Pregabalin (Lyrica®, Pfizer, Inc.)

First approved by the U.S. Federal Drug Administration (FDA) in 2004 for the treatment of neuropathic pain and partial seizures, pregabalin is increasingly being utilized in psychiatry. The European Union Licensing body approved pregabalin for treatment of Generalized Anxiety Disorder (GAD) in 2006 (Loszadi, Hemming, & Marson, 2008). In the U.S. all such usage is currently considered “off-label.” Pregabalin is a structural analog of gamma aminobutyric acid (GABA), although it does not convert to GABA, nor does it alter the uptake or degradation of GABA. Rather, it is an alpha2 [delta] ligand involved in calcium ion influx. Its binding at these receptors effects presynaptic modulation of the excessive release of various excitatory neurotransmitters, including glutamate and norepinephrine. Animal studies have shown that this binding is necessary for the drug’s analgesia, anti-anxiety, and anti-seizure properties (Frampton, Frampton, & Foster, 2006; Tassone, Boyce, Guyer, & Nuzum, 2007). By comparison, valproate interferes with both calcium and sodium ion influx, and influences both GABA and glutamate (Stahl, 2000). Several randomized-controlled trials have supported the safety and efficacy of pregabalin in GAD, as compared to placebo. At least six such studies have been published in peerreviewed journals. Some studies also compared it to alprazolam. Thus far, all published studies have been underwritten by the manufacturer. Studies for safety and efficacy in pain and treatment of partial seizures have been of longer duration. A Cochrane Library review is available for pregabalin only regarding adjunctive use in treatment-resistant partial seizure disorders (Lorzadi et al., 2008). There are no published reports of pregabalin as a mood stabilizing agent. Stein, Baldwin, Baldinett, and Mandel (2008) conducted a post-hoc analysis of the existing trial database (six studies) looking specifically for pregabalin’s effects on