Lunesta Sexual Function Impact: What Eszopiclone Does to Libido, Arousal, and Performance

What the label actually reports about libido

Eszopiclone is an oral prescription hypnotic for insomnia, the S-isomer of zopiclone, and a Schedule IV controlled substance [3][1]. The number that answers this question comes from one table in the Lunesta prescribing information: a 6-week placebo-controlled trial in nonelderly adults, with 44 days of treatment, in which 99 people took placebo, 104 took 2 mg and 105 took 3 mg [1]. The table includes only reactions that reached 2% or more and were more frequent than placebo. Decreased libido is a single row: 0% on placebo, 0% on 2 mg, 3% on 3 mg [1].

Those are patient-reported adverse events in one trial, not scores on a sexual function questionnaire. The label names the reactions that show a dose-response in that trial as viral infection, dry mouth, dizziness, hallucinations, infection, rash and unpleasant taste, clearest for unpleasant taste at 3% on placebo, 17% on 2 mg and 34% on 3 mg [1]. Decreased libido is not in that group.

Two other urogenital rows appear in the same table. Gynecomastia in males was recorded at 0% on placebo, 3% on 2 mg and 0% on 3 mg; dysmenorrhea in females showed the same pattern [1]. Neither rises with dose, and both come from a 44-day trial.

Sedation, timing and alertness

The label describes Lunesta as a CNS depressant that can impair daytime function at 2 mg or 3 mg even when used as prescribed, and states that impairment can occur without symptoms [1]. Risk of next-day impairment is higher with less than 7 to 8 hours of sleep remaining, higher doses, alcohol or other CNS depressants [1]. The half-life is about 6 hours, about 9 hours in people 65 and older, who also have 41% higher exposure [1]. The recommended starting dose is 1 mg immediately before bedtime with at least 7 to 8 hours remaining before awakening, raised to 2 mg or 3 mg if clinically indicated and never above 3 mg [1]. The label also warns that taking a hypnotic while still up and about may cause short-term memory impairment, hallucinations, impaired coordination, dizziness and lightheadedness [1].

Sex during complex sleep behaviors: the boxed warning

The boxed warning is titled COMPLEX SLEEP BEHAVIORS and names sleep-walking, sleep-driving and engaging in other activities while not fully awake, some of which have caused serious injuries, including death [1]. In its warnings section, the label gives further examples: preparing and eating food, making phone calls and having sex [1]. Patients usually do not remember these events, they may occur after the first or any subsequent dose, and they can happen with Lunesta alone at recommended doses, with or without alcohol or other CNS depressants [1]. The label says to discontinue Lunesta immediately if a complex sleep behavior occurs, and Lunesta is contraindicated in anyone who has had one [1].

This is a different problem from low desire: it is unremembered activity, including sexual activity, while not fully awake, not a change in interest while awake.

For background, FDA added the boxed warning and contraindication for eszopiclone, zaleplon and zolpidem after a safety announcement posted on 30 April 2019 [4]. Its review of 66 serious cases reported through 27 February 2018 for the three drugs found 20 deaths and 46 serious injuries (Harbourt 2020) [5]. FDA also stated that these drugs should not be prescribed to anyone who had previously had a complex sleep behavior on any of them [4].

Arousal, orgasm and hormones: what has not been measured

The label says the mechanism of the hypnotic effect is unclear and may involve interaction with GABA-receptor complexes at binding domains close to or allosterically coupled to benzodiazepine receptors [1]. The 6-month trial of 788 adults tracked sleep latency, wake time after sleep onset, total sleep time, sleep quality and next-day function, with outcomes reported through an interactive voice-response system; it did not report hormone levels or sexual function scores [2]. Any hormonal explanation for a change in desire on this drug would be extrapolation, not a measured finding.

Older adults

Half-life lengthens to about 9 hours at age 65 and older, with 41% higher exposure, and the total dose in elderly or debilitated patients should not exceed 2 mg [1]. The label notes a higher risk of falls in elderly patients taking Lunesta [1]. In the separate 14-day trials in adults aged 65 to 86 (208 on placebo, 72 on 1 mg, 215 on 2 mg), decreased libido does not appear among the reactions listed at 2% or more, nor in the footnote of reactions at or below placebo [1]. The 2023 AGS Beers Criteria say to avoid eszopiclone in older adults [6].

What the insomnia guidelines say

The American College of Physicians recommended in 2016 that all adults with chronic insomnia receive cognitive behavioral therapy for insomnia as initial treatment (strong recommendation, moderate-quality evidence), with medication added through shared decision-making only if CBT-I alone was unsuccessful (weak recommendation, low-quality evidence) [7]. The American Academy of Sleep Medicine's 2017 guideline gave a weak suggestion for eszopiclone for sleep onset and sleep maintenance insomnia [8].