Midazolam daytime residual effect evaluated by the multiple sleep latency test

Reimão, Rubens

doi:10.1590/S0004-282X1993000200002

Abstracts

Daytime sleepiness after ingestion of midazolam as a hypnotic was quantitatively studied employing the Multiple Sleep Latency Test (MSLT). We evaluated 20 healthy volunteers, 10 of which received a single oral dose of midazolam (15 mg, one tablet) and 10 of which received placebo, in a double-blind design. Tablets were administered at 2200 h, bedtime. On the following day, all subjects were submitted to a clinical evaluation, a subjective checklist and the MSLT. The mean age was 34.7 + 8.9 years in the midazolam and 38.0+10.6 years in the placebo groups (n.s.). Sex and weight distributions were similar in both groups (n.s.). Clinical evaluation and subjective symptom checklist did not make evident significant differences between midazolam and placebo groups (n.s.). The MSTL was performed at 0900, 1100, 1300, 1500 and 1700 h. Mean sleep latencies were 12.0, 12.7, 8.0, 13.5, 17.0 min in the midazolam group; mean sleep latencies were 13.8, 9.0, 6.9, 9.5, 13.6 min in the placebo group (n.s.). In the single dose, double-blind design here evaluated, midazolam did not show differences in relation to placebo on the following day, detectable by the MSLT.

sleep; midazolam; multiple sleep latency test

O objetivo foi avaliar quantitativamente a sonolência no dia seguinte após dose única de midazolam, utilizado como hipnótico ao deitar. Avaliamos 20 voluntários saudáveis, 10 dos quais receberam midazolam, por via oral (15 mg, um comprimido) e 10 receberam placebo, em esquema duplo-cego. Os comprimidos eram administrados às 22:00h, ao deitar. No dia seguinte todos os probandos foram submetidos a avaliação clínica, questionários e o Teste das Latências Múltiplas do Sono (TLMS). A média de idade foi 34,7 ± 8,9 anos no grupo com midazolam e 38,0±10,6 anos no grupo com placebo (n.s.). Sexo e peso tiveram distribuições semelhantes em ambos os grupos (n.s.). A avaliação clínica e o questionário não mostraram diferenças entre os grupos midazolam e placebo (n.s.). O TLMS permitiu quantificar as latências de sono 5 vezes consecutivas durante o dia. Mostrou no grupo com midazolam as seguintes médias de latências do sono, 12,0, 12,7, 8,0, 13,5, 17,0 min; no grupo com placebo, as médias foram 13,8, 9,0, 6,9, 9,5, 13,6 min (n.s.). O protocolo utilizado, duplo-cego com dose única de midazolam ou placebo ao deitar, não revelou diferenças mensuráveis pelo TLMS.

sono; midazolam; teste das latências múltiplas do sono

Rubens Reimão

Sleep Disorders Center, Hospital Albert Einstein and Hospital das Clinicas, University of São Paulo Medical School, São Paulo

SUMMARY

Daytime sleepiness after ingestion of midazolam as a hypnotic was quantitatively studied employing the Multiple Sleep Latency Test (MSLT). We evaluated 20 healthy volunteers, 10 of which received a single oral dose of midazolam (15 mg, one tablet) and 10 of which received placebo, in a double-blind design. Tablets were administered at 2200 h, bedtime. On the following day, all subjects were submitted to a clinical evaluation, a subjective checklist and the MSLT. The mean age was 34.7 + 8.9 years in the midazolam and 38.0+10.6 years in the placebo groups (n.s.). Sex and weight distributions were similar in both groups (n.s.). Clinical evaluation and subjective symptom checklist did not make evident significant differences between midazolam and placebo groups (n.s.). The MSTL was performed at 0900, 1100, 1300, 1500 and 1700 h. Mean sleep latencies were 12.0, 12.7, 8.0, 13.5, 17.0 min in the midazolam group; mean sleep latencies were 13.8, 9.0, 6.9, 9.5, 13.6 min in the placebo group (n.s.). In the single dose, double-blind design here evaluated, midazolam did not show differences in relation to placebo on the following day, detectable by the MSLT.

Key words: sleep, midazolam, multiple sleep latency test.

RESUMO

O objetivo foi avaliar quantitativamente a sonolência no dia seguinte após dose única de midazolam, utilizado como hipnótico ao deitar. Avaliamos 20 voluntários saudáveis, 10 dos quais receberam midazolam, por via oral (15 mg, um comprimido) e 10 receberam placebo, em esquema duplo-cego. Os comprimidos eram administrados às 22:00h, ao deitar. No dia seguinte todos os probandos foram submetidos a avaliação clínica, questionários e o Teste das Latências Múltiplas do Sono (TLMS). A média de idade foi 34,7 ± 8,9 anos no grupo com midazolam e 38,0±10,6 anos no grupo com placebo (n.s.). Sexo e peso tiveram distribuições semelhantes em ambos os grupos (n.s.). A avaliação clínica e o questionário não mostraram diferenças entre os grupos midazolam e placebo (n.s.). O TLMS permitiu quantificar as latências de sono 5 vezes consecutivas durante o dia. Mostrou no grupo com midazolam as seguintes médias de latências do sono, 12,0, 12,7, 8,0, 13,5, 17,0 min; no grupo com placebo, as médias foram 13,8, 9,0, 6,9, 9,5, 13,6 min (n.s.). O protocolo utilizado, duplo-cego com dose única de midazolam ou placebo ao deitar, não revelou diferenças mensuráveis pelo TLMS.

Palavras-chave: sono, midazolam, teste das latências múltiplas do sono.

Full text available only in PDF format.

Texto completo disponível apenas em PDF.

Aknowledgement We thank K.N. Salomão for statistical advice and support.

Aceite: 27-julh-1992.

Dr. Rubens Reimão Rua Glicíneas 128 04048-050 São Paulo SP Brasil.

1. Broughton RJ. Chronobiological aspects and models of sleep and napping. In Dinges DF, Broughton RJ (eds): Sleep and alertness Chronobiological, behavioral and medical aspects of napping. New York: Raven Press, 1989, p 71-98.
2. Carskadon MA, Dement WC. The Multiple Sleep Latency Test: What does it measure? Sleep 1982, 5 (Suppl 2): s56-s66.
3. Carskadon MA, Dement WC, Mitler MM, Roth T, Westbrook PR, Keenan S. Guidelines for the Multiple Sleep Latency Test (MSLT): a standard measure of sleepiness. Sleep 1986, 9:519-524.
4. Garzone PD, Kroboth P. Pharmacokinetics of the newer benzodiazepines Clin Pharmaco-kinet 1989, 16:337-345.
5. Gudgeon AC, Hindmarch I. Midazolam: effects on psychomotor performance and subjective aspects of sleep and sedation in normal volunteers. Br J Clin Pharmacol 1983, 16 (Suppl 1): 121-128.
6. Heizmann P, Eckert M, Ziegler WH. Pharmacokinetics and bioavailability of midazolam in man. Br J Clin Pharmacol 1983, 16:43s49s.
7. Klotz U, Ziegler G. Physiologic and temporal variation in hepatic elimination of midazolam. Clin Pharmacol Thar 1982, 32:107-112.
8. McClelland GR. Body sway and the effects of psychoactive drugs: a review. Hum Psycho-pharmacol 1989, 4:3-18.
9. Milligan KR, Lumsden J, Howard RC, Howe JP, Dundee JW. Use of auditory evoked responses as a measure of recovery from benzodiazepine sedation. J R Soc Med 1989, 82: 595-603. 168 Arq Neuropsiquiatr 1993, 51(2)
10. Monti J. Sleep in insomniac patients during short and intermediate-term midazolam administration and after its withdrawal. In Koela WP, Obal F, Schulz H, Visser P: Sleep'86. Stuttgart: Elsevier, 1988, p 115-118.
11. Monti J. Terapêutica da insônia. In Reimão R: Sono, aspectos atuais. Rio de Janeiro: Atheneu, 1990, p 41-50.
12. Nicholson AN. Transient insomnia and rapidly eliminated hypnotics. Sleep 1986, 9:317-322.
13. Nicholson AN. Hypnotics: their place in therapeutics. Drugs 1986, 31:164-176.
14. Nicholson AN, Stone RM. Midazolam: sleep and performance in the middle age. Br J Clin Pharmacol 1983, 16:115s-121s.
15. Reimão R. Terapêutica dos distúrbios do sono. In Nitrini R: Condutas em Neurologia 1989/1990. São Paulo: Clínica Neurológica HC/FMUSP, 1989, p 77-88.
16. Reimão R. Teste das Latências Múltiplas do Sono: técnica, indicação e interpretação. Reun Neurofisiol Clin 1990, 5:45-46.
17. Richardson GS, Carskadon MA, Oraw WC, Dement WC. Circaditan variation of sleep tendency in elderly and young adult subjects. Sleep 1982, 5 (Suppl 2): 82s-94s.
18. Schneider-Helmert D. Why low-dose benzodiazepine-dependent insomniacs can't escape their sleeping pills. Acta Psychiatr Scand 1988, 78:706-713.
19. Stepanski EJ, Zorick F, Roth T. Insomnia, a 24 h problem: effects of sleep deprivation in chronic insomnia. In Rarthouil P (ed): Insomnie et imidazopyridines. Amsterdam: Excerpta Medica, 1990, p 180-184.
20. Zwyghuizen-Doorenbos A, Roehrs T, Schaefer M, Roth T. Test-retest reliability of the MSLT. Sleep 1988, 11:562-565.

Midazolam daytime residual effect evaluated by the multiple sleep latency test

Midazolam e o efeito residual do dia seguinte avaliado utilizando o teste das latências múltiplas do sono

Publication Dates

Publication in this collection
19 Jan 2011
Date of issue
June 1993

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Broughton RJ. Chronobiological aspects and models of sleep and napping. In Dinges DF, Broughton RJ (eds): Sleep and alertness Chronobiological, behavioral and medical aspects of napping. New York: Raven Press, 1989, p 71-98.

[2] 2. Carskadon MA, Dement WC. The Multiple Sleep Latency Test: What does it measure? Sleep 1982, 5 (Suppl 2): s56-s66.

[3] 3. Carskadon MA, Dement WC, Mitler MM, Roth T, Westbrook PR, Keenan S. Guidelines for the Multiple Sleep Latency Test (MSLT): a standard measure of sleepiness. Sleep 1986, 9:519-524.

[4] 4. Garzone PD, Kroboth P. Pharmacokinetics of the newer benzodiazepines Clin Pharmaco-kinet 1989, 16:337-345.

[5] 5. Gudgeon AC, Hindmarch I. Midazolam: effects on psychomotor performance and subjective aspects of sleep and sedation in normal volunteers. Br J Clin Pharmacol 1983, 16 (Suppl 1): 121-128.

[6] 6. Heizmann P, Eckert M, Ziegler WH. Pharmacokinetics and bioavailability of midazolam in man. Br J Clin Pharmacol 1983, 16:43s49s.

[7] 7. Klotz U, Ziegler G. Physiologic and temporal variation in hepatic elimination of midazolam. Clin Pharmacol Thar 1982, 32:107-112.

[8] 8. McClelland GR. Body sway and the effects of psychoactive drugs: a review. Hum Psycho-pharmacol 1989, 4:3-18.

[9] 9. Milligan KR, Lumsden J, Howard RC, Howe JP, Dundee JW. Use of auditory evoked responses as a measure of recovery from benzodiazepine sedation. J R Soc Med 1989, 82: 595-603. 168 Arq Neuropsiquiatr 1993, 51(2)

[10] 10. Monti J. Sleep in insomniac patients during short and intermediate-term midazolam administration and after its withdrawal. In Koela WP, Obal F, Schulz H, Visser P: Sleep'86. Stuttgart: Elsevier, 1988, p 115-118.

[11] 11. Monti J. Terapêutica da insônia. In Reimão R: Sono, aspectos atuais. Rio de Janeiro: Atheneu, 1990, p 41-50.

[12] 12. Nicholson AN. Transient insomnia and rapidly eliminated hypnotics. Sleep 1986, 9:317-322.

[13] 13. Nicholson AN. Hypnotics: their place in therapeutics. Drugs 1986, 31:164-176.

[14] 14. Nicholson AN, Stone RM. Midazolam: sleep and performance in the middle age. Br J Clin Pharmacol 1983, 16:115s-121s.

[15] 15. Reimão R. Terapêutica dos distúrbios do sono. In Nitrini R: Condutas em Neurologia 1989/1990. São Paulo: Clínica Neurológica HC/FMUSP, 1989, p 77-88.

[16] 16. Reimão R. Teste das Latências Múltiplas do Sono: técnica, indicação e interpretação. Reun Neurofisiol Clin 1990, 5:45-46.

[17] 17. Richardson GS, Carskadon MA, Oraw WC, Dement WC. Circaditan variation of sleep tendency in elderly and young adult subjects. Sleep 1982, 5 (Suppl 2): 82s-94s.

[18] 18. Schneider-Helmert D. Why low-dose benzodiazepine-dependent insomniacs can't escape their sleeping pills. Acta Psychiatr Scand 1988, 78:706-713.

[19] 19. Stepanski EJ, Zorick F, Roth T. Insomnia, a 24 h problem: effects of sleep deprivation in chronic insomnia. In Rarthouil P (ed): Insomnie et imidazopyridines. Amsterdam: Excerpta Medica, 1990, p 180-184.

[20] 20. Zwyghuizen-Doorenbos A, Roehrs T, Schaefer M, Roth T. Test-retest reliability of the MSLT. Sleep 1988, 11:562-565.