Modified-release zolpidem has advantages over immediate-release forms

The results of a recent double-blind placebo-controlled study show a modified-release formulation of zolpidem to improve sleep maintenance, induction and duration, indicating an improvement over standard-release formulations. Previous studies have demonstrated that zolpidem is effective in accelerating sleep onset and increasing total sleep time. However, the drug has not been shown consistently to affect sleep maintenance in terms of modifying wake time after sleep onset (WASO).In this latest study researchers set out to evaluate the effects of a new zolpidem-MR formulation, comprising a two-layer coated tablet designed to release the active ingredient in two phases (immediate release followed by prolonged release), on sleep maintenance, initiation and duration.Following a two-night polysomnographic (PSG) screening phase 212 adults with primary insomnia were randomised to receive zolpidem-MR 12.5mg (n=102) or placebo (n=110) at night for three weeks, followed by a single-blind placebo discontinuation phase (night 22 onwards).Further PSG monitoring was conducted on the first two nights of the study and on nights 15, 16, 22 and 23. Subjective sleep estimates from daily sleep questionnaires were also used to assess efficacy. The researchers observed significant improvements in WASO (hours 1 to 6) and number of awakenings for patients in the zolpidem-MR group compared with placebo.After controlling for baseline differences in treatment groups, patients in the zolpidem group were awake for an average of 34 and 30 minutes less, compared with baseline, over hours 1 to 6 on nights 1/2 and 15/16, respectively (pIn addition, zolpidem-MR produced a significantly greater reduction from baseline in latency to persistent sleep (LPS) than placebo at the beginning and end of two weeks of treatment and was associated with significantly longer sleep duration than placebo on the first and last two nights of the efficacy evaluation.Psychomotor performance measured the morning after drug administration using a digit symbol substitution test and the Rey auditory verbal learning test did not decrease in either group on days 1, 2, 15 or 16.PSG monitoring showed a significant worsening of LPS, sleep efficiency and WASO compared with baseline values on the first night following abrupt discontinuation (day 22). These effects disappeared by the second night (night 23).Overall rates of adverse reactions were similar in the two groups.The researchers conclude that zolpidem-MR produced the well established hypnotic effect of decreasing sleep latency and increasing sleep duration of zolpidem, and in addition improved sleep maintenance by decreasing WASO and number of nightly awakenings.They add that the absence of unexpected adverse effects and the absence of next-morning residual effects on psychometric measures confirm the drug's safety profile.Reference...