Insomnia Insomnia

Pharmacological Treatment 181
Table 2
Nonbenzodiazepine Hypnotics
Drug T 1/2 half life Onset of action Peak plasma conc Active metabolites
Zolpidem 1.5–2.4 hours 30 minutes 1.5 hours No
Zaleplon 1 hours 30 minutes 1 hour No
Zopiclone 5–6 hours 30 minutes 2 hours No
not with altered renal function. Schlich et al. as early as 1991, studied 107 patients
with insomnia, about 60% of whom were over 60 years of age. The subjects were
given 10 mg of zolpidem on a nightly basis for 6 months. An improvement in all
efficacy parameters—time taken to fall asleep, total amount of nocturnal sleep, and
number of nocturnal awakenings—was reported by the investigator and the patients;
the improvement was evident from the first evaluation day and was maintained
throughout the trial. Improvement was also maintained during the washout
period with a lack of rebound insomnia. There was no sign of withdrawal symptoms
and tolerance to zolpidem did not develop over the 6-month treatment period.
Adverse events were mild and infrequent, and tended to resolve with a dose reduction
(41). The following year, Maarek and colleagues reported the results of their
open-label zolpidem trial. They enrolled 96 subjects who received 10–20 mg of
zolpidem a night for 6 to 12 months. Again, improvement in all sleep parameters
was noted in 90% of subjects with no rebound and withdrawal effects on discontinuation
(42). Saletu-Zyhlarz et al., in a single-blind, placebo-controlled crossover
study, compared 10 mg of zolpidem to placebo. Fifteen adult patients
diagnosed with nonorganic insomnia were enrolled. Objective and subjective sleep
and awakening quality measures were investigated in 3 subsequent nights in the
sleep laboratory. There was a significant lengthening of the total sleep period and
total sleep time, an improvement in sleep efficiency and a shortening of SLs after
zolpidem as compared with placebo. Zolpidem also increased the length of stage 4
and stage 3 + 4 non-REM sleep as compared with placebo (43).These are some of
the important studies looking at zolpidem; there are others in the medical literature
that have produced results, concordant with the above.
Zaleplon also is an effective and safe hypnotic (44). The onset of action is
approximately 30 minutes, and the duration of action is about 4 hours. Peak zaleplon
serum concentrations occur in about 1 hour, and its elimination half-life is also
about 1 hour. Similar to zolpidem, its dose needs to be adjusted with altered hepatic
function but not with renal impairment. The Zaleplon Clinical Study Group looked
at the efficacy and safety of three doses of zaleplon, a novel compared with those of
placebo in outpatients with insomnia in this 4-week study, using 10 mg of zolpidem
as active control. Post-sleep questionnaires were used to determine treatment effects
on the patient’s perception of sleep, development of tolerance during therapy,
or rebound insomnia or withdrawal on discontinuation of therapy. SL was significantly
shorter throughout the 4 weeks of study with any dose of zaleplon compared