An effect-size analysis of pharmacologic treatments for generalized anxiety disorder. J Psychopharmacol

Anxiety and Traumatic Stress Program, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA.
Journal of Psychopharmacology (Impact Factor: 2.81). 11/2007; 21(8):864-72. DOI: 10.1177/0269881107076996
Source: PubMed

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.

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Available from: Rosario Beatriz Hidalgo, Aug 22, 2015
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    • "The antihistaminic effect of some tricyclic drugs like amitriptyline , doxepin, trimipramine and cyclobenzaprine is considerable , but usually seen as undesirable rather than beneficial, because it leads to sedation and weight gain. Yet it may be recalled that the efficacy of hydroxyzine, an H1-antagonist, is ranked higher for generalized anxiety disorder (GAD) than the efficacy of benzodiazepines and SSRI drugs, when expressed as effect size versus placebo (Hidalgo et al., 2007 "
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    ABSTRACT: Serotonin (SSRI) and serotonin-norepinephrine (SNRI) reuptake inhibitors (SSRI) are the first-line recommended drug treatments for post-traumatic stress disorder (PTSD); but despite their benefits, much residual pathology remains and no new drugs have yet emerged with a clearly demonstrated benefit for treating the disorder. A case is made that tricyclic drugs deserve a closer look, based on their ability to affect several of the main neurotransmitters that are relevant to PTSD. Their promising efficacy, which was shown 30 years ago, had not been followed up, until a recent trial of desipramine found advantages over a SSRI in PTSD with comorbid alcohol dependence. Opportunities exist for studying newer and purportedly safer tricyclic formulations, as well as further the work with older, established compounds. A reappraisal of their risk:benefit ratio seems in order, when treating PTSD. © The Author(s) 2015.
    Journal of Psychopharmacology 01/2015; 29(3). DOI:10.1177/0269881114565143 · 2.81 Impact Factor
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    • "The impact of GAD on the patient's daily life (e.g., loss of well-being, utilisation of healthcare resources), particularly on functionality, is assumed to be considerable (Bereza et al., 2009). Although evidence-based pharmacological (Hidalgo et al., 2007) and psychological treatments (Hoyer and Gloster, 2009) exist, detection and treatment by family doctors is low, and many patients with anxiety do not receive adequate management, especially in primary care settings (Wittchen et al., 2002). These reasons convinced international health authorities to search for new, cost-effective treatment alternatives for anxiety (Wittchen et al., 2002). "
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    ABSTRACT: BACKGROUND: Naturalistic studies to assess the efficacy and pattern of use of computer-delivered psychotherapy programmes in real daily clinical conditions are infrequent. Anxiety disorders are the most common mental disorders, and many of them do not receive adequate management, especially in primary care settings. The objective of this study is to assess the efficacy of an internet-delivered programme for anxiety in primary care. METHODS: Multicentre, naturalistic study. Patients with generalised anxiety disorder were recruited (N=229). The generalised anxiety disorder 7-item scale (GAD-7) was the only outcome measured. Qualitative methods were used to analyse patient-therapist interactions. RESULTS: Only 13.5% of patients completed the programme. Analysis per intent-to-treat using Last Observation Carried Forward showed a significant GAD-7 decrease post-treatment (-2.17: SD=4.77; p=0.001) (Cohen׳s d=0.43) with a correlation between the number of sessions and decrease in anxiety (Rho=-0.34, p=0.001). The analysis per protocol showed significantly decreased GAD-7 (-4.13; SD=6.82; p=0.002) (d=0.80). Withdrawal was related to low programme friendliness, lack of a partner, and higher education. Only 17.47% of the patients consulted their therapists. Facilitators were patient demand for information and sufficient time. Barriers were lack of motivation and lack of connection with the programme. LIMITATIONS: The main limitations of this study included the use of an open trial design, the lack of follow-up, and the inclusion of only one outcome (GAD-7). CONCLUSIONS: To our knowledge, this is the first study with computer-delivered psychotherapy (CDP) on GAD. CDP for anxiety is efficacious in naturalistic environments. Specific facilitators and barriers should be considered.
    Journal of Affective Disorders 01/2015; 175C(175C):184-191. DOI:10.1016/j.jad.2014.12.060 · 3.71 Impact Factor
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    • "Few randomized controlled trials have permitted assessment of the relative efficacy of different treatments , when each is compared to placebo. An analysis of randomized controlled trials of acute treatment found an overall mean effect size of 0.39, with some differences between medication class : pregabalin, 0.50 ; the antihistamine hydroxyzine, 0.45 ; SNRIs, 0.42 ; benzodiazepines, 0.38 ; SSRIs, 0.36 ; and the azapirone anxiolytic buspirone, 0.17 (Hidalgo et al. 2007). The mean overall effect size in this analysis is higher than that from a previous meta-analysis (0.33) (Mitte et al. 2005), which may reflect differences in publication selection criteria. "
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    ABSTRACT: Generalized anxiety disorder (GAD) is common in community and clinical settings. The associated individual and societal burden is substantial, but many of those who could benefit from treatment are not recognized or treated. This paper reviews the pharmacological treatment of GAD, based on findings of randomized placebo-controlled studies. Particular attention is paid to response rates to acute treatment, treatment tolerability, prediction of response, duration of treatment, and further management of patients who do not respond to initial treatment approaches. On the basis of their proven efficacy and reasonable tolerability in randomized placebo-controlled trials, recent evidence-based guidelines for pharmacological management have recommended initial treatment with either a selective serotonin reuptake inhibitor or a serotonin-norepinephrine reuptake inhibitor, although there is also good evidence for the efficacy of pregabalin and quetiapine. It is difficult to predict reliably which patients will respond well to pharmacological treatment, but response to antidepressants is unlikely if there is no evidence of an onset of effect within 4 wk. The small number of placebo-controlled relapse-prevention studies causes uncertainty about the optimal duration of treatment after a satisfactory initial response, but continuing treatment for at least 12 months is recommended. There have been few investigations of the further management of patients who have not responded to first-line treatment, but switching to another evidence-based treatment, or augmentation approaches may be beneficial.
    The International Journal of Neuropsychopharmacology 06/2011; 14(5):697-710. DOI:10.1017/S1461145710001434 · 5.26 Impact Factor
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