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.

Generalized anxiety disorder (GAD) is a common, typically persistent, and disabling condition that is often not recognised, or treated in an evidence-based manner. Current pharmacological and psychological treatment approaches have a number of drawbacks, including a delay in onset of clinical effect, varying relative efficacy against psychological or somatic symptoms of anxiety, potentially troublesome adverse effects, and discontinuation symptoms on stopping treatment. Pregabalin is a structural analog of the inhibitory neurotransmitter gamma amino butyric acid (GABA) but is thought to exert its anxiolytic effects through binding in a state-dependent manner to the alpha-2-delta sub-unit of voltagegated calcium channels in "over-excited" pre-synaptic neurones, reducing release of excitatory neurotransmitters such as glutamate and substance P. At fixed doses of 200 mg/day or greater, it has consistent proven efficacy in acute treatment of DSM-IV-defined GAD, with some evidence of an early onset of clinical effect, and of efficacy across psychological and somatic anxiety symptom clusters. A pregabalin dosage of 450 mg/day is efficacious in the prevention of relapse. There is at present no published direct comparison with an SSRI. The current known adverse effect profile and studies in healthy volunteers together suggest that pregabalin may have some tolerability advantages over benzodiazepines and venlafaxine, at least in short-term treatment.

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