Lancet study provides insights of most effective pharmacologic treatment for insomnia disorder
UK: A recent study in The Lancet comparing the effectivness of pharmacological treatments for the acute and long-term treatment of adults with insomnia disorder found eszopiclone and lemborexant to have favorable profile. Eszopiclone, however, was shown to cause substantial adverse events and safety data on lemborexant were inconclusive.
Further into the study, doxepin, seltorexant, and zaleplon were found to be well-tolerated but there was a scarcity of data on efficacy and other important outcomes and did not allow firm conclusion. "Many licensed drugs (including daridorexant, benzodiazepines, trazodone, and suvorexant) can be effective for acute insomnia treatment but were linked to poor tolerability, or information about long-term effects is not available," the authors wrote in their study. "Melatonin, ramelteon, and non-licensed drugs did not show overall material benefits."
Previous studies have shown behavioural, cognitive, and pharmacological interventions to be effective for insomnia. However, medications are more frequently used worldwide due to inadequate resources. Prof Andrea Cipriani, PhD, Department of Psychiatry, University of Oxford, Oxford, UK, and colleagues therefore aimed to estimate the comparative effectiveness of pharmacological treatments for the acute and long-term treatment of adults with insomnia disorder.
In the systematic review and network meta-analysis, the researchers searched the online databases from database inception to Nov 25, 2021, to identify published and unpublished randomised controlled trials. Studies comparing pharmacological treatments or placebo as monotherapy for the treatment of adults (≥18 year) with insomnia disorder were included. The certainty of evidence was assessed using the confidence in network meta-analysis (CINeMA) framework.
Efficacy (ie, quality of sleep measured by any self-rated scale), treatment discontinuation for any reason and due to side-effects specifically, and safety (ie, number of patients with at least one adverse event) were the primary outcomes for both acute and long-term treatment. Summary standardised mean differences (SMDs) and odds ratios (ORs) were estimated using pairwise and network meta-analysis with random effects.
170 trials (36 interventions and 47 950 participants) were included in the systematic review. 154 double-blind, randomised controlled trials (30 interventions and 44 089 participants) were eligible for the network meta-analysis.
Key findings of the study are as follows:
- In terms of acute treatment, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more efficacious than placebo (SMD range: 0·36–0·83 [CINeMA estimates of certainty: high to moderate]). Benzodiazepines, eszopiclone, zolpidem, and zopiclone were more efficacious than melatonin, ramelteon, and zaleplon (SMD 0·27–0·71 [moderate to very low]).
- Intermediate-acting benzodiazepines, long-acting benzodiazepines, and eszopiclone had fewer discontinuations due to any cause than ramelteon (OR 0·72; moderate], 0·70; moderate] and 0·71; moderate], respectively).
- Zopiclone and zolpidem caused more dropouts due to adverse events than did placebo (zopiclone: OR 2·00; zolpidem: 1·79); and zopiclone caused more dropouts than did eszopiclone (OR 1·82), daridorexant (3·45), and suvorexant (3·13).
- For the number of individuals with side-effects at study endpoint, benzodiazepines, eszopiclone, zolpidem, and zopiclone were worse than placebo, doxepin, seltorexant, and zaleplon (OR range 1·27–2·78).
- For long-term treatment, eszopiclone and lemborexant were more effective than placebo (eszopiclone: SMD 0·63; lemborexant: 0·41) and eszopiclone was more effective than ramelteon (0.63) and zolpidem (0·60; very low]).
- Compared with ramelteon, eszopiclone and zolpidem had a lower rate of all-cause discontinuations (eszopiclone: OR 0·43]; zolpidem: 0·43); however, zolpidem was associated with a higher number of dropouts due to side-effects than placebo (OR 2·00).
"We hope that these findings will inform shared decision making for patients, carers, clinicians, guideline developers, and policy makers," the researchers wrote.
"Future studies should focus on the specific characteristics of patients to provide personalised estimates of comparative effectiveness and individualised predictions regarding the probability of response to treatment and of side-effects."
Reference:
The study titled, "Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis," was published in The Lancet.
DOI: https://doi.org/10.1016/S0140-6736(22)00878-9
