Anxiety Disorders: Montgomery SA

Allgulander C, Bandelow B, Hollander E, Montgomery SA, Nutt DJ, Okasha A, Pollack MH, Stein DJ, Swinson RP, Anonymous00175. · Department of Psychiatry, Harvard University School of Medicine, Boston, Massachusetts, USA. · CNS Spectr. · Pubmed #14767398 No free full text.

Abstract: What are the current recommendations for the long-term treatment of generalized anxiety disorder (GAD)? GAD is a common disorder with a lifetime prevalence of 4% to 7% in the general population. GAD is characterized by excessive, uncontrollable worry or anxiety about a number of events or activities that the individual experiences on more days than not over a 6-month period. Onset of GAD symptoms usually occurs during an individual's early twenties; however, high rates of GAD have also been seen in children and adolescents. The clinical course of GAD is often chronic, with 40% of patients reporting illness lasting >5 years. GAD is associated with pronounced functional impairment, resulting in decreased vocational function and reduced quality of life. Patients with GAD tend to be high users of outpatient medical care, which contributes significantly to healthcare costs. Currently, benzodiazepines and buspirone are prescribed frequently to treat GAD. Although both show efficacy in acute treatment trials, few long-term studies have been performed. Benzodiazepines are not recommended for long-term treatment of GAD, due to associated development of tolerance, psychomotor impairment, cognitive and memory changes, physical dependence, and a withdrawal reaction on discontinuation. The antidepressant venlafaxine extended-release (XR) has received approval for the treatment of GAD in the United States and many other countries. Venlafaxine XR has demonstrated efficacy over placebo in two randomized treatment trials of 6 months' duration as well as in other acute trials. Paroxetine is the first of the selective serotonin reuptake inhibitors (SSRIs) to receive US approval for the treatment of GAD. Paroxetine demonstrated superiority to placebo in short-term trials, and investigations into the use of other SSRIs are ongoing. This suggests that other SSRIs, and serotonin and noradrenaline reuptake inhibitors, are likely to be effective in the treatment of GAD. Of the psychological therapies, cognitive-behavioral therapy (CBT) shows the greatest benefit in treating GAD patients. Treatment gains after a 12-week course of CBT may be maintained for up to 1 year. Currently, no guidelines exist for the long-term treatment of GAD.

Van Ameringen M, Allgulander C, Bandelow B, Greist JH, Hollander E, Montgomery SA, Nutt DJ, Okasha A, Pollack MH, Stein DJ, Swinson RP, Anonymous00174. · Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, Ontario, Canada. · CNS Spectr. · Pubmed #14767397 No free full text.

Abstract: What is the best approach for treating patients with social phobia (social anxiety disorder) over the long term? Social phobia is the most common anxiety disorder, with reported prevalence rates of up to 18.7%. Social phobia is characterized by a marked and persistent fear of being observed or evaluated by others in social performance or interaction situations and is associated with physical, cognitive, and behavioral (ie, avoidance) symptoms. The onset of social phobia typically occurs in childhood or adolescence and the clinical course, if left untreated, is usually chronic, unremitting, and associated with significant functional impairment. Social phobia exhibits a high degree of comorbidity with other psychiatric disorders, including mood disorders, anxiety disorders, and substance abuse/dependence. Few people with social phobia seek professional help despite the existence of beneficial treatment approaches. The efficacy, tolerability, and safety of the selective serotonin reuptake inhibitors (SSRIs), evidenced in randomized clinical trials, support these agents as first-line treatment. The benzodiazepine clonazepam and certain monoamine oxidase inhibitors (representing both reversible and nonreversible inhibitors) may also be of benefit. Treatment of social phobia may need to be continued for several months to consolidate response and achieve full remission. The SSRIs have shown benefit in long-term treatment trials, while long-term treatment data from clinical studies of clonazepam are limited but support the drug's efficacy. There is also evidence for the effectiveness of exposure-based strategies of cognitive-behavioral therapy, and controlled studies suggest that the effects of treatment are generally maintained at long-term follow-up. In light of the chronicity and disability associated with social phobia, as well as the high relapse rate after short-term therapy, it is recommended that effective treatment be continued for at least 12 months.

Greist JH, Bandelow B, Hollander E, Marazziti D, Montgomery SA, Nutt DJ, Okasha A, Swinson RP, Zohar J, Anonymous00171. · Healthcare Technology Systems, Inc., Madison, Wisconsin 53717, USA. · CNS Spectr. · Pubmed #14767394 No free full text.

Abstract: What are the latest psychotherapeutic and pharmacotherapeutic treatment recommendations for obsessive-compulsive disorder (OCD)? OCD is a relatively common disorder with a lifetime prevalence of approximately 2% in the general population. It often has an early onset, usually in childhood or adolescence, and frequently becomes chronic and disabling if left untreated. High associated healthcare utilization and costs, and reduced productivity resulting in loss of earning, pose a huge economic burden to OCD patients and their families, employers, and society. OCD is characterized by the presence of obsessions and compulsions that are time-consuming, cause marked distress, or significantly interfere with a person's functioning. Most patients with OCD experience symptoms throughout their lives and benefit from long-term treatment. Both psychotherapy and pharmacotherapy are recommended, either alone or in combination, for the treatment of OCD. Cognitive-behavioral therapy is the psychotherapy of choice. Pharmacologic treatment options include the tricyclic antidepressant clomipramine and the selective serotonin reuptake inhibitors (SSRIs) citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. These have all shown benefit in acute treatment trials; clomipramine, fluvoxamine, fluoxetine, and sertraline have also demonstrated benefit in long-term treatment trials (at least 24 weeks), and clomipramine, sertraline, and fluvoxamine have United States Food and Drug Administration approvals for use in children and adolescents. Available treatment guidelines recommend first-line use of an SSRI (ie, fluoxetine, fluvoxamine, paroxetine, sertraline, or citalopram) in preference to clomipramine, due to the latter's less favorable adverse-event profile. Further, pharmacotherapy for a minimum of 1-2 years is recommended before very gradual withdrawal may be considered.

Montgomery SA. · Imperial College School of Medicine, University of London, PO Box 8751, W13 8WH, UK. · Expert Opin Pharmacother. · Pubmed #17020438 No free full text.

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

Baldwin DS, Montgomery SA, Nil R, Lader M. · Clinical Neurosciences Division, School of Medicine, University of Southampton, UK. · Int J Neuropsychopharmacol. · Pubmed #16359583 No free full text.

Abstract: 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.

Montgomery SA, Lecrubier Y, Baldwin DS, Kasper S, Lader M, Nil R, Stein D, Van Ree JM, Anonymous00228. · · Eur Neuropsychopharmacol. · Pubmed #15336305 No free full text.

This publication has no abstract.

Montgomery SA, Baldwin DS, Riley A. · Department of Pharmacology, Imperial College School of Medicine, P.O. Box 8751, London W13 8WH, UK. · J Affect Disord. · Pubmed #12103459 No free full text.

Abstract: BACKGROUND: Sexual dysfunction is recognised as a potential side effect of antidepressant therapy. However, there is little detailed information on the prevalence of drug-induced sexual dysfunction or the differences, if any, between available drugs. This article is a critical review of the literature in the area. METHODS: English-language studies on sexual dysfunction and depression or antidepressant treatments were identified by searching Medline and supplemented by manual review of their reference lists and recent journal issues available in a library. Trials of antidepressant use in anxiety disorders were identified from a Medline search and their adverse events tables scanned for data on sexual dysfunction. All trials were assessed according to predefined criteria. RESULTS: Sexual dysfunction is widespread in the healthy non-depressed population and is a recognised symptom of depression and/or anxiety disorders. Sexual dysfunction has been reported with all classes of antidepressants (MAOIs, TCAs, SSRIs, SNRIs and newer antidepressants) in patients with depression and various anxiety disorders. Numerous studies have been published, but only one used a validated sexual function rating scale and most lacked either a baseline or a placebo control or both. None met all of the pre-defined assessment criteria. LIMITATIONS: The search techniques may have missed some studies and publication bias cannot be ruled out. CONCLUSIONS: The existing literature confirms sexual dysfunction as a possible adverse event of all antidepressants, but it is not sufficiently robust to support claims for differences in the incidence of drug-induced sexual dysfunctions between existing antidepressant therapies. Prescribing decisions should be based on a careful assessment of the benefits and risks of therapy in the individual patient.

Brunello N, den Boer JA, Judd LL, Kasper S, Kelsey JE, Lader M, Lecrubier Y, Lepine JP, Lydiard RB, Mendlewicz J, Montgomery SA, Racagni G, Stein MB, Wittchen HU. · Centre of Neuropharmacology, Institute of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy. · J Affect Disord. · Pubmed #10940449 No free full text.

Abstract: Social phobia is a common disorder associated with significant psychosocial impairment, representing a substantial public health problem largely determined by the high prevalence, and the lifelong chronicity. Social phobia starts in early childhood or adolescence and is often comorbid with depression, other anxiety disorders, alcohol and substance abuse or eating disorders. This cascade of comorbidity, usually secondary to social phobia, increases the disability associated with the condition. The possibility that social phobia may be a trigger for later developing comorbid disorders directs attention to the need for early effective treatment as a preventive measure.The most recent drug class to be investigated for the psychopharmacological treatment of social phobia is the SSRI group for which there is growing support. The other drug classes that have been evaluated are monoamine oxidase inhibitors (MAOIs), benzodiazepines, and beta-blockers. The SSRIs represent a new and attractive therapeutic choice for patients with generalized social phobia. Recently the first, large scale, placebo-controlled study to assess the efficacy of drug treatment in generalized social phobia has been completed with paroxetine. Paroxetine was more effective in reducing the symptoms than placebo and was well tolerated. Many now regard SSRIs as the drugs of choice in social phobia because of their effectiveness and because they avoid the problems of treatment with benzodiazepines or classical MAOIs.

Montgomery SA. · Department of Pharmacology, Imperial College School of Medicine at St Mary's, London, UK. · Eur Arch Psychiatry Clin Neurosci. · Pubmed #10361959 No free full text.

Abstract: Social phobia has a direct effect on the ability of the individual to interact with others in social or work situations and as a result is associated with a high level of dysfunction. The level of impairment is as severe as that found in other chronic disorders such as depression and is increased by a cascade of comorbidity, which complicates management. Efficacy in social phobia was reported with the MAOIs and this led to the investigation of reversible inhibitors of monoamine oxidase-A (RIMA) which offer a safer alternative. The efficacy of moclobemide has been shown in social phobia and the effect is more clear cut in patients with more severe symptoms. The better effect in severe social phobia has also been reported with the SSRI paroxetine. Effective treatment of social phobia appears to be able to overcome the substantial chronicity of illness which is frequent in sufferers. The introduction of these treatments should encourage people with social phobia to seek medical help for this hitherto much neglected disorder.

Montgomery SA, Mahé V, Haudiquet V, Hackett D. · Imperial College School of Medicine, London, United Kingdom. · J Clin Psychopharmacol. · Pubmed #12454555 No free full text.

Abstract: A survival analysis of data from two placebo-controlled, randomized, long-term (6-month) studies was used to examine the effectiveness of venlafaxine, extended release (XR) formulation, in patients with generalized anxiety disorder (GAD). Patients in a placebo-controlled, flexible-dose study received 75 to 225 mg/day venlafaxine XR, while patients in a placebo-controlled, fixed-dose study received once-daily venlafaxine XR doses of 37.5 mg, 75 mg, or 150 mg. The survival analysis was based on the clinician's decision to discontinue treatment in a placebo-controlled study and incorporated data from all patients who were randomized. In each study, placebo-treated patients discontinued treatment due to lack of efficacy more frequently and earlier than those receiving venlafaxine XR (p < 0.001, log-rank test). A dose-response relationship was apparent, with the lowest rate of withdrawal seen at the highest venlafaxine XR dose. Survival curves for discontinuations due to adverse events did not differ significantly in either study. These results were consistent with the conventional intent-to-treat efficacy assessments of changes in anxiety severity, highlighting the superiority of venlafaxine XR over placebo in the long-term treatment of GAD. Overall, these results demonstrate the clinical effectiveness of venlafaxine XR in the short-term and long-term treatment of GAD.

Stein DJ, Cameron A, Amrein R, Montgomery SA, Anonymous00240. · Department of Psychiatry, University of Stellenbosch, Cape Town, South Africa. · Int Clin Psychopharmacol. · Pubmed #12131599 No free full text.

Abstract: Social phobia (social anxiety disorder) is a highly prevalent and chronic disorder that is associated with significant comorbidity and disability. Despite recent advances in the pharmacotherapy of the disorder, there is a paucity of randomized controlled trials on patients with comorbid disorders and on maintenance treatment. A randomized placebo-controlled, double-blind multi-site trial of moclobemide, a reversible inhibitor of monoamine oxidase A, was undertaken with 390 subjects. After an initial 12 weeks, there was the option of continuing for an additional 6 months of treatment. The primary efficacy parameter chosen was responder status as defined by the Clinical Global Impression scale change item. From week 4 onwards, there was a significantly higher response rate on moclobemide than on placebo. Superiority of medication over placebo was similar in patients with comorbid anxiety disorders (33% of subjects) and without, as well as in patients with different subtypes of social anxiety disorder; indeed, treatment with moclobemide rather than placebo was the strongest predictor of response. Adverse events were similar across treatment groups, and were typically mild and transient. In the extension phase, response rates remained higher in the moclobemide group, and ratings of tolerability were equally high in both groups. Thus, in a large sample of social anxiety disorder patients with and without comorbid anxiety disorders, moclobemide was both effective and well-tolerated in the short as well as long-term. These data confirm and extend previous findings on the value of moclobemide in the treatment of social anxiety disorder, and strengthen the range of therapeutic options for managing this important disorder.

Stein DJ, Montgomery SA, Kasper S, Tanghoj P. · Department of Psychiatry, University of Stellebosch, Tygerberg, Cape Town, South Africa. · Int Clin Psychopharmacol. · Pubmed #11712625 No free full text.

Abstract: Although serotonin reuptake inhibitors (SRIs) are the medications of choice in the treatment of obsessive-compulsive disorder (OCD), only 50-60% of patients respond to a single trial of any of these agents. Improved knowledge of the predictors of response to treatment may have important clinical implications. Data from a large randomized placebo-controlled trial of citalopram in OCD was analysed using logistic regression to determine predictors of response. Demographic (age, sex), clinical (OCD severity and duration, depression severity, prior treatment) and trial variables (citalopram dose, treatment duration) were included. Subjects with longer duration of OCD, more severe OCD symptoms or previous selective SRI use were less likely to be responders in the citalopram trial. In contrast, subjects who received adequate medication doses for sufficient periods of time in the citalopram trial were more likely to be responders. Despite greater awareness of OCD in recent years, there is evidence that the disorder continues to be underdiagnosed and undertreated. The data here emphasize the crucial importance of early diagnosis and treatment of OCD, and of pharmacotherapy with appropriate dose and duration.

Montgomery SA, Kasper S, Stein DJ, Bang Hedegaard K, Lemming OM. · Imperial College of Science, Technology and Medicine, London, UK. · Int Clin Psychopharmacol. · Pubmed #11236072 No free full text.

Abstract: Serotonin reuptake inhibitors appear to be uniquely effective treatments for obsessive-compulsive disorder (OCD). This double-blind, placebo-controlled study was the first trial to assess the efficacy of the most selective of the serotonin reuptake inhibitors, citalopram, in OCD. A total of 401 patients were randomized to receive citalopram 20, 40 or 60 mg/day or placebo for 12 weeks. All three doses of citalopram were significantly more effective than placebo measured on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) change score (P < 0.01). The highest response rate, defined as 25% improvement in Y-BOCS entry score, was observed in the 60 mg group (65%). This compared with 52% and 57.4% in the 40 mg and 20 mg groups. Response rate on placebo was 36.6% (P < 0.05 for all three doses of citalopram compared to placebo). There was no significant difference between the individual doses of citalopram. An advantage was seen for citalopram on the Sheehan Disability Scale compared with placebo (P < 0.05 on all three citalopram groups versus placebo for both the work situation and the family life and home responsibilities and P < 0.05 on citalopram 60 mg and 20 mg versus placebo for the social life and home activities). Citalopram was well tolerated; only 4 to 6 patients in each dose group discontinued the study prematurely due to adverse events.

Montgomery SA, Herman BK, Schweizer E, Mandel FS. · Imperial College School of Medicine, University of London, UK. · Int Clin Psychopharmacol. · Pubmed #19542983 No free full text.

Abstract: The objective of this study was to assess the impact of high levels of insomnia on response to pregabalin (PGB) in patients with generalized anxiety disorder (GAD). Pooled data were analyzed from six double-blind, placebo-controlled, 4- to 6-week trials of outpatients who met the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) criteria for GAD with a minimum Hamilton Rating Scale for Anxiety (HAM-A) score = 18. Response was evaluated for three fixed-dose PGB groups (150, 300-450, 600 mg/day), and for a benzodiazepine group (alprazolam or lorazepam). A 'high-insomnia' subgroup was defined by a baseline HAM for Depression (HAM-D) insomnia factor score greater than 3 (maximum = 6). At baseline, 1002 (54%) patients met the criteria for the high-insomnia subgroup, and 852 (46%) for the low-insomnia subgroup. Mean baseline HAM-A scores were 1-2 points higher in high-insomnia versus low-insomnia patients. In high-insomnia patients, PGB produced significantly greater improvement in HAM-A total scores at last observation carried forward endpoint on 300-450 mg (-13.1+/-0.6) and 600 mg (-11.2+/-0.5) dose groups compared with placebo (-8.3+/-0.5; P<0.0001 for both comparisons); the improvement on PGB 150 mg was not significant (-9.9+/-0.7; P = 0.051). Improvement was significant in the benzodiazepine group (-11.0+/-0.6; P<0.0001). In the high-insomnia subgroup, treatment with PGB significantly (P<0.001) improved the HAM-D insomnia factor scores on both the 300-450 mg (-2.73) and 600 mg (-2.35) doses, and on benzodiazepines (-2.52) compared with placebo (-1.51); improvement on PGB 150 mg (-1.69) was not significant. Rates of treatment-emergent insomnia were lower on PGB compared with placebo in both the high- and low-insomnia subgroups. In conclusion, PGB was well tolerated, and improved overall anxiety symptoms, while specifically improving insomnia in patients with GAD presenting with high levels of concurrent insomnia.

Cutler AJ, Montgomery SA, Feifel D, Lazarus A, Aström M, Brecher M. · Department of Psychiatry, University of Florida, Gainesville, FL, USA. · J Clin Psychiatry. · Pubmed #19358790 No free full text.

Abstract: OBJECTIVE: To evaluate the efficacy and tolerability of once-daily extended release quetiapine fumarate (quetiapine XR) as monotherapy treatment for major depressive disorder (MDD). METHOD: This 8-week (6-week active-treatment, randomized phase; 2-week posttreatment drug-discontinuation/tapering phase), multicenter, double-blind, randomized, parallel-group, placebo- and active-controlled, phase 3 study was conducted between April 2006 and May 2007. In total, 612 patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)-defined MDD were randomly assigned to quetiapine XR 150 mg/day or 300 mg/day, duloxetine 60 mg/day (active control), or placebo. The primary endpoint was the change from baseline to week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score. RESULTS: At week 6, both doses of quetiapine XR (p < .001) and duloxetine (p < .01) significantly reduced mean MADRS total score versus placebo. A significant reduction was seen at week 1 with quetiapine XR 150 mg/day and 300 mg/day versus placebo (p < .01), but not with duloxetine. Response rates (>or= 50% reduction in MADRS total score) at week 6 were significantly higher for both doses of quetiapine XR (p < .01) and duloxetine (p < .05) versus placebo. Remission rates (MADRS score <or= 8) were significantly higher for quetiapine XR 300 mg/day and duloxetine versus placebo (p < .05), but not for quetiapine XR 150 mg/day. Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, and Clinical Global Impressions-Severity of Illness total scores and the proportion of patients with Clinical Global Impressions-Improvement scores of 1 or 2 ("much/very much improved") were significantly improved with both doses of quetiapine XR and duloxetine versus placebo. The most common adverse events reported were dry mouth, sedation, and somnolence for quetiapine XR and nausea, headache, dizziness, and dry mouth for duloxetine. CONCLUSION: Quetiapine XR monotherapy (150 mg/day and 300 mg/day) is effective, with safety and tolerability consistent with the known profile of quetiapine XR, in the treatment of patients with MDD, with onset of symptom improvement demonstrated at week 1. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00321490.

Montgomery SA, Tobias K, Zornberg GL, Kasper S, Pande AC. · Imperial College School of Medicine, London, UK. · J Clin Psychiatry. · Pubmed #16841627 No free full text.

Abstract: OBJECTIVE: Pregabalin has demonstrated robust, rapid efficacy in reducing symptoms of generalized anxiety disorder (GAD) in 4 placebo-controlled clinical trials. The current study compared the efficacy and safety of pregabalin and venlafaxine in patients diagnosed with moderate to severe GAD. METHOD: The study was conducted from December 21, 1999, to July 31, 2001. Outpatients (N = 421) in primary care or psychiatry settings meeting DSM-IV criteria for GAD were randomly assigned to 6 weeks of double-blind treatment with pregabalin 400 or 600 mg/day, venlafaxine 75 mg/day, or placebo. The primary analysis was change in Hamilton Rating Scale for Anxiety (HAM-A) total score from baseline to last-observation-carried-forward (LOCF) endpoint. Secondary analyses included the change in HAM-A psychic (emotional) and somatic (physical) factor scores, significant improvement at week 1, and week 1 improvement sustained at every visit through endpoint. RESULTS: Pregabalin at both dosages (400 mg/day, p = .008; 600 mg/day, p = .03) and venlafaxine (p = .03) produced significantly-greater improvement in HAM-A total score at LOCF endpoint than did placebo. Only the pregabalin 400-mg/day treatment group experienced significant improvement in all a priori primary and secondary efficacy measures. Pregabalin in both dosage treatment groups (400 mg/day, p < .01; 600 mg/day, p < .001) significantly improved HAM-A total score at week 1, with significant improvement through LOCF endpoint. Statistically significant improvement began at week 2 for venlafaxine. Discontinuation rates due to associated adverse events were greatest in the venlafaxine treatment group: venlafaxine, 20.4%; pregabalin 400 mg/day, 6.2%; pregabalin 600 mg/day, 13.6%; placebo, 9.9%. CONCLUSION: Pregabalin was safe, well tolerated, and rapidly efficacious across the physical-somatic as well as the emotional symptoms of GAD in the majority of patients studied in primary care and psychiatric settings.

Montgomery SA, Nil R, Dürr-Pal N, Loft H, Boulenger JP. · Imperial College, London, UK. · J Clin Psychiatry. · Pubmed #16259540 No free full text.

Abstract: OBJECTIVE: Escitalopram has proven efficacy in the short-term treatment of generalized social anxiety disorder (SAD). The present relapse prevention study investigated relapse rates during a 24-week, randomized, double-blind, placebo-controlled period in patients with generalized SAD who had responded to 12-week open-label treatment with escitalopram. METHOD: A total of 517 patients with a primary diagnosis of generalized SAD (per DSM-IV criteria) and a Liebowitz Social Anxiety Scale (LSAS) total score of > or = 70 received 12 weeks of open-label treatment with flexible doses (10-20 mg/day) of escitalopram. Of these patients, 371 responded (Clinical Global Impressions-Improvement scale [CGI-I] score of 1 or 2) and were randomly assigned to 24 weeks of double-blind treatment with escitalo-pram (10 or 20 mg/day) (N = 190) or placebo (N = 181), continuing with the dose level administered at the end of the open-label period. Relapse was defined as either an increase in LSAS total score of > or = 10 or withdrawal due to lack of efficacy, as judged by the investigator. The study was conducted from January 2001 to June 2002. RESULTS: Survival analysis of relapse and time to relapse showed a significant advantage for escitalopram compared to placebo (log-rank test: p < .001). The risk of relapse was 2.8 times higher for placebo-treated patients than for escitalopram-treated patients (p < .001), resulting in significantly fewer escitalopram-treated patients relapsing (22% vs. 50%), at both doses. Escitalopram was well tolerated during double-blind treatment of generalized SAD, and only 2.6% of the escitalopram-treated patients withdrew because of adverse events. The overall discontinuation rate, excluding relapses, was 13.2% for patients treated with escitalopram and 8.3% for patients treated with placebo. CONCLUSION: Escitalopram was effective and well tolerated in the long-term treatment of generalized SAD.

Montgomery SA, Sheehan DV, Meoni P, Haudiquet V, Hackett D. · Imperial College School of Medicine, PO Box 8751, London, UK. · J Psychiatr Res. · Pubmed #12191625 No free full text.

Abstract: OBJECTIVE: To characterize the response to the serotonin and norepinephrine reuptake inhibitor, venlafaxine extended release (XR), during the long-term treatment of generalized anxiety disorder. METHODS: Data from two double-blind, placebo-controlled, 6-month trials of venlafaxine XR for the treatment of generalised anxiety disorder were pooled. Criteria for response (> or = 50% improvement from baseline HAM-A score) and remission (HAM-A score < or = 7) and their temporal profile were used to characterize patient improvement over 6 months of treatment with venlafaxine XR and placebo. RESULTS: Venlafaxine XR was associated with significantly (P<0.001) higher response and remission rates (66 and 43%, respectively) compared with placebo (39 and 19%), regardless of the level of baseline anxiety. In the venlafaxine XR group, 61% of the patients who had responded but not remitted by week 8 showed remission by the end of 6 months. In comparison, only 39% of placebo responders who did not qualify for remission at the end of the first 8 weeks of therapy remitted by the end of the 6 months (P=0.007). Relapse occurred in 6% of venlafaxine XR-treated patients and 15% of placebo-treated patients (P<0.01). CONCLUSION: This analysis provides further insight into the outcome of long-term treatment of generalised anxiety disorder with venlafaxine XR and shows for the first time that long-term treatment might be necessary to achieve and maintain remission of symptoms.

Wittchen HU, Carter RM, Pfister H, Montgomery SA, Kessler RC. · Max Planck Institute of Psychiatry, Clinical Psychology and Epidemiology Unit, Munich, Germany. · Int Clin Psychopharmacol. · Pubmed #11110007 No free full text.

Abstract: Using a nationally representative sample, this study examines the disease-specific impairments of DSM-IV generalized anxiety disorder (GAD) by comparing them to the impairments associated with major depressive disorder (MDD). Results are based on 4181 respondents between the ages of 18-65 years who were interviewed with the 12-month version of the Munich-Composite International Diagnostic Interview as part of the German National Health Interview and Examination Survey-Mental Health Supplement (GHS). After controlling for age, gender, and other psychopathology, 'pure' current GAD without MDD (n = 33), pure MDD (n = 344) and comorbid GAD and MDD (n = 40) were each associated with high impairment as defined by poor self-perceived health, at least 3 days limited or impaired in the past month, and low quality of life scores [from the Short Form-36 Health Survey (SF-36)]. Quality of life scores on several of the SF-36 scales were significantly lower for respondents with pure GAD as compared to respondents with pure MDD. Overall, the results show that DSM-IV GAD is associated with high impairment even after controlling for other psychopathology. The impairment outcomes for GAD were comparable in size to those for MDD. These findings underline the significance of this disorder from a clinical and social perspective and provide support for the independent diagnostic status of GAD.

Montgomery SA, Judge R. · Imperial College of Medicine, St Mary's Hospital, London, UK. · Acta Psychiatr Scand Suppl. · Pubmed #11019930 No free full text.

Abstract: OBJECTIVE: Evidence indicates that alleviating anxiety symptoms early in the treatment of depression improves treatment compliance, limits treatment discontinuations and contributes to a positive treatment outcome. Because of their sedating effects, the tricyclic antidepressants (TCAs) have historically been the first-choice agent in treating comorbid depression and anxiety. However, a growing body of evidence suggests that the selective serotonin reuptake inhibitors (SSRIs) can also be suitable therapy. METHOD: We reviewed literature regarding the use of TCAs and SSRIs in depressed patients with comorbid anxiety. RESULTS: SSRIs are at least as effective as TCAs in the treatment of both overall depression as well as anxiety symptoms. TCAs can cause significant and sometimes unacceptable side effects which limit their therapeutic potential. SSRIs, on the other hand, have little or no effect on cholinergic, histaminergic or adrenergic receptors, and have a very favourable tolerability profile. CONCLUSION: The traditional selection of antidepressants based on the presence or absence of anxiety has little scientific support. In considering the overall risk:benefit ratio, SSRIs should be the first line treatment for depression with associated anxiety.