Investigation of preference for nightly triazolam versus placebo in moderate social alcohol drinkers

Abstract

This study was designed to examine whether the widely prescribed benzodiazepine hypnotic triazolam has reinforcing effects in moderate social alcohol drinkers, without histories of drug abuse or insomnia, in the context of its use as a hypnotic. Eleven healthy adult volunteers who met criteria for ‘good sleepers’ participated in a 60-session double-blind choice study which was conducted on an outpatient basis with participants sleeping at home. Twenty three-session sampling/choice tests were conducted sequentially to provide 20 evaluations of the reinforcing effects of 0.25 mg/70 kg triazolam versus placebo, ingested orally 30 min before bedtime. Each three-session test consisted of two sampling sessions, in which participants received exposure to each of the two drug conditions in different colored capsules, followed by one choice session, in which participants were asked to choose one of the two colour-coded capsules for self-administration. Four participants exhibited a significant choice of triazolam, three, a significant choice of placebo (i.e. triazolam avoidance), and four, a random (i.e. non-significant) choice between triazolam and placebo. The reasons provided by participants were consistent with their choices and with the expected effects of triazolam versus placebo. Analyses of post-sleep questionnaires indicated that triazolam did not produce a clinically meaningful improvement in sleep. The finding that triazolam functioned as a reinforcer in participants without insomnia suggests that triazolam has reinforcing effects in some individuals for which hypnotic treatment is not clinically indicated, and that health care professionals must continue to assess the risk/benefit ratio of benzodiazepine hypnotic prescription.

Keywords

benzodiazepine human hypnotic reinforcement triazolam

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References

Ashton H (1994) Guidelines for the rational use of benzodiazepines. When and what to use. Drugs 48: 25–40

Balter M B , Uhlenhuth E H (1991) The beneficial and adverse effects of hypnotics. J Clin Psychiatry 52 (Suppl. 7): 16–23

Balter M B , Uhlenhuth E H (1992) New epidemiologic findings about insomnia and its treatment. J Clin Psychiatry 53 (Suppl. 12): 34–39

Cahalan D , Cisin I M , Crossley H M (1969) American drinking practices: a national study of drinking behavior and attitudes. Rutgers Center of Alcohol Studies, Monograph 6, New Brunswick, NJ

Chevalier H , Los F , Boichut D , Bianchi M , Nutt D J , Hajak G , Hetta J , Hoffmann G , Crowe C (1999) Evaluation of severe insomnia in the general population: results of a European multinational survey. J Psychopharmacol 13 (Suppl. 1): S21–S24

Colburn T R , Smith B M , Guarini J J , Simmons N N (1976) An ambulatory activity monitor with solid state memory. ISA Trans 15: 149–154

Curran H V (1991) Benzodiazepines, memory, and mood: a review. Psychopharmacology 105: 1–8

de Wit H , Uhlenhuth E H , Johanson C E (1984) Lack of preference for flurazepam in normal volunteers. Pharmacol Biochem Behav 21: 865–869

de Wit H , Pierri J , Johanson C E (1989) Reinforcing and subjective effects of diazepam in nondrug-abusing volunteers. Pharmacol Biochem Behav 33: 205–213

10.

de Wit H , Doty P (1994) Preference for ethanol and diazepam in light and moderate social drinkers: a within-subjects study. Psychopharmacology 115: 529–538

11.

Dellemijn P L I , Fields H L (1994) Do benzodiazepines have a role in chronic pain management? Pain 57: 137–152

12.

Duka T , Curran H V , Rusted J M , Weingartner H J (1996) Perspectives on cognitive psychopharmacology research. Behav Pharmacol 7: 401–410

13.

Evans S M , Griffiths R R , de Wit H (1996) Preference for diazepam, but not buspirone, in moderate drinkers. Psychopharmacology 123: 154–163

14.

Gorny S , Allen R P , Krausman D T , Cammarata J , Earley C J (1997) A parametric and sleep hysteresis approach to assessing sleep and wake from a wrist activity meter with enhanced frequency range. Sleep Res 26: 662-662

15.

Grad R M (1995) Benzodiazepines for insomnia in communitydwelling elderly: a review of benefit and risk. J Fam Pract 41: 473–481

16.

Griffiths R R , Weerts E (1997) Benzodiazepine self-administration in humans and laboratory animals – implications for problems of long-term use and abuse. Psychopharmacology 134: 1–37

17.

Heinz R D , Turkhan J S , Spear D J , Sannerud C A , Kaminski B J , Allen R P (1992) General activity in baboons measured with a computerized, lightweight piezoelectric motion sensor: effects of drugs. Pharmacol Biochem Behav 42: 497–507

18.

Herings R M C , Stricker B H Ch , de Boer A , Bakker A , Sturmans F (1995) Benzodiazepines and the risk of falling leading to femur fractures. Dosage more important than elimination half-life. Arch Int Med 155: 1801–1807

19.

Hollister L E , Müller-Oerlinghausen B , Rickels K , Shader R I (1993) Clinical uses of benzodiazepines. J Clin Psychopharmacol 13: 1S–169S

20.

Johanson C E , Uhlenhuth E H (1980) Drug preference and mood in humans: diazepam. Psychopharmacology 71: 269–273

21.

Kales A , Manfredi R L , Vgontzas A N , Bixler E O , Vela-Bueno A , Fee E C (1991) Rebound insomnia after only brief and intermittent use of rapidly eliminated benzodiazepines. Clin Pharmacol Therapeut 49: 468–476

22.

King S A , Strain J J (1990) Benzodiazepines and chronic pain. Pain 41: 3–4

23.

Krska J , MacLeod T N N (1995) Sleep quality and the use of benzodiazepine hypnotics in general practice. J Clin Pharmacol Therapeut 20: 91–96

24.

Lader M (1998) Withdrawal reactions after stopping hypnotics in patients with insomnia. CNS Drugs 10: 427–439

25.

Maxwell C J , Neutel C I , Hirdes F , Hirdes J P (1997) A prospective study of falls after benzodiazepine use: a comparison of new and repeated use. Pharmacoepidemiol Drug Safety 6: 27–35

26.

Monane M , Glynn R J , Avorn J (1996) Pharmacoepidemiology and drug utilization. The impact of sedative-hypnotic use on sleep symptoms in elderly nursing home residents. Clin Pharmacol Therapeut 59: 83–92

27.

National Institutes of Health (1984) Drugs and insomnia. Consensus Development Conference Summary, Bethesda, MD, 4: 1–19

28.

Neutel C I , Hirdes J P , Maxwell C J , Patten S B (1996) New evidence on benzodiazepine use and falls: the time factor. Age Ageing 25: 273–278

29.

Ray W A , Fought R L , Decker M D (1992) Psychoactive drugs and the risk of injurious motor vehicle crashes in elderly drivers. Am J Epidemiol 136: 873–883

30.

Redmond D G , Hegge F W (1985) Observations on the design and specification of a wrist-worn human activity monitoring system. Behav Res Meth Instr Comput 17: 659–669

31.

Roache J D , Griffiths R R (1989) Diazepam and triazolam self-administration in sedative abusers: concordance of subject ratings, performance and drug self-administration. Psychopharmacology 99: 309–315

32.

Roache J D , Stanley M A , Creson D R , Meisch R A , Shah N N (1996) Diazepam reinforcement in anxious patients. Exp Clin Psychopharmacol 4: 308–314

33.

Roache J D , Stanley M A , Creson D R , Shah N N , Meisch R A (1997) Alprazolam-reinforced medication use in outpatients with anxiety. Drug Alcohol Depend 45: 143–155

34.

Roehrs T , Merlotti L , Zorick F , Roth T (1992) Rebound insomnia and hypnotic self administration. Psychopharmacology 107: 480–484

35.

Roehrs T , Zorick F J , Sicklesteel J M , Wittig R M , Hartse K M , Roth T (1983) Effects of hypnotics on memory. J Clin Psychopharmacol 3: 310–313

36.

Roehrs T , Pedrosi B , Rosenthal L , Zorick F , Roth T (1997) Hypnotic self administration: forced choice versus single choice. Psychopharmacology 133: 121–126

37.

Roth T (1999) New trends in insomnia management. J Psychopharmacol 13 (Suppl. 1): S37–S40

38.

Salzman C , Watsky E (1993) Rational prescribing of benzodiazepines. In Hallström C (ed.), Benzodiazepine Dependence, pp. 13–33. Oxford University Press, Oxford

39.

Thomas R E (1998) Benzodiazepine use and motor vehicle accidents: Systematic review of reported association. Can Family Physic 44: 799–808

40.

Uhlenhuth E H , de Wit H , Balter M B , Johanson C E , Mellinger G D (1988) Risks and benefits of long-term benzodiazepine use. J Clin Psychopharmacol 8: 161–167

41.

Woods J H , Katz J L , Winger G (1992) Benzodiazepines: use, abuse, and consequences. Pharmacol Rev 44: 151–347