Since their introduction in 1993, these drugs have become two of the most commonly prescribed medications, with a significant proportion likely to have been off-label. Pregabalin has similar indications, as well as for fibromyalgia in the USA and generalised anxiety disorder (GAD) in the UK. Gabapentin is licensed for use in the USA for the treatment of focal seizures and post-herpetic neuralgia and in the UK for focal seizures and peripheral neuropathic pain.
The gabapentinoids comprise gabapentin and pregabalin. This recommendation applies despite the attractive pharmacological and genetic rationale for targeting voltage-gated calcium channels. We conclude that there is moderate evidence of the efficacy of gabapentinoids in anxiety states, but minimal evidence in bipolar disorder and insomnia and they should be used for these disorders only with strong justification. Notably, pregabalin (SMD -0.55, 95% CI -0.92 to -0.18) and gabapentin (SMD -0.92, 95% CI -1.32 to -0.52) were more effective than placebo in reducing preoperative anxiety. Across the anxiety spectrum, a consistent but not universal effect in favour of gabapentinoids compared to placebo was seen (standardised mean difference ranging between -2.25 and -0.25). A quantitative synthesis could not be performed due to heterogeneity in the study population, design and outcome measures. For bipolar disorder, four double-blind RCTs investigating gabapentin, and no double-blind RCTs investigating pregabalin, were identified. Fifty-five double-blind randomised controlled trials (RCTs) and 15 open-label studies were identified. We conducted a systematic review and meta-analysis of the evidence for three of their common psychiatric uses: bipolar disorder, anxiety, and insomnia. Many of these uses are off-label for psychiatric indications, and there is increasing concern about their safety, so it is particularly important to have good evidence to justify this usage. Initially licensed for pain and seizures, they have become widely prescribed drugs. The gabapentinoids, gabapentin, and pregabalin, target the α 2δ subunits of voltage-gated calcium channels.