Dayvigo Mental Health and Mood Impact: What the Evidence Shows

Does Dayvigo affect mood or mental health?

Lemborexant is a dual orexin receptor antagonist. It is thought to work by blocking orexin A and orexin B at the OX1R and OX2R receptors, reducing the brain's wake drive [1]. It is not a benzodiazepine or a Z-drug and does not act on GABA-A receptors [1].

The label does not establish that Dayvigo treats depression or anxiety. Its mood-related warnings concern possible worsening depression and suicidal thinking, while its interaction information mainly concerns sedation and changes in drug exposure [1].

What the label says about depression and suicidal ideation

The Dayvigo label carries a Warnings and Precautions section titled 'Worsening of Depression/Suicidal Ideation' [1]. In the clinical studies in people with insomnia, the incidence of suicidal ideation or any suicidal behavior, assessed by questionnaire, was 0.3% with 10 mg, 0.4% with 5 mg and 0.2% with placebo [1].

The label goes further than the questionnaire numbers. It states that in primarily depressed patients treated with hypnotics, worsening of depression and suicidal thoughts and actions, including completed suicides, have been reported; that suicidal tendencies may be present in such patients and protective measures may be required; and that because intentional overdose is more common in this group, the lowest number of tablets that is feasible should be prescribed at any one time [1]. It also says any new behavioral sign or symptom of concern requires careful and immediate evaluation [1].

Could insomnia be the psychiatric problem rather than the side effect?

The label addresses this directly. Sleep disturbances may be the presenting manifestation of a medical or psychiatric disorder, so insomnia treatment should start only after careful evaluation [1]. Insomnia that does not remit after 7 to 10 days may point to a primary psychiatric or medical illness, and worsening insomnia or new cognitive or behavioral abnormalities during treatment may come from an unrecognized underlying disorder [1].

Narcolepsy is the only contraindication on the label [1]. A prior episode of complex sleep behavior is not a labeled contraindication for lemborexant, unlike for zolpidem and eszopiclone [1].

Nightmares, unusual dreams and other sleep-wake symptoms

These are the psychiatric-adjacent adverse reactions the label quantifies. In the first 30 days of the two controlled trials, nightmare or abnormal dreams were reported in 2.2% on 10 mg, 0.9% on 5 mg and 0.9% on placebo [1]. Over the 6-month placebo-controlled period, nightmares led to discontinuation in 1.3% of patients on 10 mg, 0.3% on 5 mg and 0% on placebo [1].

The label also warns about sleep paralysis, hypnagogic and hypnopompic hallucinations, and cataplexy-like leg weakness. Sleep paralysis was reported in 1.6% of patients on 10 mg and 1.3% on 5 mg, versus no reports on placebo; hypnagogic hallucinations in 0.7% and 0.1%, again versus none on placebo [1]. Complex sleep behaviors such as sleep-walking, sleep-driving, eating or making phone calls can occur with hypnotics such as Dayvigo; two events occurred in the trials, both at 10 mg, and the label says to discontinue immediately if one occurs [1].

What SUNRISE 1 and SUNRISE 2 actually measured

SUNRISE 1 studied adults aged 55 and older with insomnia disorder in a 1-month randomized, double-blind trial that compared lemborexant with placebo and with zolpidem extended release; the primary endpoint was change in latency to persistent sleep measured on polysomnography [2]. SUNRISE 2 randomized 949 adults aged 18 and older to placebo, lemborexant 5 mg or 10 mg for a 6-month placebo-controlled period inside a 12-month trial [3]. In SUNRISE 2, patient-reported sleep onset latency and wake after sleep onset fell and sleep efficiency rose significantly versus placebo at month 6 and at most time points, and participants on lemborexant reported significantly better quality of sleep after 6 months; most adverse events were mild or moderate [3].

The SUNRISE outcomes described above are sleep measures, so they do not show whether Dayvigo improves depression or anxiety [2][3].

Taking Dayvigo with antidepressants and other psychiatric drugs

Lemborexant is metabolized mainly by CYP3A4, and the label's interaction table sets out what to do in three situations [1].

• Strong or moderate CYP3A inhibitors such as itraconazole, clarithromycin, fluconazole and verapamil raise lemborexant exposure, and the label recommends avoiding use with these. With weak inhibitors such as chlorzoxazone or ranitidine, the maximum dose the label gives is 5 mg [1].
• Strong or moderate CYP3A inducers such as rifampin, carbamazepine, St. John's wort, bosentan, efavirenz, etravirine and modafinil lower lemborexant exposure, which may reduce efficacy, and the label recommends avoiding use with these as well [1].
• CYP2B6 substrates, with bupropion and methadone as the label's examples, go the other way: lemborexant lowers their AUC, which may reduce their efficacy. The label says to monitor for adequate clinical response and that increasing the substrate dose may be considered [1].

The label also lists other CNS depressants — benzodiazepines, opioids, tricyclic antidepressants and alcohol — as increasing the risk of CNS depression, with possible dose adjustments of either drug, and it states that using Dayvigo with another insomnia drug is not recommended [1].

Alcohol raises lemborexant Cmax and AUC, and the combination produced a numerically greater negative effect on postural stability and memory than alcohol alone when assessed near the lemborexant Tmax at 2 hours; the label says to avoid alcohol with Dayvigo [1].

Next-day impairment, sleepiness and mood

Dayvigo is a CNS depressant that can impair daytime wakefulness even when used as prescribed, and those effects may persist for up to several days after stopping [1]. Driving ability was impaired in some subjects taking 10 mg, and the label cautions patients on 10 mg against next-day driving and other activities requiring complete mental alertness [1]. Risk rises with a shorter night of sleep or a higher-than-recommended dose, and the label notes a higher falls risk, particularly in older adults [1].

Somnolence is the most common adverse reaction: in the first 30 days of the two controlled trials it was 10% on 10 mg, 7% on 5 mg and 1% on placebo. A combined somnolence-or-fatigue category was 9.6%, 6.9% and 1.3%, and headache 4.5%, 5.9% and 3.4% [1]. In the first 30 days, 2.6% of patients on 10 mg, 1.4% on 5 mg and 1.5% on placebo stopped for adverse reactions; over 6 months the figures were 8.3%, 4.1% and 3.8% [1].

Does stopping Dayvigo cause rebound anxiety?

The label's dependence section reports that in animal studies and clinical trials, chronic administration of lemborexant did not produce withdrawal signs or symptoms upon discontinuation, which suggests it does not produce physical dependence [1]. Dayvigo is a Schedule IV controlled substance, and a human abuse potential study in 29 recreational sedative users found drug-liking responses at 10, 20 and 30 mg statistically similar to zolpidem 30 mg and suvorexant 40 mg and greater than placebo [1].