Pregabalin for the treatment of generalized anxiety disorder: an update

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.

Development of a theoretically-derived human anxiety syndrome biomarker

“…We also found that GCSR was sensitive to pregabalin (a calcium channel inhibitor), which is positive in our rodent RSA test [90], effective in generalised anxiety disorder [115], and has not been reported to be clinically either primarily by the preSMA [99] With somewhat slower go responses stopping is controlled primarily by rIFG [97,98] but BIS output is too slow to affect stopping in the SST [102].With even slower go responses (as in go/no go tasks) activation of the BIS would generate response inhibition via rIFG/preSMA. avPFC = anteroventral prefrontal cortex; preSMA = presupplementary motor area; rIFG = right inferior frontal gyrus.…”

Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: A revision of the 2005 guidelines from the British Association for Psychopharmacology

“…There is no known untoward interaction with lithium. Spontaneous reports of adverse sexual side effects are uncommon but the incidence of treatment-emergent sexual dysfunction with pregabalin is uncertain [IV] (Baldwin et al, 2013). Discontinuation symptoms after abrupt withdrawal of pregabalin have been reported, as has the abuse of pregabalin generally in individuals with a history of other substance abuse: but the relative potential for developing tolerance and abuse, when compared to with medications, is not established [IV] (Baldwin et al, 2013).…”

The pharmacological management of anxiety disorders

“…By changing the conformation of the calcium channel, pregabalin is proposed to: reduce the release of excitatory neurotransmitters such as glutamate, reduce the synthesis of excitatory synapses, and block the progression of new calcium channels to the cell surface. 22 Pregabalin has robust evidence in the treatment of GAD both in the acute phase and in relapse prevention. 1,22 It has evidence of efficacy in young patients and the elderly, and may enhance the effects of an SSRI or SNRI.…”

“…22 Pregabalin has robust evidence in the treatment of GAD both in the acute phase and in relapse prevention. 1,22 It has evidence of efficacy in young patients and the elderly, and may enhance the effects of an SSRI or SNRI. 22 NICE recommends pregabalin as a treatment option if the SSRIs or SNRIs are poorly tolerated in GAD.…”

“…1,22 It has evidence of efficacy in young patients and the elderly, and may enhance the effects of an SSRI or SNRI. 22 NICE recommends pregabalin as a treatment option if the SSRIs or SNRIs are poorly tolerated in GAD. 2 Although unlicensed and not recom mended by NICE, there are also trials supporting pregabalin in social anxiety disorder.…”