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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One hundred sixty-six patients suffering from major depressive disorders were treated for 8 weeks with nefazodone in an open study in dosage ranges from 200 to 600 mg. This report focuses primarily on the first week of therapy and on the concomitant use of several benzodiazepines, one of which is not metabolized by the cytochrome system (temazepam). Triazolam response was further evaluated as a function of two nefazodone dosage regimens provided during the first week of therapy, one group receiving nefazodone 200 mg/day for 7 days, and another group receiving nefazodone 200 mg/day for 3 days, followed by 4 days with 400 mg/day. Finally, a comparison of three different nefazodone dosages, the third being 400 mg from day 1 on, was also carried out. Outcome measures included Hamilton Rating Scale for Depression total and the total of the three Hamilton Rating Scale for Depression insomnia items, as well as global improvement, a daily completed sleep questionnaire, and adverse event assessment. A combination of nefazodone with a benzodiazepine (BZ) caused more sedation than nefazodone alone; triazolam, the BZ with the shortest half-life and the highest dependence on the cytochrome 450 system for its metabolism, caused the least amount of sedation, and alprazolam and diazepam, the two daytime benzodiazepines, caused the most sedation. Triazolam caused significant and identical reduction of insomnia in both nefazodone groups. Compared with nefazodone 200 mg given as monotherapy, insomnia was significantly improved--not only by triazolam, but also alprazolam and diazepam, but not temazepam. The addition of nefazodone raised triazolam plasma levels to almost 500%, the plasma level of desmethyl-diazepam 87%, and that of alprazolam 34%. Temazepam plasma levels remained unchanged. When prescribing nefazodone with a benzodiazepine, one should expect an improved sleep pattern initially, but at the cost of clinically relevant daytime sedation. The prediction that temazepam, the only BZ not dependent on the cytochrome mechanism for metabolism, should be the least sedating, and triazolam, because of its cytochromic metabolism interference with nefazodone should be the most sedating, could not be confirmed. In fact, triazolam 0.25 mg capsules seem to be the safest treatment of choice when one has to combine a benzodiazepine with nefazodone in initial stages of therapy, at least of the four benzodiazepines tested in this study.
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PMID:Nefazodone in major depression: adjunctive benzodiazepine therapy and tolerability. 958 Mar 69

Triazolam reportedly causes phase advances in hamster wheel-running rhythm after injection during subjective daytime. However, it is unclear whether benzodiazepine affects the PER: gene expression accompanying a behavioural phase shift. Brotizolam (0.5 - 10 mg kg(-1)) induced large phase advances in hamster rhythm when injected during mid-subjective daytime (circadian time 6 or 9), but not at circadian time 0, 3 or 15. Brotizolam (5 mg kg(-1)) significantly reduced the expression of PER:1 and PER:2 in the suprachiasmatic nucleus 1 and 2 h after injection at circadian time 6, and slightly reduced them at circadian time 20. Injection of 8-OH-DPAT (5 mg kg(-1)) at subjective daytime induced similar phase advances with a reduction of PER:1 and PER:2 expression. Co-administration of brotizolam with 8-OH DPAT failed to potentiate the 8-OH DPAT-induced phase advances and reduced PER: expression. Both phase advance and rapid induction of PER:1 and PER:2 in the suprachiasmatic nucleus after light exposure (5 lux, 15 min) at circadian time 20 was strongly attenuated by co-treatment with brotizolam 5 mg kg(-1). The present results strongly suggest that reduction of PER:1 and/or PER:2 expression during subjective daytime by brotizolam may be an important step in causing a behavioural phase advance. The co-administration experiment suggests that common mechanism(s) are involved in brotizolam- or 8-OH DPAT-induced phase advances and the reduction of PER: gene expression. These results suggest that brotizolam is not only a good drug for insomnia but also a drug capable of facilitating re-entrainment like melatonin.
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PMID:Inhibitory action of brotizolam on circadian and light-induced per1 and per2 expression in the hamster suprachiasmatic nucleus. 1113 54

Night-time bright light (BL) treatment and triazolam (0.125 mg/day) were given to three healthy elderly people in a cross-over design. They kept a daytime sleepiness test and a sleep log, and their wrist-activity was monitored simultaneously. Subjectively, BL increased daytime sleepiness and naps, and decreased night-time sleep. Triazolam decreased daytime sleepiness and naps, and increased night-time sleep. Actigraphic night-time sleep and naps on the first day were similar to these results. However, on the fourth day night-time insomnia induced by BL had recovered, and naps were shorter than the baseline. Triazolam increased actigraphic naps as the days passed.
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PMID:Bright light treatment for night-time insomnia and daytime sleepiness in elderly people: comparison with a short-acting hypnotic. 1118 20

The effects of two nights of treatment with the short-acting benzodiazepine receptor agonist zaleplon, triazolam, or placebo was assessed in chronic primary insomniacs using two concurrent, multi-center, randomized, double-blind, Latin Square crossover studies. Study 1 (n = 47) compared zaleplon (10 and 40 mg) to triazolam (0.25 mg) and placebo. Study 2 (n = 36) compared zaleplon (20 and 60 mg) to triazolam (0.25 mg) and placebo. For each study, polysomnographically recorded sleep parameters and patient reports of sleep quality were collected during baseline and two consecutive nights during the four treatment phases in each study. All doses of zaleplon produced significant decreases in latency to persistent sleep. Although no minimally effective dose could be determined, dose-response effects were apparent. Triazolam 0.25 mg produced a decrease in latency to persistent sleep that was comparable to that of zaleplon 10 mg. Only the triazolam dose and the 60 mg dose of zaleplon produced significant increases in total sleep time over placebo. Zaleplon 40 and 60 mg and triazolam produced decreases in the percentage of REM sleep compared to placebo. Patient reports of efficacy were consistent with objective findings. In addition, all doses of zaleplon tended to increase while triazolam decreased the percentage of stage 3/4 sleep. There was no evidence of residual daytime impairment for any of the zaleplon doses, however, triazolam administration produced significant impairment in performance on a digit copying test. A higher number of adverse events were seen with the 40 and 60 mg doses of zaleplon compared to triazolam (0.25) and placebo. At higher doses, zaleplon is more effective than triazolam at reducing latency to persistent sleep in chronic insomnia and is not associated with the decrease in slow-wave sleep or residual impairment observed with triazolam. However, increases in total sleep time were apparent only at doses which produced concomitant increases in the number of adverse events. In contrast, triazolam (0.25 mg) produced increases in total sleep time (;25 min) and decreases in latency to persistent sleep at a dose of 0.25 mg. Copyright 2000 John Wiley & Sons, Ltd.
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PMID:Dose-response effects of zaleplon as compared with triazolam (0.25 mg) and placebo in chronic primary insomnia. 1240 12

According to the National Institutes of Health, approximately 30 percent of all Americans complain of sleep disruption, while 10 percent display symptoms congruent with chronic insomnia. One of the most common treatments for insomnia is prescription sleep medications that help people fall asleep and remain asleep. Historically barbiturates were initially popular for treating insomnia, but their long "hangover" effect made them easily replaced with the introduction of the benzodiazepines. Triazolam (Halcion), diazepam (Valium), and oxazepam (Serax) rapidly became the treatment of choice for insomnia. Recently a new class of nonbenzodiazepines---the "z-sedatives"--has overtaken the older benzodiazepines as the most commonly prescribed sleep medications. The three most popular z-drugs are zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta). The Food and Drug Administration (FDA) also recently approved the production of zolpidem tartrate, a generic form of Ambien. Many dentists prescribe these medications for patients who have difficulty sleeping the night prior to an appointment or as a procedural sedative. With 43 million prescriptions for sleep medications filled in 2005, generating $2.7 billion for pharmaceutical companies, it is important that dentists be aware of these drugs' mechanism of action and potential drug interactions.
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PMID:What every dentist should know about the "z-sedatives". 1806 95

Drugs that act as allosteric activators at the benzodiazepine site of the gamma-aminobutyric acid (GABA(A)) receptor complex are used commonly to treat insomnia but relatively little is known of how such use affects learning and memory. Although anterograde effects on memory acquisition have been shown, possible retrograde effects on consolidation are more relevant when such agents are administered at bedtime. We tested the effects of two GABA(A) allosteric activators on sleep-dependent motor skill memory consolidation in 12 healthy male subjects. Subjects slept in a sleep laboratory for four consecutive nights (one accommodation night followed by three experimental nights). Placebo, triazolam 0.375 mg, and zolpidem 10 mg were given to each subject in counterbalanced order on the experimental nights. Polysomnographic (PSG) sleep measurement and sleep-dependent motor learning were assessed at each condition. Triazolam was associated with longer total sleep time and increased Stage 2 sleep. Both zolpidem and triazolam were associated with increased latency to rapid eye movement (REM) sleep. Overnight motor learning correlated with total sleep time in the placebo condition but not in the triazolam or zolpidem conditions. A statistically significant impairment in motor performance occurred overnight in the triazolam condition only. Triazolam, given in sufficient doses to prolong sleep in healthy people, affected overnight motor learning adversely. Zolpidem, in a dose sufficient to prolong REM onset latency but without other effects on PSG-measured sleep, degraded the relationship between total sleep time and overnight motor learning. These data indicate that non-selective or alpha1-preferring benzodiazepine site allosteric activators can interfere with sleep-dependent memory consolidation.
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PMID:Retrograde effects of triazolam and zolpidem on sleep-dependent motor learning in humans. 1968 31

The effect of treatment (28 days) with zopiclone, triazolam, flunitrazepam and placebo on sleep quality and daytime well-being was proven in a randomised, double-blind, parallel group, multicentre study in private practice. Results of an exploratory statistic of treatment efficacy in a subgroup of 1,291 patients suffering from insomnia are presented. Patients met the following criteria: insomnia lasting at least four weeks and the presence of at least two of the following: 1) sleep latency >/= 45 minutes, 2) total sleep time </= 6 hours, and 3) nocturnal awakening >/=3 times. Treatment efficacy was assessed according to the following factors: either a shortening of sleep latency by at least 15 minutes, or prolongation of total sleep time by at least 20%, or reduction of the number of nocturnal awakenings to three or less and a refreshed feeling in the morning as well as no impairment in daytime well-being due to tiredness or anxiety. The total response rate was markedly higher with zopiclone (42.3%; p = 0.0003) than with placebo (29.0%). Triazolam (36.6%; p = 0.0905) and flunitrazepam (33.1%; p = 0.3401) were also more effective than the placebo, but they both tended to have a lower response rate than with zopiclone (p = 0.1199 and 0.0151, respectively). Total response was found to be essentially a reflection of the response of the socially important parameter of daytime well-being. These results suggest that zopiclone is more effective in the treatment of insomnia than either triazolam or flunitrazepam. Since the response of daytime well-being to therapy was generally poor, this parameter embodies the next main therapeutic challenge in the treatment of patients with insomnia.
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PMID:Effects of hypnotics on sleep quality and daytime well-being. Data from a comparative multicentre study in outpatients with insomnia. 1969 15


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