Insomnia

Insomnia is a complex issue in medical practice (Reference Pałasz, Lapray and Peyron1). Sleep disturbances are a problem for nearly a third of all people (Reference Roth2). Insomnia is associated with deleterious medical and psychiatric consequences for patients, and a challenge for clinicians. Inadequate sleep decreases cognitive function and increases cardiovascular risk (Reference Saper, Chou and Scammell3). Sleep hygiene, regular exercise and treating the underlying causes of insomnia, which includes psychiatric conditions, would greatly benefit people having problems with sleep. Many current pharmaceuticals prescribed as sleep aids are associated with difficulties of cognitive disturbance, somatic side effects, and addiction or habituation (Reference Scammell and Winrow4).

Orexin

Discovery of the neuropeptide orexin and its receptors adds a new option for the management of insomnia (Reference Scammell and Winrow4). Orexin was discovered while investigating the etiology of narcolepsy (Reference Scammell and Winrow4). It is synthesised by neurons in the lateral and posterior hypothalamus, and it has potent effects on arousal and sleep. This peptide facilitates alertness by activating neurons in the locus ceruleus and tuberomamillary nucleus, basal forebrain, and cortex during wakefulness (Reference España and Scammell5). The activity of orexins is mediated through the G protein-coupled receptors, OX1 and OX2 (Reference Scammell and Winrow4,Reference España and Scammell5). They are normally at lower concentrations during sleep and are deficient in persons with narcolepsy (Reference Scammell and Winrow4). Similarly, exogenous orexin injected into the brain, augments arousal at a cellular and behavioral level (Reference España and Scammell5).

Suvorexant

This dual orexin receptor antagonist, suvorexant, has the potential to counter orexin activity (Reference Scammell and Winrow4). Initial studies suggest that it has efficacy in combating insomnia (Reference Herring, Snyder and Budd6–Reference Hopkins8). Suvorexant works by diminishing alertness (Reference Scammell and Winrow4–Reference Hopkins8). In May 2013, suvorexant was approved by an advisory panel for the United States Food and Drug Administration (FDA) for the treatment of patients with sleep difficulties (9).

Suvorexant

Once orexin peptides were discovered, investigations began to develop an antagonist (Reference Scammell and Winrow4). Several researchers tried to discover different orexin receptor antagonists. Among them suvorexant is a potent and selective dual orexin receptor antagonist; this diazepine-based substance is the one most prominently considered (Reference Cox, Breslin and Whitman7–Reference Winrow, Gotter and Cox11). Orexin receptor antagonists counteract the effect of orexin at central nervous system receptors and might be advantageous for patients with trouble in sleeping (Reference Sun, Kennedy and Wilbraham12).

Suvorexant is orally bioavailable, penetrates the blood–brain barrier easily, and occupies rat central nervous system orexin receptors (Reference Scammell and Winrow4). The estimated absolute bioavailability for 40 mg Suvorexant is ~47% (13). In humans, suvorexant reaches maximum plasma concentration in 3 h with dissipation of its effect in 9–13 h (Reference Sun, Kennedy and Wilbraham12). The metabolism of suvorexant in humans is primarily by the hepatic cytochrome P450 3 A family and hydroxylation as the predominant metabolic pathway (13). Metabolites are then eliminated through faeces and urine (13). In May 2013, suvorexant was positively reviewed by an American advisory panel for the United States FDA in the treatment of patients with sleep difficulties (9).

Indications

Insomnia is the indication for prescribing suvorexant (Reference Herring, Snyder and Budd6–Reference Sun, Kennedy and Wilbraham12).

Reportedly, it does not have side effects of sedation or cognitive disturbances (Reference Sun, Kennedy and Wilbraham12), which are associated with sedative hypnotics, including benzodiazepines and related drugs (Reference Scammell and Winrow4). Thus, suvorexant might offer an advantage in treating persons with the aforementioned adversities. These same properties might make it particularly desirable in patients with psychiatric illness, where the primary conditions, or their treatments, might be associated with inattention or reduced cognitive function. In addition, without sedative properties, it may be less likely to cause falling, especially in geriatric populations (Reference Winrow, Gotter and Cox11,Reference Sun, Kennedy and Wilbraham12).

Studies

In animal research, suvorexant has less effect on reducing attention or memory as compared with benzodiazepines (Reference Scammell and Winrow4–Reference Uslaner, Tye and Eddins14). In rodents, it reduced wakefulness and increased rapid eye movement (REM) and non-REM sleep (Reference Scammell and Winrow4).

Numerous clinical studies with suvorexant in humans, mostly in adults aged 18 to 65, document that it helps patients fall asleep with safety and long-term efficacy (Reference Cox, Breslin and Whitman7–13). It also decreases nocturnal awakenings (Reference Sun, Kennedy and Wilbraham12). Subjects prescribed suvorexant do not exhibit rebound insomnia or evidence withdrawal upon abrupt discontinuation of the drug following 4 weeks of ingestion (Reference Herring, Snyder and Budd6). Suvorexant usage does not induce disruption in sleep architecture nor sleep fragmentation (Reference Herring, Snyder and Budd6–Reference Sun, Kennedy and Wilbraham12).

Dosage

Suvorexant has been tested in several different strength versions; the manufacturer offered to market in tablets of 10, 15, and 20mg formulations (Reference Herring, Snyder and Budd6). The initial dosing regimens have been under review (Reference Scammell and Winrow4–15). In debilitated patients or those over age 65, the initial recommended dose should be 15mg nightly. For healthy people under age 65, the initial dosage is 20 mg before bed time.

Adverse effects

The most common side effect of this pharmaceutical is somnolence, and that occurs in 7% of subjects prescribed 15–20 mg dosages (13). Undesired sleepiness is more prevalent as a complaint in about 11% of subjects prescribed quantities at or above 30 mg/day (13). Headaches have been documented in 8% of those receiving 15–20 mg daily (13). One case of hypnagogic hallucination and another of hypnopompic hallucination is reported at 15–20 mg dosage administrations (13). Suicidal ideation is 0.2% to 0.6% in patients on Suvorexant (13).

Drug interaction

Ketoconazole is not recommended for use along with Suvorexant. Diltiazem is to be used in lower dose, and Rifampin is to be used in maximum dose. There are no concerns for patients with hepatic or renal disease.