Assessing Interventions for Insomnia in Peri- and Postmenopausal Women

Selected nonpharmacologic approaches were deemed robust, first-line options for chronic insomnia in peri- and postmenopausal women in a recent systematic review and meta-analysis.¹ That finding, however, was contrary to the investigators' initial hypothesis that pharmacological agents would demonstrate advantage for potentially mediating neurovascular-hormonal changes associated with menopause.

"Indirect comparisons suggest that cognitive behavioral therapy for insomnia (CBT-I) yields improvements comparable to Z drugs (eg, zolpidem, zaleplon) and greater than those reported for antidepressants or estrogen on sleep outcomes," indicated Marie Bruyneel, MD, PhD, department of pulmonary medicine, Saint-Pierre University Hospital, Brussels, Belgium, and colleagues. "Conversely, pharmacological treatments may offer more rapid symptomatic relief, particular in the presence of VMS (vasomotor symptoms),” she added.

"Consequently, there remains a need for a systematic synthesis of available interventions, evaluating both efficacy and safety, to obtain evidence-based and shared decision making treatment recommendations for managing sleep disorders during peri-menopause and menopause," Bruyneel, et al observed.

The investigators conducted the systematic review and meta-analysis to address this need, identifying 24 randomized controlled trials (RCTs) for qualitative synthesis and 17 for quantitative synthesis, comprising a total of 2125 women. Studies compared an active approach or agent for chronic insomnia with an active comparator, placebo, or no treatment. Only 1 trial had directly compared pharmacological and nonpharmacologic interventions.

The primary assessment of sleep quality was drawn from measures such as the Pittsburgh sleep quality index (PSQI), insomnia severity index (ISI), and/or polysomnography (PSG) or actigraphy of total sleep time (TST). These measures served as the primary basis to compare efficacy across trials and interventions; with investigators also considering such secondary measures as other sleep outcomes, mental distress or measures of depression and anxiety, and specific outcomes related to peri- or post-menopausal symptoms.

Nonpharmacologic approaches in the trials included CBT-I (n=4), acupuncture (n=3), as well as "multimodal treatment", yoga and stretching, massage and passive movement and sleep-restriction therapy (SRT). The duration of these treatments ranged from 5 to 16 weeks.

Pharmacological treatment included estradiol (n=2), escitalopram (n=1), escitalopram in combination with femoston (n=1), as well as vitamin E, suvorexant, venlafaxine, citalopram, estradiol in combination with trimegestone, valerian, eszopiclone, zolpidem, climodien, and lavandula. Treatment duration in these trials ranged from 4 to 16 week, but with the mean duration notably shorter than with nonpharmacologic approaches (6.77 ± 3.79 weeks vs 8.36 ± 3.91 weeks).

"The short duration of the pharmacological studies included in this meta-analysis and systematic review means that their long-term effects could not be assessed," the investigators noted. They also noted, however, that dependency producing agents are indicated for only short duration.

They found the trials with pharmacologic agents also marred by high loss of follow-up and withdrawal from treatment arms. In the studies evaluating eszopiclone and zolpidem, for example, the withdrawal rates due to side effects ranged from 5.5% to 16%.

Differentiating Interventions for Insomnia

Bruyneel and colleagues found, contrary to their initial hypothesis, that nonpharmacologic approaches could be more effective than pharmacologic to mitigate subjective sleep disturbances, on the PSQI and ISL measures. No intervention from either category was found to affect TST, albeit the investigators note that there were few studies taking that measure.

Within the nonpharmacologic category, acupuncture and CBT-I were associated with the greatest improvement in PSQI scores, and yoga with the greatest improvement in ISI score. Among pharmacologic agents, eszopiclone was associated with the greatest improvement in ISI scores, and escitalopram with the greatest improvement in PSQI.

The selected trials comprised a diverse range of pharmacologic agents, from antidepressants to valerian and hormone therapy. The investigators suggested that the various mechanisms—serotonergic, GABAergic, estrogenic, others—could "contribute to the genesis of insomnia and may be interesting targets."

The investigators also recognized the heterogeneity of the trials, with an array of methodologies and designs. "Indeed, dividing studies into pharmacological and non-pharmacological interventions can be considered arbitrary, limiting their value in providing clinical guidance," they acknowledge.

With only one study directly comparing 2 treatments, there was insufficient power for the meta-analysis to rank interventions by effectiveness; nor was any comparison of long-term effects possible, as most trials were of short duration.

In their conclusion, the investigators point out that selecting an intervention is not necessarily an either/or proposition, and that there has been recent evidence that combining CBT-I with medication can be useful when CBT-I alone does not improve chronic insomnia.²

Bruyneel, et al also advise that the results "need to be interpreted cautiously," and that longer-term trials are necessary to document the safety and efficacy of both treatment categories.

References

1. Bruyneel M, Rozenberg S, Sanida C, et al. Pharmacological and non-pharmacological treatments for chronic insomnia in perimenopausal and postmenopausal women: a systematic review and meta-analysis. Sleep Med. 2026;146:109040.

2. Buysse DJ, Arnedt JT, Buenaver L, et al. Combination treatment for chronic insomnia disorder in adults: an American academy of sleep medicine systematic review, meta-analysis, and GRADE assessment. J Clin Sleep Med. 2026;22:58.