Efficacy of sertraline in a 12-week trial for generalized anxiety disorder

University of Oslo, Kristiania (historical), Oslo, Norway
American Journal of Psychiatry (Impact Factor: 12.3). 10/2004; 161(9):1642-9. DOI: 10.1176/appi.ajp.161.9.1642
Source: PubMed


Sertraline's efficacy and tolerability in treating generalized anxiety disorder were evaluated.
Adult outpatients with DSM-IV generalized anxiety disorder and a total score of 18 or higher on the Hamilton Anxiety Rating Scale were eligible. After a 1-week single-blind placebo lead-in, patients were randomly assigned to 12 weeks of double-blind treatment with placebo (N=188, mean baseline anxiety score=25) or flexible doses (50-150 mg/day) of sertraline (N=182, mean anxiety score=25). The primary outcome measure was baseline-to-endpoint change in the Hamilton anxiety scale total score. A secondary efficacy measure was the Clinical Global Impression (CGI) improvement score; response was defined as a score of 2 or less.
Sertraline patients had significantly greater improvement than placebo patients on all efficacy measures at week 4. Analysis of covariance of the intent-to-treat group at endpoint (with the last observation carried forward) showed a significant difference in the decrease from baseline of the least-square mean total score on the Hamilton anxiety scale between sertraline (mean=11.7) and placebo (mean=8.0). Significantly greater endpoint improvement with sertraline than placebo was obtained for mean scores on the Hamilton anxiety scale psychic factor (6.7 versus 4.1) and somatic factor (5.0 versus 3.9). The rate of responders, based on CGI improvement and last observation carried forward, was significantly higher for sertraline (63%) than placebo (37%). Sertraline was well tolerated; 8% of patients versus 10% for placebo dropped out because of adverse events.
Sertraline appears to be efficacious and well tolerated in the treatment of generalized anxiety disorder.

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Available from: Christer Allgulander, Oct 12, 2015
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    • "Sertraline, along with the SSRIs escitalopram and paroxetine, is seen as a first-line pharmacologic treatment for GAD [12]. Randomised, placebo controlled trials have found sertraline efficacious for GAD in adults [13,14], children and adolescents [15,16]. The treatment period ranged from 9 to 12 weeks in these pharmacological trials. "
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    ABSTRACT: Generalised anxiety disorder (GAD) is a high prevalence, chronic psychiatric disorder which commonly presents early in the lifespan. Internet e-health applications have been found to be successful in reducing symptoms of anxiety and stress for post traumatic stress disorder (PTSD), panic disorder, social phobia and depression. However, to date, there is little evidence for the effectiveness of e-health applications in adult GAD. There are no studies which have directly compared e-health applications with recognised evidence-based medication. This study aims to determine the effectiveness of a web-based program for treating GAD relative to sertraline and attention placebo. 120 community-dwelling participants, aged 18-30 years with a clinical diagnosis of GAD will be recruited from the Australian Electoral Roll. They will be randomly allocated to one of three conditions: (i) an online treatment program for GAD, E-couch (ii) pharmacological treatment with a selective serotonin re-uptake inhibitor (SSRI), sertraline (a fixed-flexible dose of 25-100 mg/day) or (iii) an attention control placebo, HealthWatch. The treatment program will be completed over a 10 week period with a 12 month follow-up. As of February 2010, there were no registered trials evaluating the effectiveness of an e-health application for GAD for young adults. Similarly to date, this will be the first trial to compare an e-health intervention with a pharmacological treatment. Current Controlled Trials ISRCTN76298775.
    Trials 04/2010; 11(4):48. DOI:10.1186/1745-6215-11-48 · 1.73 Impact Factor
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    • "Although there is a paucity of randomized , controlled studies examining treatment strategies for patients with symptomatic GAD following first-line therapy, case-report data suggest that combination therapy with antidepressants and benzodiazepines may be effective (Pollack, 2001). SSRIs and SNRIs have a delayed onset of action (2–4 wk) (Allgulander et al. 2004 ; Gelenberg et al. 2000 ; Rickels et al. 2003), thus short-term adjunct benzodiazepine therapy is common when initiating treatment with these agents. For benzodiazepines, cognitive effects , rebound anxiety, withdrawal symptoms, and abuse potential, limit their use in clinical practice (Chouinard, 2004), while SSRIs and SNRIs are associated with sexual dysfunction (Bandelow et al. 2008) and discontinuation effects (Fava et al. 2007). "
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    ABSTRACT: The efficacy and tolerability of extended-release quetiapine fumarate (quetiapine XR) once-daily monotherapy in generalized anxiety disorder (GAD) was assessed. This multicentre, double-blind, randomized, placebo- and active-controlled, phase III trial consisted of a 1- to 4-wk enrolment/wash-out period and a 10-wk (8-wk active treatment, 2-wk post-treatment drug-discontinuation) study period; 873 patients were randomized to 50 mg or 150 mg quetiapine XR, 20 mg paroxetine, or placebo. Primary endpoint was change from randomization at week 8 in Hamilton Rating Scale for Anxiety (HAMA) total score. At week 8, all active agents produced significant improvements in HAMA total and psychic subscale scores vs. placebo; HAMA somatic subscale scores were significantly reduced only by 150 mg quetiapine XR. Significant separation from placebo (-2.90) in HAMA total score was observed at day 4 for 50 mg quetiapine XR (-4.43, p<0.001) and 150 mg quetiapine XR (-3.86, p<0.05), but not for paroxetine (-2.69). Remission (HAMA total score 7) rates at week 8 were significantly higher for 150 mg quetiapine XR (42.6%, p<0.01) and paroxetine (38.8%, p<0.05) vs. placebo (27.2%). The most common adverse events (AEs) were dry mouth, somnolence, fatigue, dizziness, and headache, for quetiapine XR, and nausea, headache, dizziness for paroxetine. A lower proportion of patients reported sexual dysfunction with quetiapine XR [0.9% (50 mg), 1.8% (150 mg)] than with placebo (2.3%) or paroxetine (7.4%). The incidence of AEs potentially related to extrapyramidal symptoms was: quetiapine XR: 50 mg, 6.8%, 150 mg, 5.0%; placebo, 1.8%; and paroxetine, 8.4%. Once-daily quetiapine XR is an effective and generally well-tolerated treatment for patients with GAD, with symptom improvement seen as early as day 4.
    The International Journal of Neuropsychopharmacology 08/2009; 13(3):305-20. DOI:10.1017/S1461145709990423 · 4.01 Impact Factor
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    • "; escitalopram n ϭ3 [Davidson et al., 2004; Goodman et al., 2005 and unpublished data from Forest Laboratories]; sertraline n ϭ2 [Rynn et al., 2001; Allgulander et al., 2004]; and fluvoxamine n ϭ1 [Walkup et al., 2001]). Of three AH studies (Ferreri et al., 1995; Lader and Scotto, 1998; Llorca et al., 2002), two included active comparators: buspirone (Lader and Scotto, 1998) and bromazepam (Llorca et al., 2002), although the efficacy data for bromazepam was not provided and, hence, not included in the analysis . "
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    ABSTRACT: Generalized anxiety disorder (GAD) is a prevalent and impairing disorder, associated with extensive psychiatric and medical comorbidity and usually characterized by a chronic course. Different drugs have been investigated in GAD; among them are the following: 1) SSRIs: paroxetine, sertraline, fluvoxamine and escitalopram; 2) SNRI1s: venlafaxine; 3) benzodiazepines (BZs): alprazolam, diazepam and lorazepam; 4) azapirones (AZAs): buspirone; 5) antihistamines (AHs): hydroxyzine; 6) pregabalin (PGB); and 7) complementary/alternative medicine (CAM): kava-kava and homeopathic preparation. We conducted an effect size (ES) analysis of 21 double-blind placebo-controlled trials of medications treating DSM-III-R, DSM-IV or ICD-10 GAD using HAM-A change in score from baseline or endpoint score as the main efficacy measure. Literature search was performed using MEDLINE and PsycINFO databases including articles published between 1987 and 2003 and personal communications with investigators and sponsors. comparing all drugs versus placebo, the ES was 0.39. Mean ESs, excluding children, were PGB: 0.50, AH: 0.45, SNRI: 0.42, BZ: 0.38, SSRI: 0.36, AZA: 0.17 and CAM: -0.31. Comparing ES for adults versus children/adolescents (excluding CAM) and conventional drugs versus CAM (excluding children/adolescents) we found significantly higher ES for children/adolescents and for conventional drugs (p < 0.001 and p < 0.01, respectively). No significant differences were found when comparing date of publication, location of site (i.e. US versus other), fixed versus flexible dosing, number of study arms, or number of outcome measures used. Medications varied in the magnitude of their ES, ranging from moderate to poor. Adolescents and children showed a much greater ES compared with adults. Subjects taking CAM had worse outcomes than placebo.
    Journal of Psychopharmacology 11/2007; 21(8):864-72. DOI:10.1177/0269881107076996 · 3.59 Impact Factor
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