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Objective: There is a paucity of data on the effects of coprescribed benzodiazepines on treatment response variability and adherence to antidepressant pharmacotherapy for depression and anxiety in late life. The objective of this transdiagnostic analysis was to examine the effect of benzodiazepines on treatment outcomes in older patients with generalized anxiety disorder (GAD) or major depressive disorder (MDD)., Methods: Secondary analyses of data from 2 clinical trials of antidepressant pharmacotherapy for GAD (escitalopram vs placebo, 2006-2009) or MDD (open treatment with venlafaxine, 2009-2014) were conducted. Participants included 640 adults aged 60+ years with DSM-IV-defined GAD (n = 177) or MDD (n = 463). Benzodiazepine data were collected at baseline. Adherence and treatment response were assessed over 12 weeks. The analysis addressed whether coprescribed benzodiazepines are associated with treatment response, antidepressant medication adherence, dropout, final dose of antidepressant medication, and report of antidepressant-related adverse effects., Results: Participants with GAD and coprescribed benzodiazepines were treated with a lower mean dosage of escitalopram and were less likely to complete the trial; there was no difference in adherence or treatment response. Participants with MDD and coprescribed benzodiazepines were less likely to tolerate a therapeutic dose of venlafaxine and reported more medication-related adverse effects; there was no difference in adherence, dropout, or treatment response., Conclusions: Coprescription of benzodiazepines was associated with increased dropout in older patients with GAD and more medication-related adverse effects in older patients with MDD. However, with the systematic clinical attention offered in a clinical trial, they do not impede treatment response. Clinicians should be aware that a coprescribed benzodiazepine may be a marker of a more challenging treatment course., Trial Registration: Data analyzed were from studies with ClinicalTrials.gov identifiers NCT00892047 and NCT00105586., (© Copyright 2020 Physicians Postgraduate Press, Inc.)

Anxiety disorders (generalized anxiety disorder, social anxiety disorder, panic disorder, and agoraphobia) are common, distressing, and impairing. While pharmacotherapy and psychotherapy are first-line treatment strategies for anxiety disorders, many patients are reluctant to take psychiatric medication, and many prefer to avoid any kind of mental health treatment due to stigma or distrust of traditional medical care. We present the trial protocol for the first study comparing first-line medication treatment with Mindfulness-Based Stress Reduction (MBSR), a popular mindfulness meditation training program, for the treatment of anxiety disorders. We will use a non-inferiority, comparative effectiveness trial design, in which individuals with diagnosed anxiety disorders will be randomized to either pharmacotherapy with escitalopram or MBSR for 8 weeks of treatment. Treatment outcome will be based on gold standard symptom severity measures assessed by trained independent evaluators blind to treatment allocation. Secondary outcomes will include key symptom and function measures, as well as tolerability and satisfaction with treatment. Findings will provide crucial information to inform decision making about the relative benefits of MBSR versus a first line medication for anxiety disorders by patients, medical care providers, healthcare insurers and other stakeholders., (Copyright © 2020. Published by Elsevier Inc.)

Introduction: This study tests the efficacy of pregabalin versus placebo as adjunctive treatment in patients with generalized anxiety disorder (GAD) comorbid with unipolar major depression (UMD) and with an early nonresponse to escitalopram., Methods: This is a double-blind, placebo-controlled 8-week add-on study of pregabalin, 75-600 mg/day (n=31) versus placebo (n=29) on open-label escitalopram in outpatients meeting the DSM-IV-TR criteria for GAD and UMD. The main outcome measures were change from baseline to endpoint in total STAI-S, Trail-Making Test B (TMT-B) and the Center of Epidemiological Studies Depression Scale (CES-D). Also changes in the parameters of the pupil's reaction to light stimuli., Results: There was no significant difference in any of the primary or secondary outcomes or response and remission rates concerning any analysis (last observation carried-forward of at least visit 2 or completers) between the 2 treatment arms. One additional finding of the current study is that adding pregabalin does not have a significant effect on autonomic function., Discussion: This study does not support the usefulness of adding pregabalin in patients with GAD and UMD and with an early nonresponse to escitalopram (EudraCT Number: 2012-004062-17, Sponsor's Protocol Code Number: WS1702721)., Competing Interests: The study was supported by a grant from the Pfizer foundation. KNF, VK, IN, and SK have received honoraria for speeches and support to attend congresses by various pharmaceutical companies including Pfizer. SM, KP, NP, DM, and KP have no conflicts of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Treatment of severely symptomatic patients with generalized anxiety disorder (GAD) raises particular concerns for clinicians. This 12-week double-blind study evaluated the efficacy of agomelatine (25-50 mg/day) in the treatment of patients with severe GAD, using escitalopram (10-20 mg) as active comparator. The primary outcome measure was the change from baseline of the total score on the Hamilton Anxiety scale (HAM-A) at week 12. Secondary outcome measures included rate of response to treatment (at least 50% score reduction from baseline) in the HAM-A psychic and somatic anxiety sub-scores, Clinical Global Impression severity and change scores, the Toronto Hospital Alertness Test, the Snaith-Hamilton Pleasure Scale, and the Leeds Sleep Evaluation Questionnaire Scores. Sixty one clinical centers (Australia, Canada, Czech Republic, Finland, Germany, Hungary, Poland, Russia, Slovakia) participated from April 2013 to February 2015. Patient characteristics and demographic data were comparable between treatment groups. Both treatments were associated with a clinically significant decrease in HAM-A total score at week 12; the non-inferiority of agomelatine versus escitalopram was not demonstrated (E(SE) = -0.91(0.69), 95%CI = [-2.26, 0.44], p = 0.195). At week 12, the response rate was 60.9% in the agomelatine group, and 64.8% in the escitalopram group. In both treatment arms, HAM-A psychic and somatic anxiety scores decreased, alertness and sleep parameters improved, and ability to experience pleasure increased. In these secondary outcome measures, there were no significant differences between the treatment groups. Agomelatine was well-tolerated, with a lower incidence of adverse events than escitalopram. Agomelatine and escitalopram are efficacious in treating GAD patients with severe symptoms., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Pharmacogenetic approach to antidepressant (AD) response is a promising avenue toward individualizing AD treatment. This is particularly relevant in pediatric populations because of concerns about the suicide risk of serotonin selective reuptake inhibitors (SSRIs), resulting in a black-box warning. However, to date, no specific gene or polymorphism has been consistently implicated as a marker of AD side effect (SE) in the pediatric population. The aim of this study was to examine the association between polymorphisms in genes related to the serotonergic system and citalopram SE's in children and adolescents with major depressive disorder (MDD)/dysthymia and/or anxiety disorders. Outpatients (N = 87, 44 % males), aged 7-18 years with a DSM-IV-TR diagnosis of MDD/dysthymia and/or an anxiety disorder were treated in an 8-week open trial with 20-40 mg/day of citalopram. SE's were rated using a questionnaire devised specifically for this study. Association analysis between known/candidate genetic variants in three genes (5-HTR2A, 5-HTR1Dβ, 5-HTR2C) and SE's was conducted. Agitation was more common in boys than girls (male:female 42.1 vs. 18.7 %, χ 2  = 5.61, df = 1, p = 0.018). Subjects with 5-HTR1Dβ CC genotype showed more agitation vs. both CG and GG genotypes (CC:CG:GG 71.4 vs. 33.3 vs. 18.1 %, χ 2  = 8.99, df = 2, p = 0.011). The 5-HTR1Dβ CC genotype was associated with more reports of agitation. It has been suggested that agitation may be an intermediate phenotype to suicidal behavior. Thus, it seems that 5-HTR1Dβ polymorphism may be involved in citalopram-related agitation in children and adolescents treated for depression and/or anxiety.

Objective: Antidepressant side effects are a significant public health issue, associated with poor adherence, premature treatment discontinuation, and, rarely, significant harm. Older adults assume the largest and most serious burden of medication side effects. We investigated the association between antidepressant side effects and genetic variation in the serotonin system in anxious, older adults participating in a randomized, placebo-controlled trial of the selective serotonin reuptake inhibitor (SSRI) escitalopram., Methods: Adults (N = 177) aged ≥ 60 years were randomized to active treatment or placebo for 12 weeks. Side effects were assessed using the Udvalg fur Kliniske Undersøgelser side-effect rating scale. Genetic polymorphisms were putative functional variants in the promoters of the serotonin transporter and 1A and 2A receptors (5-HTTLPR [L/S + rs25531], HTR1A rs6295, HTR2A rs6311, respectively)., Results: Four significant drug-placebo side-effect differences were found: increased duration of sleep, dry mouth, diarrhea, and diminished sexual desire. Analyses using putative high- versus low-transcription genotype groupings revealed six pharmacogenetic effects: greater dry mouth and decreased sexual desire for the low- and high-expressing serotonin transporter genotypes, respectively, and greater diarrhea with the 1A receptor low-transcription genotype. Diminished sexual desire was experienced significantly more by high-expressing genotypes in the serotonin transporter, 1A, or 2A receptors. There was not a significant relationship between drug concentration and side effects nor a mean difference in drug concentration between low- and high-expressing genotypes., Conclusion: Genetic variation in the serotonin system may predict who develops common SSRI side effects and why. More work is needed to further characterize this genetic modulation and to translate research findings into strategies useful for more personalized patient care., (Published by Elsevier Inc.)

Background: Short-term antidepressant administration has been reported to decrease amygdala response to threat in healthy volunteers and depressed patients. Neuroticism (N) is a risk factor for depression but has also been associated with slow or incomplete remission with antidepressant drug treatment. Our aim was to investigate early selective serotonin reuptake inhibitor (SSRI) administration neural effects on implicit processing of fearful facial expressions in volunteers with high levels of N., Method: Highly neurotic subjects received 20 mg/day citalopram versus placebo for 7 days in a double-blind, between-groups design. On the last day haemoperfusion and functional magnetic resonance imaging (fMRI) data during a gender discrimination task with fearful and happy faces were acquired. A control group of non-neurotic volunteers was also tested., Results: High-N volunteers had reduced responses to threatening facial expressions across key neural circuits compared to low-N volunteers. SSRI treatment was found to elevate resting perfusion in the right amygdala, increase bilateral amygdalae activation to positive and negative facial expressions and increase activation to fearful versus happy facial expressions in occipital, parietal, temporal and prefrontal cortical areas., Conclusions: These results suggest that 7 days of SSRI administration can increase neural markers of fear reactivity in subjects at the high end of the N dimension and may be related to early increases in anxiety and agitation seen early in treatment. Such processes may be involved in the later therapeutic effects through decreased avoidance and increased learning about social 'threat' cues.

The purpose of this study was to investigate the neuropsychological functioning and the effect of antidepressant drug intake on cognitive performance in a group of relatively young generalized anxiety disorder (GAD) patients. Forty patients with a DSM-IV diagnosis of GAD and 31 healthy subjects participated in the study (Control group, CON). None of the selected subjects had comorbid depression. GAD subjects were divided into two different subgroups: 18 were taking antidepressants [GAD-pharmacotherapy (GAD-p group)] and 22 were treatment-naïve (GAD group). Each group was administered with a comprehensive neuropsychological battery to assess attention, memory and executive functions. Performance on executive and non-verbal memory tasks of both GAD groups was largely worse than the CON group. However, these deficits seem to be more marked in patients taking antidepressants, especially in the domains of attention, non-verbal memory and executive functions. The present study indicates that GAD is associated with cognitive impairments among young adults. However, the observed association of neuropsychological deficits and the use of pharmacotherapy suggest a possible effect of antidepressant treatment on attention, executive functioning and non-verbal memory., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: These studies were designed to evaluate the efficacy and tolerability of the first nonpeptide vasopressin V(1b) receptor antagonist, SSR149415, in the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD)., Method: Studies were randomized 8-week, double-blind, placebo-controlled trials evaluating 100- and 250-mg twice daily doses of SSR149415, placebo, and escitalopram 10 mg/day or paroxetine 20 mg/day, conducted from August 2006 through February 2008. Participants met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for MDD or GAD. Baseline Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HDRS) total scores were ≥ 24 and 18, respectively, and in the GAD trial baseline Hamilton Anxiety Rating Scale (HARS) score was ≥ 22. Primary efficacy variables included changes from baseline in total score on HDRS or HARS and MADRS, and the secondary variable included changes in the Clinical Global Impressions-Severity of Illness score (CGI-S). A 4-week, double-blind, placebo-controlled study evaluating the effect of 100- and 250-mg twice daily doses of SSR149415 on the hypothalamic-pituitary-adrenal (HPA) axis in MDD patients was also conducted., Results: In the GAD trial, SSR149415 did not separate from placebo on the primary (HARS-100 mg: P = .29; 250 mg: P = .21) and secondary (CGI-S-100 mg: P = .18; 250 mg: P = .24) outcome measures, while paroxetine demonstrated efficacy (HARS: P = .003; CGI-S: P = .01). In 2 MDD trials, SSR149415-treated patients did not show significant improvement from baseline on any outcome measure compared with placebo-treated patients (HDRS-100 mg: P = .21 and .48, respectively; 250 mg: P = .22 and P = .46, respectively; CGI-S-100 mg: P = .64 and P = .82, respectively; 250 mg: P = .33 and P = .08, respectively). In the third MDD study, SSR149415 250 mg (P = .04), but not escitalopram (P = .15), demonstrated significant improvement compared to placebo on the HDRS total score at week 8. SSR149415 had no deleterious effects on the HPA axis., Conclusions: These studies demonstrate that SSR149415 may not be useful for the treatment of GAD and that its antidepressant potential needs to be further evaluated., Trial Registration: ClinicalTrials.gov identifiers: NCT00374166 (Sanofi ID number: DFI5880), NCT00361491 (Sanofi ID number: DFI5879), NCT00358631 (Sanofi ID number: DFI5878), NCT01606384 (Sanofi ID number: PDY5467)., (© Copyright 2012 Physicians Postgraduate Press, Inc.)

Selective serotonergic reuptake inhibitors (SSRIs) and cognitive therapies are effective in the treatment of anxiety and depression. Previous research suggests that both forms of treatments may work by altering cognitive biases in the processing of affective information. The current study assessed the effects of combining an SSRI with a cognitive intervention on measures of affective processing bias and resilience to external challenge. A total of 62 healthy participants were randomly assigned to receive either 7 days of citalopram (20 mg) or placebo capsules while also completing either an active or a control version of a computerized cognitive bias training task. After treatment, standard measures of affective processing bias were collected. Participants' resilience to external stress was also tested by measuring the increase in negative symptoms induced by a negative mood induction. Participants who received both citalopram and the active cognitive bias training task showed a smaller alteration in emotional memory and categorization bias than did those who received either active intervention singly. The degree to which memory for negative information was altered by citalopram predicted participants' resistance to the negative mood induction. These results suggest that co-administration of an SSRI and a cognitive training intervention can reduce the effectiveness of either treatment alone in terms of anxiety- and depression-relevant emotional processing. More generally, the findings suggest that pinpointing the cognitive actions of treatments may inform future development of combination strategies in mental health.

Introduction: Disturbed sleep is a key symptom in major depressive disorder (MDD) and generalized anxiety disorder (GAD). First-line antidepressants, including the selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs), may have different effects on sleep., Methods: Data from 22 randomized, controlled trials comparing escitalopram with SSRIs, SNRIs, or placebo in the treatment of adult MDD or GAD were included. Both last observation carried forward (LOCF) and repeated measurements (MMRM) were used to analyze the sleep item of the Montgomery Åsberg Depression Rating Scale (MADRS) or Hamilton Anxiety Rating Scale (HAM-A) after 8 weeks of treatment. Sleep-related treatment-emergent adverse events were also compared across groups., Results: For patients with MDD (n = 5133), the treatment difference on MADRS item 4 ("reduced sleep") was significantly in favor of escitalopram versus placebo (LOCF [P = 0.0017] and MMRM [P = 0.0002]), versus SSRIs (LOCF [P = 0.0020] and MMRM [P < 0.0031]), and versus SNRIs (LOCF [P = 0.0002] and MMRM [P = 0.0352]). For the 53% of patients with MDD who suffered from sleep problems at baseline (baseline MADRS item 4 score ≥ 4), the improvement in sleep symptoms was significantly in favor of escitalopram versus placebo (LOCF [P = 0.0022] and MMRM [P < 0.0005]), versus SSRIs (LOCF [P = 0.0001] and MMRM [P = 0.0002]), and versus SNRIs (LOCF [P < 0.0067] but not MMRM [P > 0.0787]). For patients with GAD (n = 2052) the treatment difference in sleep symptoms measured by HAM-A item 4 ("insomnia") was significantly in favor of escitalopram versus placebo (LOCF [P = 0.0005] and MMRM [P < 0.0001]), but not different to paroxetine or venlafaxine. The same pattern was seen for the large proportion (67%-82%) of GAD patients reporting sleep problems at baseline (baseline HAM-A item 4 score ≥ 2). In MDD, the rate of insomnia as an adverse event after escitalopram was higher than placebo, similar to SSRIs, and lower than SNRIs., Conclusions: Additional research assessing the comparative effects of antidepressants with polysomnography is needed. In the interim, from a clinical perspective, escitalopram appears to be beneficial for the treatment of sleep problems in MDD and GAD.

Several recent studies have underlined the importance of anxiety in major depressive disorders. It has been shown that anxiety was responsible for worsening of depression and reduction of the efficacy of the antidepressant treatment. While it is well known that SSRI are efficient in treating depression or anxiety disorders, the authors tried to determine the influence of baseline anxiety on the response to SSRI treatment in patients with severe depression receiving either escitalopram or paroxetine. In a 24-week double-blind clinical trial, 459 patients with a primary diagnosis of severe major depressive disorder were randomised to receive escitalopram (20mg) or paroxetine (40mg). Post hoc analyses of efficacy in patients with a baseline HAM-A total score less or equal to 20 (n=171) or greater than 20 (n=280) were based on analysis of covariance. (ANCOVA) (ITT, LOCF). At week 24, the mean change from baseline in MADRS total score was -24.2 for escitalopram-treated patients (n=141) and -21.5 for paroxetine treated patients (n=139) (p<0.05, between both groups) in high baseline anxiety patients (HAM-A>20) and the mean change from baseline in HAM-A total score was -17.4 (escitalopram) and -15.1 (paroxetine) (p<0.05, between both groups). As far as complete remitters (CGI-S=1) after 24-week treatment were concerned, their number was significantly higher with escitalopram in the case of marked baseline anxiety. No difference was shown in the low baseline anxiety group. Looking for the influence of baseline anxiety on SSRI treatment effects, the authors showed that antidepressant efficacy of 20mg escitalopram was better than 40mg paroxetine for patients highly depressed with comorbid anxiety symptoms and that, contrary to paroxetine, escitalopram maintained sustained antidepressant activity in patients featuring increased baseline anxiety levels., (Copyright © 2010 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Cognitive behavioral therapy (CBT) and pharmacotherapy are each efficacious for generalized anxiety disorder (GAD). It is not known, however, whether GAD partial and nonresponders to one treatment modality benefit from the other. This study explored acceptability and efficacy of escitalopram for persons with persistent GAD symptoms after a course of CBT. Twenty-four patients with GAD were treated with CBT and 15 completed at least 12 sessions. Eight completers continued to have clinically significant symptoms and were offered 12 weeks of treatment with escitalopram, and 7 started escitalopram treatment. During CBT, patients evidenced significant improvement in GAD, depression, and quality of life. During escitalopram treatment, patients evidenced trends toward further improvement in GAD, depression, and quality of life. Escitalopram phase completers had initially reported low-to-moderate preferences for medication treatment. Escitalopram may benefit GAD patients with clinically significant symptoms after CBT and merits further study under controlled conditions in a larger sample.

To assess the effectiveness and tolerability of citalopram for the acute treatment of children and adolescents suffering from depression and/or anxiety disorders. As much as 78 outpatients, aged 7-18 years with a diagnosis of depressive and/or anxiety disorder, completed an 8-week open trial with citalopram (20-40 mg/day). Outcome, side effects and suicidality were assessed weekly to bi-weekly using appropriate rating scales. At endpoint 56% of subjects were found to be responders (Clinical Global Impression-Improvement [CGI-I] Scale

Introduction: Anxiety disorders are highly prevalent and disabling disorders, for which selective serotonin reuptake inhibitor (SSRI) antidepressants are an effective treatment. Escitalopram is the most selective SSRI available. Beyond its well-established efficacy in depression with or without anxiety, preclinical studies have demonstrated that escitalopram has a broad spectrum of anxiolytic activity., Aim of the Review: This review focuses on the therapeutic use and the tolerability issues of escitalopram in the treatment of adult patients with panic disorder, generalized anxiety disorder (GAD), social anxiety disorder, and obsessive-compulsive disorder (OCD), on the basis of numerous recent short-term and long-term controlled studies in these disorders. In a 10-week randomised, double-blind trial in patients with panic disorder, escitalopram (flexible doses 5-10 mg/d) was significantly more effective than placebo in reducing the panic attack frequency, with a faster onset of action than citalopram. Fifty percent of escitalopram recipients and 38% of placebo recipients experienced no panic attacks, with a similar incidence of the most common adverse events for both groups. LITERATURE FINDINGS IN PD: In an open-label study in elderly (>65 years) patients with panic disorder, improvement in panic attack frequency and secondary efficacy variables occurred more rapidly in escitalopram than citalopram recipients. LITERATURE FINDINGS IN GAD: In four double-blind, comparative, eight- to 12-week studies in patients with GAD, escitalopram was more effective than placebo and at least as effective as paroxetine in reducing the mean Hamilton Rating Scale for Anxiety total score. Escitalopram 10-20 mg/d demonstrated continued efficacy in a 24-week extension study of short double-blind trials and in a placebo-controlled, double-blind, 24/76-week relapse-prevention study. In this trial, escitalopram recipients showed a significantly longer time to relapse and reduced risk of relapse than placebo recipients, and the risk of relapse was 4.04 times higher in the placebo group than in the escitalopram group. Escitalopram was well tolerated and only 7% patients withdrew, due to adverse events in the escitalopram group, versus 8% in the placebo group. LITERATURE FINDINGS IN SOCIAL PHOBIA: In two randomised, double-blind, 12- and 24-week studies in patients with social anxiety disorder (social phobia), escitalopram 10-20 mg/d was generally more effective than placebo and at least as effective as paroxetine in reducing the mean Liebowitz Social Anxiety Scale total scores. In a 24-week double-blind, placebo-controlled relapse-prevention study, escitalopram recipients had a longer time to relapse and reduced risk of relapse compared with placebo recipients, and significantly fewer escitalopram than placebo recipients relapsed (22% versus 50%). In these studies, the treatment effects of escitalopram were independent of gender, symptom severity and chronicity, and comorbid depressive symptoms, and the drug was tolerated well. LITERATURE FINDINGS IN OCD: Finally, in patients with OCD, escitalopram 20mg/d for 12 weeks was more effective than placebo, and at least as effective as paroxetine 40 mg/day, with respect to a mean reduction from baseline in the Yale-Brown Obsessive Scale total score. In a 24-week, randomised, placebo-controlled relapse-prevention study, the proportion of patients who relapsed in the escitalopram group (23%) was 2.74 times lower than in the placebo group (52%). In both groups, the majority of adverse events reported were mild to moderate., Conclusion: On the whole, numerous clinical data indicate that escitalopram, 10-20 mg/d, is an effective and well-tolerated first-line treatment option for the management of panic disorder, GAD, social anxiety and OCD. Beyond short-term demonstrations of efficacy in these disorders, several controlled relapse-prevention studies showed the necessity and utility of maintaining the treatment six months or more after the remission has been obtained.

Administration of the same Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) in major depressive disorder (MDD) and in generalized anxiety disorder (GAD) before and after treatment allowed us to compare quality of life enjoyment and satisfaction in these two disorders and to compare outcome based on symptoms versus functioning. Q-LES-Q and symptom-specific Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Scale (HAMA) data from eight randomized, 8-week, double-blind, placebo-controlled clinical trials with escitalopram were used. MDD (n=1,140) or GAD (n=1,045) patients report a substantial degree of quality of life enjoyment and satisfaction impairment (baseline scores 64% and 76% of community norm, respectively). Treatment resulted in statistically and clinically significant improvement in quality of life enjoyment and satisfaction. The improvement was greater in patients treated with escitalopram than with placebo. In MDD, the majority of remitters (MADRS

Context: Insomnia and generalized anxiety disorder (GAD) are prevalent disorders that may coexist., Objective: To determine the efficacy of eszopiclone combined with escitalopram oxalate in treating insomnia comorbid with GAD., Design: Double-blind, randomized, placebo-controlled, parallel-group, add-on therapy 10-week study., Setting: Multicenter outpatient study from July 2005 to April 2006., Patients: Adults aged 18 to 64 years meeting DSM-IV-TR criteria for GAD and insomnia., Interventions: Patients received 10 mg of escitalopram oxolate for 10 weeks and were randomized to also receive either 3 mg of eszopiclone (n = 294) or placebo (n = 301) nightly for 8 weeks. For the last 2 weeks, eszopiclone was replaced with a single-blind placebo., Main Outcome Measures: Sleep, daytime functioning, psychiatric measures, and adverse events., Results: Compared with treatment with placebo and escitalopram, treatment with eszopiclone and escitalopram resulted in significantly improved sleep and daytime functioning (P < .05), with no evidence of tolerance. Patients taking eszopiclone and escitalopram had greater improvements in total Hamilton Anxiety Scale (HAM-A) scores at each week (P < .05) and at weeks 4 through 10 with the insomnia item removed. Clinical Global Impressions (CGI) of Improvement scores were improved with eszopiclone and escitalopram at every point (P < .02), while CGI of Severity of Illness scores were not significantly different after week 1. The HAM-A response (63% vs 49%, respectively, P = .001) and remission (42% vs 36%, respectively, P = .09) rates at week 8 were higher in patients treated with eszopiclone and escitalopram than those treated with placebo and escitalopram, and median time to onset of anxiolytic response was significantly reduced (P < or = .05). After eszopiclone discontinuation, there was no evidence of rebound insomnia, and while treatment differences in anxiety measures were maintained, differences in sleep outcomes were not. Overall adverse event rates were 77.6% with cotherapy and 67.9% with monotherapy. The most common adverse events with cotherapy were unpleasant taste, headache, dry mouth, and somnolence., Conclusions: Coadministration of eszopiclone and escitalopram was well tolerated and associated with significantly improved sleep, daytime functioning, anxiety, and mood in patients with insomnia and GAD., Trial Registration: clinicaltrials.gov Identifier: NCT00235508.

Objective: About half of outpatients with major depressive disorder also have clinically meaningful levels of anxiety. The authors conducted a secondary data analysis to compare antidepressant treatment outcomes for patients with anxious and nonanxious major depression in Levels 1 and 2 of the STAR*D study., Method: A total of 2,876 adult outpatients with major depressive disorder, enrolled from 18 primary and 23 psychiatric care sites, received citalopram in Level 1 of STAR*D. In Level 2, a total of 1,292 patients who did not remit with or tolerate citalopram were randomly assigned either to switch to sustained-release bupropion (N=239), sertraline (N=238), or extended-release venlafaxine (N=250) or to continue taking citalopram and receive augmentation with sustained-release bupropion (N=279) or buspirone (N=286). Treatment could last up to 14 weeks in each level. Patients were designated as having anxious depression if their anxiety/somatization factor score from the 17-item Hamilton Depression Rating Scale (HAM-D) was 7 or higher at baseline. Rates of remission and response as well as times to remission and response were compared between patients with anxious depression and those with nonanxious depression., Results: In Level 1 of STAR*D, 53.2% of patients had anxious depression. Remission was significantly less likely and took longer to occur in these patients than in those with nonanxious depression. Ratings of side effect frequency, intensity, and burden, as well as the number of serious adverse events, were significantly greater in the anxious depression group. Similarly, in Level 2, patients with anxious depression fared significantly worse in both the switching and augmentation options., Conclusions: Anxious depression is associated with poorer acute outcomes than nonanxious depression following antidepressant treatment.

Generalized anxiety disorder (GAD) is a highly prevalent and disabling condition. Escitalopram and venlafaxine extended release (XR) both are indicated for the treatment of GAD. Outpatients (ages 18-65 years) with DSM-IV-defined GAD (Hamilton Anxiety Scale [HAMA] >or=20) were eligible to participate in this randomized, double-blind, placebo-controlled, multicenter, flexible-dose trial. Following randomization, patients received 8 weeks of double-blind treatment with escitalopram (10-20 mg/day; N=127), venlafaxine XR (75-225 mg/day; N=129), or placebo (N=136). The primary efficacy parameter was mean change from baseline at week 8 in HAMA total score, using the Last Observation Carried Forward (LOCF) approach. Secondary efficacy parameters were HAMA psychic anxiety subscale, Clinical Global Impressions of Severity (CGI-S) and Improvement (CGI-I) scales. Treatment was completed by 77% of patients. The least square mean difference for change from baseline at week 8 in HAMA total score for escitalopram and venlafaxine XR versus placebo were -1.52 (P=.09) and -2.27 (P=.01), respectively, for LOCF, and -1.92 (P=.033) and -3.02 (P=.001), respectively, for Observed Cases (OC). On all secondary parameters, both active treatments were significantly superior to placebo on the LOCF and OC analyses. Discontinuation due to adverse events was not different for escitalopram versus placebo (7 versus 5%, P=.61), but was significantly greater for venlafaxine XR (13%) versus placebo (P=.03). Venlafaxine XR, but not escitalopram, separated from placebo on the primary efficacy measure, using the LOCF approach. However, overall efficacy analyses suggest that escitalopram and venlafaxine XR are both effective treatments for GAD. Escitalopram was better tolerated., (Depression and Anxiety, 2008. (c) 2007 Wiley-Liss, Inc.)

Objective: The aim of this study was to examine the association between polymorphism in the serotonin transporter gene and citalopram effectiveness and side effects in children and adolescents with major depressive disorder (MDD) and/or anxiety disorders., Methods: Outpatients, aged 7- 18 years with a Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) MDD and/or anxiety disorder were treated in an 8-week open trial with 20-40 mg/day of citalopram. Subjects were genotyped with respect to short (s) versus long (l) forms of the 5-HTTLPR polymorphism of the serotonin transporter, and the relationship between genotype and outcome and side effects was assessed., Results: Subjects with 5-HTTLPR ss genotype showed a less vigorous response with regard to depressive symptoms measured by the Children's Depression Rating Scale-Revised (CDRS-R) scores over time compared to subjects with sl/ll genotypes (beta = 0.67, z = 2.02, p = 0.04). In addition, the 5-HTTLPR ss group exhibited lower rates of agitation compared to those with sl/ll genotype (6.3% vs. 32.8%, p = 0.05). Also, subjects with 5-HTTLPR ss genotype had consistently higher scores of suicidality at each week compared to the sl/ll group (beta = 0.76, z = 2.04, p = 0.04) as measured by item number 13 of the CDRS-R., Conclusions: The 5-HTTLPR ss genotype was associated with a poorer clinical response with regard to depressive symptoms as well with fewer reports of agitation. The 5-HTTLPR polymorphism may be a genetic marker of response to citalopram in children and adolescents with depression and/or anxiety.

Escitalopram, the active (S)-enantiomer of citalopram, has been approved in many countries throughout the world for the treatment of depression and anxiety disorders. It is more potent and selective than citalopram in inhibiting serotonin re-uptake in the CNS, and less potent than various other selective serotonin re-uptake inhibitors in relation to other transporter proteins and receptors: in particular, it is six times less potent than citalopram in binding to the histamine H1 and muscarinic receptors. Escitalopram has favourable pharmacokinetics: it is rapidly absorbed, has a bioavailability of 80% and is not affected by food intake. It has little potential for drug interactions: it has low protein binding and, as it is metabolised by three CYP isozymes, any impairment in the activity of one is unlikely to have a significant effect on metabolic clearance. Caution is necessary only when it is coadministered with drugs metabolised by CYP2D6, such as metoprolol, or administered to the elderly or patients with severe hepatic or renal impairment. The multiple-dose pharmacokinetics of oral escitalopram are proportional at a range of doses including its therapeutic doses. Escitalopram is approved for the treatment of a number of anxiety disorders. It seems to be well tolerated and induces few or no discontinuation symptoms, and may be considered a first-line agent for the pharmacotherapy of obsessive-compulsive disorder, generalised anxiety disorder, panic disorder and social phobia. Further studies are needed to define its activity in impulse control disorders.

Background: Randomized controlled clinical trials have demonstrated that escitalopram is efficacious in a range of mood and anxiety disorders, but the individual trials are insufficiently large to allow a full exploration of its tolerability., Objective: To assess the tolerability and safety of escitalopram through analysis of all randomized controlled clinical trials in major depressive disorder and anxiety disorders., Methods: Analyses of tolerability were based on data from all available randomized, double-blind, controlled studies completed by December 2006 in which escitalopram was compared with placebo or active compounds (citalopram, fluoxetine, paroxetine, sertraline, venlafaxine). Adverse events (AEs) that occurred more frequently with escitalopram than with placebo were listed, and tolerability and safety were evaluated., Results: Nausea was the only AE with an incidence greater than or equal to 10% and 5 percentage points greater than with placebo during short-term treatment. In general, AEs were mild to moderate in severity. AEs related to sexual dysfunction were similarly frequent with escitalopram and citalopram, but were higher with paroxetine. No suicide occurred among escitalopram-treated patients, and there were no significant differences between escitalopram and placebo in incidence of suicidal behavior, measured by self-harm and suicidal thoughts. The 8 week withdrawal rate due to AEs was higher with escitalopram than with placebo (7.3% vs 2.8%; p < 0.001) but lower than with paroxetine (6.6% vs 9.0%; p < 0.01) or venlafaxine (6.1% vs 13.2%; p < 0.01) (Fisher's Exact test, 2 tailed). Compared with paroxetine, escitalopram resulted in significantly fewer discontinuation symptoms (average increase in Discontinuation Emergent Signs and Symptoms Scale of 1.6 vs 3.9; p < 0.01). There were no clinically relevant changes in clinical laboratory values in patients treated with escitalopram. Mean weight change after 6 months of treatment with escitalopram (0.58 +/- 2.63 kg) was similar to that with placebo (0.15 +/- 2.33 kg). The incidence of cardiovascular events was similar to that with placebo. The risk of AEs was no higher in special patient populations, such as the elderly (> or =65 y of age) or those with hepatic dysfunction., Conclusions: Based on data from randomized controlled trials involving more than 4000 escitalopram-treated patients, escitalopram (10-20 mg/day) is safe and well tolerated in short- and long-term treatment.

Generic agents do not require large clinical trials of safety and efficacy to enter the market, although they must demonstrate both pharmacological and bioequivalence to the brand name drug. Bioequivalence is attained when the extent of absorption of the generic falls within an FDA predefined range relative to the brand name drug. This potential variation in bioequivalence is not thought to be clinically meaningful, however, there are reports of a lack of therapeutic equivalence between some generic medications and the brand name. This study examines the potential risks posed by a switch from Celexa to generic citalopram. Twenty patients at an Anxiety Disorders Clinic who were unknowingly switched to generic citalopram, from Celexa (Lundbeck, Montreal, Quebec, Canada) and experienced a re-emergence of their anxiety symptoms or development of new adverse events are described in this case series report. The mean time for re-emergence of symptoms or development of adverse events was 3.4 +/- 1.6 weeks (range 0.5-8 weeks). All patients reestablished previous treatment response with a change back to Celexa in a mean time of 3.8 +/- 2.6 weeks (range 0.7-12 weeks). Given these results, it is important for clinicians to be aware of the potential for loss of treatment effect or symptom re-emergence posed by a switch to a generic agent. Randomized, double blind, controlled investigations would likely provide useful information as current bioequivalence and pharmacological equivalence do not necessarily translate into clinical equivalence.

Objective: The aim of this observational study was to evaluate the effectiveness of escitalopram in a naturalistic sample of employed people with mood and anxiety disorders., Method: Days on sick leave 3 months prior and 3 months during treatment with escitalopram were recorded and compared (mirror study design) in 2378 patients (949 men and 1376 women). A further clinical examination including the clinical global impression of severity (CGI-S) and improvement (CGI-I) scales and assessments of tolerability were used to evaluate treatment effects in a subgroup of 807 study subjects., Results: Escitalopram treatment (mean final daily dosage: 12.4+/-5.0 mg) led to a significant reduction (baseline versus end of study) of sick leave (11.0+/-12.8 days versus 5.4+/-11.0 days; p<0.001). CGI-S scores decreased from 4.7+/-0.9 at baseline to 2.4+/-1.1 after 3 months (p<0.001), the CGI-I after 3 months was 1.9+/-0.9. The incidence of adverse events after initiation of treatment with escitalopram was 13.1%, with only 1.3% of patients experiencing severe adverse events interfering with patient functioning., Conclusion: Our results suggest that escitalopram is an efficacious and overall well-tolerated treatment in a naturalistic sample of working patients. A decrease in the days on sick leave is indicative of indirect cost-effectiveness of this treatment.

The present overview investigates whether different antidepressants have differing discontinuation symptoms upon treatment cessation, if these symptoms vary between depression and anxiety disorders, and with length of treatment. Data came from two comparative studies of escitalopram in major depressive disorder (MDD) (one vs. venlafaxine XR and one vs. paroxetine), two studies in social anxiety disorder (SAD) (one of which used paroxetine as the active reference), and one study in generalized anxiety disorder (GAD), using paroxetine as an active reference [total number of patients: escitalopram (n=1051); paroxetine (n=336); venlafaxine XR (n=124); placebo (n=239)]. All studies included a defined discontinuation period and used the Discontinuation Emergent Signs and Symptoms (DESS) checklist to record the number of discontinuation symptoms. All three antidepressants showed more discontinuation symptoms compared with placebo (p<0.001). Patients reported significantly fewer discontinuation symptoms with escitalopram than with paroxetine and venlafaxine XR in MDD (p<0.05). Escitalopram showed significantly fewer discontinuation symptoms than paroxetine in SAD (p<0.05) and GAD (p<0.001). For each antidepressant, no differences in discontinuation symptoms were observed between the three indications and there was no evidence for increased symptom incidence with increased length of treatment. Thus, discontinuation profiles differ between antidepressants of the same class and are broadly similar in different disorders. No evidence was seen for a higher discontinuation burden with longer treatment.

Most patients with depression have symptoms of anxiety associated with their illness. Our aim in this study was to investigate the efficacy of escitalopram, a proven antidepressant, on symptoms of anxiety in patients with major depressive disorder (MDD). Data from five placebo-controlled escitalopram studies in MDD were analyzed. Three of the studies also included a comparison with citalopram. In all studies, anxiety was assessed using the Inner Tension item (item 3) of the Montgomery-Asberg Depression Rating Scale (MADRS). In three studies, anxiety symptoms were also specifically assessed, either continuously over time or at baseline and end point, by using the Hamilton Rating Scale for Anxiety (HAM-A), the Anxious Mood item of the HAM-A (item 1), the Psychic Anxiety subscale of the HAM-A (items 1-6 and 14), the Anxiety Psychic item (item 10) of the Hamilton Rating Scale for Depression (HAM-D-24), and the Anxiety/Somatization subfactor (items 10-13, 15, and 17) of the HAM-D-24. Escitalopram was significantly superior to placebo in all comparisons. Citalopram was also consistently better than placebo in all comparisons, except in the HAM-D-24 Anxiety/Somatization subfactor. In some comparisons with placebo, escitalopram showed a significantly earlier onset of action or an earlier separation. Escitalopram was significantly more effective compared to placebo in treating both anxiety symptoms and the entire depression in the total depressive population, as well as in depressive patients with a high degree of anxiety.

This open, multicenter, prospective study in France assessed the efficacy and tolerability of escitalopram in patients with depression, with or without comorbid anxiety. Escitalopram was administered over a 12-week treatment period to 790 depressed patients, including 482 patients with at least one concomitant anxiety disorder. The study was completed by 649 patients. At baseline, the mean Montgomery-Asberg Depression Rating Scale (MADRS) total score was 31.5 and decreased to 12.4 at end point (last observation carried forward [LOCF]). The MADRS score decreased by 20.5 points in patients with no anxiety disorder and by 18.3 points in patients with at least one concomitant anxiety disorder. The mean Hamilton Anxiety Rating Scale (HAM-A) total score at baseline was 25.6, which decreased to 10.8 at end point (LOCF). The HAM-A score decreased by 13.8 points in patients with no anxiety disorder and by 15.5 points in patients with at least one anxiety disorder. Adverse events were reported by 246 patients (31%). The most frequent adverse events were nausea in 65 patients (8%) and headache in 38 patients (5%); 61 patients (8%) discontinued treatment due to adverse events. Escitalopram was well tolerated and efficacious in reducing symptoms of depression in patients with or without comorbid anxiety over a 12-week treatment period.

Background: Comorbid depression and anxiety may result in greater symptom severity and poorer treatment response than either condition alone. Selective serotonin reuptake inhibitors have been found to be effective in treating both depression and anxiety; however, pharmacodynamic and pharmacokinetic changes associated with aging warrant special attention in medication trials in older patients., Objective: The objective of this study was to assess the efficacy and tolerability of short-term (12-week) administration of escitalopram oxalate 10 to 20 mg/d for moderate to marked comorbid depression and anxiety in elderly patients., Methods: This open-label, flexible-dose (10-20 mg/d), pilot trial was conducted at the Psychiatry Service, Veterans Affairs Medical Center, Cincinnati, Ohio. Outpatients aged > or =65 years were included if they met the criteria for comorbid major depressive disorder (MDD) and generalized anxiety disorder (GAD), as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, for > or =4 weeks and had a baseline Montgomery-Asberg Depression Rating Scale (MADRS) score of >22 and a Hamilton Rating Scale for Anxiety (HAM-A) score of > or =18. All patients received escitalopram 10 to 20 mg/d. The primary efficacy variables were the mean changes from baseline in total MADRS and HAM-A scores at 12 weeks (last observation carried forward). The secondary efficacy end point was the change from baseline in Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) 8 subscale scores. Adverse events were assessed at each visit (treatment weeks 1, 2, 3, 4, 6, 8, 10, and 12) with the use of open-ended questioning., Results: Twenty patients were enrolled (mean [SD] age, 73.0 [4.8] years; 6 [30%] women; race: 17 [85%] white, 2 [10%] black, and 1 [5%] "other"). Seventeen (85%) of 20 patients completed the study; 3 (15%) withdrew: 1 (5%) due to lack of efficacy and 2 (10%) due to adverse events (dizziness and somnolence [1 (5%) patient each]). Statistically significant improvements from baseline to end point were found with escitalopram treatment (MADRS: t19 = 7.38, P < 0.001, effect size = 2.93; HAM-A: t19 = 4.19, P < 0.001, effect size = 1.83). Significant changes from baseline in scores on 4 (Social Functioning, Role Functioning-Emotional, Mental Health, and Energy/Fatigue) of the 8 subscales of the SF-36 were also found (all, P < 0.01)., Conclusion: In this small study in elderly patients with comorbid MDD and GAD, treatment with escitalopram 10 to 20 mg/d for 12 weeks was associated with significant improvements in symptoms of depression and anxiety.

Background: It is uncertain whether higher doses of selective serotonin reuptake inhibitors have greater efficacy in generalised anxiety disorder., Aims: To assess the efficacy of different doses of escitalopram in generalised anxiety disorder., Method: Randomised, double-blind, placebo-controlled, fixed-dose, parallel-group, 12-week study, with 681 patients: placebo (n=139); escitalopram, 5 mg/day, (n=134); 10 mg/day (n=136); 20 mg/day (n=133); paroxetine, 20 mg/day (n=139)., Results: Mean change in the primary efficacy measure was greater with escitalopram 10 and 20 mg than with placebo; 10 mg was more efficacious than paroxetine. Paroxetine was superior to placebo on some secondary measures, at some time points. Compared with placebo, more patients withdrew because of adverse events with escitalopram 20 mg and paroxetine., Conclusions: Escitalopram was efficacious in generalised anxiety disorder, 20 was not significantly superior to 10 mg/day. Escitalopram 10 mg was more efficacious than paroxetine.

The suicide-related data on citalopram from controlled clinical trials in depression and anxiety disorders were analysed. Safety data from placebo-controlled and relapse prevention citalopram trials in depression/major depressive disorder (MDD) and anxiety were searched for specific events relating to fatal suicide, non-fatal self-harm or suicidal thoughts. Efficacy data (item 10, suicidal thoughts, on the Montgomery-Asberg Depression Rating Scale [MADRS]) were also analysed. In the clinical trial database, the number of adverse events (fatal suicide, non-fatal self-harm or suicidal thoughts) was low, both during the first 2 weeks of treatment and during the full treatment period, with no statistically significant differences between citalopram and placebo. There was one fatal suicide during treatment (after 12 weeks of double-blind treatment in a relapse-prevention trial) for a patient treated with citalopram (incidence: 0.4%; rate: 0.010) and none on placebo. Citalopram was significantly more efficacious than placebo in lowering suicidal thoughts, based on efficacy rating (MADRS, item 10). There was no indication from this review of clinical trial data that citalopram may increase the risk of suicide in patients with MDD or anxiety. However, the patients in these clinical trials represent a selected group, as those patients with a significant risk of suicide were excluded at trial onset.

Our aim in this observational study was to evaluate the feasibility of a multiphasic screening project for the detection and treatment of mood and anxiety disorders among cancer patients in a natural setting. One hundred sixty-five patients with cancer, consecutively admitted to the Oncology Division of San Camillo-Forlanini Hospital, were recruited to the study. All patients had solid tumors; the majority of them were colon, breast, and lung cancers. All patients completed the Hospital Anxiety and Depression Scale (HADS). Patients screened as positive were administered the following instruments by a psychiatrist: the Structured Clinical Interview for DSM-IV (SCID-I), the Beck Depression Inventory (BDI), the Hamilton Anxiety Rating Scale (HARS), and a validated scale for the rapid dimensional assessment of psychopathology (SVARAD). The BDI, HARS, and SVARAD were administered again at 4 and 10 weeks to all treated patients. Out of 45 patients administered the SCID-I, 37 had a mood or anxiety disorder. Adjustment disorders were identified in 20 patients, depressive disorders in 14, and anxiety disorders in three patients. Most patients were prescribed psychotropic medications: mirtazapine was prescribed to 15 patients, citalopram to 13 patients, and escitalopram to four patients. A significant improvement in symptoms of depression and anxiety was observed on all measures (P<.001). Although the design of the study prevents any firm conclusions about effectiveness, this study suggests that including psychiatric expertise in an oncology division is feasible and may lead to improved detection and treatment of psychiatric disorders among cancer patients. Further randomized trials are needed to elaborate on our findings.

Introduction: Generalized anxiety disorder (GAD) is a chronic disorder that requires long-term treatment. Escitalopram has previously been shown to be effective and well tolerated in the acute treatment of GAD., Method: Three 8-week, double-blind, placebo-controlled trials of nearly identical design were conducted of escitalopram in moderate-to-severe GAD (DSM-IV criteria). Patients completing these trials were given the option of entering a 24-week, open-label, flexible-dose trial of escitalopram (10-20 mg/day). Data were collected from September 20, 2000, to August 15, 2002., Results: Two hundred ninety-nine (56.8%) of 526 patients completed 24 weeks of open-label treatment. The mean Hamilton Rating Scale for Anxiety (HAM-A) score at baseline of open-label treatment was 13.1. Long-term escitalopram treatment led to continuing improvement on all anxiety and quality-of-life (QOL) scores. Of those completing 24 weeks of treatment, 92.0% were responders (Clinical Global Impressions-Improvement scale score < or = 2), and the mean HAM-A score in the completed analysis was 6.9; using the last observation carried forward (LOCF), 75.9% were responders, and the mean HAM-A score in the LOCF analysis was 9.2 at endpoint. Insufficient therapeutic response and adverse events led to withdrawal of 4.2% and 9.9% of patients, respectively. Mean increase in weight from baseline was 3.0 lb. No clinically notable changes in mean laboratory, vital sign, or electrocardiographic values were observed., Conclusion: These results support the long-term tolerability and effectiveness of escitalopram in the treatment of GAD.

Background: Escitalopram 10 mg/day is an effective and well-tolerated antidepressant. Three randomized controlled trials recently evaluated the safety and efficacy of escitalopram in the treatment of generalized anxiety disorder (GAD)., Methods: The trial designs were virtually identical, allowing data to be pooled across studies. Male and female outpatients, ages 18-80 years, with DSM-IV-defined GAD were randomized to double-blind treatment with escitalopram or placebo for 8 weeks. Escitalopram dose was fixed at 10 mg/day for the first 4 weeks, after which increases to 20 mg/day were permitted. The primary efficacy variable was the mean change from baseline in total Hamilton Anxiety Scale (HAMA) score., Results: Approximately 850 patients were randomized to double-blind treatment. In each individual study, escitalopram was significantly superior to placebo (p<0.05) as measured by change from baseline in HAMA score. By-visit analyses of data pooled across studies revealed significantly greater improvement (p<0.05) in the escitalopram group beginning at week 1 or 2 and continuing through week 8 for all primary and secondary efficacy variables. The mean change in HAMA total score from baseline to endpoint also was significantly greater for patients maintained at escitalopram 10 mg/day than for those receiving placebo. Escitalopram was generally well tolerated., Limitations: The studies included in this analysis were of short-term duration and excluded patients with significant medical and psychiatric comorbidities, such as major depressive disorder., Conclusion: Results from the individual trials and the pooled analysis demonstrate that escitalopram is effective and well tolerated for the treatment of GAD.

The escitalopram clinical trial database, consisting of all placebo-controlled and relapse prevention trials within major depressive disorder (MDD) and anxiety disorders, was analysed for specific adverse events indicative of suicidal behaviour (fatal suicide, non-fatal self-harm or suicidal thoughts) in relation to treatment. The number of events was low, with no fatal suicides in the first 2 weeks of treatment. There was one fatal suicide during the full treatment period on placebo (incidence 0.1%; rate 0.003), and none on escitalopram. None of these figures were significantly different between escitalopram (n=2277) and placebo (n=1814) patients. There was no indication that escitalopram provokes suicidal behaviour compared to placebo in either MDD or anxiety disorders. Based on efficacy ratings (Montgomery-Asberg Depression Rating Scale, item 10), escitalopram was more efficacious versus placebo in lowering suicidal thoughts from weeks 1 through 8 in the treatment of patients with MDD.

Background: This study compared the efficacy and tolerability of escitalopram, a newer SSRI, with paroxetine in the treatment of generalized anxiety disorder (GAD)., Methods: Patients with DSM-IV-defined GAD were randomized to receive 24 weeks of double-blind flexible-dose treatment with either escitalopram (10-20 mg/day) or paroxetine (20-50 mg/day), followed by a 2-week, double-blind, down-titration period. Mean change from baseline to endpoint (LOCF) in Hamilton Anxiety Scale (HAMA) scores was the primary efficacy variable., Results: Mean baseline HAMA scores for the escitalopram (N = 60) and paroxetine (N = 61) groups were 23.7 and 23.4, respectively. After 24 weeks of treatment, mean changes in HAMA scores were -15.3 and -13.3 for escitalopram and paroxetine, respectively (p = 0.13). Significantly fewer patients withdrew from escitalopram than paroxetine treatment due to adverse events (6.6% vs. 22.6%; p = 0.02). The frequency of treatment-emergent adverse events was higher with paroxetine vs. escitalopram: overall (88.7% vs. 77.0%), insomnia (25.8% vs. 14.8%), constipation (14.5% vs. 1.6%), ejaculation disorder (30.0% vs. 14.8%), anorgasmia (26.2% vs. 5.9%), and decreased libido (22.6% vs. 4.9%). Conversely, diarrhea and upper respiratory tract infection were reported more with escitalopram than paroxetine (21.3% vs. 8.1%, and 14.8% vs. 4.8%, respectively)., Conclusions: These results support the use of escitalopram as a first-line treatment for GAD.

Objective: Anxiety disorders are highly prevalent in elderly persons. However, to date, the efficacy of selective serotonin reuptake inhibitors (SSRIs) for the treatment of anxiety disorders in this age group has not been established., Method: Thirty-four participants age 60 and older with a DSM-IV anxiety disorder (mainly generalized anxiety disorder) and a Hamilton Anxiety Rating Scale score of 17 or higher were randomly assigned under double-blind conditions to either citalopram or placebo. Response was defined as a score of 1 (very much improved) or 2 (much improved) on the Clinical Global Improvement scale or a 50% reduction in the Hamilton anxiety scale score. Response and side effects with citalopram and placebo were compared by using chi-square tests and linear modeling., Results: Eleven (65%) of the 17 citalopram-treated participants responded by 8 weeks, versus four (24%) of the 17 placebo-treated participants. The most common and problematic side effect in the citalopram group was sedation., Conclusions: The authors believe this to be the first prospective controlled study to test the efficacy of an SSRI in the management of anxiety disorders among the elderly. These results support the efficacy of citalopram in late-life anxiety disorders. They need to be replicated in a larger study group.

With or without drugs, most people who sought care for depression or anxiety gained relief. A survey of thousands of CR subscribers who recently received treatment for those conditions found that: (1) a combination of talk therapy and drugs often worked best. But "mostly talk" therapy was almost as effective if it lasted for 13 or more visits. (2) "Mostly drug" therapy was also effective for many people. Drugs had a quicker impact on symptoms than talk therapy, but it often took trial and error to find a drug that worked without unacceptable side effects. (3) Forty percent of people who took antidepressants complained of adverse sexual side effects. (4) Care from primary-care doctors was effective for people with mild problems, but less so for people with severe ones.

Objective: To assess the potential efficacy, tolerability, and safety of citalopram in the treatment of functional pediatric recurrent abdominal pain and comorbid internalizing disorders., Method: Twenty-five clinically referred children and adolescents with recurrent abdominal pain aged 7 to 18 years, inclusive, participated in a 12-week, flexible-dose, open-label trial of citalopram. Primary outcome measure was the Clinical Global Impression Scale-Improvement, with responders defined by ratings of 1 (very much improved) or 2 (much improved). Secondary measures included self- and parent reports of abdominal pain, anxiety, depression, other somatic symptoms, and functional impairment. Side effects were assessed using a standardized checklist. Data were analyzed using an intent-to-treat format and the last observation carried forward procedure., Results: Twenty-one subjects (84%) were classified as responders (Clinical Global Impression Scale-Improvement score < or =2). Citalopram was generally well tolerated. Four subjects withdrew prematurely, one due to reported visual side effects. Ratings of abdominal pain, anxiety, depression, other somatic symptoms, and functional impairment all improved significantly over the course of the study compared with baseline., Conclusions: Citalopram is a promising treatment for functional pediatric recurrent abdominal pain and deserves additional study with a randomized, placebo-controlled clinical trial.

The effects of auditory statements describing a personal worry on brain activation as measured by functional magnetic resonance imaging were examined in patients with generalized anxiety disorder (GAD) before and after anxiety reduction with citalopram. Six patients were imaged while listening to verbal descriptions of a personal worry or a neutral statement before treatment with citalopram and after 7 weeks of treatment. Pre-post drug analyses showed treatment with citalopram reduced self-reported anxiety and reduced BOLD responses to a pathology-specific worry and a neutral stimulus. After treatment, worry sentences, compared to neutral statements, elicit reduced BOLD responses in prefrontal regions, the striatum, insula and paralimbic regions. In addition, contrasts before and after treatment revealed reductions in the differential response that existed between worry and neutral statements. Overall reduction of BOLD response was most prominent during neutral statements, particularly in the left hemisphere. These findings support the clinical impression that GAD patients overreact to both pathology-specific and non-specific cues and that the reduction of anxiety attenuates the response to both types of cues.

Escitalopram has been shown in clinical trials to improve anxiety symptoms associated with depression, panic disorder, and social anxiety disorder. This study was designed to evaluate the efficacy and tolerability of escitalopram in the treatment of generalized anxiety disorder (GAD). Outpatients (18 years or older) who met DSM-IV criteria for GAD, with baseline Hamilton Rating Scale for Anxiety (HAMA) scores > or = 18, were randomly assigned to double blind treatment with escitalopram (10 mg/day for the first 4 weeks and then flexibly dosed from 10-20 mg/day) or placebo for 8 weeks, following a 1-week, single-blind, placebo lead-in period. The primary efficacy variable was the mean change from baseline in total HAMA score at Week 8. The escitalopram group (N = 158) showed a statistically significant, and clinically relevant, greater improvement at endpoint compared with placebo (N = 157) in all prospectively defined efficacy parameters. Significant improvement in HAMA total score and HAMA psychic anxiety subscale score for the escitalopram-treated group vs. the placebo-treated group was observed beginning at Week 1 and at each study visit thereafter. Mean changes from baseline to Week 8 on the HAMA total score using a last-observation-carried-forward (LOCF) approach were -11.3 for escitalopram and -7.4 for placebo (P<.001). Response rates at Week 8 were 68% for escitalopram and 41% for placebo (P<.01) for completers, and 58% for escitalopram and 38% for placebo LOCF values (P<.01). Treatment with escitalopram was well tolerated, with low rates of reported adverse events and an incidence of discontinuation due to adverse events not statistically different from placebo (8.9% vs. 5.1%; P=.27). Escitalopram 10-20 mg/day is effective, safe, and well tolerated in the treatment of patients with GAD.

This case illustrates that compliance with the basic principles of geriatric pharmacology (start low, go slow, and avoid polypharmacy) might have prevented a clinical syndrome that could have caused serious complications. Fortunately, serotonin syndrome was recognized early, the offending agents were discontinued, and supportive treatment was provided. The patient was ultimately treated with mirtazapine, an antidepressant not associated with serotonergic effects.