Jump to content

Triazolam

From Wikipedia, the free encyclopedia

This is an old revision of this page, as edited by Mauvila (talk | contribs) at 02:14, 6 August 2010 (→History: FDA approval). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

Triazolam
Clinical data
Pregnancy
category
Routes of
administration		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability44% (oral) 53% (sublingual)
MetabolismHepatic
Elimination half-life1.5-5.5 hours
ExcretionRenal
Identifiers
  • 8-chloro-6-(2-chlorophenyl)-1-methyl-4H-
    [1,2,4]triazolo[4,3-    a][1,4]benzodiazepine
CAS Number
PubChem CID
DrugBank
ChemSpider
CompTox Dashboard (EPA)
ECHA InfoCard100.044.811 Edit this at Wikidata
Chemical and physical data
FormulaC17H12Cl2N4
Molar mass343.2 g·mol−1
  (verify)

Triazolam (marketed in English speaking countries under the brand names Apo-Triazo, Halcion, Hypam, and Trilam) is a benzodiazepine derivative drug.[2] It possesses pharmacological properties similar to that of other benzodiazepines, but it is generally only used as a sedative to treat insomnia.[3] In addition to the hypnotic properties triazolam possesses, amnesic, anxiolytic, sedative, anticonvulsant and muscle relaxant properties are also present.[4] Due to its short half-life, triazolam is not effective for patients that suffer from frequent awakenings or early wakening.[5]

History

The pharmaceutical company Upjohn received FDA approval for Triazolam in 1982.

Triazolam was withdrawn from the market in several countries because of concerns about serious side-effects (mostly psychological) associated with the drug. Its use at low doses has been deemed acceptable by the American Food and Drug Administration (FDA) and several other countries.[3] In Canada, manufacturers of triazolam have voluntarily made the medication only available in seven-day "blister packs", attached to patient information sheets. It is believed that blister packing reduces the probability of inadvertently taking extra doses when the drug's amnesiac properties take effect.

Studies have found a much higher incidence of psychiatric disturbances (sometimes severe) with triazolam, even when using the lower doses of 0.125 mg. Clinical trials which UpJohn had withheld from publishing showed a very unfavourable risk benefit ratio with 9.9% of patients dropping out of one triazolam study versus 1.9% of trial subjects taking a comparison benzodiazepine, flurazepam. Another study not published by UpJohn found 12.2% of triazolam patients dropped out, again due to psychiatric adverse effects compared against 4.1% for flurazepam. A further study found that after only 3 weeks use of triazolam patients typically became markedly anxious. As a result of these studies, both published and unpublished, coming to light showing frequent severe psychiatric disturbances the United Kingdom and Brazil decided to ban triazolam.[6][7]

The medical literature has shown that triazolam is much more likely than other benzodiazepines to cause strange behavior and in some instances psychotic or violent reactions. The increased incidence of side-effects with triazolam is due to the pharmacological characteristics of triazolam, including its ultra-short elimination half-life, high affinity receptor-binding (high potency). The short half-life and very high potency of triazolam are the reasons why daytime rebound anxiety, amnesia, confusion, and psychiatric symptoms are much more common and severe than with other benzodiazepines. The risk/benefit ratio of triazolam even at low dosage is so poor in the words of one psychiatrist in the USA who has published numerous papers on hypnotic medications that he questioned if triazolam should remain on the market in the USA.[8][9] While triazolam as the instigator of violence has been accepted in some trials (particularly criminal offenses of defendants without violent tendencies).[10]

Indications

Triazolam is usually used for short-term treatment of acute insomnia including jet lag. It is an ideal benzodiazepine for this use, because its fast onset of action and short half-life (approximately 2 – 4 hours) allows its user to avoid morning drowsiness. Triazolam is also sometimes used as an adjuvant in medical procedures requiring anesthesia[3] or to reduce anxiety during brief events like MRI scans. Triazolam is ineffective in maintaining sleep however, due to its short half life with quazepam showing superiority.[11]

Triazolam is frequently prescribed as a sleep aid for passengers travelling on short to medium duration flights. If this use is contemplated, it is especially important to avoid the consumption of alcoholic beverages, and to do a ground based 'trial' of the medication to ensure that the side effects and potency of this medication are understood by the user prior to using it in a relatively more public environment (as disinhibition can be a common side effect, with potentially severe consequences).

Dosage

Dosages for triazolam are significantly lower than other benzodiazepines, and should be individualized depending on the needs of the patient. For insomnia, 0.125 mg to 0.25 mg are given at bedtime. Up to 0.5 mg may be needed for resistant individuals. Dosages exceeding 0.5 mg are generally considered to be unsafe.[citation needed] [Abraham, John, "Transnational....: Adverse Drug Reactions and the Crisis Over the Safety of Halcion [triazolam] in the Netherlands and the UK. Social Science and Medicine: 55 (2002)1671-1690. http://www.sussex.ac.uk/sociology/documents/ssm02.pdf]

Side-effects

Severe side-effects both while using triazolam and after its discontinuation are more common with triazolam than with other hypnotic drugs.[12] Triazolam causes a rapid development of tolerance and withdrawal symptoms including rebound insomnia and rebound anxiety. Other adverse effects include amnesia, confusion, and disinhibition, and occur much more commonly with triazolam than with other benzodiazepines such as quazepam.[13] Triazolam, although a short-acting benzodiazepine, may still cause residual impairment into the next day, especially the next morning. A meta-analysis demonstrated that residual 'hangover' effects after nighttime administration of triazolam such as sleepiness, impaired psychomotor, and cognitive functions may persist into the next day, which may impair the ability of users to drive safely and increase risks of falls and hip fractures.[14] Confusion and amnesia has been reported.[15]

Tolerance, dependence and withdrawal

Main article: Benzodiazepine withdrawal syndrome

A review of the literature found that long term use of benzodiazepines including triazolam is associated with drug tolerance, drug dependence, rebound insomnia and CNS related adverse effects. It recommended that benzodiazepine hypnotics are used at their lowest possible dose and for a short period of time. Non-pharmacological treatment options however, were found to have sustained improvements in sleep quality.[16] The risk of withdrawal reactions and drug dependence is much higher with triazolam than with other benzodiazepines.[17] Triazolam has a very high risk of dependency with chronic users often taking exceedingly high daily doses.[18] Regular use of triazolam may cause a hypnotic drug dependence. Withdrawal symptoms typically appear when triazolam dosage is reduced or stopped altogether. Withdrawal symptoms including a worsening of insomnia (rebound insomnia) compared to baseline typically occurs after discontinuation of triazolam even after short term single nightly dose therapy.[19][20]

Daytime withdrawal symptoms are commonly associated with triazolam. This is due to its very short half-life. After only 10 nights of triazolam use, patients report anxiety, become distressed, display weight loss, experience panics, and experience depression, feel unreal, and develop paranoia. These reactions occurred more commonly with triazolam than lormetazepam, which has an intermediate half-life. Thus the more short-acting a benzodiazepine hypnotic the more severe the daytime withdrawal symptoms.[21] This phenomena of day time withdrawal anxiety from nightly hypnotic use does not seem to be exclusive to triazolam but occurs with other hypnotic drug although reactions are not as severe as those seen with triazolam.[22]

Abrupt withdrawal after long-term use from therapeutic doses of triazolam may result in a severe benzodiazepine withdrawal syndrome. A psychotic state was reported in a patient, developing after abrupt withdrawal from triazolam and nitrazepam. The withdrawal symptoms included auditory hallucinations and visual cognitive disorder. Gradual and careful reduction of the dosage was recommended to prevent severe withdrawal syndromes from developing.[23]

Contraindications and special cautions

Benzodiazepines require special precaution if used in the elderly, during pregnancy, in children, alcohol or drug-dependent individuals and individuals with comorbid psychiatric disorders.[24] Triazolam belongs to the Pregnancy Category X of the FDA[25]. This means that it is known to have the potential to cause birth defects.

Elderly

Triazolam, similar to other benzodiazepines and nonbenzodiazepines causes impairments in body balance and standing steadiness in individuals who wake up at night or the next morning. Falls and hip fractures are frequently reported. The combination with alcohol increases these impairments. Partial, but incomplete tolerance develops to these impairments.[26]

An extensive review of the medical literature regarding the management of insomnia and the elderly found that there is considerable evidence of the effectiveness and durability of non-drug treatments for insomnia in adults of all ages and that these interventions are underutilized. Compared with the benzodiazepines including triazolam, the nonbenzodiazepine sedative-hypnotics appeared to offer few, if any, significant clinical advantages in efficacy or tolerability in elderly persons. It was found that newer agents with novel mechanisms of action and improved safety profiles, such as the melatonin agonists, hold promise for the management of chronic insomnia in elderly people. Long-term use of sedative-hypnotics for insomnia lacks an evidence base and has traditionally been discouraged for reasons that include concerns about such potential adverse drug effects as cognitive impairment (anterograde amnesia), daytime sedation, motor incoordination, and increased risk of motor vehicle accidents and falls. In addition, the effectiveness and safety of long-term use of these agents remain to be determined. It was concluded that more research is needed to evaluate the long-term effects of treatment and the most appropriate management strategy for elderly persons with chronic insomnia.[27]

Pharmacology

The pharmacological effects of triazolam are similar to those of most other benzodiazepines. Triazolam does not generate active metabolites.[3] Triazolam is a short acting benzodiazepine, is lipophilic, and is metabolised hepatically via oxidative pathways. The main pharmacological effects of triazolam are the enhancement of the neurotransmitter GABA at the GABAA receptor.[28] The half life of triazolam is only 2 hours making it a very short acting benzodiazepine drug.[29] Triazolam has anticonvulsant effects on brain function.[30]

In EEG studies in rats triazolam significantly increased the energy of the beta frequency band and significantly increased the relative EEG power density in the delta frequency band and decreased the energy of the theta frequency band. Triazolam caused EEG changes characterised by high-voltage slow waves and desynchronization of hippocampal theta waves and an increase in the energy of the delta frequency band on the spectral analysis of the electroencephalogram in rats. Benzodiazepines induce a light sleep, and, as a result, suppress deep-sleep stages, making benzodiazepines, in general, poor treatments for insomnia. This is especially true in elderly patients that already have naturally less deep sleep.[31] Triazolam produced a decrease in delta activity in rats. The effect of benzodiazepine drugs on delta activity may not be mediated via benzodiazepine receptors. Delta activity is an indicator of depth of sleep within non-REM sleep. Delta activity is thought to reflect sleep quality with lower levels of delta sleep reflecting poorer quality of sleep. Cyproheptadine may be superior to benzodiazepines in the treatment of insomnia as it enhances sleep quality in rats, based on EEG studies in rats.[32]

Interactions

Ketoconazole and itraconazole have a profound effect on the pharmacokinetics of triazolam, leading to greatly enhanced effects.[33] Anxiety, tremor and depression have been documented in a case report following administration of nitrazepam and triazolam. Following administration of erythromycin repetitive hallucinations and abnormal bodily sensations developed. The patient had, however, acute pneumonia and renal failure. Co-administration of benzodiazepine drugs at therapeutic doses with erythromycin may cause serious psychotic symptoms, especially in those with other physical complications.[34] Caffeine reduces the effectiveness of triazolam.[35] Other important interactions include cimetidine, diltiazem, erythromycin, fluconazole, grapefruit juice, isoniazid, itraconazole, ketoconazole, nefazodone, rifampicin, ritonavir, troleandomycin.[36][37]

Overdose

See also: Benzodiazepine overdose

Symptoms of an overdose[3] include

Death can occur from triazolam overdose but is more likely to occur in combination with other depressant drugs such as opiates, alcohol, or tricyclic antidepressants.[39]

Drug misuse

See also: Benzodiazepine drug misuse

Triazolam is a drug with the potential for misuse: recreational, wherein the drug is taken to achieve a high "euphoria", or continued long-term dosing against medical advice.[40] A study in baboons showed that triazolam was the most preferred benzodiazepine in drug liking self injection tests.[41] Serial killer Jeffrey Dahmer used triazolam (Halcion) to sedate his victims, and in his biography Mötley Crüe member Nikki Sixx referenced using Halcion in combination with cocaine and heroin.[42]

Triazolam is a Schedule IV drug under the Convention on Psychotropic Substances.[43]

See also

Notes

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  2. ^ "Benzodiazepine Names". non-benzodiazepines.org.uk. Retrieved 2008-12-29.
  3. ^ a b c d e Wishart, David (2006). "Triazolam". DrugBank. Retrieved 2006-03-23.
  4. ^ Mandrioli R, Mercolini L, Raggi MA (2008). "Benzodiazepine metabolism: an analytical perspective". Curr. Drug Metab. 9 (8): 827–44. doi:10.2174/138920008786049258. PMID 18855614. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  5. ^ Rickels K. (1986). "The clinical use of hypnotics: indications for use and the need for a variety of hypnotics". Acta Psychiatrica Scandinavica Suppl. 332: 132–41. doi:10.1111/j.1600-0447.1986.tb08990.x. PMID 2883820.
  6. ^ Adam K, Oswald I (1993). "Triazolam. Unpublished manufacturers research unfavourable" (PDF). BMJ. 306 (6890): 1475–6. doi:10.1136/bmj.306.6890.1475-b. PMC 1677863. PMID 8292128. {{cite journal}}: Unknown parameter |month= ignored (help)
  7. ^ Bramness JG, Olsen H (1998). "[Adverse effects of zopiclone]". Tidsskr. Nor. Laegeforen. (in Norwegian). 118 (13): 2029–32. PMID 9656789. {{cite journal}}: Unknown parameter |month= ignored (help)
  8. ^ Kales A (1990). "Benzodiazepine hypnotics and insomnia". Hosp. Pract. (Off. Ed.). 25 Suppl 3: 7–21, discussion 22–3. PMID 1976124. {{cite journal}}: Unknown parameter |month= ignored (help)
  9. ^ Manfredi RL, Kales A (1987). "Clinical neuropharmacology of sleep disorders". Semin Neurol. 7 (3): 286–95. doi:10.1055/s-2008-1041429. PMID 3332464. {{cite journal}}: Unknown parameter |month= ignored (help)
  10. ^ Abraham, John, "Transnational....: Adverse Drug Reactions and the Crisis Over the Safety of Halcion [triazolam] in the Netherlands and the UK. Social Science and Medicine: 55 (2002)1671–1690. http://www.sussex.ac.uk/sociology/documents/ssm02.pdf
  11. ^ Mauri MC, Gianetti S, Pugnetti L, Altamura AC (1993). "Quazepam versus triazolam in patients with sleep disorders: a double-blind study". Int J Clin Pharmacol Res. 13 (3): 173–7. PMID 7901174.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  12. ^ Kales A (1990). "Quazepam: hypnotic efficacy and side effects". Pharmacotherapy. 10 (1): 1–10, discussion 10–2. PMID 1969151.
  13. ^ Kales A, Bixler EO, Vela-Bueno A, Soldatos CR, Niklaus DE, Manfredi RL (1986). "Comparison of short and long half-life benzodiazepine hypnotics: triazolam and quazepam". Clin. Pharmacol. Ther. 40 (4): 378–86. PMID 3530586. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  14. ^ Vermeeren A. (2004). "Residual effects of hypnotics: epidemiology and clinical implications". CNS Drugs. 18 (5): 297–328. doi:10.2165/00023210-200418050-00003. PMID 15089115. {{cite journal}}: Cite has empty unknown parameter: |coauthors= (help)
  15. ^ Lieberherr, S; Scollo-Lavizzari, G; Battegay, R (1991). "Confusional states following administration of short-acting benzodiazepines (midazolam/triazolam)". Schweizerische Rundschau fur Medizin Praxis = Revue suisse de medecine Praxis. 80 (24): 673–5. PMID 2068441.
  16. ^ Kirkwood CK (1999). "Management of insomnia". J Am Pharm Assoc (Wash). 39 (5): 688–96, quiz 713–4. PMID 10533351.
  17. ^ Altamura AC, Colacurcio F, Mauri MC; et al. (1989). "[Controlled clinical study on the effect of quazepam versus triazolam in patients with sleep disorders]". Minerva Psichiatr (in Italian). 30 (3): 159–64. PMID 2691808. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  18. ^ Veje JO (1989-08-21). "Prescription of tranquilizers and hypnotics in the municipality of Holbaek". Ugeskr Laeger. 151 (34): 2134–6. PMID 2773144. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  19. ^ Kales A (1979-04-20). "Rebound insomnia. A potential hazard following withdrawal of certain benzodiazepines". JAMA : the Journal of the American Medical Association. 241 (16): 1692–5. doi:10.1001/jama.241.16.1692. PMID 430730. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  20. ^ Mamelak M, Csima A, Price V (1984). "A comparative 25-night sleep laboratory study on the effects of quazepam and triazolam on chronic insomniacs". J Clin Pharmacol. 24 (2–3): 65–75. PMID 6143767.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  21. ^ Adam K (1989). "Can a rapidly-eliminated hypnotic cause daytime anxiety?". Pharmacopsychiatry. 22 (3): 115–9. doi:10.1055/s-2007-1014592. PMID 2748714. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  22. ^ Fontaine, R; Beaudry, P; Le, Morvan, P; Beauclair, L; Chouinard, G (1990). "Zopiclone and triazolam in insomnia associated with generalized anxiety disorder: a placebo-controlled evaluation of efficacy and daytime anxiety". International clinical psychopharmacology. 5 (3): 173–83. doi:10.1097/00004850-199007000-00002. ISSN 0268-1315. PMID 2230061. {{cite journal}}: |format= requires |url= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  23. ^ Terao T (1988-09-01). "Two cases of psychotic state following normal-dose benzodiazepine withdrawal". J Uoeh. 10 (3): 337–40. PMID 2902678. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  24. ^ Authier, N.; Balayssac, D.; Sautereau, M.; Zangarelli, A.; Courty, P.; Somogyi, AA.; Vennat, B.; Llorca, PM.; Eschalier, A. (2009). "Benzodiazepine dependence: focus on withdrawal syndrome". Ann Pharm Fr. 67 (6): 408–13. doi:10.1016/j.pharma.2009.07.001. PMID 19900604. {{cite journal}}: Unknown parameter |month= ignored (help)
  25. ^ http://www.fda.gov/medwatch/SAFETY/2003/03Jun_PI/Halcion_PI.pdf
  26. ^ Mets, MA.; Volkerts, ER.; Olivier, B.; Verster, JC. (2010). "Effect of hypnotic drugs on body balance and standing steadiness". Sleep Med Rev. 14 (4): 259–67. doi:10.1016/j.smrv.2009.10.008. PMID 20171127. {{cite journal}}: Unknown parameter |month= ignored (help)
  27. ^ Bain KT (2006). "Management of chronic insomnia in elderly persons". Am J Geriatr Pharmacother. 4 (2): 168–92. doi:10.1016/j.amjopharm.2006.06.006. PMID 16860264. {{cite journal}}: Unknown parameter |month= ignored (help)
  28. ^ Oelschläger H. (1989-07-04). "Chemical and pharmacologic aspects of benzodiazepines". Schweiz Rundsch Med Prax. 78 (27–28): 766–72. PMID 2570451. {{cite journal}}: Cite has empty unknown parameter: |coauthors= (help)
  29. ^ Professor heather Ashton (2007). "BENZODIAZEPINE EQUIVALENCY TABLE". Retrieved September 23, 2007. {{cite web}}: Unknown parameter |month= ignored (help)
  30. ^ Chweh AY (February 25, 1985). "Effect of GABA agonists on the neurotoxicity and anticonvulsant activity of benzodiazepines". Life Sci. 36 (8): 737–44. doi:10.1016/0024-3205(85)90193-6. PMID 2983169. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  31. ^ Noguchi H (2004). "Electroencephalographic properties of zaleplon, a non-benzodiazepine sedative/hypnotic, in rats" (pdf). J Pharmacol Sci. 94 (3): 246–51. doi:10.1254/jphs.94.246. PMID 15037809. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  32. ^ Tokunaga S (2007). "Effects of some H1-antagonists on the sleep-wake cycle in sleep-disturbed rats" (pdf). J Pharmacol Sci. 103 (2): 201–6. doi:10.1254/jphs.FP0061173. PMID 17287588. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  33. ^ Varhe A, Olkkola KT, Neuvonen PJ (1994). "Oral triazolam is potentially hazardous to patients receiving systemic antimycotics ketoconazole or itraconazole". Clin. Pharmacol. Ther. 56 (6 Pt 1): 601–7. PMID 7995001. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  34. ^ Tokinaga N (1996). "Hallucinations after a therapeutic dose of benzodiazepine hypnotics with co-administration of erythromycin". Psychiatry and clinical neurosciences. 50 (6): 337–9. doi:10.1111/j.1440-1819.1996.tb00577.x. PMID 9014234. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
  35. ^ Mattila, Me; Mattila, Mj; Nuotto, E (1992). "Caffeine moderately antagonizes the effects of triazolam and zopiclone on the psychomotor performance of healthy subjects". Pharmacology & toxicology. 70 (4): 286–9. doi:10.1111/j.1600-0773.1992.tb00473.x. ISSN 0901-9928. PMID 1351673. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  36. ^ Wang JS, DeVane CL (2003). "Pharmacokinetics and drug interactions of the sedative hypnotics" (PDF). Psychopharmacol Bull. 37 (1): 10–29. PMID 14561946.
  37. ^ Arayne, MS.; Sultana, N.; Bibi, Z. (2005). "Grape fruit juice-drug interactions". Pak J Pharm Sci. 18 (4): 45–57. PMID 16380358. {{cite journal}}: Unknown parameter |month= ignored (help)
  38. ^ Hung DZ, Tsai WJ, Deng JF (1992). "Anterograde amnesia in triazolam overdose despite flumazenil treatment: a case report". Hum Exp Toxicol. 11 (4): 289–90. doi:10.1177/096032719201100410. PMID 1354979. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  39. ^ Kudo K, Imamura T, Jitsufuchi N, Zhang XX, Tokunaga H, Nagata T (1997). "Death attributed to the toxic interaction of triazolam, amitriptyline and other psychotropic drugs". Forensic Sci. Int. 86 (1–2): 35–41. doi:10.1016/S0379-0738(97)02110-5. PMID 9153780. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  40. ^ Griffiths RR, Johnson MW (2005). "Relative abuse liability of hypnotic drugs: a conceptual framework and algorithm for differentiating among compounds". J Clin Psychiatry. 66 Suppl 9: 31–41. PMID 16336040.
  41. ^ Griffiths RR, Lamb RJ, Sannerud CA, Ator NA, Brady JV (1991). "Self-injection of barbiturates, benzodiazepines and other sedative-anxiolytics in baboons". Psychopharmacology (Berl.). 103 (2): 154–61. doi:10.1007/BF02244196. PMID 1674158.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  42. ^ Tom Mathews (3 February 1992). "Secrets of a Serial Killer - Jeffrey Dahmer Is A Case Study Of A Criminal Soul In Torment, Languid One Moment, Frantic The Next -- And Always Deadly". NEWSWEEK. Retrieved 5 February 2009.


Retrieved from "https://en.wikipedia.org/enwiki/w/index.php?title=Triazolam&oldid=377410104"