Delirium in the Elderly: Medications, Causes, and Treatment

Release Date: June 1, 2008

Expiration Date: June 30, 2010

FACULTY:

Kari A. Mergenhagen, PharmD
PGY1 Geriatric Pharmacy Practice Resident
James J. Peters VA Medical Center
Bronx, New York
Clinical Pharmacist Infectious
Disease/Antibiotic Surveillance (July 2008)
Buffalo VA Medical Center
Buffalo, New York

Sally Arif, PharmD
Assistant Professor of Pharmacy Practice
Arnold and Marie Schwartz College of
Pharmacy and Health Sciences
Internal Medicine Pharmacy Specialist
James J. Peters VA Medical Center
Bronx, New York

FACULTY DISCLOSURE STATEMENTS:

Drs. Mergenhagen and Arif have no actual or potential conflicts of interest in relation to this program.

U.S. Pharmacist does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced, objective, and scientifically rigorous. Occasionally, authors may express opinions that represent their own viewpoint. Conclusions drawn by participants should be derived from objective analysis of scientific data.

ACCREDITATION STATEMENT:

Pharmacy
acpePostgraduate Healthcare Education, LLC is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.
Program No.: 430-000-08-010-H01-P; 430-000-08-010-H01-T
Credits: 2.0 hours (0.20 ceu)

Exam processing inquiries:
CE Customer Service (800) 825-4696

Direct educational content inquiries to:
CE Director (800) 331-9396

DISCLAIMER:

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients’ conditions and possible contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.

GOAL:

To provide participants with an enhanced understanding of the medication-related etiology, pathophysiology, diagnosis, and therapeutic management of delirium in elderly patients.

OBJECTIVES:

At the completion of this article, the participant should be able to:

  1. Recognize the etiology and pathophysiology of delirium as it relates to medication use.*
  2. Identify when medication is necessary for the proper management of delirium in the elderly.*
  3. Discuss the various therapeutic options for the management of delirium in the elderly.*
  4. Describe the potential contributions of pharmacists in the care of elderly patients with delirium.*

* Also applies to pharmacy technicians.


Delirium is an acute confusional state characterized by fluctuations in severity, mood, and attention. There are three types of delirium. Hyperactive delirium is typically characterized by agitation, hypoactive delirium is often diagnosed based on lethargy, and mixed delirium is somewhere in between.1 The patient may have an altered sleep-wake cycle and fleeting symptoms of fear, paranoia, apprehension, irritability, and anger.1 Patients with delirium will often have difficulty focusing and shifting attention; conversation may be characterized by disorganized speech or an irrational flow of ideas.1,2

The criteria for identifying delirium are based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) (TABLE 1).2-4 The Delirium Rating Scale (DRS) is useful to gauge the severity of delirium, and the Mini-Mental State Exam (MMSE) quantifies cognitive impairment.5

Table 1
Criteria for Identifying Delirium
Deficits in environmental awareness
Inability to attend to tasks
Difficulty changing attention
Problems following directions

Cognitive disturbance

Presentation of agitation, drowsiness, psychosis,
    and detachment
Memory and orientation deficits
Fluctuations in cognition

Evidence of a physiologic cause

Contributory medication (i.e., benzodiazepines)
Medical conditions (i.e., infections, electrolyte
    disturbance)
Drug withdrawal

Acute onset with fluctuations of mental status
Development over short period of time
May develop in hours or days
Acute change in consciousness
div

Source: References 2-4.

Epidemiology and Economic Impact

Delirium occurs in 20% of hospitalized elderly at a cost of an additional $2,500 per patient.1,6,7 If delirium were decreased by one day per elderly patient admitted, Medicare spending could be reduced by $1 to $2 billion per year.8 In elderly patients with new-onset delirium, 32% to 96% will leave the hospital without complete resolution of symptoms.9

Pathogenesis

The pathogenesis of delirium is complex, and the precise mechanisms may be multifactorial. Dopamine appears to be central to the development of delirium. Other pathways contributing to the onset of delirium include glucocorticoid excess and the serotoninergic system. The proposed changes in neurotransmitters seen in delirium are shown in FIGURE 1.1,7-11

fig1

Etiology

Common causes of delirium are infections, electrolyte disturbances, and medications. Additional sources include substance intoxication/withdrawal, metabolic changes, brain lesions, postoperative sequelae, sensory/sleep deprivation, fecal impaction, and environmental changes.1,5 In a hospital setting, patients are subject to unfamiliar sounds, medical tests, and schedule disruptions that contribute to disorientation and delirium.

Causative Agents: Approximately 40% of delirium cases are caused by medications.8 Medications that contribute to delirium are stratified in TABLE 2.12

Table 2
Medications Associated with Delirium
High-Risk Medications Low-Risk Medications
Analgesics
NSAIDs, opioids
Cardiovascular agents
Antiarrhythmics, beta-blockers, clonidine, digoxin
div
Anticholinergics
Atropine, benztropine,
diphenhydramine,
scopolamine
Antimicrobials
Acyclovir, aminoglycosides, amphotericin B,
cephalosporins, fluoroquinolones, linezolid,
macrolides, penicillin, sulfonamides
div
Antidepressants
Mirtazapine, SSRIs, TCAs
Anticonvulsants
Carbamazepine, phenytoin, valproate
div
Sedative-hypnotics
Benzodiazepines, propofol
Gastrointestinal agents
Antiemetics, H2 -receptor antagonists
div
Corticosteroids
Hydrocortisone, prednisone,
methylprednisone, dexamethasone
Skeletal muscle relaxants
Baclofen
div
Dopamine agonists
Amantadine, bromocriptine, levodopa,
pergolide, pramipexole, ropinirole
 
div

NSAIDs: nonsteroidal anti-inflammatory drugs; SSRIs: selective serotonin reuptake inhibitors; TCAs: tricyclic antidepressants; H2: histamine-2. Source: Reference 12.

A large prospective study evaluated 47 medications including diphenhydramine, prochlorperazine, cimetidine, and ranitidine.6 Findings indicated that exposure to anti-cholinergic agents was independently associated with an increase in delirium symptom severity in elderly inpatients.

Dopaminergic agents contribute to delirium by influencing the release of acetylcholine. This mechanism is the proposed basis for levodopa and bupropion-induced delirium.1 Conversely, antipsychotic agents acting as dopamine antagonists are effective in treating the symptoms of delirium.13

Benzodiazepines have a high affinity for gamma-aminobutyric acid (GABA) receptors, which may contribute to delirium. In an ICU study, lorazepam was an independent risk factor for the daily transition to delirium (odds ratio 1.33, P = .003).7

Opioids can lead to cognitive impairment and delirium. A metabolite of morphine, morphine-3-glucuronide, has been associated with delirium; however, other opioids, such as fentanyl or hydrocodone, may have a decreased incidence of delirium.8,14,15 Meperidine has a long half-life, and the primary metabolite, normeperidine, has anticholinergic properties that can accumulate, causing seizures and delirium.8

Management of Delirium

Nonpharmacologic: Tranquil surroundings, objects from home, and low arousal scents such as lavender provide a calming influence for patients.16,17 Serene music may muffle disorienting, loud hospital noises. Support from relatives provides orienting influences, and family members are often the first to recognize a change in mental status of their loved one. To reduce the development or effects of delirium in an older patient, a normal sleep-wake cycle should be maintained through the use of longer-acting medications and scheduling tests during the daytime.1

Pharmacologic: The use of medications to prevent delirium has not proven to be efficacious.5,18 A study of 430 elderly hip-surgery patients found no significance in the incidence of postoperative delirium with preventative preoperative haloperidol treatment as compared to placebo.18

Treatment of delirium is indicated for acute agitation, when the safety of the patient or others is in question. Neuroleptics such as quetiapine, olanzapine, and risperidone are often used. The duration of treatment commonly ranges from days to weeks; however, some patients may require antipsychotics for months due to underlying chronic cerebral dysfunction, such as irreversible dementia.19 Low doses should be utilized with frequent reassessments to minimize the duration of therapy.20 Risks associated with long-term atypical antipsychotic treatment include hyperlipidemia, hyperglycemia, cardiac events, and obesity; whereas, tardive dyskinesia is related to long-term use of conventional antipsychotics.19

Considerable controversy surrounds the use of conventional (e.g., haloperidol) versus atypical antipsychotics (e.g., aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone) for treatment in the elderly. A retrospective study determined that mortality rates were at least as high using conventional antipsychotics as using atypical antipsychotics.21 Although the authors of this study advocate against switching patients from atypical to conventional antipsychotics, a prospective controlled trial is warranted.21 A Cochrane review found that for short-term use, such as treatment of delirium, a conventional antipsychotic may be equally efficacious and safer than an atypical agent.22

When deciding upon medication treatment for delirium, the appropriate agent, dose, route, and drug-interaction potential must be taken into account. The available dosage forms, routes of metabolism, and side effects of commonly used antipsychotics are provided in TABLE 3.13,23,24 Antipsychotic medication should be correlated with the needs of the patient to reduce toxicity. For example, a baseline ECG can identify a patient with a predisposition to QT prolongation.20 Another consideration is the patient’s susceptibility to extrapyramidal symptoms (EPS).19 If sedation is desired, a more tranquilizing agent may be preferred.

Table 3
Comparison of Antipsychotics
Medication Formulations Metabolism Sedation EPS Anticholinergic Orthostasis Seizures Prolactin Increase in QT
Prolongation
div
Aripiprazole T, L, ODT CYP3A4, 2D6 ++ + ++ ++ ++ 0 Not statistically different
from placebo
div
Haloperidol T, L, LAI, IM, IV N-dealkylation + ++++ + + ++ +++ 4.7 msec
div
Olanzapine T, ODT, IM CYP1A2, 3A4 +++ + +++ ++ ++ + 6.4 msec
div
Quetiapine T CYP3A4 +++ + ++ ++ ++ 0 14.5 msec
div
Risperidone T, ODT, L, LAI CYP2D6 +++ + ++ ++ ++ 0 to +++ 10 msec
div
Ziprasidone T, IM CYP3A4, 1A2 ++ + ++ ++ ++ 0 20.6 msec
div

EPS: extrapyramidal symptoms; T: tablet; L: liquid; ODT: oral disintegration tablet; LAI: long-acting injection; IM: intramuscular; IV: intravenous; +: low risk; ++: moderate risk; +++: moderately high risk; ++++: high risk. Source: References 13, 23, 24.

Conventional Antipsychotics

Conventional antipsychotics block central dopamine receptors, especially dopamine-2 (D2) receptors. The pathways of the dopamine system, including mesolimbic, mesocortical, nigrostriatal, and tuberoinfundibular, are associated with specific clinical functions responding to conventional and atypical antipsychotics in different ways (FIGURE 2).25

fig2

Haloperidol: Haloperidol works at cerebral synapses and the basal ganglia by blocking dopamine-mediated neurotransmission to facilitate stabilization of cerebral function.12 Haloperidol has demonstrated a positive effect on both the duration and severity of delirium by decreasing hallucinations, delusions, and disorganized thinking.12,26

Haloperidol can be initiated at 0.25 to 1 mg twice daily and every four hours as needed for elderly patients. Its onset of action is 10 to 30 minutes, and it can be administered every 30 minutes until agitation subsides.4,9 The IV route may have the least incidence of EPS, but it should be administered under continuous ECG monitoring because haloperidol can prolong the QT interval. If the QT segment in the ECG lasts longer than normal, a patient may be predisposed to syncope, dizziness, and sudden death. If the QT interval increases by 25% or is greater than 450 msec, haloperidol should be discontinued.4 At this time, haloperidol is not FDA approved for IV use.

A Cochrane review of haloperidol, risperidone, quetiapine, olanzapine, and ziprasidone showed that side effects with low-dose haloperidol were similar to patients treated with atypical antipsychotics. Patients experienced greater EPS when haloperidol exceeded 4.5 mg/day. Overall, haloperidol decreased the severity and duration of delirium in postoperative patients, with effectiveness and safety comparable to olanzapine and risperidone.22

Atypical Antipsychotics

Atypical antipsychotics substantially block cortical serotonergic receptors (5-HT2A).25 High 5-HT2A and D2 receptor affinity may increase therapeutic efficacy and decrease EPS. Serotonin inhibits the release of dopamine, so when 5-HT2A is blocked, the dopaminergic transmission is augmented in the mesocortical and nigrostriatal pathways. Caution is advised when antipsychotics are administered to the elderly.25

Clinical Presentation:
Case Report

An 85-year-old man with a past medical history of short-term memory loss, depression, and generalized anxiety disorder was being treated with diphenhydramine, doxepin, and chlordiazepoxide as an outpatient. He was admitted to the hospital for elective surgery and subsequently developed a urinary tract infection, dehydration, and delirium.

What factors are contributing
to this patient’s delirium?
div
Nonpharmacologic causes consist of an unfamiliar environment, advanced age, dehydration, and a urinary tract infection. Pharmacologic sources include diphenhydramine and doxepin, which are medications with anticholinergic effects, and the benzodiazepine chlordiazepoxide. Other causative influences to consider may be restraint use, inadequate pain control, reduced hearing, or decreased vision.

What would be the most appropriate therapy
for this patient’s delirium?
div
Management of this patient is multifaceted, including proper hydration and treatment of the urinary tract infection. The drugs suspected of contributing to the delirium should be discontinued. If the patient’s agitation increases to a level at which he might harm himself or others, he could be given haloperidol as needed. Encouragement of family member visits and orientation to time and place would be ideal. For anxiety and insomnia, this patient could receive lorazepam as needed at bedtime, while his depression would be better managed with sertraline.

Risperidone: Risperidone works predominantly at D2, 5-HT2A, and alpha1 receptors and has a faster onset of action than haloperidol. It exhibits linear pharmacokinetics, and steady state is reached within 24 hours.27 Risperidone may be started at 0.5 mg by mouth twice a day. Availability in various formulations allows for greater flexibility in selecting the most appropriate delivery method. The liquid formulation provides an onset of action within an hour and may be given for acute delirium; conversely, long-acting risperidone would not be appropriate as the duration of action lasts for two weeks.28

A retrospective study comparing risperidone and haloperidol found that both treatments were effective for treating hyperactive delirium in elderly patients.29 An open-label trial using low-dose risperidone demonstrated improvement in cognitive and behavioral symptoms of delirium in medically ill patients, with no development of movement disorders.30 A prospective, multicenter, observational study of hospitalized patients with delirium found that risperidone (mean dose 2.6 mg/day) significantly improved all symptoms measured from baseline to day 7 in 90.6% of the patients without evidence of EPS.31

Olanzapine: Olanzapine, a thienobenzodiazepine structurally similar to clozapine, blocks serotonin type 2 receptors and dopamine receptors.27 It has an oral bioavailability of 80% with no active metabolites.32 The intramuscular injection has a faster onset of action than the oral formulation and can induce hypotension, bradycardia, and respiratory or central nervous system (CNS) depression. Concomitant use with parenteral benzodiazepines is not recommended.

Equivalent efficacy of olanzapine and haloperidol was found in two small prospective studies of delirious hospitalized patients.12,33 The patients who were treated with olanzapine experienced no side effects, while some haloperidol-treated patients experienced EPS or excessive sedation. The major adverse effects of olanzapine, typically seen with long-term use, include dyslipidemia, diabetes, and weight gain.12

Quetiapine: Quetiapine, a dibenzothiazepine derivative related to olanzapine and clozapine, has high affinity for alpha1-adrenergic receptors and some affinity for 5-HT2A, histamine, and D2 receptors.27 Quetiapine has rapid absorption and a short half-life. The clearance of quetiapine is decreased by 30% to 50% in the elderly when compared to younger adults.34

A small, open-label study was conducted with 12 male patients (mean age 74 years) diagnosed with delirium and treated with quetiapine (mean dose 94 mg/day) with a follow-up of three monthly evaluations.35 The DRS and MMSE scores improved over the three-month treatment duration. The most common side effects experienced by the patients included vivid dreams and sedation.

Twelve patients (mean age 67 years) with delirium were treated with quetiapine in an open-label study.34 Prior to the study, eight of the patients had undergone drug therapy for delirium but did not experience any beneficial effect. The mean duration of treatment until remission of delirium was 4.8 ± 3.5 days. The mean DRS decreased by half. None of the patients experienced excessive sedation or anticholinergic effects such as constipation or dry mouth.

Ziprasidone: Ziprasidone displays a high-affinity blockade of the D2 and D3 receptors, the serotonin-5HT2A, 5HT2c, and 5HTID receptors, and apha1-adrenergic receptors.23 The data on the use of ziprasidone in delirium are limited to case reports.

A 34-year-old, HIV-positive male with cryptococcal meningitis was started on ziprasidone 20 mg by mouth twice daily and received a maximum dose of 100 mg/day for 21 days.36 Although the patient showed improvement in delirium symptoms, the medication was discontinued due to an 8.4% increase in his QT interval and electrolyte abnormalities.

A second case study demonstrated the efficacy of ziprasi-done subsequent to failure of haloperidol.37 The patient was a 47-year-old man admitted to the ICU with postoperative delirium who was treated with high-dose lorazepam and haloperidol, with no effect on his agitation. The patient was subsequently started on IV ziprasidone. He experienced an increase in his QT interval from 470 msec to 476 msec five seconds later. Four hours postadministration, the patient’s QT interval decreased to 436 msec, and his delirium was controlled. Ziprasidone was discontinued one week later.

Aripiprazole: Aripiprazole has partial agonist activity at D2 and 5-HT1A receptors, working as a D2-receptor blocker when too much dopamine exists and as an agonist when there are low amounts of dopamine present.38 This unique mechanism of action may assist in improving attention, concentration, and the sleep-wake cycle.19 Aripiprazole has a low side-effect profile and a negligible effect on the QT interval and glucose and prolactin levels, which may make it an ideal agent for the treatment of delirium.19 Additionally, it is minimally sedating and has nominal affinity for cholinergic muscarinic receptors.

A study of 14 patients with delirium (mean age 71 years) using a mean daily dose of aripiprazole of 8.9 mg found a maximum treatment response after six days with minimal side effects.19 There were no cerebrovascular accidents or cases of ventricular arrhythmias during therapy. Follow-up ECGs were obtained in 10 out of the 14 patients, which revealed a decrease in QT interval from 451 msec to 434 msec. Blood glucose levels decreased from a mean of 176.1 mg/dL to 116.2 mg/dL; however, two of the patients experienced a slight rise in their fasting glucose levels.

Miscellaneous Agents

Physostigmine: Physostigmine, a cholinesterase inhibitor, reverses delirium associated with anticholinergic drugs and may have some benefit, even when the delirium is nondrug related.1

Benzodiazepines: Benzodiazepines should generally be avoided in delirium, as they may depress the CNS and actually exacerbate delirium. Benzodiazepines are considered first-line in alcohol or sedative withdrawal and may be used in combination with an antipsychotic in patients who cannot tolerate a dose increase of antipsychotic drugs.10 Diazepam is an alternative to physostigmine in patients with anticholinergic toxicity; it has a long half-life and few adverse effects.10

Melatonin: The use of melatonin has been limited in delirium. In two postoperative case reports of patients who received 2 mg melatonin for three to four nights (one for treatment and the other for prevention), a reduction in delirium without side effects was noted.39

A study of elderly patients who progressed to delirium postoperatively demonstrated decreased levels of melatonin when they were measured two days postoperatively as compared to preoperatively.40 Patients who became delirious with complications by another factor such as an infection developed elevated melatonin levels. Similar studies did not visibly identify an association between melatonin and delirium. It is unknown if there is an alteration of quantity or rhythm of melatonin in relation to delirium.40 Data are currently too unsubstantiated to routinely recommend the use of this agent.

Role of the Pharmacist

Polypharmacy can be a prevalent complication of drug therapy in the elderly. It is important to review a patient’s medication list and eliminate medications that have a high probability of causing delirium. Often when a causative medication is discontinued, delirium is alleviated without the need for further pharmacologic management. It is the pharmacist’s duty to determine the feasibility of removing or substituting the causative drug with an alternative less likely to induce delirium. Medication reconciliation is of high importance when determining the drugs most likely to propagate delirium. Evaluation of potential substance abuse or withdrawal is also important when determining origins or risk for delirium.

Pharmacologic treatment choices should be based on specific dosage forms for administration needs and known toxicities of the drug. For instance, if the patient is under cardiac care, an antipsychotic, which has a lower incidence of QT prolongation, would be ideal. Regardless of the agent chosen, psychoactive medications should be used for the shortest period of time as possible.

Summary

Delirium is a common complication in elderly patients during hospitalization. Causes are diverse and may be multifactorial, ranging from infection to medications. Delirium should only be treated with pharmacologic agents if the patient is at risk of self-harm or harm to others. Haloperidol is considered first line in delirious patients who cannot be safely managed with nonpharmacologic treatments. The lowest dose possible should be utilized for the least amount of time.

REFERENCES

  1. Inouye SK. Delirium in older persons. N Engl J Med. 2006;354: 1157-1165.
  2. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association; 2000:143.
  3. Dipiro J, Talbert R, Yee G, et al. Pharmacotherapy: A Pathophysiologic Approach. 5th ed. New York, NY: McGraw Hill; 2002.
  4. Gleason OC. Delirium. Am Fam Physician. 2003;67:1027-1034.
  5. Michaud L, Bula C, Berney A, et al. Delirium: guidelines for general hospitals. J Psychosom Res. 2007;62:371-383.
  6. Han L, McCusker J, Cole M, et al. Use of medications with anti-cholinergic effect predicts clinical severity of delirium symptoms in older medical inpatients. Arch Intern Med. 2001;161:1099-1105.
  7. Pandharipande P, Ely EW. Sedative and analgesic medications: risk factors for delirium and sleep disturbances in the critically ill. Crit Care Clin. 2006;22:313-327.
  8. Demeure MJ, Fain MJ. The elderly surgical patient and postoperative delirium. J Am Coll Surg. 2006;203:752-757.
  9. Practice guideline for the treatment of patients with delirium. American Psychiatric Association. Am J Psychiatry. 1999;156(suppl 5): 1-20.
  10. Tisdale J, Miller D, eds. Drug-Induced Diseases: Prevention, Detection and Management. Bethesda, MD: American Society of Health-System Pharmacists; 2005.
  11. van der Cammen TJ, Tiemeier H, Engelhart MJ, et al. Abnormal neurotransmitter metabolite levels in Alzheimer patients with a delirium. Int J Geriatr Psychiatry. 2006;21:838-843.
  12. Short MR, Winstead PS. Delirium dilemma. Orthopedics. 2007;30:273-276.
  13. Farthing K, Ferrill M, Jones B, et al. Drug Facts and Comparisons Pocket Version. 12th ed. St. Louis, MO: Wolters Kluwer Health; 2008.
  14. Herrick IA, Ganapathy S, Komar W, et al. Postoperative cognitive impairment in the elderly. Choice of patient-controlled analgesia opioid. Anaesthesia. 1996;51:356-360.
  15. Rapp SE, Egan KJ, Ross BK, et al. A multidimensional comparison of morphine and hydromorphone patient-controlled analgesia. Anesth Analg. 1996;82:1043-1048.
  16. Mattila A, Wirtz J. Congruency of scent and music as a driver of in-store evaluations and behavior. J Retailing. 2001;77:273-289.
  17. Butcher D. Aromatherapy—its past and future. Drug Cosmet Ind. 1998;162:22-24.
  18. Kalisvaart KJ, de Jonghe JF, Bogaards MJ, et al. Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study. J Am Geriatr Soc. 2005;53:1658-1666.
  19. Straker DA, Shapiro PA, Muskin PR. Aripiprazole in the treatment of delirium. Psychosomatics. 2006;47:385-391.
  20. Seitz DP, Gill SS, van Zyl LT. Antipsychotics in the treatment of delirium: a systematic review. J Clin Psychiatry. 2007;68:11-21.
  21. Wang PS, Schneeweiss S, Avorn J, et al. Risk of death in elderly users of conventional vs. atypical antipsychotic medications. N Engl J Med. 2005;353:2335-2341.
  22. Lonergan E, Britton AM, Luxenberg J, et al. Antipsychotics for delirium. Cochrane Database Syst Rev. 2007;(2):CD005594.
  23. Koda-Kimble M, Young L, Kradjan W, eds. Applied Therapeutics: The Clinical Use of Drugs. 8th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2005:78.
  24. Potkin SG, Saha AR, Kujawa MJ, et al. Aripiprazole, an antipsychotic with a novel mechanism of action, and risperidone vs placebo in patients with schizophrenia and schizoaffective disorder. Arch Gen Psychiatry. 2003;60:681-690.
  25. Risch SC. Pathophysiology of schizophrenia and the role of newer antipsychotics. Pharmacotherapy. 1996;16:11-14.
  26. Michaud L, Bula C, Berney A, et al. Delirium: guidelines for general hospitals. J Psychosom Res. 2007;62:371-383.
  27. Boettger S, Breitbart W. Atypical antipsychotics in the management of delirium: a review of the empirical literature. Palliat Support Care. 2005;3:227-237.
  28. Ereshefsky L, Lacombe S. Pharmacological profile of risperidone. Can J Psychiatry. 1993;38(suppl 3):S80-S88.
  29. Liu CY, Juang YY, Liang HY, et al. Efficacy of risperidone in treating the hyperactive symptoms of delirium. Int Clin Psychopharmacol.2004;19:165-168.
  30. Mittal D, Jimerson NA, Neely EP, et al. Risperidone in the treatment of delirium: results from a prospective open-label trial. J Clin Psychiatry. 2004;65:662-667.
  31. Parellada E, Baeza I, de Pablo J, Martinez G. Risperidone in the treatment of patients with delirium. J Clin Psychiatry. 2004;65:348-353.
  32. Skrobik YK, Bergeron N, Dumont M, et al. Olanzapine vs haloperidol: treating delirium in a critical care setting. Intensive Care Med. 2004;30:444-449.
  33. Sipahimalani A, Masand PS. Olanzapine in the treatment of delirium. Psychosomatics. 1998;39:422-430.
  34. Sasaki Y, Matsuyama T, Inoue S, Gropper D. A prospective, open-label, flexible-dose study of quetiapine in the treatment of delirium. J Clin Psychiatry. 2003;64:1316-1321.
  35. Kim KY, Bader GM, Kotlyar V, et al. Treatment of delirium in older adults with quetiapine. J Geriatr Psychiatry Neurol. 2003;16:29-31.
  36. Leso L, Schwartz TL. Ziprasidone treatment of delirium. Psychosomatics. 2002;43:61-62.
  37. Young CC, Lujan E. Intravenous ziprasidone for treatment of delirium in the intensive care unit. Anesthesiology. 2004;101:794-795.
  38. Kane JM, Carson WH, Saha AR, et al. Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry. 2002;63:763-771.
  39. Hanania M, Kitain E. Melatonin for treatment and prevention of postoperative delirium. Anesth Analg. 2002;94:338-339.
  40. Bourne RS, Mills GH. Melatonin: possible implications for the postoperative and critically ill patient. Intensive Care Med. 2006;32:371-379.

Back to Top


  Take Test  |  View Questions