Role of pregabalin in the treatment of generalized anxiety disorder

Abstract

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.

A Meta-Analysis of the Efficacy of Pregabalin in the Treatment of Generalized Anxiety Disorder

“…Pregabalin is a novel analogue of the inhibitory neurotransmitter GABA, 10 which has been used to treat GAD in a series of RCTs (Table 1). 11 Pregabalin does not interact with GABA receptors and does not alter GABA metabolism or reuptake.…”

“…18 Pregabalin does not inhibit or potentiate CYP enzyme activity, and its metabolism is not itself CYP-dependent. 10 No active metabolites are produced by the small proportion of pregabalin that is metabolized. 10 The half-life of pregabalin from a single dose is between 4.6 and 6.8 hours.…”

“…10 No active metabolites are produced by the small proportion of pregabalin that is metabolized. 10 The half-life of pregabalin from a single dose is between 4.6 and 6.8 hours. 18 A total of 7 published RCTs [19][20][21][22][23][24][25] have investigated the efficacy of pregabalin in the treatment of adult GAD.…”

Biological rationale and potential clinical use of gabapentin and pregabalin in bipolar disorder, insomnia and anxiety: protocol for a systematic review and meta-analysis

“…Pregabalin has been found to be effective in the management of generalised anxiety disorder, 19 and is licenced in the UK for this indication. There is also some evidence, from an open-label observational study, that pregabalin is effective in the adjunctive treatment of acute mania, depression, and maintenance of refractory bipolar disorder.…”

Simultaneous Estimation of Pregabalin and Methylcobalamine in Pharmaceutical Formulation by RP-HPLC Method

“…Pregabaline (PRG; (3S)-3-(aminomethyl)-5-methylhexanoic acid; figure 1a) is a widely used Anticonvulsant and Analgesic for Epilepsy [1]. Methylcobalamine (MC; carbanide; cobalt; [5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]1-[3-[2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl) -3,5,8,8,13,15,18,19-octamethyl-2,7,12,17-tetrahydrocorrin-3-yl] propanoylamino] propan-2-yl hydrogen phosphate figure 1b) is derivative form of vitamin B12.…”