Getting a good night’s sleep is among the most important considerations for maintaining overall health in people of all ages. Sleep is a vital function that supports healthy brain function as well as physical health, growth, and development. Regularly not getting an adequate amount of good-quality sleep can increase the risk of developing chronic health problems and, evidence suggests, worsen existing conditions.
Despite the importance of sleep, figures show that a significant proportion of the population is affected by sleep disorders, including insomnia. Insomnia is a particularly burdensome disorder characterised by difficulties getting to sleep or maintaining sleep. It is associated with daytime impairment and can affect various aspects of a person’s life, including social and occupational functioning.
It is estimated that around a third of adults in Western countries experience sleep problems at least once a week with 6-10% fulfilling the criteria for insomnia disorder. Effective treatment options are vital for limiting the effects of insomnia on overall health.
Various drug options are available for the treatment of insomnia; however, the authors of a recent systematic review note that “these options coupled with optimally matching drug action to insomnia symptom presentation and the high heterogeneity of supporting evidence can lead to uncertainty in the decision making of healthcare professionals and patients for the most appropriate approach to treat insomnia.”
Design and Methods of the Review
Researchers aimed to provide an objective evidence-based hierarchy of the comparative efficacy and tolerability of drugs for the treatment of primary insomnia. The findings should help clinicians, patients, and policymakers to make informed decisions on the best medications for the treatment of insomnia in adults.
To do this, a systematic review and network meta-analysis of placebo-controlled and head-to-head randomised controlled trials (RCTs) was performed. The researchers searched eight databases and seven trial registers from inception to March 1st, 2022, in addition to the lists of studies from previous reviews. A total of 69 (60 studies from the database search and 9 unpublished studies from trial registries) were included in the final review.
Primary outcomes included sleep latency (SL), awake time after sleep onset (WASO), and discontinuation for adverse events (AED). Secondary outcomes included total sleep time (TST), sleep efficiency (SE), sleep quality (SQ), and adverse events (ADE).
Findings of the Review
Across the 69 eligible studies, 10,321 participants were randomly assigned to an active drug and 6998 to placebo. A total of 20 drugs were compared in the review, which were classified into seven classes: benzodiazepines (BZDs), Z-drugs, aldosterone receptor antagonists (MRAs), non-selective antihistamines, orexin receptor antagonists (ORAs), antidepressants (ADPs), and anticonvulsants.
The results of the included studies indicated that ORAs were the best recommendation in sleep-maintenance insomnia with greater efficacy and tolerability. Both ORAs and Z-drugs were effective in improving objective outcomes of insomnia, including sleep latency, WASO, TST, and SE compared with placebo. BDZs also produced greater improvements in subjective sleep quality when compared with placebo, however, they had a low performance of safety in this setting. ORAs were found to be more efficacious than MRAs, Z-drugs and ADPs in improving WASO and SE.
These results indicate that ORAs should be the best recommendation for insomnia due to their superior efficacy and tolerability. However, these findings are contradictory to those of previous reviews, notably Xue et al., which found that ORAs were associated with a higher risk in adverse events than placebo. Furthermore, further analysis suggests that suvorexant (a typre of ORA commonly used to treat insomnia) caused high risk of adverse events, but only three trials of this drug were included in the current review. The authors note that this could contribute to bias.
Nonetheless, two ORAs, lemborexant and daridorexant showed greater efficacy than placebo for SL, WASO, TST, and SE with good tolerability. Z-drugs were also more efficacious than placebo for SL, WASO, TST, and SE, but with higher risk to safety. The researchers note that MRAs may also be beneficial for sleep-onset insomnia with good safety; however, the long-term adverse effects of all medicines remain unclear.
Conclusions
The authors of this review hope that these findings may help clinicians and patients to make more informed decisions when choosing the best pharmacological treatments for insomnia based on the safety and efficacy of available products. However, they do acknowledge some limitations to their study, including substantial heterogeneity of SL and WASO which could be seen as increasing the external validity of these findings.
Nonetheless, the researchers conclude that these findings “represent the comprehensive currently available evidence base to guide the choice about pharmacological treatment for primary insomnia in adults, when a balance has to be made between efficacy and tolerability.”
