The effects of zolpidem, an imidazopyridine derivative, were studied in 107 patients suffering from insomnia, 60.9% of whom were over 60 years of age, in a 6-month, single-blind, flexible dose, general practitioner study. Comparison was made between baseline, last day of treatment and 10 days after the end of treatment to assess efficacy and rebound insomnia. 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. It is concluded that 10 mg/day zolpidem is an appropriate starting dose and is effective and safe for the treatment of sleep disturbances of different origins.

The efficacy and tolerability of the imidazopyridine hypnotic, zolpidem, were investigated in 119 elderly psychiatric in-patients complaining of insomnia in a double-blind, parallel-group, placebo-controlled trial. After a 7-day placebo washout period, patients were randomized to receive 10 or 20 mg/day zolpidem, or placebo for 21 days; thereafter, all patients received placebo for 7 days. Sleep was assessed by patient observation on days 0, 1, 7, 14, 21, 22 and 28. Compared with placebo, 20 mg/day zolpidem significantly improved total duration of sleep between day 0 and day 21, and this was maintained at day 28. After 10 or 20 mg/day zolpidem, there was also a trend towards improvement in all other sleep parameters, which remained above baseline at day 28. Zolpidem was well tolerated with no withdrawal symptoms during the second 7-day placebo treatment period. Daytime drowsiness was reported in three patients receiving 20 mg/day zolpidem and in one receiving 10 mg/day zolpidem, but there was no significant increase in daytime drowsiness between days 0 and 21. Ataxia occurred in two, one and one patient, respectively, treated with 20 mg/day zolpidem, 10 mg/day zolpidem and placebo. The incidences of other adverse events or effects on clinical and laboratory parameters were minimal and similar in all three treatment groups. It is concluded that, in elderly psychiatric patients, 10 mg/day zolpidem can be used to treat insomnia and can be safely added to concomitant psychotropic treatment without inducing daytime drowsiness.

In a pilot double-blind trial in 21 patients with learned or idiopathic insomnia (DSM-IIIR), patients received placebo for 1 week (nights 1-7), either active (zolpidem, 10 mg) or placebo treatment for 2 weeks (nights 8-21) and then placebo for a further week (nights 22-28). Variables to measure efficacy, rebound and withdrawal were assessed daily from day 1 to day 28. Polysomnographic recordings together with sleep cycle analysis were performed on nights 7, 21 and 28. Patients treated with 10 mg zolpidem for 2 weeks had significantly improved sleep efficiency at the end of the randomised double-blind phase compared with the placebo group. Fractionated sleep-cycle analysis showed an increase in slow-wave sleep during the first 2-hour cycle after sleep onset. During the withdrawal placebo week, most of the main sleep variables remained relatively stable in the zolpidem group (nights 22-28), and deteriorated further in the placebo group. At the end of the withdrawal phase, there was a statistically significant difference between groups, in favour of the zolpidem treatment, in sleep efficiency, total sleep time, absolute and percentage of time awake, and percentage of REM sleep. REM sleep, which was normal in both groups at baseline, decreased significantly in the placebo group between nights 22 and 28 (during the withdrawal placebo week) compared with the zolpidem treatment group, and the number of periods of time awake increased. Minor subjective complaints were recorded under zolpidem and were comparable with those under placebo. Zolpidem seemed to improve some important sleep variables, when assessed both objectively and subjectively. The sleep cycle analysis suggested a possible shift of slow-wave sleep to an earlier period of the night, with a more physiological sleep structure. There was no evidence for withdrawal or rebound after stopping the 2 weeks of zolpidem treatment, but rather signs that the effect of zolpidem outlasted active treatment. The present pilot study justifies a prospective confirmatory comparison of zolpidem with benzodiazepines in an adequate number of patients and withdrawal after 6-8 weeks of treatment.

The safety and efficacy of 10 or 20 mg/day zolpidem, a new hypnotic belonging to the imidazopyridine class, were studied over a 180-day period in 96 patients with sleep disorders. The treatment was continued for a further 180 days by 49 of these patients. Follow-up information from 21 patients who discontinued treatment after 180 days showed no rebound insomnia or withdrawal signs. Efficacy of treatment with respect to reduction of sleep onset latency and number of nocturnal wakenings, and improvement in duration of sleep, quality of sleep and morning wakenings was found in nearly 90% of patients and was maintained in those patients who continued treatment for 360 days. This efficacy was achieved with a stable percentage of patients receiving 10 mg/day and 20 mg/day zolpidem from day 30 to the final visit. Zolpidem, therefore, has been shown to be an effective and safe hypnotic, and to be devoid of rebound and withdrawal effects.

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