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Biomedical subjects

M B Scharf

Publications and source records attributed to M B Scharf.

At least 55 records · Page 3Linked to original sources
PubMed1982

Lorazepam-efficacy, side effects, and rebound phenomena.

Lorazepam, 4 mg, was evaluated in an 18-night sleep-laboratory study involving five insomniac subjects. Hypnotic effectiveness and effects on sleep stages and related parameters were assessed. Placebo was given on baseline nights 1 to 4, lorazepam on nights 5 to 11, and placebo was given again on withdrawal nights 12 to 18. Subjective and objective data clearly demonstrated that lorazepam was effective for both inducing and maintaining sleep. Sleep latency was reduced from a baseline value of 34.6 min to 17.9 min (P less than 0.01) and total wake time was reduced from 75.9 to 38.5 min (P less than 0.01). On the third and fifth nights of drug withdrawal total wake time rose above baseline levels (termed rebound insomnia) and sleep latency increased by 77% and 60% over baseline (P less than 0.01). Subjective estimates of daytime anxiety also increased above baseline (rebound anxiety) during the withdrawal period. All subjects experienced severe hangover and varying degrees of impaired functioning during the first 3 days on drug. Three subjects also experienced anterograde amnesia during the day after the first drug night. These side effects diminished in intensity over the course of the study. Our results suggest that while 4 mg lorazepam may be effective in inducing and maintaining sleep, this dose induces clinically significant side effects that are followed by consistent rebound phenomena after withdrawal.

Amnesia↗
PubMed1981

Dose-response studies of quazepam.

Quazepam, an investigational benzodiazepine, was evaluated in doses of 7.5, 15, and 30 mg in a 12-night protocol including four nights of drug trial. All three doses were effective in inducing and maintaining sleep, with the highest degree of effectiveness after the first drug night. Carry-over effectiveness, which was seen after withdrawal of all three doses, persisted throughout the withdrawal period after the 30-mg dose. Quazepam's effects during both drug use and withdrawal appeared to be dose related; 15 mg induced a greater reduction in wake time after sleep onset than the 7.5-mg dose, and 30 mg induced even greater differences in both wake time after sleep onset and total wake time. Subjective reports of improved sleep were in general agreement with the objective data at each dose level. Side effects appeared to be dose related in terms of severity. The efficacy and comparatively less severe side effects of the 7.5- and 15-mg doses of quazepam suggest that these doses may be optimal when the drug is considered for the adjunctive treatment of insomnia.

Adult↗
PubMed1980

Cigarette smoking associated with sleep difficulty.

A group of 50 smokers experienced greater sleep difficulty than a group of 50 nonsmokers matched by age and sex. The two groups did not differ in personality patterns or drug consumption. Also, sleep patterns significantly improved in a group of eight chronic smokers when they abstained from cigarette smoking. These findings are consistent with reports on the stimulant effects of nicotine.

Adult↗
PubMed1979

Rebound insomnia. A potential hazard following withdrawal of certain benzodiazepines.

Five benzodiazepine drugs (diazepam, flunitrazepam, flurazepam hydrochloride, nitrazepam, and triazolam) were evaluated separately in 15 sleep laboratory studies. Rebound insomnia, a worsening of sleep compared with baseline, occurred following withdrawal of triazolam, nitrazepam, and flunitrazepam after they had been given in only single, nightly doses for short periods. The rebound insomnia was attributed to the short and intermediate half-lives of these drugs. Diazepam and flurazepam, which have longer half-lives, did not cause rebound insomnia on withdrawal. Rebound insomnia may play a role in the development of hypnotic drug dependence with shorter-acting benzodiazepine drugs.

Acute Disease↗
PubMed1979

Clinical evaluation of hypnotic drugs: contributions from sleep laboratory studies.

The most thorough and clinically relevant approach to hypnotic drug evaluation is one that balances the strengths and weaknesses of clinical trials and sleep laboratory evaluations. Advantages of clinical trials include the ability to evaluate large numbers of subjects and specific target groups and to thoroughly assess and quantify a drug's side effects, whereas sleep laboratory studies are very limited in all of these areas. Sleep laboratory studies however provide a rigorous, precise, and comprehensive profile of a drug's activity since there is more control over experimental variables and measurements are objective as well as continuous throughout the night. These benefits offset the shortcomings of clinical trials, which include a lack of objective measurements, less control over experimental variables, failure to evaluate a drug's effectiveness with continued use, and inattention to drug interaction and withdrawal effect. Several basic principles derived from sleep laboratory findings have been incorporated into both the clinical trials and sleep laboratory evaluations recommended in the new FDA Guidelines for the Clinical Evaluation of Hypnotic Drugs. These principles include provision for adequate baseline and withdrawal periods, use of multiple consecutive drug nights to assess a drug's effectiveness with continued use, and inclusion of an adequate washout period when a cross-over design is used. The guidelines do not emphasize either clinical trials or sleep laboratory studies at the expense of each other, but rather stress their complementary utilization.

Clinical Trials as Topic↗
PubMed1979

Long-term sleep laboratory evaluation of flunitrazepam.

A sleep laboratory hypnotic drug evaluation study was conducted in which 2 mg flunitrazepam, a benzodiazepine with a half life of intermediate duration, was administered nightly to 6 insomniac subjects for 4 consecutive weeks. The drug was effective with short-term use. However, tolerance developed for sleep maintenance during the intermediate- and long-term drug administration periods. Following drug withdrawal, a significant worsening of sleep above baseline levels occurred. These data are consistent with our previous findings of rebound insomnia following withdrawal of short- and intermediate-acting benzodiazepines.

Adult↗
PubMed1978

Rebound insomnia: a new clinical syndrome.

Rebound insomnia followed the withdrawal of three benzodiazepine hypnotic drugs, each of which had been administered in a single nightly dose for only short-term periods. The intense worsening of sleep is attributed to the short duration of the action of these drugs. A hypothesis involving benzodiazepine receptors in the brain is proposed in which there is a delay or lag in replacement of endogenous benzodiazepine-like molecules after the abrupt withdrawal of exogenous drugs.

Benzodiazepines↗
PubMed1978

Hypnotic effectiveness of sodium salicylamide with short-term use: sleep laboratory studies.

Sodium salicylamide in doses of 650 and 1,300 mg was evaluated in two separate sleep laboratory drug evaluation studies of insomniac patients. Each study utilized a standard protocol of 10 consecutive laboratory nights consisting of four placebo nights for adaptation and baseline, three drug nights for short-term drug administration and three placebo nights for evaluating withdrawal. Neither dose had a clear-cut hypnotic effect in inducing or maintaining sleep. Sleep stages were not effected by drug administration or drug withdrawal. Both the objective findings and subjective estimates suggest that the 1,300-mg dose may have a slight sedative effect. However, when salicylamide is used as an ingredient in over-the-counter preparations, the usual dose is only 200-400 mg.

Adult↗
PubMed1977

Comparative effectiveness of nine hypnotic drugs: sleep laboratory studies.

The effectiveness of nine hypnotic drugs was compared using a standard protocol in separate sleep laboratory drug evaluation studies. All of these drugs were relatively effective in improving sleep with initial and short-term use. However, with intermediate-term use (two weeks), most of the drugs showed a marked decrease in their effectiveness. Following withdrawal, sleep was similar to baseline with most of the drugs, continued to be improved with flurazepam (Dalmane), 30 mg, and worsened beyond baseline levels with triazolam (U33030), 0.5 mg. The determination of a drug's effectiveness with continued use is most important clinically in enabling the physician to rationally and effectively use hypnotic drugs in the adjunctive treatment of insomnia.

Adult↗
PubMed1975

Effectiveness of hypnotic drugs with prolonged use: flurazepam and pentobarbital.

This study represents the first attempt to rigorously evaluate the effectiveness of hypnotic drugs under conditions of prolonged use. Flurazepam, 30 mg, and pentobarbital, 100 mg, were separately evaluated in identical 47-night sleep laboratory drug evaluation studies on insomniac subjects, which included 4 weeks of drug administration. Flurazepam was found to be effective in inducing and maintaining sleep over all treatment conditions. With long-term use, only a slight loss of effectiveness was suggested. Flurazepam also produced a moderate decrease in REM sleep and marked decrease in eye movement density and stage 4 sleep with short- and intermediate-term use. While the decreases in both REM sleep and eye movement density lessened with long-term use, stage 4 sleep remained markedly suppressed. No rebound was noted in any of these parameters after withdrawal. Pentobarbital was found to be effective in inducing and maintaining sleep only with short-term drug administration. This strongly suggests that it is of limited value for insomniac patients who require nightly medication beyond short-term use. Pentobarbital caused a minimal decrease in REM sleep with short- and intermediate-term administration, and slight rebound following withdrawal. Stages 3 and 4 sleep were decreased with short-term use and increased above baseline levels after withdrawal.

Adult↗
PubMed1974

Role of RNA in induction of hepatic microsomal mixed function oxidases.

Induction of hepatic microsomal cytochrome P-450 and ethylmorphine N-demethylase activity by phenobarbital requires de novo synthesis of mRNA. Inhibition of RNA synthesis by alpha-amanitin given up to 8 hr after phenobarbital administration substantially inhibits this induction. However, beyond 8 hr after phenobarbital administration, RNA synthesis is not required for induction of these hepatic microsomal systems. Thus, mRNAs for cytochrome P-450 and ethylmorphine N-demethylase appear to be stable. Furthermore, these experiments reveal that the lag period for RNA synthesis approximates the length of the lag period for induction of the hepatic microsomal enzyme systems.

Animals↗