Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via HighWire Citing Articles via Google Scholar Articles by Hill, K. P. Articles by Dunn, E. R. Search for Related Content PubMed Citation Articles by Hill, K. P. Articles by Dunn, E. R. Delirium

Zolpidem-Induced Delirium With Mania in an Elderly Woman

TO THE EDITOR: Zolpidem has become a popular alternative to benzodiazepines for sleep, comparing favorably with respect to efficacy and side effect profile, particularly in the elderly population.¹ CNS side effects reported with zolpidem include headache (19%), depression (2%), memory deficits (1.8%), and abnormal dreams (1%).² Several cases of delirium related to zolpidem use have been reported.^3–7

We report the case of an elderly woman who experienced an episode of delirium with symptoms of mania after repeated use of zolpidem over 6 weeks.

Case Report
Ms. A was a 67-year-old former teacher with no significant psychiatric history who was brought to an emergency room after 2 weeks of progressively worsening confusion, agitation, rapid speech, poor sleep, limited appetite, and increasingly disorganized and paranoid thoughts. She shifted through several topics in rapid succession, claiming that the "FBI was watching" her, that interviewers were posing "tricky questions," and that she wanted us to phone "the president," who would clarify the situation.

Ms. A's daughter noted that she had become more confused over the past 2 weeks. Her mother "talked and talked and talked" in a hurried manner but generally about appropriate topics. In the past 4 days, however, her comments gradually shifted to more bizarre and paranoid topics, such as how the FBI was following her. Additionally, Ms. A had complained of an inability to concentrate and of insomnia during this time.

There was no history of recent falls, a sudden change in consciousness, or seizures. Ms. A did endorse a recent onset of urinary incontinence. She had no significant past psychiatric history. Her medical history was notable for hypertension and knee replacement surgery 7 weeks previously, prompting a 10-day rehabilitation stay. Her sole medication was zolpidem, 10 mg at bedtime, which had been started 6 weeks earlier. Ms. A was a divorced, retired teacher with two children who lived alone. Her family psychiatric history was notable only for a history of "mild depression" in both children.

Results of laboratory studies revealed a normal CBC and metabolic panel. Liver function studies were notable for ALT 91, AST 51, and alkaline phosphatase 545. The results of serum and urine toxicology screens were negative, as was a urinalysis. The result of a neurological examination was noted to be nonfocal. A computerized tomography scan of the patient's head was unremarkable.

Ms. A was an alert, neatly groomed woman who appeared to be her stated age. She was restless and was constantly shifting her position while gesticulating to emphasize points in her conversation. Her speech was pressured, rambling, and of high volume. She remained quite suspicious throughout the interview, making such comments as, "I know my rights. Call the president. Trick question." She reported her mood as, "I'm crazy." Her affect was labile, agitated, and frightened. Her thought process was tangential, with a flight of ideas. She reported no hallucinations but did report thought broadcasting; she reported no suicidal or homicidal ideation. Her thought content was notable for delusional ideation regarding the FBI having "tapped" the room and about people following and trying to harm her. She also reported having violent thoughts during the interview: "You can kill me and then you can kill my daughter, too."

Ms. A's cognitive examination was limited by her mental status. She was alert and able to state her name and the name of the hospital. She was unable to state the day of the week, the month, or the date and stated that the month was "2002 or 2003." Her attention was poor, and she could not register three objects. Her comprehension appeared intact, and there were no word-finding deficits or paraphasias.

Discussion
The pharmacokinetics of zolpidem may play a significant role in adverse drug reactions. It has been shown that women have zolpidem serum concentrations 45% higher than men at the same dose. In elderly women, this difference is exacerbated; this group has a 63% higher serum concentration than men in the same age group.⁸ Several studies have suggested that higher doses of zolpidem predispose patients to adverse reactions, particularly delirium and psychosis.^7,9,10 A dose of 5 mg is recommended for patients older than 65 years. Thus, our patient's age and gender may have resulted in a higher concentration of zolpidem at a seemingly appropriate dose. Finally, zolpidem is hepatically metabolized, with 79%–96% excreted as metabolites in urine, bile, and feces, and plasma protein binding of zolpidem is markedly decreased in the presence of hepatic impairment.¹¹ The result may have been an increased risk of an adverse reaction.

REFERENCES

1. Roger M, Attali P, Coquelin JP: Multicenter, double-blind, controlled comparison of zolpidem and triazolam in elderly patients with insomnia. Clin Ther 1993; 15:127–136[Medline]
2. Prescribing information for Ambien (zolpidem tablets). Skokie, Ill, GD Searle, 1997
3. Katz SE: Possible paroxetine-zolpidem interaction (letter). Am J Psychiatry 1995; 152:1689
4. Toner LC, Tsambiras BM, Catalano G, Catalano MC, Cooper DS: Central nervous system side effects associated with zolpidem treatment. Clin Neuropharmacol 1999; 23:54–58[CrossRef]
5. Hoyler CL, Tekell JL, Silva JA: Zolpidem-induced agitation and disorganization. Gen Hosp Psychiatry 1996; 18:452–453[Medline]
6. Freudenrich O, Menza M: Zolpidem-related delirium: a case report. J Clin Psychiatry 2000; 61:449–450
7. Brodeur MR, Stirling AL: Delirium associated with zolpidem. Ann Pharmacother 2001; 35:1562–1564[Abstract]
8. Bianchetti G, Dubruc C, Thiercelin JF, Bercoff E, Bouchet JL, Emeriau JP, Galperine I, Lambert D, Vandel B, Thebalt JJ: Clinical pharmacokinetics of zolpidem in various physiological and pathological conditions, in Imidazopyridines in Sleep Disorders. Edited by Sauvanet JP, Langer SZ, Morselli PL. New York, Raven Press, 1988, pp 155–163
9. Markowitz JS, Brewerton TD: Zolpidem-induced psychosis. Ann Clin Psychiatry 1996; 8:89–91[Medline]
10. Pitner JK, Gardner M, Neville M, Mintzer J: Zolpidem-induced psychosis in an older woman (letter). J Am Geriatr Soc 1997; 45:533–534[Medline]
11. Pacifici GM, Viani A, Rizzo G, Carrai M, Ganansia J, Bianchetti G, Morselli PL: Plasma protein binding of zolpidem in liver and renal insufficiency. Int J Pharmacol Ther Toxicol 1988; 26:439–443

This article has been cited by other articles:

				Eszopiclone (Lunesta), a New Hypnotic Obstet. Gynecol., August 1, 2005; 106(2): 398 - 401. [Full Text] [PDF]

Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via HighWire Citing Articles via Google Scholar Articles by Hill, K. P. Articles by Dunn, E. R. Search for Related Content PubMed Citation Articles by Hill, K. P. Articles by Dunn, E. R. Delirium

Get information about faster international access.

Privacy Policy

Copyright © 2004 Academy of Psychosomatic Medicine. All rights reserved.

Home | Search | Current Issue | Past Issues | Subscribe | All APPI Journals | Help | Contact Us