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: 3.59). 11/2007; 21(8):864-72. DOI: 10.1177/0269881107076996
Source: PubMed


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,
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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 · 3.59 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 · 3.38 Impact Factor
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    • "Taken together, these studies demonstrate that pregabalin is efficacious in both acute treatment and relapse prevention. Its relative efficacy in acute treatment when compared to other medications is not firmly established, though an analysis of randomized controlled trials which found an overall mean effect size of 0.39, also found some differences between medication class: pregabalin, 0.50; SNRI, 0.42; benzodiazepines, 0.38; SSRI, 0.36; and buspirone, 0.17.72 The relative efficacy of pregabalin and antidepressant drugs in preventing relapse in patients with GAD, when compared to antidepressant drugs,73 is uncertain. "
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    ABSTRACT: A PREVIOUS REVIEW SUMMARIZED WHAT WAS THEN KNOWN ABOUT THE POTENTIAL ROLE OF PREGABALIN IN THE TREATMENT OF PATIENTS WITH GENERALIZED ANXIETY DISORDER (GAD): this review provides an update on its pharmacological properties and presumed mechanism of action, the liability for abuse, and efficacy and tolerability in patients with GAD. Pregabalin has a similar molecular structure to the inhibitory neurotransmitter gamma amino butyric acid (GABA) but its mechanism of action does not appear to be mediated through effects on GABA. Instead, its anxiolytic effects may arise through high-affinity binding to the alpha-2-delta sub-unit of the P/Q type voltage-gated calcium channel in "over-excited" presynaptic neurons, thereby reducing the release of excitatory neurotransmitters such as glutamate. The findings of randomized controlled trials and meta-analyses together indicate that pregabalin is efficacious in both acute treatment and relapse prevention in GAD, with some evidence of an early onset of effect, and broad efficacy in reducing the severity of psychological and physical symptoms of anxiety. It also has efficacy as an augmenting agent after non-response to antidepressant treatment in GAD. Continuing vigilance is needed in assessing its potential abuse liability but the tolerability profile of pregabalin may confer some advantages over other pharmacological treatments in the short term for treatment in patients with GAD.
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