Zaleplon is also a selective compound with a very short half-life that averages only 1 hour. The drug shortens sleep onset without usually prolonging total sleep time. Residual effects are absent, and memory is minimally disturbed.
A meta-analysis of benzodiazepines and related drugs in the treatment of insomnia found definite efficacy with respect to prolonging total sleep duration by over an hour but only a nonsignificant reduction in sleep latency.10 Memory impairment was reported in several of the studies that were cited.
Another risk-to-benefit meta-analysis in the elderly concluded that the risks may outweigh the benefits.11 The newer compounds, including eszopiclone and ramelteon, may be more effective in the elderly and better tolerated than standard hypnotic benzodiazepines.12
The most common adverse effects of the hypnotic benzodiazepines are tiredness, drowsiness, and torpor—all features of oversedation. The effects are dose- and time-related and are maximal within the first 2 hours after large doses. This presents a danger if the person with insomnia takes a dose of medication and then wakes up.13 Next-day drowsiness is most noticeable during the first week of treatment, after which it largely disappears, probably because of a true tolerance effect. Patients should be warned of the potential adverse effects of any prescribed benzodiazepine and the initial dosage should be considered carefully. Most benzodiazepines can cause problems, especially when given at higher doses and in the elderly.
Residual effects can be a problem, especially when long-acting drugs are used repeatedly. Dosage is important because as the dosage is increased, residual effects increase in both magnitude and duration. Remember that hypnotics are the only class of drugs in which the main therapeutic effect (drowsiness) is the same as the main unwanted effect; the 2 are merely separated by 8 hours. Psychomotor performance may be affected the next day, with elderly drivers at particularly high risk. In addition, potentiating effects of alcohol(Drug information on alcohol) can occur. Paradoxical behavioral responses (such as uncontrollable weeping; increased aggression and hostility; and acute rage reactions or uncharacteristic criminal behavior, such as shoplifting) can develop in patients taking a benzodiazepine.
Other unwanted effects include respiratory depression, excessive weight gain, rash, impaired sexual function, menstrual irregularities and, rarely, blood dyscrasias. The use of benzodiazepines in pregnancy is generally regarded as reasonably safe, but benzodiazepines pass into the fetus and can produce respiratory depression in the neonate. Benzodiazepines and related drugs cross over into the mother’s milk and can oversedate the baby. Breastfeeding should therefore be discouraged if benzodiazepines are prescribed, especially in high dosages.
Overdosing with benzodiazepines is common; death is not. By themselves, benzodiazepines are only hazardous to children and the physically frail, especially those with respiratory illness. Typically, the person falls into a deep sleep but can be roused with the benzodiazepine antagonist, flumazenil(Drug information on flumazenil). However, the combination of a benzodiazepine and alcohol can be lethal.
Discontinuation of many hypnotics is often followed by worsening of sleep disruptions relative to pretreatment levels. In practical terms, patients with insomnia find that their sleep is disturbed for a night or 2 after abrupt discontinuation of what appeared to be effective medication. The risk of rebound is greater with drugs that have a short half-life than with those that have a longer half-life. Tapering lessens the likelihood of rebound. However, there is little evidence that rebound insomnia leads to the resumption of medication.14
Dependence may supervene on the longer-term use of hypnotics; giving a long-acting benzodiazepine drug only once in 24 hours does not protect against such an eventuality. Because of such concerns, hypnotics are usually prescribed for no more than 2 to 4 weeks. Tapering manages the withdrawal syndrome.
A growing problem with these drugs is abuse—nonmedical use, on a regular or sporadic basis, often in a polydrug context. The injected drug has a marked sedative and/or disinhibiting effect, and its use may result in chaotic behavior.
Insomnia is common, especially in the elderly.15,16 In patients who complain of severe insomnia secondary to physical concerns—pain, breathlessness, or pruritus—the primary symptoms are treated first. In other cases, the insomnia may be either a symptom of psychiatric distress, anxiety, or depression, or it may be iatrogenic, caused by the very drugs prescribed to relieve it. In this instance, a careful regimen of drug withdrawal, or substitution and subsequent withdrawal, should be initiated.