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

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. A systematic review and meta-analysis of the evidence for three of their common psychiatric uses – bipolar disorder, anxiety disorders/states, and insomnia – was carried out. Published and unpublished literature were searched and a random-effects pairwise meta-analysis was performed for each outcome where possible. Efficacy and acceptability were assessed using only double-blind randomised controlled trials. Assessment of tolerability also included single blind or open-label trials and non-randomised evidence. Where a quantitative synthesis could not be conducted, results were presented narratively. 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 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 state anxiety, with gabapentin showing a dose effect. In insomnia, results were inconclusive. There is moderate evidence of efficacy of gabapentinoids in state anxiety and anxiety disorders, 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. It may be possible to develop modified α2δ ligands, targeting particular subtypes or isoforms, with a more beneficial therapeutic profile. A future direction for clinical research would be to explore the targeted treatment of comorbid anxiety in bipolar disorder using gabapentinoids or modified α2δ ligands.</p

Impact of the COVID-19 pandemic on the global delivery of mental health services and telemental health: systematic review

Background: The COVID-19 pandemic required mental health services around the world to adapt quickly to the new restrictions and regulations put in place to reduce the risk of transmission. As face-to-face contact became difficult, virtual methods were implemented to continue to safely provide mental health care. However, it is unclear to what extent service provision transitioned to telemental health worldwide. Objective: We aimed to systematically review the global research literature on how mental health service provision adapted during the first year of the pandemic. Methods: We searched systematically for quantitative papers focusing on the impact of the COVID-19 pandemic on mental health services published until April 13, 2021, in the PubMed, Embase, medRxiv, and bioXriv electronic bibliographic databases, using the COVID-19 Open Access Project online platform. The screening process and data extraction were independently completed by at least two authors, and any disagreement was resolved by discussion with a senior member of the team. The findings were summarized narratively in the context of each country’s COVID-19 Stringency Index, which reflects the stringency of a government’s response to COVID-19 restrictions at a specific time. Results: Of the identified 24,339 records, 101 papers were included after the screening process. Reports on general services (n=72) showed that several countries’ face-to-face services reduced their activities at the start of the pandemic, with reductions in the total number of delivered visits and with some services forced to close. In contrast, telemental health use rapidly increased in many countries across the world at the beginning of the pandemic (n=55), with almost complete virtualization of general and specialistic care services by the end of the first year. Considering the reported COVID-19 Stringency Index values, the increased use of virtual means seems to correspond to periods when the Stringency Index values were at their highest in several countries. However, due to specific care requirements, telemental health could not be used in certain subgroups of patients, such as those on clozapine or depot treatments and those who continued to need face-to-face visits. Conclusions: During the pandemic, mental health services had to adapt quickly in the short term, implementing or increasing the use of telemental health services across the globe. Limited access to digital means, poor digital skills, and patients’ preferences and individual needs may have contributed to differences in implementing and accessing telemental health services during the pandemic. In the long term, a blended approach, combining in-person and virtual modalities, that takes into consideration the needs, preferences, and digital skills of patients may better support the future development of mental health services. It will be required to improve confidence with digital device use, training, and experience in all modalities for both clinicians and service users