report ratings of anxiety, and quality-of-life outcome. Tolerability was assessed using the Systematic Assessment for Treatment Emergent Events questionnaire for treatment-emergent symptoms. RESULTS: The intent-to-treat sample consisted of 53 patients who received medication for at least 1 week. Of the 53 patients, 43 completed the entire 8 weeks of treatment. Both paroxetine and sertraline resulted in significant decreases in mean HAM-A scores (paroxetine = 57% +/- 28%; sertraline = 56% +/- 28%). There were no differences between medication groups on response or remission rates, and tolerability was comparable. CONCLUSIONS: Both paroxetine and sertraline appear similarly effective and well tolerated for the treatment of generalized anxiety disorder.     

Treatment of social anxiety disorder with citalopram

Selective serotonin reuptake inhibitors (SSRIs) are used as treatment for generalized and specific social phobias (social anxiety disorders). The efficacy of citalopram, an SSRI, for the treatment of social anxiety disorders has not yet been fully evaluated. These cases suggest that citalopram may be an effective treatment for social anxiety disorder (social phobia). These cases are consistent with two other published reports with citalopram from outside the US. Randomized controlled studies are warranted.     

Social phobia: the clinical efficacy and tolerability of the monoamine oxidase -A and serotonin uptake inhibitor brofaromine. A double-blind placebo-controlled study

Seventy-seven patients with a primary diagnosis of social phobia (DSM-III-R) were randomized to treatment with the reversible and selective monoamine oxidase type A inhibitor brofaromine (n= 37) or placebo (n= 40) for 12 weeks in a double-blind trial. A fixed dose of 150 mg/day or a matching placebo was given after a 2-week dose titration phase. Patients with additional diagnoses of simple phobia, generalized anxiety disorder, dysthymia or major depressive disorder currently in remission were accepted. Patients with other Axis I mental disorders were excluded. In the brofaromine group, 78% of the patients scored much or very much improved on the Clinical Global Impression scale compared with 23% in the placebo group. The anxiety and avoidance scores on the Liebowitz Social Anxiety Scale (LSAS) were significantly reduced in favor of brofaromine. The clinical effects were not significantly correlated with the plasma concentration of brofaromine. After 12 weeks the brofaromine group scored significantly Jower than the placebo group on a core depression part of the Montgomery-Åsberg Depressid Rating Scale. After 12 weeks of treatment the brofaromine group had significantly higher total scores on the LSAS than an age- and gender-matched group of healthy controls. The brofaromine group improved further during 9-month follow-up treatment period, whereas 60% of the placebo responders who continued long-term treatment relapsed. The most common side effects in the brofaromine group were sleep disturbances, dry mouth and nausea.     

Paroxetine reduces social anxiety in individuals with a co-occurring alcohol use disorder

Patients with social anxiety disorder who are seen in clinical practice commonly have additional psychiatric comorbidity, including alcohol use disorders. The first line treatment for social anxiety disorder is selective-serotonin-reuptake-inhibitors (SSRIs), such as paroxetine. However, the efficacy of SSRIs has been determined with studies that excluded alcoholics. Forty two subjects with social anxiety and a co-occurring alcohol use disorder participated in a 16-week, double-blind, placebo-controlled clinical trial to determine the efficacy of paroxetine for social anxiety in patients with co-occurring alcohol problems. Paroxetine was superior to placebo in reducing social anxiety, as measured by the Liebowitz Social Anxiety Scale total and subscale scores and additional measures of social anxiety. This study provides the first evidence-based recommendation for the use of an SSRI to treat social anxiety in this patient population.     

Suicidality in pediatric patients treated with antidepressant drugs

CONTEXT: There has been concern that widely used antidepressant agents might be associated with an increased risk of suicidal ideation and behavior (suicidality) in pediatric patients. OBJECTIVE: To investigate the relationship between antidepressant drugs and suicidality in pediatric patients participating in randomized, placebo-controlled trials. DATA SOURCES: Data were derived from 23 trials conducted in 9 drug company-supported programs evaluating the effectiveness of antidepressants in pediatric patients and 1 multicenter trial (the Treatment for Adolescents With Depression Study) that evaluated fluoxetine hydrochloride. STUDY SELECTION: All placebo-controlled trials submitted to the Food and Drug Administration were eligible for inclusion. Evaluable data were derived from 4582 patients in 24 trials. Sixteen trials studied patients with major depressive disorder, and the remaining 8 studied obsessive-compulsive disorder (n = 4), generalized anxiety disorder (n = 2), attention-deficit/hyperactivity disorder (n = 1), and social anxiety disorder (n = 1). Only 20 trials were included in the risk ratio analysis of suicidality because 4 trials had no events in the drug or placebo groups. DATA EXTRACTION: Individual patient data were available for all the trials. DATA SYNTHESIS: A meta-analysis was conducted to obtain overall suicidality risk estimates for each drug individually, for selective serotonin reuptake inhibitors in depression trials as a group, and for all evaluable trials combined. There were no completed suicides in any of these trials. The multicenter trial was the only individual trial to show a statistically significant risk ratio (4.62; 95% confidence interval [CI], 1.02-20.92). The overall risk ratio for selective serotonin reuptake inhibitors in depression trials was 1.66 (95% CI, 1.02-2.68) and for all drugs across all indications was 1.95 (95% CI, 1.28-2.98). The overall risk difference for all drugs across all indications was 0.02 (95% CI, 0.01-0.03). CONCLUSION: Use of antidepressant drugs in pediatric patients is associated with a modestly increased risk of suicidality.     

An effect-size analysis of the relative efficacy and tolerability of serotonin selective reuptake inhibitors for panic disorder.

OBJECTIVE: Serotonin selective reuptake inhibitors (SSRIs) are now considered the first-line pharmacotherapy for panic disorder. The preferential use and the presumption of greater tolerability of SSRIs relative to older agents, such as tricyclic antidepressants, occurred without direct comparisons between the two classes of medication. In this study the authors used an effect-size analysis to provide an initial comparison. METHOD: The authors conducted an effect-size analysis of 12 placebo-controlled, efficacy trials of SSRIs for panic disorder and compared these results to findings obtained in a recent meta-analysis of non-SSRI treatments for panic disorder. RESULTS: The mean effect size for acute treatment outcome for SSRIs relative to placebo was 0.55, not significantly different from that for antidepressants in general (0.55) and for imipramine in particular (0.48). More recent studies of SSRIs, and studies using larger samples, were associated with lower effect sizes. No significant differences were found in dropout rates between those taking SSRIs and those taking older agents during acute treatment. CONCLUSIONS: An effect-size analysis of controlled studies of treatments for panic disorder revealed no significant differences between SSRIs and older antidepressants in terms of efficacy or tolerability in short-term trials. An inverse relationship was evident between sample size and effect size for SSRIs. Early studies of small samples may have led to initial overestimations of the efficacy of SSRIs for panic disorder.     

Mental disorders and asthma in the community

OBJECTIVE: To determine the association between asthma and mental disorders among adults in the community. SETTING: Germany. PARTICIPANTS: Representative sample of the general population aged 18 to 65 years. MAIN OUTCOME MEASURES: Diagnoses of current (the past 4 weeks) and lifetime asthma were based on physician diagnosis; current and lifetime DSM-IV mental disorders were assessed using the Composite International Diagnostic Interview. RESULTS: Current severe asthma (the past 4 weeks) was associated with a significantly increased likelihood of any anxiety disorder (odds ratio [OR], 2.65; 95% confidence interval [CI], 1.35-5.18), specific phobia (OR, 4.78; 95% CI, 2.35-4.05), panic disorder (OR, 4.61; 95% CI, 1.09-9.4), and panic attacks (OR, 4.12; 95% CI, 1.32-12.8). Lifetime severe asthma was associated with the increased likelihood of any anxiety disorder (OR, 2.09; 1.3-3.36), panic disorder (OR, 2.61; 95% CI, 1.29-5.25), panic attacks (OR, 2.84; 95% CI, 1.66, 4.89), social phobia (OR, 3.28; 95% CI, 1.42, 7.59), specific phobia (OR, 2.93; 95% CI, 1.71-5.0), generalized anxiety disorder (OR, 5.51; 95% CI, 2.29-13.22), and bipolar disorder (OR, 5.64; 95% CI, 1.95-16.35). Current nonsevere asthma was associated with the increased likelihood of any affective disorder (OR, 2.42; 95% CI, 1.03-5.72); and lifetime nonsevere asthma was associated with increased odds of any anxiety disorder (OR, 1.51; 95% CI, 1.0-2.32), anxiety disorder not otherwise specified (OR, 2.08; 95% CI, 1.03-4.23), and any somatoform disorder (OR, 1.7; 95% CI, 1.14-2.53). CONCLUSIONS: To our knowledge, these findings are consistent with and extend the findings of previous reports by providing the first available information on the association between physician-diagnosed asthma and DSM-IV mental disorders in a representative population sample of adults. Our results suggest an association between asthma and a range of mental disorders. Longitudinal studies that can examine the sequence of onset and the role of genetic and environmental factors in the association between asthma and affective and anxiety disorders are needed next to further elucidate possible shared causative mechanisms.     

Pharmacotherapy of childhood anxiety disorders

Anxiety disorders are among the most common psychiatric disorders of childhood, yet limited data is available regarding the use of psychotropic medications for these conditions. Until recently, much of the data on the pharmacologic treatment of pediatric anxiety disorders has consisted of case reports and small open-label studies, with the exception of pediatric obsessive-compulsive disorder (OCD), which has had a comparatively rich literature consisting of several double blind trials. This void has been lessening, however, with four double blind, placebo-controlled studies published in the past year alone. Although the majority of pharmacologic studies of pediatric anxiety continue to focus on the treatment of OCD, additional reports on treatment of generalized anxiety disorder, panic disorder, social anxiety disorder, and separation anxiety disorder have recently been published. This article will review significant pharmacologic studies published in the prior year, and the role of pharmacotherapy in the treatment of pediatric anxiety disorders.     

Efficacy of escitalopram in the treatment of major depressive disorder compared with conventional selective serotonin reuptake inhibitors and venlafaxine XR: a meta-analysis

OBJECTIVE: Escitalopram is the most selective of the selective serotonin reuptake inhibitor (SSRI) antidepressants. Previous studies have suggested that escitalopram is superior to citalopram in efficacy. We conducted a meta-analysis of studies in which escitalopram was compared with other antidepressants to assess the relative efficacy of these agents. METHODS: Data from all randomized, double-blind studies in major depression in which escitalopram was compared with active controls (citalopram, fluoxetine, paroxetine, sertraline and venlafaxine XR [extended release]) were pooled. The 10 studies were conducted in both specialist settings and general practice. Patients met the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), for major depressive disorder and were at least 18 years old. In all but 2 studies, patients were required to have a score of 22 or more on the Montgomery-Asberg Depression Rating Scale (MADRS). The primary outcome measure was the estimated difference in treatment effect in MADRS total score at the end of the study. Secondary outcome measures were the response to treatment (defined as a > or = 50% reduction in baseline MADRS total score) and remission rate (defined as MADRS total score < or = 12 at end of study). RESULTS: A total of 2687 patients were included in the analyses (escitalopram n = 1345, conventional SSRIs n = 1102, venlafaxine XR n = 240). Escitalopram was superior to all comparators in overall treatment effect, with an estimated difference in treatment effect of 1.07 points (95% confidence interval [CI] 0.42-1.73, p < 0.01), and in response (odds ratio [OR] 1.29, 95% CI 1.07-1.56, p < 0.01) and remission (OR 1.21, 95% CI 1.01-1.46, p < 0.05) rates. In analysis by medication class, escitalopram was significantly superior to the SSRIs and comparable to venlafaxine, although the overall results do not necessarily reflect a significant difference between escitalopram and individual SSRIs. These results were similar in the severely depressed population (patients with baseline MADRS > or = 30). The withdrawal rate due to adverse events was 6.7% for escitalopram compared with 9.1% for the comparators (p < 0.05). CONCLUSIONS: In this meta-analysis, escitalopram showed significant superiority in efficacy compared with the active controls.     

A meta-analysis of clinical trials comparing the serotonin (5HT)-2 receptor antagonists trazodone and nefazodone with selective serotonin reuptake inhibitors for the treatment of major depressive disorder.

OBJECTIVE: To compare response rates among patients with major depressive disorder (MDD) treated with either a serotonin-2 (5HT2-) receptor antagonist or a selective serotonin reuptake inhibitor (SSRI). METHODS: Medline and PubMed were searched for double-blind, randomized clinical trials comparing either trazodone or nefazodone with an SSRI for the treatment of MDD. Data from 9 reports involving a total 988 patients were identified and combined using a random-effects model. RESULTS: Patients randomized to treatment with a 5HT2 antagonist were as likely to experience clinical response as patients randomized to treatment with an SSRI (RR=1.002, 95% CI: 0.85-1.17, P=0.978). Pooled response rates for trazodone/nefazodone and the SSRIs were 61.1% and 61.7%, respectively. There was also no difference in overall discontinuation rates (P=0.334), discontinuation due to adverse events (P=0.676), or discontinuation due to inefficacy (P=0.289) between the two groups. CONCLUSIONS: These results suggest that the 5HT2-receptor antagonists trazodone and nefazodone and the SSRIs do not differ with respect to their overall efficacy and tolerability in the treatment of MDD. Although the sample size was relatively large and conveyed sufficient statistical power to test for differences in the overall sample, depression is a heterogeneous condition and differences may exist between treatments in particular subgroups of patients.