Gabapentin and pregabalin in bipolar disorder, anxiety states, and insomnia: Systematic review, meta-analysis, and rationale

Abstract

The gabapentinoids, gabapentin, and pregabalin, target the α2δ subunits of voltage-gated calcium channels. Initially licensed for pain and seizures, they have become widely prescribed drugs. 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. We conducted a systematic review and meta-analysis of the evidence for three of their common psychiatric uses: bipolar disorder, anxiety, and insomnia. Fifty-five double-blind randomised controlled trials (RCTs) and 15 open-label studies were identified. For bipolar disorder, four double-blind RCTs investigating gabapentin, and no double-blind RCTs investigating pregabalin, were identified. A quantitative synthesis could not be performed due to heterogeneity in the study population, design and outcome measures. Across the anxiety spectrum, a consistent but not universal effect in favour of gabapentinoids compared to placebo was seen (standardised mean difference [SMD] ranging between -2.25 and -0.25). 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. In insomnia, results were inconclusive. 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. This recommendation applies despite the attractive pharmacological and genetic rationale for targeting voltage-gated calcium channels.

Co-prescribing of Central Nervous System–Active Medications for COPD Patients: Impact on Emergency Room Visits and Hospitalization

“…28 There is evidence to suggest efficacy of GABA in the treatment of anxiety disorders. 29,30 In a systematic review and meta-analysis by Hong et al, 29 GABA (gabapentin, pregabalin) were effective in the treatment of anxiety disorders, including generalized anxiety disorder, social anxiety disorder, and preoperative anxiety disorder. A 1-year open label study by Montgomery et al 31 found that long-term use of pregabalin is relatively safe for the treatment of anxiety disorders.…”

Pharmacological treatment for older adults with epilepsy and comorbid neurodegenerative disorders

“…The phenomenon of ‘sun downing’, a state of confusion and anxiety, often accompanied by aggressive behaviors and sleep problems that are triggered by little sunlight, is often a symptom that not only affects the patient's but also the caregiver's quality of life. GBP has been employed by psychiatrists in various anxiety and insomnia states [53] and is one of the most commonly prescribed ASMs in this population [32]. Low-dose GBP has been shown to have similar seizure control as LTG [11], and it is our experience that a slightly higher dose given in the evening can help ‘sun downing’ while also controlling seizures.…”

Gabapentin as a drug with a broad potential. Presentation of its use in medical conditions beyond the official registration

“…Nie ma jednoznacznych dowodów na terapię gabapentyną w depresji, profilaktyce PTSD (z ang. post-traumatic stress disorder), lub innych rodzajach nadużywania substancji psychoaktywnych [18,3].…”