Zolpidem tartrate as conventional tablets, oral spray, or sublingual tablets (Edluar) is used as a hypnotic agent in the short-term management of insomnia characterized by difficulties with sleep initiation. Because zolpidem has a short half-life, the drug may be of particular benefit in the initiation of sleep (i.e., decreasing sleep latency). In controlled clinical studies of 4-5 weeks' duration, the drug reportedly has been effective in decreasing sleep latency for periods up to 35 days in duration.
Zolpidem tartrate as extended-release tablets is used in the management of insomnia characterized by difficulty with sleep onset or sleep maintenance. However, zolpidem tartrate extended-release tablets may not be an appropriate treatment choice for patients (men or women) with insomnia who need to drive or perform activities that require full alertness the next morning
Zolpidem tartrate as sublingual tablets (Intermezzo) is used as needed for the management of insomnia when middle-of-the-night awakening is followed by difficulty returning to sleep. The drug should be used in this manner only when 4 or more hours remain before the patient plans to awaken. In 2 randomized, double-blind, placebo-controlled clinical trials in patients with primary insomnia characterized by difficulty returning to sleep after a middle-of-the-night awakening, sublingual zolpidem tartrate improved sleep latency (as measured by polysomnography and patient-estimated reports) after middle-of-the-night awakening compared with placebo. In one crossover study, adults 19-64 years of age received each of 3 treatments (a 1.75- or 3.5-mg dose of zolpidem tartrate sublingual tablets or placebo) after a scheduled middle-of-the-night awakening on 2 consecutive nights in a sleep laboratory; the effect on sleep latency was similar for women receiving a 1.75-mg dose and men receiving a 3.5-mg dose. In the second study, adults 18-64 years of age received a 3.5-mg dose of zolpidem tartrate sublingual tablets or placebo on an as-needed basis over 4 weeks in an outpatient setting when the patient had difficulty returning to sleep after awakening in the middle of the night, provided at least 4 hours remained before the patient planned to awaken.
The choice of hypnotic agent must be individualized based on patient tolerance and response, taking into consideration pharmacokinetic and pharmacodynamic characteristics of the drug, patient age and other characteristics, and the underlying sleep disorder being treated.
Hypnotics with a relatively short half-life may be more likely to result in transient rebound insomnia after discontinuance and in pharmacodynamic tolerance and adaptation to the hypnotic effect, with resultant diminished effectiveness during the end of each night's use (early morning insomnia) and, possibly, increased daytime anxiety. However, despite zolpidem's short half-life, the manufacturer states that increased wakefulness during the last third of the night and objective evidence of rebound insomnia following discontinuance of zolpidem tartrate as conventional tablets have not been observed in clinical trials to date, although there was subjective evidence of impaired sleep on the first posttreatment night in geriatric patients receiving zolpidem tartrate as conventional tablets in doses that exceeded the recommended geriatric dose of 5 mg. Rebound insomnia was observed in two 3-week clinical trials on the first night after abrupt discontinuance of zolpidem tartrate as extended-release tablets, but there was no worsening compared with baseline on the second night. In a 24-week clinical trial evaluating zolpidem tartrate extended-release tablets administered as needed 3-7 nights per week, a rebound effect was observed within the first month for total sleep time, but not for WASO, during the first night that the drug was not used; however, no further rebound insomnia was observed after the first month or after final treatment discontinuance.
In addition, hypnotics with relatively short half-lives may be less likely to result in residual daytime sedative effects and in impaired psychomotor and mental performance during continued therapy. Residual daytime sedative effects of zolpidem were evaluated in several placebo-controlled studies in healthy adults and in geriatric individuals. A small but statistically significant decrease in performance (determined by the Digit Symbol Substitution test [DSST]) was observed in some adults and geriatric individuals receiving zolpidem tartrate as conventional tablets compared with those receiving placebo. Several studies of zolpidem tartrate as conventional tablets in adults with insomnia found no evidence of residual daytime sedative effects, determined by DSST, the Multiple Sleep Latency Test (MSLT), and patient rating of alertness. In studies of zolpidem tartrate extended-release tablets (given at recommended doses) in adult and geriatric patients, neurocognitive tests performed 8 hours after a dose and patient reports of sedation revealed no evidence of decreased performance or next-day residual effects. However, during the 3-week clinical trials evaluating the extended-release tablets, next-day somnolence was reported by 15 or 2% of adults receiving zolpidem or placebo, respectively, and by 6 or 5% of geriatric patients receiving zolpidem or placebo, respectively. In the 24-week clinical trial, the overall incidence of next-day somnolence was 5.7 or 2% in patients receiving zolpidem tartrate as extended-release tablets or placebo, respectively. The minimal effect of zolpidem on sleep stages at usual hypnotic dosages may offer a therapeutic advantage. However, the fact that zolpidem has minimal anxiolytic and muscle relaxant properties at usual hypnotic doses also should be considered. Blood concentrations of zolpidem may be high enough in some patients on the morning after use to impair performance of activities that require alertness, including driving, and the US Food and Drug Administration (FDA) states that all drugs used in the management of insomnia can impair driving and performance of activities that require alertness on the morning after use. For additional information,
Additional experience is needed to elucidate more fully the comparative efficacy and safety of zolpidem and benzodiazepines. For additional information on the management of insomnia, .