Role of pregabalin in the treatment of generalized anxiety disorder

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 voltage-gated 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.