Somnolence Subject

There are several MWT variants with respect to trial duration. This variation stems from the fact that the MWT can be adapted to a variety of situations depending on the degree of sleepiness and motivational characteristics of the population to be studied. As examples, with extremely somnolent subjects such as patients with narcolepsy, a shorter trial duration, say 20 min, can be used with minimal ceiling effects. In individuals who are only moderately sleepy (say, MSLT sleep latencies in the 6-10 min range), as opposed to extremely sleepy (say, MSLT sleep latencies in the 0-5 min range), MWT trial durations of 30 min or 40 min are needed to reduce problems with ceiling effects (15-17). 

Most common adverse reactions in all controlled clinical studies Blurred vision, dizziness, dry mouth, edema, somnolence, thinking abnormal (primarily difficulty with concentration/attention), and weight gain were more commonly reported by subjects treated with pregabalin. 

The MSLT has also been used for assessment of other types of compounds that may affect diurnal somnolence. Antihistamines, for example, are commonly associated with subjective sleepiness. Roehrs et al. (58) showed that certain types of antihistamines increase sleepiness, with the MSLT used as the objective measure, while other types do not. 

One could reasonably believe that complaining of chronic daytime somnolence is a major risk for traffic accidents. Surprisingly, studies on patients suffering from chronic daytime somnolence (9,10) failed to find a link between the risk of traffic accidents and sleepiness measured on a behavioral scale (i.e., Epworth Sleepiness Scale). This could be explained by the fact that subjective questionnaires do not correlate with objective measures of daytime vigilance (11). Another possible explanation could be that sleepiness is dangerous only when perceived during at risk activities. 

Studies on apneic subjects (12,13) have shown that chronic subjective daytime somnolence is not responsible for traffic accidents but sleepiness at the wheel while driving is responsible for traffic accidents. These findings confirm the importance of behavioral somnolence and justify the responsibility of this symptom in the occurrence of an accident. 

Subjective (e.g., Epworth Sleepiness Scale) and objective [e.g., Multiple Sleep Latency Test (MSLT)] daytime somnolence quantification does not seem to provide valuable information on patients risks. This could be explained by the fact that sleep-related accidents occur at certain times when behavioral and chronobiological factors play an important role. Medical and legal issues could nevertheless require an objective test, such as the Maintenance of Wakefulness Test (MWT), to confirm that treated apneic patients present a normal level of vigilance. 

Narcolepsy is a major pathology responsible for excessive daytime somnolence, and it has also been studied as a risk factor for traffic accidents. Aldrich (35) showed that narcoleptic patients presented a higher risk of sleep-related accidents than apneic subjects. Here again, the MSLT did not correlate with the rate... 

Philip P, Taillard J, Niedhammer I, Guilleminault C, Bioulac B. Is there a link between subjective daytime somnolence and sickness absenteeism A study in a working population. J Sleep Res 2001 10 111-115. 

A lower dose of amisulpride (50 mg) has been tested in 20 healthy elderly volunteers (aged 65-79 years) (2). There were no serious adverse events, but one subject reported a moderate headache for 18 hours, a second subject vomited 9 hours after dosing, and a further subject complained of mild somnolence for 12 hours starting 4 hours after dosing however, there were no extrapyramidal symptoms, clinically significant hemodynamic variations, or electrocardiographic abnormalities. 

In a retrospective study in 499 in-patients with schizophrenia or schizoaffective disorder (39) 259 subjects were taking olanzapine and 240 risperidone. Treatment was considered effective in most cases (74% with olanzapine and 78% with risperidone). There were adverse effects in 19% of the patients taking olanzapine and 22% of those taking risperidone they were mainly somnolence (n = 15 and n = 17 respectively) and extrapyramidal symptoms (n = 9 and n = 6 respectively) there were also three cases of weight gain with olanzapine. 

In a multicenter, randomized, double-blind, 12-week trial in Australia and New Zealand, 384 patients with dementia, mainly Alzheimer s disease, were initially enrolled and received at least one dose of risperidone (n = 167 71% women mean age 83 years modal dose 0.99 mg/day) or placebo (n = 170 72% women mean age 83 years) (47). Clinical improvement in aggression and psychotic symptoms was evidenced by means of specific scales 45 subjects taking risperidone and 56 taking placebo did not complete the trial, mainly because of insufficient responses and adverse effects. In the whole sample there was a high prevalence and variety of adverse events (94% of those taking risperidone and 92% of those taking placebo), mainly injuries, falls, somnolence, and urinary tract infections however, only the last two were more common in those taking risperidone than in those... 

Ketoconazole caused a modest increase in the mean AUC (33%) and the mean Cmax (34%) of ziprasidone. This effect was not considered clinically relevant and suggests that other inhibitors of CYP3A4 are unlikely to affect the pharmacokinetics of ziprasidone significantly. Most of the reported adverse events were mild. The adverse events that were most commonly reported in subjects who took the drugs concomitantly were dizziness, weakness, and somnolence. There were no treatment-related laboratory abnormalities or abnormal vital signs during the study and at the 6-day follow-up evaluation. 

The pharmacokinetics and absolute oral systemic availability of zaleplon have been assessed in a partially randomized, single-dose, crossover study in 23 healthy subjects, who received intravenous infusions of zaleplon 1 and 2.5 mg during the first and second periods and were then randomly assigned to receive an oral dose of 5 mg or an intravenous infusion of 5 mg in a crossover design (7). The oral and intravenous doses of zaleplon were well tolerated. Somnolence, abnormal vision, diplopia, and dizziness were the most commonly reported adverse events. 

Zaleplon and zolpidem have been compared in two concurrent multicenter, randomized, double-blind, placebo-controlled crossover studies in chronic insomniacs (12). In study 1, zaleplon 10 mg, zolpidem 10 mg, or placebo were given double-bhnd to 36 healthy subjects under standardized conditions in a six-period, incomplete-block, crossover study (13). The subjects were gently awakened and given the medication at predetermined times, 5, 4, 3, or 2 hours before morning awakening, which occurred 8 hours after bedtime. When they awoke in the morning, subjective and objective assessments of residual effects of hypnotics were administered. There were no serious adverse experiences during the study all adverse events were mild to moderate. The most commonly reported adverse events associated with zaleplon were weakness and somnolence. Weakness, depersonalization, dizziness, and somnolence were the most frequent nervous system adverse events associated with zolpidem. 

Somnolence was reported in a 27-year-old subject following an overdose of opipramol a maximum serum concentration of 0.115 pg/ml was determined ethanol was also detected (O. L. Pedersen et ai, Eur. J. clin. Pharmac., 1982, 23, 513-521). 

The combination of loss of sleep for one night and scopolamine at 10 Mg/kg had a more than additive effect on performance In the Number Facility Test and considerably more effect on manual dexterity chan the scopolamine alone. The combination also produced hallucinations In about 2.7 times as many subjects as the same dose of scopolamine alone. The results with the lover dose of scopolamine were similar to chose reported above, but less striking. The men deprived of sleep for two nights became so somnolent after the dose of scopolamine chat the tests could not be run. 

Seasonal allergic rhinitis affects about 10% of school-age children, and there is evidence of a significant impact of the disease on health-related quality of life. The effect on health-related quality of life of once-daily of cetirizine syrup 10 mg/day for 4 weeks has been studied in 544 children with seasonal allergic rhinitis in a multicenter, open, non-comparative study (2). In addition to improvements in symptom scores the authors also reported significant improvements in health-related quality of life, with good tolerability of the drug. Treatment-related adverse effects were reported in 22 subjects, of which somnolence was the most frequent problem, reported by six of the subjects. Only 12 of subjects discontinued treatment owing to an adverse effect. 

Morphi Dex contains morphine sulfate and dextromethorphan in a 1 1 ratio. Double-blind, single-dose analgesic efficacy studies in over 800 patients with post-surgical pain have shown superior analgesic activity for the combination (60 60 mg) than separate doses of the individual components (28,29). In double-bhnd, multiple-dose studies in 321 patients with chronic pain the combination provided satisfactory pain control with a significantly lower mean daily dose of morphine sulfate. Other studies have shown similar responses (28) and an adverse events profile similar to that of a similar dose of morphine sulfate (30). The most common adverse events seen in a multiple-dose, non-placebo-controlled study in 1400 subjects were nausea, dizziness, vomiting, somnolence, confusion, and pruritus. There was a significant trend toward lower incidence of constipation with the combination than with morphine sulfate alone (31,32). 

Adverse effects have included insomnia, somnolence, headache, nausea, diarrhea, and dry mouth. Mild withdrawal symptoms on abrupt discontinuation have been described in studies with healthy subjects. 

Glyoxal is a skin and eye irritant the effect may be mild to severe. Its vapors are irritating to the skin and respiratory tract. An amount of 1.8 mg caused severe irritation in rabbits eyes. Glyoxal exhibited low toxicity in test subjects. Ingestion may cause somnolence and gastrointestinal pain. 

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