Pharmacotherapy Update: Pregabalin in the Treatment of Generalized Anxiety Disorder

Abstract

Generalized anxiety disorder (GAD) is a common disorder that is chronic, disabling, and often goes undiagnosed. Currently, four distinct classes of medications have demonstrated efficacy in the treatment of GAD: benzodiazepines, serotonin and/or norepinephrine reuptake inhibitors (SSRIs/SNRIs), histamine H 1 receptor blockers (hydroxyzine), and pregabalin. Pregabalin acts via binding to an α2-δ subunit presynaptic membrane protein that inhibits neurotransmitter release in excited neurons. Pregabalin is renally excreted and undergoes minimal (2%) hepatic metabolism, thus limiting the risk of drug-drug interactions. The efficacy of pregabalin for the treatment of GAD has been established based on the results of 8 double-blind, placebo-controlled, short-term led trials, and one 6-month relapse prevention study. The current review summarizes data showing that pregabalin has a significantly different safety profile from the benzodiazepines (eg, less sedation, less cognitive and psychomotor impairment, less risk of dependence and withdrawal), and SSRI/ SNRI anxiolytics (eg, less gastrointestinal side effects and sexual dysfunction). The review also summarizes efficacy data showing that pregabalin is a broad spectrum anxiolytic that with a speed of onset similar to the benzodiazepines.

Efficacy and safety of pregabalin in generalised anxiety disorder: A critical review of the literature

“…In addition to safety data contained in the clinical trials cited above, four additional citations summarised results of studies with safety as the primary outcome (Frame et al, 2009; Hindmarch et al, 2005a, 2005b; Rubio et al, 2011). Finally, 11 review articles were identified that specifically evaluated the safety and efficacy of pregabalin in the treatment of GAD (Bandelow et al, 2007; Bech, 2007; Boschen, 2011, 2012; Frampton and Foster, 2006; Holsboer-Trachsler and Prieto, 2013; Lauria-Horner and Pohl, 2003; Montgomery, 2006; Montgomery and Kasper, 2010; Owen, 2007; Wensel et al, 2012). These articles were each reviewed to determine whether they contained additional citations not identified in the MEDLINE and PsychINFO literature searches.…”

“…It appears to achieve its anxiolytic effect by binding to the α 2 δ subunit of the P/Q-type of voltage-gated calcium channel, resulting in a reduction in neurotransmission in excited neurons (Micó and Prieto, 2012). At the time of writing this review, it has been three years since the last comprehensive review of the efficacy and safety of pregabalin in GAD was published (Montgomery and Kasper, 2010). Since then, a brief clinical review has appeared that examines published data up to December 2011 (Wensel et al, 2012), but the availability of several recently published clinical trials of pregabalin suggests a new review might be useful.…”

Pregabalin: Dose-Response Relationship in Generalized Anxiety Disorder

“…While these results present some suggestion that moderate doses of pregabalin may be associated with greatest reduction in anxiety symptoms, high doses (i. e., those above 450 mg/day) may not provide additional benefi ts, but still expose the patient to higher risk of adverse events. In previous research on pregabalin in the treatment of GAD, adverse events have been higher on a dose of 600 mg/day compared with lower doses [ 27 ] . Adverse events such as dizziness and somnolence may also make independent contributions to functional impairment if they are severe and/or prolonged.…”

Pharmacotherapy of anxiety disorders in German-speaking countries: current status and changes between 1994 and 2011

“…The treatment of patients with GAD in our study raised certain issues. The most interesting result is the high rate of prescriptions of pregabalin [19,20,26]; it was prescribed for 29.1 % of patients with GAD in the years 2009-2011. From 1997 to 2011, the prescription rate of anticonvulsants showed a significant annual increase, and as in 2004, pregabalin was approved for the treatment of GAD by the European Medicines Agency (EMA).…”