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DELIRIUM – PHARMACOLOGIE (PAR ORDRE D’AUTEUR). 2000-2006
Al-Samarrai, S., J. Dunn, et al. (2003). "Quetiapine for treatment-resistant delirium."
Psychosomatics 44(4): 350-1.
Alao, A. O., W. Armenta, et al. (2000). "de Clerambault syndrome successfully treated
with olanzapine." Annals of Pharmacotherapy 34(2): 266-9.
Anand, H. S. (1999). "Olanzapine in an intensive care unit." Canadian Journal of
Psychiatry - Revue Canadienne de Psychiatrie 44(4): 397.
Anderson, S. D. and R. A. Hewko (2003). "Studying delirium.[comment]." CMAJ
Canadian Medical Association Journal 168(5): 541; author reply 541-2.
Barber, J. M. (2003). "Pharmacologic management of integrative brain failure." Critical
Care Nursing Quarterly 26(3): 192-207.
Integrative brain failure is often a comorbidity of critical illness, and although not
uncommon, is perhaps the least understood of all the various organ failure
phenomena. Factors that contribute to integrative brain failure include inadequate
management of pain, stress, anxiety, and the several underlying mechanisms
that create agitation in the intensive care unit patient. Delirium, a resultant
organic mental syndrome, is reversible when promptly recognized and
aggressively managed. The nurse who is astute in clinical assessments and
skillful in the management of the environment of care can prevent and control
states of anxiety, irritability, restlessness, and sleep disturbances that contribute
to the development of delirium. [References: 14]
Bayindir, O., B. Akpinar, et al. (2000). "The use of the 5-HT3-receptor antagonist
ondansetron for the treatment of postcardiotomy delirium.[see comment]." Journal of
Cardiothoracic & Vascular Anesthesia 14(3): 288-92.
OBJECTIVE: To evaluate the effect of the 5-HT3-receptor antagonist
ondansetron in patients with postcardiotomy delirium. DESIGN: Prospective
study. SETTING: University hospital. PARTICIPANTS: Thirty-five patients who
had undergone coronary artery bypass graft surgery. INTERVENTIONS: Thirtyfive patients, 23 men and 12 women, who developed delirium in the intensive
care unit after coronary artery bypass graft surgery were included. Mean patient
age was 51.3 years (range, 36 to 79 years). A mental status scoring scale was
developed, and patients were scored 0 to 4 according to their delirium status
after confirming that there were no correctable metabolic abnormalities as an
underlying cause for delirium. Normal behavior was scored as 0, and severe
verbal and physical agitation was scored as 4. Patients received a single dose of
ondansetron, 8 mg, intravenously and were reevaluated 10 minutes later.
MEASUREMENTS AND MAIN RESULTS: Before the treatment, 7 patients had a
score of 2 (20%); 10 patients (28.6%), 3; and 18 patients (51.4%), 4. After the
treatment, 28 patients (80%) dropped their score to 0; 6 patients (17.1%)
dropped to a score of 1, and 1 patient (2.9%) remained at a score of 4. The mean
score dropped from 3.20 + 1.01 to 0.29 + 0.75 after treatment. Wilcoxon signed
ranks test was used for statistical evaluation, and the fall in delirium score after
ondansetron treatment was found to be statistically significant (p < 0.001).
CONCLUSIONS: The use of ondansetron was effective and safe and without
important side effects. This positive effect of the 5-HT3-receptor antagonist
ondansetron led to speculation that impaired serotonin metabolism may play a
role in postcardiotomy delirium.
Bayindir, O., M. Guden, et al. (2001). "Ondansetron hydrochloride for the treatment of
delirium after coronary artery surgery." Journal of Thoracic & Cardiovascular Surgery
121(1): 176-7.
Bekker, A. Y. and E. J. Weeks (2003). "Cognitive function after anaesthesia in the
elderly." Best Practice & Research Clinical Anaesthesiology 17(2): 259-72.
Despite advances in peri operative care, a significant percentage of elderly
patients experience transient post operative delirium and/or long-term postoperative cognitive dysfunction (POCD). This chapter reviews the aetiology,
clinical features, preventive strategies and treatment of these syndromes. Preoperative, intra-operative, and post-operative risk factors for delirium and POCD
following cardiac and non-cardiac surgery are discussed. It is most likely that the
aetiology of delirium and POCD is multifactorial and may include factors such as
age, decreased pre-operative cognitive function, general health status and,
possibly, intra-operative events. Currently there is no single therapy that can be
recommended for treating post-operative cognitive deterioration. Primary
prevention of delirium and POCD is probably the most effective treatment
strategy. Several large clinical trials show the effectiveness of multicomponent
intervention protocols that are designed to target well-documented risk factors in
order to reduce the incidence of post-operative delirium and, possibly, POCD in
the elderly. [References: 70]
Bourgeois, J. A. and D. M. Hilty (2005). "Prolonged delirium managed with risperidone."
Psychosomatics 46(1): 90-1.
Bourgeois, J. A., A. K. Koike, et al. (2005). "Adjunctive valproic acid for delirium and/or
agitation on a consultation-liaison service: a report of six cases." Journal of
Neuropsychiatry & Clinical Neurosciences 17(2): 232-8.
The authors present six cases in which valproate was used in patients seen by a
consultation-liaison service (CLS) to manage delirium and/or psychotic agitation.
The intravenous (IV) preparation (Depacon, Abbott Laboratories) was used in
two nothing by mouth (NPO) patients, while the liquid oral preparation
(Depakene, Abbott Laboratories) was used via nasogastric tube (NGT) in the
other patients. All of these cases had suboptimal responses and/or concerning
side effects from conventional therapy with benzodiazepines and/or
antipsychotics. In all six cases, the CLS use of valproic acid combined with
conventional antidelirium medications resulted in improved control of behavioral
symptoms without significant side effects from valproic acid. Consultation-liaison
psychiatrists should consider the addition of valproic acid to control behavioral
symptoms of delirium when conventional therapy is inadequate. This may be
especially advisable when problematic side effects result from more conventional
psychopharmacological management. Specifically, intravenous valproate sodium
may be a viable option for NPO patients.
Breitbart, W., A. Tremblay, et al. (2002). "An open trial of olanzapine for the treatment of
delirium in hospitalized cancer patients." Psychosomatics 43(3): 175-82.
We conducted an open, prospective trial of olanzapine for the treatment of
delirium in a sample of 79 hospitalized cancer patients. Patients all met DSM-IV
criteria for a diagnosis of delirium and were rated systematically with the
Memorial Delirium Assessment Scale (MDAS) as a measure of delirium severity,
phenomenology, and resolution, over the course of a 7-day treatment period.
Sociodemographic and medical variables and measures of physical performance
status and drug-related side effects were collected. Fifty-seven patients (76%)
had complete resolution of their delirium on olanzapine therapy. No patients
experienced extrapyramidal side effects; however, 30% experienced sedation
(usually not severe enough to interrupt treatment). Several factors were found to
be significantly associated with poorer response to olanzapine treatment for
delirium, including age >70 years, history of dementia, central nervous system
spread of cancer and hypoxia as delirium etiologies, "hypoactive" delirium, and
delirium of "severe" intensity (i.e., MDAS >23). A logistic-regression model
suggests that age >70 years is the most powerful predictor of poorer response to
olanzapine treatment for delirium (odds ratio, 171.5). Olanzapine appears to be a
clinically efficacious and safe drug for the treatment of the symptoms of delirium
in the hospitalized medically ill.
Broadhurst, C., K. C. Wilson, et al. (2003). "Clinical pharmacology of old age
syndromes." British Journal of Clinical Pharmacology 56(3): 261-72.
Several syndromes occur in old age. They are often associated with increased
mortality and in all there is a paucity of basic and clinical research. The recent
developments in the clinical pharmacology of three common syndromes of old
age (delirium, urinary incontinence, and falls) are discussed along with directions
for future research. [References: 169]
Buchman, N., E. Mendelsson, et al. (1999). "Delirium associated with vitamin B12
deficiency after pneumonia." Clinical Neuropharmacology 22(6): 356-8.
A case is presented of a 65-year-old man with chronic schizophrenia who, after
four years of remission, developed psychotic symptoms after pneumonia. The
patient was found to be deficient in vitamin B12. His psychosis remitted within 5
days of administration of vitamin B12 and folic acid. This case emphasizes the
need to measure vitamin B12 in psychogeriatric patients, especially when they
present with a severe infection and organic mental symptoms.
Caeiro, L., J. M. Ferro, et al. (2004). "Delirium in acute stroke: a preliminary study of the
role of anticholinergic medications." European Journal of Neurology 11(10): 699-704.
The pathogenesis of delirium in acute stroke is incompletely understood. The use
of medications with anticholinergic (ACH) activity is associated with an increased
frequency of delirium. We hypothesized that the intake of medications with ACH
activity is associated with delirium in acute stroke patients. Delirium was
assessed using the DSM-IV-TR criteria and the Delirium Rating Scale, in a
sample of consecutive patients with an acute (< or =4 days) cerebral infarct or
intracerebral haemorrhage (ICH). We performed a gender and age matched
case-control study. Twenty-two delirious stroke patients (cases) and 52 nondelirious patients (controls) were compared concerning the intake of ACH
medications (i) before stroke, (ii) during hospitalization but before the
assessment. The variables associated with delirium on bivariate analysis were
entered in a stepwise logistic regression analysis. The final regression model
(Nagelkerke R2 = 0.65) retained non-neuroleptics ACH medication during
hospitalization (OR = 24.4; 95% CI = 2.18-250), medical complications (OR =
20.8; 95% CI = 3.46-125), ACH medication taken before stroke (OR = 17.5; 95%
CI = 1.00-333.3) and ICH (OR = 16.9; 95% CI = 2.73-100) as independent
predictors of delirium. This preliminary result indicates that drugs with subtle ACH
activity play a role in the pathogeneses of delirium in acute stroke. Medication
with ACH activity should be avoided in acute stroke patients.
Cavaliere, F., F. D'Ambrosio, et al. (2005). "Postoperative delirium." Current Drug
Targets 6(7): 807-14.
Delirium is a global impairment of upper brain functions caused by an organic
substrate. It is frequently observed in the postoperative period, particularly in
elderly people. Vascular and orthopedic surgery and long-duration surgery are
associated with a higher incidence of postoperative delirium. When it occurs,
postoperative delirium makes patient management much more difficult, increases
costs, and, above all, causes severe discomfort to the patient. Delirium is also
associated with higher postoperative mortality and morbidity, and with delayed
functional recovery, but it is still unclear whether worse prognosis is directly
caused by delirium or results from the neurological damage of which delirium is
simply a symptom. Drug therapy should be part of a complex approach to
prevent and treat this complication. Neuroleptics like haloperidol and droperidol,
and benzodiazepines are usually employed in order to control symptoms like
agitation, restlessness, and altered perceptions. Atypical neuroleptics, like
risperidone, have not yet been studied in postoperative delirium, although some
case reports in which they were successfully used have been published.
Physiostigmine is effective in delirium caused by anticholinergic syndrome;
vitamins may be useful in alcoholics; melatonin use has been suggested in order
to prevent and treat delirium by normalizing sleep-wake cycle alterations.
Environmental interventions are often costless and may be very useful to prevent
and treat postoperative delirium in patients at risk. [References: 80]
Centorrino, F., M. J. Albert, et al. (2003). "Delirium during clozapine treatment:
incidence and associated risk factors." Pharmacopsychiatry 36(4): 156-60.
BACKGROUND: Incidence and risk factors for delirium during clozapine
treatment require further clarification. METHODS: We used computerized
pharmacy records to identify all adult psychiatric inpatients treated with clozapine
(1995-96), reviewed their medical records to score incidence and severity of
delirium, and tested associations with potential risk factors. RESULTS: Subjects
(n = 139) were 72 women and 67 men, aged 40.8 +/- 12.1 years, hospitalized for
24.9 +/- 23.3 days, and given clozapine, gradually increased to an average daily
dose of 282 +/- 203 mg (3.45 +/- 2.45 mg/kg) for 18.9 +/- 16.4 days. Delirium was
diagnosed in 14 (10.1 % incidence, or 1.48 cases/person-years of exposure);
71.4 % of cases were moderate or severe. Associated factors were co-treatment
with other centrally antimuscarinic agents, poor clinical outcome, older age, and
longer hospitalization (by 17.5 days, increasing cost); sex, diagnosis or medical
co-morbidity, and daily clozapine dose, which fell with age, were unrelated.
CONCLUSIONS: Delirium was found in 10 % of clozapine-treated inpatients,
particularly in older patients exposed to other central anticholinergics. Delirium
was inconsistently recognized clinically in milder cases and was associated with
increased length-of-stay and higher costs, and inferior clinical outcome.
Cheng, S. W., W. H. Hu, et al. (2002). "Anticholinergic poisoning from a large dose of
Scopolia extract." Veterinary & Human Toxicology 44(4): 222-3.
Scopolia extract (SE) contains hyoscyamine and scopolamine, which are both
anticholinergic. It is usually used as a patent medicine to treat gastrointestinal
disorders, to relieve spasmotic discomfort, or to decrease the secretion of gastric
acid. Poisoning by SE presents similar symptoms and signs as other types of
anticholinergic poisoning. We report a case of severe anticholinergic poisoning
after accidentally drinking 8 ml of SE. The patient presented with acute delirium
and was successfully treated with physostigmine.
Conn, D. K. and S. Lieff (2001). "Diagnosing and managing delirium in the elderly."
Canadian Family Physician 47: 101-8.
OBJECTIVE: To outline current approaches to diagnosing and managing
delirium in the elderly. QUALITY OF EVIDENCE: A literature review was based
on a MEDLINE search (1966 to 1998). Selected articles were reviewed and used
as the basis for discussion of diagnosis and etiology. We planned to include all
published randomized controlled trials regarding management but found only
two. Consequently, we also used review articles and recent practice guidelines
for delirium published by the American Psychiatric Association. MAIN FINDINGS:
Clinical diagnosis of delirium can be aided by using DSM-IV criteria, the Delirium
Symptom Interview, or the confusion assessment method. Management must
include investigation and treatment of underlying causes and general supportive
measures. Providing optimal levels of stimulation, reorienting patients, education,
and supporting families are important. Pharmacologic management of delirium
should be considered only for specific symptoms or behaviours, e.g., aggression,
severe agitation, or psychosis. Only one randomized controlled trial of
tranquilizer use for delirium in medically ill people has been published. Findings
support the current belief that neuroleptics are superior to benzodiazepines in
most cases of delirium. Most authorities still consider haloperidol the neuroleptic
of choice. Controlled trials of the new atypical neuroleptics for treating delirium
are not yet available. Benzodiazepines with relatively short half-lives, such as
lorazepam, are the drugs of choice for withdrawal symptoms. CONCLUSION:
Delirium is frequently underdiagnosed in clinical practice. It should be suspected
with acute changes in behaviour. Careful investigation of the underlying cause
permits appropriate management. [References: 44]
Dautzenberg, P. L., L. J. Mulder, et al. (2004). "Adding rivastigmine to antipsychotics in
the treatment of a chronic delirium." Age & Ageing 33(5): 516-7.
Dautzenberg, P. L., L. J. Mulder, et al. (2004). "Delirium in elderly hospitalised patients:
protective effects of chronic rivastigmine usage." International Journal of Geriatric
Psychiatry 19(7): 641-4.
OBJECTIVES: To investigate the efficacy of the chronic usage of the
cholinesterase inhibitor rivastigmine in patients with dementia in the prevention of
delirium in case of hospitalisation. DESIGN: Retrospective cohort study.
SETTING: Non-geriatric wards of an 1120 bed general teaching hospital in sHertogenbosch, The Netherlands. PARTICIPANTS: Of a group of 366
hospitalised patients, treated by the geriatric consultation team from January
2002 until June 2003, the patients who used rivastigmine chronically were
compared with a randomly selected subgroup of all patients not treated with
rivastigmine. MEASUREMENTS: The occurrence and duration of a delirium, comorbidity, use of medication, length of hospitalisation and psychosocial data
were collected from the medical charts of the geriatric consultation team.
RESULTS: 11 patients (3%) were chronic rivastigmine users. A control group of
29 subjects was randomly selected from the non-rivastigmine users of the patient
population. In the group that used rivastigmine five patients (45.5%) developed a
delirium, compared with 8 (88.9%) in the control group (p < 0.05).
CONCLUSIONS: Chronic rivastigmine use may contribute to the prevention of a
delirium in a high-risk group of elderly hospitalised patients suffering from
dementia. Copyright 2004 John Wiley & Sons, Ltd.
Dautzenberg, P. L., C. J. Wouters, et al. (2003). "Rivastigmine in prevention of delirium
in a 65 years old man with Parkinson's disease." International Journal of Geriatric
Psychiatry 18(6): 555-6.
Dibert, C. (2004). "Delirium and the older adult after surgery." Perspectives 28(1): 10-6.
Nurses are in an excellent position to positively impact the quality of care for this
group of patients. By developing a knowledge base of risk factors with a special
emphasis on modifiable risks factors, nurses become pivotal in the development
of an client focused plan of care. The value of the plan of care is to target
intervention protocols to ameliorate the effect of the hospital environment on the
at-risk patient with the goal of decreasing the incidence of delirium. Careful
screening and a systematic approach to assessment (using a validated
assessment tool) can result in early detection and rapid intervention to treat the
modifiable causative factors while continuing to provide supportive
pharmacological and nonpharmacological care. A sample care path for
hospitalized older patients at-risk for developing delirium is described in Figure 1.
Delirium is a common occurrence in the older surgical patient and is a
contributing cause of functional disability, morbidity, and mortality. Unfortunately,
it remains underdiagnosed and undertreated. Nurses can improve patients'
quality of care and outcomes by implementing interventions targeted at
modifiable risk factors and early recognition of delirium. The care of older surgical
patients requires a rigorous approach to prevention, detection and management.
Close attention to ensure adequate oxygenation, perfusion, hydration, nutrition
and stimulation is critical. Commitment to improve outcomes in a decidedly
vulnerable patient population holds the potential to reduce morbidity and mortality
as well as reducing costs and length of stay for the older surgical population who
experience an episode of acute post-operative delirium. [References: 26]
DuBeau, C. E. (2002). "The continuum of urinary incontinence in an aging population."
Geriatrics 57 Suppl 1: 12-7.
Duggal, M. K., A. Singh, et al. (2005). "Olanzapine-induced vasculitis." American
Journal Geriatric Pharmacotherapy 3(1): 21-4.
INTRODUCTION: Elderly patients are particularly vulnerable to adverse drug
reactions as a result of polypharmacy and metabolic changes associated with
aging. We present a case of leukocytoclastic vasculitis induced by olanzapine, a
medication commonly used in elderly patients. CASE SUMMARY: An 82-year-old
woman was admitted to the extended-care center for short-term rehabilitation
after prolonged hospitalization for a pulmonary embolism requiring mechanical
ventilation. The pulmonary problem resolved, but her hospitalization and
subsequent rehabilitation were complicated by agitated delirium, which was
treated with olanzapine and modification of contributory factors. At the time of
admission to the rehabilitation facility, the patient had been receiving warfarin for
2 weeks and olanzapine for 6 days. On the eighth day after initiation of
olanzapine, erythematous skin lesions developed on dependent areas. The
international normalized ratio for warfarin was within the acceptable range;
however, because warfarin has been associated with subcutaneous bleeding
presenting as petechiae and ecchymosis, subcutaneous enoxaparin was
substituted for warfarin. The skin lesions continued to worsen over the next week
and developed into palpable lesions. Biopsy of the rash revealed leukocytoclastic
vasculitis. In the absence of another cause, olanzapine was discontinued and the
rash improved significantly. When the agitation recurred, risperidone was
initiated, but the patient experienced dizziness with this agent. Olanzapine was
resumed and the skin lesions recurred. Olanzapine was then changed to
quetiapine, and the skin lesions improved over the next few weeks.
DISCUSSION: Olanzapine is commonly used in elderly patients to control
behavioral disturbances associated with dementia, delirium, and other psychiatric
disorders. Leukocytoclastic vasculitis is an infrequently reported adverse drug
reaction with olanzapine. Its exact pathogenic mechanism is unknown, but both
cell-mediated and humoral immunity appear to play important roles. Because
drug-induced vasculitis has an identical clinical presentation and identical
serologic/pathologic parameters to idiopathic forms of vasculitis, a high index of
suspicion is necessary for its accurate diagnosis. CONCLUSIONS: Because
adverse drug reactions are common in elderly patients taking multiple
medications, physicians should be vigilant when starting new medications and
should attempt to eliminate unnecessary medications. Clinicians should be aware
of the potential for leukocytoclastic vasculitis in association with olanzapine.
Fainsinger, R. L., D. De Moissac, et al. (2000). "Sedation for delirium and other
symptoms in terminally ill patients in Edmonton." Journal of Palliative Care 16(2): 5-10.
The use of sedation and the management of delirium and other difficult
symptoms in terminally ill patients in Edmonton has been reported previously.
The focus of this study was to assess the prevalence in the Edmonton region of
difficult symptoms requiring sedation at the end of life. Data were collected for 50
consecutive patients at each of (a) the tertiary palliative care unit, (b) the
consulting palliative care program at the Royal Alexandra Hospital (acute care),
and (c) three hospice inpatient units in the city. Patients on the tertiary palliative
care unit were significantly younger. Assessments confirmed the more
problematic physical and psychosocial issues of patients in the tertiary palliative
care unit. These patients had more difficult pain syndromes and required
significantly higher doses of daily opioids. Approximately 80% of patients in all
three settings developed delirium prior to death. Pharmacological management
of this problem was needed by 40% in the acute care setting, and by 80% in the
tertiary palliative care unit. The patients sedated varied from 4% in the hospice
setting to 10% in the tertiary palliative care unit. Of the 150 patients, nine were
sedated for delirium, one for dyspnea. The prevalence of delirium and other
symptoms requiring sedation in our area is relatively low compared to others
reported in the literature. Demographic variability between the three Edmonton
settings highlights the need for caution in comparing results of different palliative
care groups. It is possible that some variability in the use of sedation
internationally is due to cultural differences. The infrequent deliberate use of
sedation in Edmonton suggests that improved management has resulted in fewer
distressing symptoms at the end of life. This is of benefit to patients and to family
members who are with them during this time.
Fainsinger, R. L., A. Waller, et al. (2000). "A multicentre international study of sedation
for uncontrolled symptoms in terminally ill patients." Palliative Medicine 14(4): 257-65.
The issue of symptom management at the end of life and the need to use
sedation has become a controversial topic. This debate has been intensified by
the suggestion that sedation may correlate with 'slow euthanasia'. The need to
have more facts and less anecdote was a motivating factor in this multicentre
study. Four palliative care programmes in Israel, South Africa, and Spain agreed
to participate. The target population was palliative care patients in an inpatient
setting. Information was collected on demographics, major symptom distress,
and intent and need to use sedatives in the last week of life. Further data on level
of consciousness, adequacy of symptom control, and opioids and psychotropic
agents used during the final week of life was recorded. As the final week of life
can be difficult to predict, treating physicians were asked to complete the data at
the time of death. The data available for analysis included 100 patients each from
Israel and Madrid, 94 patients from Durban, and 93 patients from Cape Town.
More than 90% of patients required medical management for pain, dyspnoea,
delirium and/or nausea in the final week of life. The intent to sedate varied from
15% to 36%, with delirium being the most common problem requiring sedation.
There were variations in the need to sedate patients for dyspnoea, and
existential and family distress. Midazolam was the most common medication
prescribed to achieve sedation. The diversity in symptom distress, intent to
sedate and use of sedatives, provides further knowledge in characterizing and
describing the use of deliberate pharmacological sedation for problematic
symptoms at the end of life. The international nature of the patient population
studied enhances our understanding of potential differences in definition of
symptom issues, variation of clinical practice, and cultural and psychosocial
influences.
Fann, J. R. (2002). "Psychiatric effects of neuropharmacological agents." Seminars in
Clinical Neuropsychiatry 7(3): 206-12.
Fischer, P. (2001). "Successful treatment of nonanticholinergic delirium with a
cholinesterase inhibitor." Journal of Clinical Psychopharmacology 21(1): 118.
Flacker, J. M. and L. A. Lipsitz (1999). "Serum anticholinergic activity changes with
acute illness in elderly medical patients." Journals of Gerontology Series A-Biological
Sciences & Medical Sciences 54(1): M12-6.
BACKGROUND: Elevated serum anticholinergic activity levels have been
associated with delirium in cross-sectional studies of ill older persons. This study
used serial measures of serum anticholinergic activity levels to determine
whether these levels change following illness resolution, and if such changes are
specific to those with delirium. METHODS: Twenty-two nursing home residents
with a febrile illness had serum specimens drawn and were evaluated for the
presence of delirium during the acute illness and at 1-month follow-up. Delirium
was diagnosed using the Confusion Assessment Method. Serum anticholinergic
activity was determined using a previously described radionuclide competitivebinding assay. RESULTS: Delirium was present during illness in 8 of 22 subjects
(36%), and had resolved by 1-month follow-up in all but one resident. Serum
anticholinergic activity levels were significantly higher during illness than at 1month follow-up in both the delirious (0.69 +/- 0.85 nM atropine equivalents/200
microL sample versus 0.10 +/- 0.16; p =.06) and non-delirious (0.65 +/- 0.51 nM
atropine equivalents/200 microL sample versus 0.08 +/- 0.12; p <.001) groups.
Medication changes did not seem to be related to changes in serum
anticholinergic activity. CONCLUSIONS: In older nursing home residents with a
fever, serum anticholinergic activity appears to be elevated during illness, and
declines following recovery from illness. This effect does not seem to be specific
to those residents with delirium, nor does it seem related to medication changes.
Frank, C. (1999). "Delirium, consent to treatment, and Shakespeare. A geriatric
experience." Canadian Family Physician 45: 875-6.
Gagnon, B., G. Low, et al. (2005). "Methylphenidate hydrochloride improves cognitive
function in patients with advanced cancer and hypoactive delirium: a prospective clinical
study." Journal of Psychiatry & Neuroscience 30(2): 100-7.
OBJECTIVE: To investigate the clinical improvement observed in patients with
advanced cancer and hypoactive delirium after the administration of
methylphenidate hydrochloride. METHODS: Fourteen patients with advanced
cancer and hypoactive delirium were seen between March 1999 and August
2000 at the Palliative Care Day Hospital and the inpatient Tertiary Palliative Care
Unit of Montreal General Hospital, Montreal. They were chosen for inclusion in a
prospective clinical study on the basis of (1) cognitive failure documented by the
Mini-Mental State Examination (MMSE), (2) sleep-wake pattern disturbances, (3)
psychomotor retardation, (4) absence of delusions or hallucinations, and (5)
absence of an underlying cause to explain the delirium. All patients were treated
with methylphenidate, and changes in their cognitive function were measured
using the MMSE. RESULTS: All 14 patients showed improvement in their
cognitive function as documented by the MMSE. The median pretreatment
MMSE score (maximum score 30) was 21 (mean 20.9, standard deviation [SD]
4.9), which improved to a median of 27 (mean 24.9, SD 4.7) after the first dose of
methylphenidate (p < 0.001, matched, paired Wilcoxon signed rank test). One
patient died before reaching a stable dose of methylphenidate. In the other 13
patients, the median MMSE score further improved to 28 (mean 27.8, SD 2.4) (p
= 0.02 compared with the median MMSE score documented 1 hour after the first
dose of methylphenidate). All patients showed an improvement in psychomotor
activities. CONCLUSIONS: Hypoactive delirium that cannot be explained by an
underlying cause (metabolic or drug-induced) in patients with advanced cancer
appears to be a specific syndrome that could be improved by the administration
of methylphenidate.
Gleason, O. C. (2003). "Donepezil for postoperative delirium." Psychosomatics 44(5):
437-8.
Goy, E. and L. Ganzini "End-of-life care in geriatric psychiatry." Clinics in Geriatric
Medicine 19(4): 841-56.
Depression, anxiety and delirium are relatively common during the final stages of
terminal disease, and each can profoundly impact the quality of those last days
for both patient and involved family. In this article the authors review the
assessment and treatment of each syndrome in the context of palliative care for
older adults. Treatment of mental disorders at the end of life warrants special
consideration due to the need to balance the benefits of treatment against the
potential burden of the intervention, especially those that might worsen quality of
life. Dementia and the complications of depression and behavioral disturbance
within dementia are also discussed. Finally, caregivers of dying patients are
vulnerable to stress, depression, grief, and complicated bereavement.
Interventions for caregivers who are debilitated by these states are briefly
summarized. [References: 113]
Gupta, N., P. Sharma, et al. (2005). "Effectiveness of risperidone in delirium." Canadian
Journal of Psychiatry - Revue Canadienne de Psychiatrie 50(1): 75.
Han, C. S. and Y. K. Kim (2004). "A double-blind trial of risperidone and haloperidol for
the treatment of delirium." Psychosomatics 45(4): 297-301.
To compare the clinical efficacy of haloperidol and risperidone for the treatment
of delirium, the authors performed a double-blind comparative study. Twentyeight patients with delirium were recruited and randomly assigned to receive a
flexible-dose regimen of haloperidol or risperidone over 7 days. The severity of
delirium was assessed by using Memorial Delirium Assessment Scale scores.
Scores for each group decreased significantly over the study period. However,
no significant differences in mean Memorial Delirium Assessment Scale scores
between groups were found. The group-by-time effect was not significant. In
addition, there was no significant difference in the frequency of response to the
drugs between the two groups. One patient in the haloperidol group experienced
mild akathisia, but no other patients reported clinically significant side effects.
These data show no significant difference in the efficacy or response rate
between haloperidol and risperidone in the treatment of delirium.
Hanania, M. and E. Kitain "Melatonin for treatment and prevention of postoperative
delirium." Anesthesia & Analgesia 94(2): 338-9.
Postoperative delirium is a common problem associated with increased morbidity
and mortality, prolonged hospital stay, additional tests and consultations and
therefore, increased cost (1,2). The reported incidence of delirium or confusion
after surgery ranges from 8% to 78% (2,3-5), depending on methods and
population studied. The elderly seem to be at significantly increased risk for this
complication. Sleep-wake cycle disruption has been associated with delirium and
behavioral changes (5) and sleep deprivation can even result in psychosis (6).
Environmental changes (i.e., hospital stay), medications, and general anesthesia
can affect the sleep-wake cycle (3,4). Plasma melatonin levels, which play an
important role in the regulation of the sleep-wake cycle, are decreased after
surgery (18) and in hospitalized patients (7,11). We report the successful use of
melatonin in treating severe postoperative delirium unresponsive to
antipsychotics or benzodiazepines in one patient. In another patient with a history
of postoperative delirium, melatonin was used to prevent another episode of
delirium after repeat lower extremity surgery. IMPLICATIONS: Postoperative
delirium or confusion after surgery is a common problem associated with
complications and death. Delirium has been linked to sleep-wake cycle
disruption. Melatonin levels, which play an important role in regulating the sleepwake cycle, are decreased after surgery. Two cases are presented where
melatonin was used to treat and prevent postoperative delirium.
Horikawa, N., T. Yamazaki, et al. (2003). "Treatment for delirium with risperidone:
results of a prospective open trial with 10 patients." General Hospital Psychiatry 25(4):
289-92.
Delirium is a common psychiatric illness among medically compromised patients.
There is an increasing opportunity to use atypical antipsychotics to treat delirium.
The effects of these drugs on delirium, however, the most appropriate way to use
them, and the associated adverse effects remain unclear. To clarify these points,
a prospective open trial on risperidone was carried out in 10 patients with
delirium. At a low dose of 1.7 mg/d, on average, risperidone was effective in 80%
of patients, and the effect appeared within a few days. There were no serious
adverse effects. However, sleepiness (30%) and mild drug-induced parkinsonism
(10%) were observed; the symptom of sleepiness was a reason for not
increasing the dose. One patient responded to a dose as low as 0.5 mg/d, so it is
recommended that treatment start at a low dose, which may then be increased
gradually. This trial is a preliminary open study with a small sample size, and
further controlled studies will be necessary.
Kaldune, A., J. Strnad, et al. (1999). "Apnea syndrome in a patient with Alzheimer
dementia under chlormethiazole treatment: a clinical experience report.[see comment]."
Acta Psychiatrica Scandinavica 99(1): 79-81.
Sleep apnea syndromes in conjunction with dementia have attracted
considerable interest among geropsychiatrists in recent years. This clinical case
report describes a demented and delirious elderly patient with a history of
alcoholism who developed a sleep apnea syndrome under treatment with
chlormethiazole. The risk of chlormethiazole treatment may be underestimated in
vulnerable patients, e.g. those suffering from severe respiratory diseases or
dementia. Alternative treatments for delirious states need to be evaluated
instead.
Kato, D., C. Kawanishi, et al. (2005). "Delirium resolving upon switching from
risperidone to quetiapine: implication of CYP2D6 genotype." Psychosomatics 46(4):
374-5.
Kawashima, T., M. Oda, et al. (2004). "Metyrapone for delirium due to Cushing's
syndrome induced by occult ectopic adrenocorticotropic hormone secretion." Journal of
Clinical Psychiatry 65(7): 1019-20.
Kim, K. S., C. U. Pae, et al. (2001). "An open pilot trial of olanzapine for delirium in the
Korean population." Psychiatry & Clinical Neurosciences 55(5): 515-9.
This study was performed to assess the efficacy and safety of olanzapine for the
treatment of delirium in a Korean population. An open trial of olanzapine was
conducted in Korean patients with delirium caused by multiple medicosurgical
conditions. All subjects were evaluated by Delirium Rating Scale (DRS), which is
known to be one of the most sensitive scales for delirium. In addition, other data
for profiles of side-effects were collected and analyzed. Twenty patients were
treated by olanzapine with doses of 5.9 +/- 1.5 mg/day. The initial dose was 4.6
+/- 0.9 mg/day and maximal dose of olanzapine was 8.8 +/- 2.2 mg/day. The
average duration of treatment was 6.6 +/- 1.7 days and the day of maximal
response was 3.8 +/- 1.7 treated days. The scores of DRS were significantly
improved from 20.0 +/- 3.6 at the time of pretreatment to 9.3 +/- 4.6 at the posttreatment. All subjects showed no definite serious side-effects including
anticholinergic and extrapyramidal symptoms. Olanzapine treatment for patients
with delirium was effective and safe. This newer drug may be a useful alternative
agent to classical antipsychotics in the treatment of delirium.
Kim, K. Y., G. M. Bader, et al. (2003). "Treatment of delirium in older adults with
quetiapine." Journal of Geriatric Psychiatry & Neurology 16(1): 29-31.
Delirium is a neuropsychiatric syndrome characterized by impairment of
consciousness, changes in cognition, or perceptual disturbances. In addition,
delirium is often accompanied by delusions, hallucinations, and agitation. In this
study, 12 older patients with delirium were treated for neuropsychiatric symptoms
with quetiapine. The mean duration for stabilization was 5.91 +/- 2.22 days, and
the mean dose was 93.75 +/- 23.31 mg/day. None of the 12 patients developed
extrapyramidal symptoms. There were significant improvements on all measures
used in this study. Interestingly, the Delirium Rating Scale scores along with
scores of the Mini-Mental State Examination and Clock Drawing Test continued
to improve throughout the 3-month study period. In our study, we found that
quetiapine was a safe and effective treatment in hospitalized older patients with
delirium.
Kobayashi, K., M. Higashima, et al. (2004). "Severe delirium due to basal forebrain
vascular lesion and efficacy of donepezil." Progress in Neuro-Psychopharmacology &
Biological Psychiatry 28(7): 1189-94.
A severe intractable delirium caused by the basal forebrain vascular lesion and
its dramatic recovery after donepezil administration were reported. A 68-year-old
man had suffered for a month from delirium of mixed type caused by the right
basal forebrain vascular lesion after surgery for craniopharyngioma. Magnetic
resonance imaging (MRI) showed hemorrhagic infarcts in the head of the right
caudate nucleus and the right basal forebrain of the medial septal nucleus,
diagonal band of Broca and nucleus basalis of Meynert. He had been treated
with anti-psychotics, anti-depressants and hypnotics, which resulted in little
improvement. Donepezil administration dramatically improved his intractable
delirium at the 19th post-donepezil administration day, but this was followed by
amnestic symptoms. Clinical correlates of delirium with the basal forebrain lesion
and efficacy of donepezil support the hypocholinergic theory of delirium.
Kunkel, E. J. and O. Aliu (2000). "Management of the agitated patient." Delaware
Medical Journal 72(11): 473-8.
Unfortunately, although delirium is common in the general hospital, the diagnosis
is frequently missed. As delirium often indicates a serious, sometimes lifethreatening, medical or surgical condition, successful management and
subsequent prevention of morbidity and mortality require prompt recognition and
early intervention. Failure to recognize, diagnose, and treat delirium and the
underlying pathology can result in death. This article presents current thinking on
the management of delirium and related agitation in the general medical hospital.
[References: 17]
Liptzin B, L. A., Garb JL, Fingeroth R, Krushell R (2005). "Donepezil in the prevention
and treatment of post-surgical delirium." The American Journal of Geriatric Psychiatry
13(12): 1100-1106.
Liu, C. Y., Y. Y. Juang, et al. (2004). "Efficacy of risperidone in treating the hyperactive
symptoms of delirium." International Clinical Psychopharmacology 19(3): 165-8.
Forty-one delirious patients who received risperidone treatment and 36 who
received haloperidol treatment were retrospectively analysed. Ten-point visual
analog scales (scored 0 for none to 10 for extremely severe) for hyperactive and
hypoactive syndromes of delirium were used for efficacy evaluation. Psychiatrists
scrutinized the medical records and determined the global severity of the
syndrome for each patient. The results showed that risperidone and haloperidone
were both effective for treating hyperactive symptoms of delirium. The liaison
psychiatrists tended to recommend haloperidol for patients with severely
hyperactive symptoms and risperidone for older patients and patients with
moderate hyperactive symptoms. The patients on risperidone needed much less
anticholinergic agent. The maximal daily dose of risperidone was in the range
0.5-4.0 mg, with a mean of 1.17+/-0.76 mg, which was much lower than that for
schizophrenia. The present study showed that risperidone appears to be
effective and safe for the treatment of delirium.
Malur, C., M. Fink, et al. (2000). "Can delirium relieve psychosis?" Comprehensive
Psychiatry 41(6): 450-3.
A delirium presages a poor prognosis in hospitalized patients, but an incidental
delirium is a feature of some psychiatric treatments. We report five cases in
which delirium preceded the relief of affective and psychotic symptoms of a major
mental illness. The experience stimulated a review of the literature on delirium in
psychiatric treatments. Five inpatients (aged 53 to 69 years) with an exacerbation
of chronic mental illness developed deliria from medications (n = 4) and
electrolyte disturbance (n = 1). The deliria were managed with medication
washout or correction of electrolyte imbalance. The progress of the patients was
noted clinically and summarized. The clinical signs of delirium such as confusion,
disorganized speech, sleep-wake cycle changes, and hallucinations persisted for
24 to 72 hours. As the delirium cleared, psychotic and affective symptoms
improved or resolved. The improvements persisted for 1 to 5 months, with low
doses of medications in two of the cases. A delirium may precede clinical
improvement in affective and psychotic symptoms. Historically, some treatments
for mental illness induce an incidental delirium (e.g., electroconvulsive therapy
[ECT] and insulin coma). Why a delirium should presage a beneficial effect on
psychosis is unclear, but the emergence of delirium may herald a beneficial
pathophysiology.
Meagher, D. J. (2001). "Delirium: optimising management.[see comment]." BMJ
322(7279): 144-9.
Milbrandt, E. B., A. Kersten, et al. (2005). "Haloperidol use is associated with lower
hospital mortality in mechanically ventilated patients.[see comment]." Critical Care
Medicine 33(1): 226-9; discussion 263-5.
OBJECTIVE: To determine whether haloperidol use is associated with lower
mortality in mechanically ventilated patients. DESIGN: Retrospective cohort
analysis. SETTING: A large tertiary care academic medical center. PATIENTS: A
total of 989 patients mechanically ventilated for >48 hrs. MEASUREMENTS AND
MAIN RESULTS: We compared differences in hospital mortality between
patients who received haloperidol within 2 days of initiation of mechanical
ventilation and those who never received haloperidol. Despite similar baseline
characteristics, patients treated with haloperidol had significantly lower hospital
mortality compared with those who never received haloperidol (20.5% vs. 36.1%;
p =.004). The lower associated mortality persisted after adjusting for age,
comorbidity, severity of illness, degree of organ dysfunction, admitting diagnosis,
and other potential confounders. CONCLUSIONS: Haloperidol was associated
with significantly lower hospital mortality. These findings could have enormous
implications for critically ill patients. Because of their observational nature and the
potential risks associated with haloperidol use, they require confirmation in a
randomized, controlled trial before being applied to routine patient care.
Mittal, D., N. A. Jimerson, et al. (2004). "Risperidone in the treatment of delirium: results
from a prospective open-label trial." Journal of Clinical Psychiatry 65(5): 662-7.
BACKGROUND: Effective treatment is necessary to reverse delirium and prevent
potentially serious consequences. METHOD: Patients were identified for
screening by initial chart review of all consecutive admissions to the general
medical or surgical wards at the Department of Veterans Affairs hospital and the
University of Mississippi Medical Center in Jackson, Mississippi, between
November 2000 and April 2002. Medically ill patients with delirium defined by
DSM-IV criteria and a Delirium Rating Scale (DRS) score of >or= 13 were given
risperidone, 0.5 mg, twice daily, with additional doses permitted on day 1 for
target symptoms. Total day 1 dosage was given daily until the DRS score was
<or= 12; dosage was then decreased by 50% (maintenance dose) and continued
until day 6. Daily assessment included DRS, Cognitive Test for Delirium (CTD),
and modified Extrapy-ramidal Symptom Rating Scale. Functional status
(Karnofsky Scale of Performance Status; KSPS) and medical burden
(Cumulative Illness Rating Scale) were assessed at baseline and day 6.
RESULTS: Ten patients (mean age = 64.7 years) were enrolled. Mean daily
maintenance risperidone dosage was 0.75 mg. Mean CTD scores improved from
day 1 to the day maintenance dose was initiated (p <.0005) and remained
improved at day 6 (7.1 +/- 2.0 and 16.9 +/- 3.0, days 1 and 6, respectively; p
=.0078). Mean DRS scores improved from day 1 to the day maintenance dose
was initiated (p <.0001) and remained improved at day 6 (25.2 +/- 0.9 and 11.3
+/- 1.5, days 1 and 6, respectively; p <.0001). Mean KSPS scores improved from
32.0 on day 1 to 45.5 on day 6 (p =.044). No patient developed movement
disorders. One patient each discontinued because of sedation and hypotension.
CONCLUSION: Low-dose risperidone can improve cognitive and behavioral
symptoms of delirium in medically ill patients.
Moore, A. R. and S. T. O'Keeffe (1999). "Drug-induced cognitive impairment in the
elderly." Drugs & Aging 15(1): 15-28.
Elderly people are more likely than younger patients to develop cognitive
impairment as a result of taking medications. This reflects age- and diseaseassociated changes in brain neurochemistry and drug handling. Delirium (acute
confusional state) is the cognitive disturbance most clearly associated with drug
toxicity, but dementia has also been reported. The aetiology of cognitive
impairment is commonly multifactorial, and it may be difficult to firmly establish a
causal role for an individual medication. In studies of elderly hospital patients,
drugs have been reported as the cause of delirium in 11 to 30% of cases.
Medication toxicity occurs in 2 to 12% of patients presenting with suspected
dementia. In some cases CNS toxicity occurs in a dose-dependent manner, often
as a result of interference with neurotransmitter function. Drug-induced delirium
can also occur as an idiosyncratic complication. Finally, delirium may occur
secondary to iatrogenic complications of drug use. Almost any drug can cause
delirium, especially in a vulnerable patient. Impaired cholinergic
neurotransmission has been implicated in the pathogenesis of delirium and of
Alzheimer's disease. Anticholinergic medications are important causes of acute
and chronic confusional states. Nevertheless, polypharmacy with anticholinergic
compounds is common, especially in nursing home residents. Recent studies
have suggested that the total burden of anticholinergic drugs may determine
development of delirium rather than any single agent. Also, anticholinergic effects
have been identified in many drugs other than those classically thought of as
having major anticholinergic effects. Psychoactive drugs are important causes of
delirium. Narcotic agents are among the most important causes of delirium in
postoperative patients. Long-acting benzodiazepines are the commonest drugs
to cause or exacerbate dementia. Delirium was a major complication of treatment
with tricyclic antidepressants but seems less common with newer agents.
Anticonvulsants can cause delirium and dementia. Drug-induced confusion with
nonpsychoactive drugs is often idiosyncratic in nature, and the diagnosis is easily
missed unless clinicians maintain a high index of suspicion. Histamine H2
receptor antagonists, cardiac medications such as digoxin and beta-blockers,
corticosteroids, non-steroidal anti-inflammatory agents and antibiotics can all
cause acute, and, less commonly, chronic confusion. Drug-induced confusion
can be prevented by avoiding polypharmacy and adhering to the saying 'start low
and go slow'. Special care is needed when prescribing for people with cognitive
impairment. Early diagnosis of drug-induced confusion, and withdrawal of the
offending agent or agents is essential. [References: 123]
Moretti, R., P. Torre, et al. (2004). "Cholinesterase inhibition as a possible therapy for
delirium in vascular dementia: a controlled, open 24-month study of 246 patients."
American Journal of Alzheimer's Disease & Other Dementias 19(6): 333-9.
The goal of this study was to determine whether rivastigmine, a dual inhibitor of
acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), has any effect
on delirium in vascular dementia (VaD). The results from this follow-up study
suggest that although delirium is frequent in elderly, cognitively impaired patients,
it might not be a simple consequence of acute disease and hospitalization.
Rather, delirium can be secondary to brain damage and to metabolic
disturbances. According to the Lewy body dementia model, delirium could be
induced by a lack of acetylcholine in the brain. Rivastigmine may help reduce the
frequency of delirium episodes and help shorten their duration. Additional studies
are required to better define the causes of delirium, which currently has no
definitive treatment.
Morikawa, M. and T. Kishimoto (2002). "Probable dementia with Lewy bodies and
risperidone-induced delirium." Canadian Journal of Psychiatry - Revue Canadienne de
Psychiatrie 47(10): 976.
Mussi, C., R. Ferrari, et al. (1999). "Importance of serum anticholinergic activity in the
assessment of elderly patients with delirium." Journal of Geriatric Psychiatry &
Neurology 12(2): 82-6.
To evaluate the importance of serum anticholinergic activity (SAA) in elderly
patients who developed delirium following hospital admission, we performed a
cross-sectional study with consecutively referred inpatients in a university
geriatric medical ward. Sixty-one patients aged 66 to 95 years (mean age:
79.2+/-11.6; 54% females) were recruited. Delirium was assessed by means of
the Confusion Assessment Method, SAA determination, questionnaire for current
drug treatment, past medical history and clinical examination, and blood
chemistries. Patients were divided into two groups according to the absence (N =
49) or the presence (N = 12) of delirium. Delirious patients showed a significantly
higher SAA (23.0 vs 3.9 pmol/mL atropine equivalents, P <.004); they were using
antibiotics (P <.05), neuroleptics (P <.002), barbiturates (P <.004), and
benzodiazepines (P <.005) more frequently. Subjects with delirium were more
likely to have infections and a lower Body Mass Index; they had higher plasma
glucose and creatinine. The multivariate analysis identified SAA and use of
neuroleptics, and benzodiazepines as the most important features independently
associated with delirium. SAA may be a suitable marker for identifying people at
risk of developing delirium. Moreover, neuroleptics and benzodiazepines must be
carefully used in the elderly because of their relationship with the onset of
delirium.
Nakamura, H., P. G. Rose, et al. (2000). "Acute encephalopathy due to aluminum
toxicity successfully treated by combined intravenous deferoxamine and hemodialysis."
Journal of Clinical Pharmacology 40(3): 296-300.
Acute aluminum intoxication is uncommon in clinical practice but can be fatal.
This limited experience is reflected in the paucity of data assessing a viable
approach to the treatment of these patients. In this report, the authors describe
the clinical course and successful, pharmacokinetic-based deferoxaminehemodialysis treatment regimen of a patient with severe aluminum
encephalopathy following alum bladder irrigation. The combined use of
deferoxamine and appropriately timed hemodialysis appears to be a very
reasonable means of treating patients with severe acute aluminum intoxication.
Nakasato, Y., J. Servat, et al. (2005). "Delirium in the older hospitalized patient." Journal
- Oklahoma State Medical Association 98(3): 113-6.
Nayeem, K. and S. O'Keeffe (2003). "Delirium." Clinical Medicine 3(5): 412-5.
Neil, W., S. Curran, et al. (2003). "Antipsychotic prescribing in older people.[see
comment]." Age & Ageing 32(5): 475-83.
Antipsychotic medications have made a significant contribution to the care of the
mentally ill people over the past 50 years, with good evidence that both typical
and atypical agents are effective in the treatment of schizophrenia and related
conditions. In addition they are widely used to good effect in other disorders
including psychotic depression, dementia and delirium. Both typical and atypical
agents may cause severe side-effects and, in the elderly in particular, there is an
increased propensity for drug interactions. If used with care, antipsychotics are
usually well tolerated, especially the atypical drugs. Although antipsychotics are
effective at reducing psychotic symptoms their limitations should be recognised.
They do not 'cure' the underlying illness, and the management of psychotic and
behavioural symptoms must take into consideration treatment of physical illness
as well as psychosocial interventions. In addition, the antipsychotic effect may
take one to two weeks to be evident so doses should not be increased too
rapidly. Often small doses are effective in the elderly if they are given sufficient
time to work. As our understanding of the mechanisms of psychosis improves it
is hoped that new drugs will be developed with novel mechanisms of action with
improved efficacy and reduced side-effects. There are several drugs in
development, some sharing similarities to currently available agents whilst others
have novel mechanisms of actions involving glutamate and nicotinic receptors.
Pharmacogenetics is also likely to be increasingly important over the next few
years. As the genetic basis of many psychiatric disorders becomes more clearly
established it is likely that drugs specifically designed for particular sub-groups of
receptors will be developed. Finally, although the pharmacological treatment of
psychotic disorders in younger people has been given considerable attention,
there is a paucity of good quality research on antipsychotic drug use in older
people. There is a need to redress this balance to ensure that the prescribing of
antipsychotics in older people is evidence based. [References: 80]
Nielsen, J. and A. M. Bruhn (2005). "Atypical neuroleptic malignant syndrome caused
by olanzapine." Acta Psychiatrica Scandinavica 112(3): 238-40; discussion 240.
OBJECTIVE: Neuroleptic malignant syndrome (NMS) is a rare syndrome with
four main symptoms: rigidity, hyperthermia, altered mental status and autonomic
instability. We report a patient with an atypical manifestation of NMS. METHOD:
A single case was reported. RESULTS: A patient with pneumonia developed
delirium and was treated with olanzapine and developed a NMS with fluctuating
hyperthermia and autonomic instability during a month. Only slight rigidity was
present. Creatine kinase was not elevated. The patient was severely agitated
and manic. After discontinuation of olanzapine the patient showed no
psychopathology or hyperthermia. CONCLUSION: NMS should be considered
when patients treated with antipsychotics develop one or more symptoms of
NMS. Copyright (c) 2005 Blackwell Munksgaard
Noyan, M. A., H. Elbi, et al. (2003). "Donepezil for anticholinergic drug intoxication: a
case report." Progress in Neuro-Psychopharmacology & Biological Psychiatry 27(5):
885-7.
We present a case of delirium due to amitriptyline overdose, which resolved
rapidly following initiation of the cholinesterase inhibitor donepezil. The authors
discuss the possibility of cholinesterase inhibitors being an effective choice in the
management of anticholinergic drug induced delirium.
O'Keeffe, S. T. and J. N. Lavan (1999). "Clinical significance of delirium subtypes in
older people." Age & Ageing 28(2): 115-9.
OBJECTIVE: to examine the relative frequency and outcome of clinical subtypes
of delirium in older hospital patients. DESIGN: prospective observational study.
SETTING: acute geriatric unit in a teaching hospital. SUBJECTS: 94 patients
with delirium from a prospective study of 225 admissions. MEASUREMENTS:
clinical subtypes of delirium were determined according to predefined criteria.
Characteristics examined in these subgroups included illness severity on
admission, prior cognitive impairment, mortality, duration of hospital stay and
hospital-acquired complications. RESULTS: of the 94 patients, 20 (21%) had a
hyperactive delirium, 27 (29%) had a hypoactive delirium, 40 (43%) had a mixed
hypoactive-hyperactive psychomotor pattern and seven (7%) had no
psychomotor disturbance. There were significant differences between the four
groups in illness severity (P < 0.05), length of hospital stay (P < 0.005) and
frequency of falls (P < 0.05). Patients with hypoactive delirium were sicker on
admission, had the longest hospital stay and were most likely to develop
pressure sores. Patients with hyperactive delirium were most likely to fall in
hospital. There were no differences in aetiological factors between the groups.
CONCLUSION: outcomes of hospitalization differ in different clinical subtypes of
delirium.
Okamoto, Y., Y. Matsuoka, et al. (1999). "Trazodone in the treatment of delirium."
Journal of Clinical Psychopharmacology 19(3): 280-2.
Omata, N., T. Murata, et al. (2003). "A patient with lithium intoxication developing at
therapeutic serum lithium levels and persistent delirium after discontinuation of its
administration." General Hospital Psychiatry 25(1): 53-5.
Pae, C. U., S. J. Lee, et al. (2004). "A pilot trial of quetiapine for the treatment of
patients with delirium." Human Psychopharmacology 19(2): 125-7.
Twenty-two Korean inpatients with delirium were administered prospectively a
flexible dose of quetiapine. The delirium rating scale-revised-severity 98 (DRS-R98) and clinical global impression scale-severity (CGI-s) scores were assessed at
the time of pre- and post-treatment. The DRS-R-98 and CGI-s scores were
significantly reduced by 57.3% and 55.1%, respectively. Quetiapine was effective
and safe for the treatment of patients with delirium, and could be a useful
alternative agent to classical antipsychotics in the treatment of delirium.
Copyright 2004 John Wiley & Sons, Ltd.
Parellada, E., I. Baeza, et al. (2004). "Risperidone in the treatment of patients with
delirium." Journal of Clinical Psychiatry 65(3): 348-53.
BACKGROUND: The aim of this study was to evaluate the efficacy and safety of
risperidone in the treatment of patients with delirium. METHOD: We conducted a
prospective, multicenter, observational 7-day study in 5 university general
hospitals. Sixty-four patients (62.5% male [N = 40]; mean age: 67.3 +/- 11.4
years) hospitalized due to a medical condition who met criteria for delirium
according to DSM-IV were enrolled in the study. Fifty-six patients received 7 days
of treatment or less, while 8 patients continued treatment for more than 7 days.
Effectiveness was assessed using the Trzepacz Delirium Rating Scale (DRS),
the positive subscale of the PANSS (PANSS-P), the Mini-Mental State
Examination (MMSE), and the Clinical Global Impressions scale (CGI). Safety
assessment included the UKU Side Effect Rating Scale. Risperidone was
administered at the time of diagnosis, and treatment was maintained according to
clinical response. Response to treatment was defined as a reduction in DRS
score to below 13 within the first 72 hours. Data were gathered from April to
December 2000. RESULTS: Risperidone (mean dose = 2.6 +/- 1.7 mg/day at day
3) was effective in 90.6% (58/64) of the patients and significantly improved all
symptoms measured by the scales from baseline to day 7 (mean scores: DRS,
22.5 +/- 4.6 at baseline to 6.8 +/- 7.0 at day 7; PANSS-P, 21.5 +/- 8.8 to 10.1 +/7.3; MMSE, 13.1 +/- 10.9 to 26.4 +/- 8.9; and CGI, 4.5 +/- 0.9 to 1.9 +/- 1.2)
(Friedman test, p <.001 in all cases). Two patients (3.1%) experienced adverse
events, but none showed extrapyramidal symptoms. CONCLUSIONS: Low-dose
risperidone proved to be a safe and effective drug in the treatment of symptoms
of delirium in medically hospitalized patients. These data provide the rationale for
a prospective randomized controlled trial.
Park, C. W. and S. Riggio (2001). "Disulfiram-ethanol induced delirium." Annals of
Pharmacotherapy 35(1): 32-5.
OBJECTIVE: To report a case of delirium, without major autonomic symptoms,
as the primary manifestation of concomitant use of alcohol while taking
disulfiram. CASE SUMMARY: A 50-year-old white woman with a history of
bipolar disorder, type I, and alcohol dependence being treated with disulfiram
was admitted to an inpatient psychiatric unit with a three- to four-day history of a
change in mental status, including deficits in orientation, concentration, and
visual hallucinations. Significant finding on review of systems included the
spurious report of a 9.1-kg weight loss. Tachycardia and nonfocal neurologic
signs on physical examination were also noted. Extensive metabolic, infectious,
and neurologic work-up revealed no abnormalities that alone could explain the
patient's acute confusional state. It was subsequently discovered that the patient
had imbibed alcohol on at least two separate occasions while taking disulfiram
prior to her change in mental status and that a similar, although shorter,
experience had occurred previously. DISCUSSION: This is the first case, to the
authors' knowledge, that describes an acute confusional state as the primary
manifestation of a patient taking alcohol while being prescribed disulfiram as
aversive therapy for alcohol abuse. Possible pathophysiologic mechanisms for
delirium as a complication of alcohol ingestion while taking disulfiram include
disturbances in various neuroendocrine axes, neurotransmitter systems, and
metabolic derangements. Other reports of possible neuropsychiatric
complications of disulfiram therapy are also reviewed. CONCLUSIONS: The
differential diagnosis for the presentation of delirium in a patient known to be
undergoing aversive therapy for alcohol dependence with disulfiram should
include nonadherence to alcohol abstinence.
Park, K. S., C. S. Korn, et al. (2001). "Agitated delirium and sudden death: two case
reports.[see comment]." Prehospital Emergency Care 5(2): 214-6.
Patten, S. B., J. V. Williams, et al. (2001). "Delirium in psychiatric inpatients: a casecontrol study." Canadian Journal of Psychiatry - Revue Canadienne de Psychiatrie
46(2): 162-6.
OBJECTIVE: To investigate the clinical and pharmacoepidemiological
determinants of delirium in a psychiatric inpatient population. METHOD: A casecontrol study design was used. Potential cases and potential controls were
identified using hospital discharge data. The clinical record of each subject was
reviewed using a validated protocol to confirm case and control status.
Subsequently, exposure data were recorded from clinical records. RESULTS:
Subjects admitted to hospital with delirium tended to be older, to have preexisting cognitive deficits, and to have diagnoses of substance use disorders.
Subjects who developed delirium after their admission to hospital were older than
control subjects, more likely to have a history of cognitive impairment, and were
significantly more likely to be treated during the hospitalization with lithium or
anticholinergic antiparkinsonian medications. Antipsychotic medication
exposures were also associated with delirium, but only at standard or abovestandard dosage levels. Antidepressant and sedative-hypnotic medications were
not associated with delirium. CONCLUSIONS: These findings indicate that using
conservative dosages of antipsychotic medications and minimizing the use of
anticholinergic medications for parkinsonian symptoms may help to prevent
delirium in psychiatric inpatients. Anticonvulsant mood stabilizers may convey
less delirium risk than lithium. Antidepressant medications and sedativehypnotics were not important determinants of delirium in this population.
Pi-Figueras, M., A. Aguilera, et al. (2004). "Prevalence of delirium in a geriatric
convalescence hospitalization unit: patient's clinical characteristics and risk precipitating
factor analysis." Archives of Gerontology & Geriatrics - Supplement(9): 333-7.
The aim was to evaluate the prevalence of delirium among patients discharged
from an acute care hospital and admitted to a geriatric convalescence unit
(GCU), and to analyze patient's characteristics and risk precipitating factors.
Sixty-eight patients were analyzed during a 2-week period. The confusion
assessment method (CAM) was used to detect delirium. The precipitating factors
evaluated were: major surgery-intensive care unit(ICU) stay, pulmonary and
heart failure, acute infections, metabolic disorders/anemia,psychoactive
medications, other drugs, severe pain, changing environmental influences and
others. According to CAM, fifteen patients presented delirium (22%), and in 14 of
them(93.3 %) the delirium was developed before admission at GCU. The
precipitating factors in the studied population were the following: changing
environmental influences in 66 patients(97%) (15 with delirium and 51 without
delirium); other drugs 56 (82.3 %) (11 vs. 45);others 56 (82.3%) (9 vs. 24);
psychoactive medications 50 (73.5%) (12 vs. 38); acute infections 48 (70.5 %)
(13 vs. 35); metabolic disorders/anemia 40 (58.8 %) (9 vs. 31); major surgeryICU stay 28 (41.1%) (8 vs. 20); severe pain 26 (38.2%) (6 vs. 20); pulmonary and
heart failure 22 (32.3%) (5 vs. 17). The univariant analysis showed that, none of
the precipitating factors studied was significantly related to delirium. Seventy-two
patients (91.1%) had simultaneously >3 precipitating factors. There were 16
patients with >6 precipitating factors, 7 of 15 with delirium and 9 of the 53 without
delirium (46.6 % vs 16.9 %) (p < 0.05).The prevalence of delirium has been 22
%. Most of the patients had developed delirium before the admission at GCU. A
high proportion of patients had >3 precipitating factors. In the study the presence
of > 6 precipitating factors simultaneously has been significantly related to
delirium.
Raivio, M. M., J. V. Laurila, et al. (2005). "Psychotropic medication and stroke
outcome.[comment]." American Journal of Psychiatry 162(5): 1027; author reply 1027-8.
Rincon, H. G., M. Granados, et al. (2001). "Prevalence, detection and treatment of
anxiety, depression, and delirium in the adult critical care unit." Psychosomatics 42(5):
391-6.
This study assesses the levels of depression, anxiety, and delirium during
admission to three adult critical care units (CCU) and the performance of CCU
staff with respect to detection and treatment. During a 1-month period, 96
consecutive patients were evaluated on the first day of admission by an
independent rater, using the Hospital Anxiety Depression Scale and the
Confusional Assessment Method. Frequency of alcohol use and demographic
data were recorded. CCU teams rarely made diagnoses of anxiety, depression,
or delirium. On at least one screening test, 29.2% of patients were positive.
Delirium was present in 7.3%, depression in 13.7%, anxiety in 24%, and possible
problem drinking in 37.9%. Although some form of psychiatric treatment was
offered to 58%, there was low agreement between psychiatric diagnoses made
by the independent rater and the diagnoses made and treatments used by CCU
staff. This suggests that the CCU staff are using psychotropic medications
without any clear documentation and perhaps clear understanding of the
psychiatric diagnoses they are treating. In summary, we found high rates of
psychiatric disorders in adult CCU patients but low rates of detection and only
moderate rates of treatment by CCU staff.
Samuels, S. and M. Fang (2004). "Olanzapine may cause delirium in geriatric patients."
Journal of Clinical Psychiatry 65(4): 582-3.
Samuels, S. C. and M. M. Evers (2002). "Delirium. Pragmatic guidance for managing a
common, confounding, and sometimes lethal condition." Geriatrics 57(6): 33-8; quiz 40.
Virtually any medical illness, intoxication, or medication can precipitate delirium,
an acute confusional state common among older persons. Delirium is associated
with a high risk of morbidity and mortality, thus management requires thorough
assessment and swift but careful action. A range of nonpharmacologic
interventions can aid management of delirium, but in general, emergent, empiric
pharmacotherapy is indicated for acute cases. Key to assessment and diagnosis
is ruling out dementia and depression, determining the presence of delirium, and
establishing an underlying cause. Several screening tools are available to aid this
effort. Vigilance can help reduce the high number of patients discharged with
unresolved symptoms.
Sasaki, Y., T. Matsuyama, et al. (2003). "A prospective, open-label, flexible-dose study
of quetiapine in the treatment of delirium." Journal of Clinical Psychiatry 64(11): 131621.
BACKGROUND: Delirium is an organic psychiatric syndrome characterized by
fluctuating consciousness and impaired cognitive functioning. High-potency
typical neuroleptics have traditionally been used as first-line drugs in the
treatment of delirium. However, these drugs are frequently associated with
undesirable adverse events including extrapyramidal symptoms (EPS). The
purpose of the present open-label, flexible-dose study was to provide preliminary
data on the usefulness and safety of quetiapine for patients with delirium.
METHOD: Twelve patients with DSM-IV delirium were treated with flexible doses
of open-label quetiapine (mean +/- SD dosage = 44.9 +/- 31.0 mg/day). To
evaluate the usefulness and safety of quetiapine, scores from the Delirium Rating
Scale, Japanese version, were assessed every day (for 1 outpatient, at least
twice per week), and scores from the Mini-Mental State Examination, Japanese
version, and the Drug-Induced Extrapyramidal Symptom Scale were assessed at
baseline and after remission of delirium. Data were gathered from April to
October 2001. RESULTS: All patients achieved remission of delirium several
days after starting quetiapine (mean +/- SD duration until remission = 4.8 +/- 3.5
days). Quetiapine treatment was well tolerated, and no clinically relevant change
in EPS was detected. CONCLUSION: Quetiapine may be a useful alternative to
conventional neuroleptics in the treatment of delirium due to its rapid onset and
relative lack of adverse events. Further double-blind, placebo-controlled studies
are warranted.
Schneir, A. B., S. R. Offerman, et al. (2003). "Complications of diagnostic physostigmine
administration to emergency department patients." Annals of Emergency Medicine
42(1): 14-9.
STUDY OBJECTIVES: Literature exists describing the complications associated
with therapeutic physostigmine administration. No series exists detailing strictly
diagnostic use. Our objective was to document the complications associated with
diagnostic physostigmine administration in emergency department (ED) patients
suspected of having antimuscarinic delirium. METHODS: Two reviewers blinded
to the study purpose performed a retrospective chart review on all adult patients
administered physostigmine diagnostically over a 79-month period at a tertiarycare hospital. Twenty percent of charts were reviewed by both abstractors. The
data abstracted from the chart included total dose of physostigmine, effect on
mental status, any subsequent complications, or any use of atropine. Discharge
summaries, toxicology consultations, and urine drug screens were used to
determine the cause of the altered mental status. RESULTS: Thirty-nine adult
patients were administered varying doses of physostigmine (range 0.5 to 2 mg).
The reviewers were able to determine the cause of the altered mental status in
35 patients. The cause was purely antimuscarinic in 19 patients, purely
nonantimuscarinic in 10 patients, mixed antimuscarinic and nonantimuscarinic in
2 patients, psychiatric in 4 patients, and unknown in 4 patients. A total of 22
patients had full reversal of delirium, and this group comprised all 19 patients
with a purely antimuscarinic cause and 3 patients in whom a cause was never
determined. One (2.6%) in 39 patients had a brief convulsion without adverse
sequelae. This patient was poisoned with an antimuscarinic drug. No patient had
dysrhythmias, had signs of cholinergic excess, or was administered atropine.
CONCLUSION: Diagnostic physostigmine administration was without significant
complication when given to ED patients suspected of having antimuscarinic
delirium. Although a relatively small series, it contributes to the safety profile of
physostigmine.
Segatore, M. and D. Adams (2001). "Managing delirium and agitation in elderly
hospitalized orthopaedic patients: Part 2--Interventions." Orthopaedic Nursing 20(2): 6173; quiz 73-5.
Delirium, a disorder of consciousness that may afflict over one-half of elderly
surgical orthopaedic patients is a common sequela of surgery in the elderly.
Agitation, either as an element of the delirium or dimension of a preexisting
dementia, is another common behavioral problem that can confront the
orthopaedic nurse in acute care. It is time now to tear down the barriers to
intelligent and compassionate care of patients with agitation and delirium,
including late or missed recognition and diagnosis, biases about what is "normal"
and acceptable behavior in the elderly, and lack of familiarity with pharmacologic
strategies. In Part 1 (Jan/Feb issue), current thinking about the phenomena was
presented, including hypotheses about causation and pathophysiology. That
foundation is intended to serve as the basis for the current discussion. The triad
of interventions available to manage disorganized behavior in elderly orthopaedic
patients is presented in Part 2. They include an extensive selection of
pharmacologic options, a discussion of therapeutic use of self and
environmental-organizational issues to address and consider on a case-by-case
basis. Though it may be impossible to prevent behavioral decompensation during
an acute orthopaedic admission, it is certainly possible to improve our
performance to date, using a compassionate, intelligent, and inclusive approach
with every patient.
Serio, R. N. (2004). "Acute delirium associated with combined diphenhydramine and
linezolid use." Annals of Pharmacotherapy 38(1): 62-5.
OBJECTIVE: To report a case of delirium with hallucinations presumably caused
by the combination of diphenhydramine and linezolid. CASE SUMMARY: A 56year-old white man was receiving diphenhydramine 300 mg/d for 2 days to treat
pruritus caused by a bullous rash possibly induced by vancomycin. He
subsequently developed visual and auditory hallucinations, with erratic,
aggressive behavior persisting for 3 days. Central anticholinergic syndrome was
first suspected, but the long duration and exaggerated response by a patient not
prone to anticholinergic toxicity suggest that a second agent may have enhanced
the reaction. DISCUSSION: The pharmacodynamic properties of linezolid make
this drug a likely contributor to the marked, prolonged effects experienced by this
patient. The Naranjo probability scale suggests a possible relationship between
the reaction and the combination of diphenhydramine and linezolid.
CONCLUSIONS: Drug-induced delirium can occur with several drugs, including
diphenhydramine. Linezolid has dopaminergic properties that may enhance the
central nervous system effects of anticholinergics. Precautionary monitoring of
mental status should be advised when concomitantly administering linezolid with
drugs in this class.
Sim, F. H., D. G. Brunet, et al. (2000). "Quetiapine associated with acute mental status
changes." Canadian Journal of Psychiatry - Revue Canadienne de Psychiatrie 45(3):
299.
Skrobik, Y. K., N. Bergeron, et al. (2004). "Olanzapine vs haloperidol: treating delirium
in a critical care setting.[see comment]." Intensive Care Medicine 30(3): 444-9.
OBJECTIVE: To compare the safety and estimate the response profile of
olanzapine, a second-generation antipsychotic, to haloperidol in the treatment of
delirium in the critical care setting. DESIGN: Prospective randomized trial.
SETTING: Tertiary care university affiliated critical care unit. PATIENTS: All
admissions to a medical and surgical intensive care unit with a diagnosis of
delirium. INTERVENTIONS: Patients were randomized to receive either enteral
olanzapine or haloperidol. MEASUREMENTS: Patient's delirium severity and
benzodiazepine use were monitored over 5 days after the diagnosis of delirium.
MAIN RESULTS: Delirium Index decreased over time in both groups, as did the
administered dose of benzodiazepines. Clinical improvement was similar in both
treatment arms. No side effects were noted in the olanzapine group, whereas the
use of haloperidol was associated with extrapyramidal side effects.
CONCLUSIONS: Olanzapine is a safe alternative to haloperidol in delirious
critical care patients, and may be of particular interest in patients in whom
haloperidol is contraindicated.
Slatkin, N. and M. Rhiner (2004). "Treatment of opioid-induced delirium with
acetylcholinesterase inhibitors: a case report." Journal of Pain & Symptom Management
27(3): 268-73.
A 55-year-old woman with advanced ovarian cancer and severe pain developed
hypoactive delirium after an increase in her opioid dosage. Myoclonus and
delirium improved dramatically with the intravenous injection of the
acetylcholinesterase inhibitor physostigmine, and this improvement was
maintained during the administration of donepezil, an oral medication with similar
pharmacodynamic properties. Evidence for a disorder of cholinergic
neurotransmission in opioid-induced delirium is discussed, as is the rationale for
treatment with acetylcholinesterase inhibitors and other cholinomimetic agents.
Sommer, B. R., L. C. Wise, et al. (2002). "Is dopamine administration possibly a risk
factor for delirium?" Critical Care Medicine 30(7): 1508-11.
OBJECTIVE: We explored the possibility that the administration of intravenous
dopamine increases the risk for delirium as manifested by need for haloperidol.
DESIGN: This study was based on a retrospective analysis. To examine the
contribution of dopamine in the prediction of need for haloperidol, a multivariate
logistic regression model was used. SETTING: University hospital. PATIENTS:
All inpatient admissions to Stanford University Hospital over a 1-year period (n =
21,844). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
Dopamine administration was associated with nearly a tripling of the odds of
subsequent need of the antipsychotic drug (chi-square = 108, df = 1, p =.0001,
odds ratio = 2.89), even after intensive care unit admission and diagnostic related
group weight were considered as indicators of severity of illness. Even when
analysis was limited to patients seen in the intensive care unit setting (n = 3,308),
dopamine administration remained a very strong risk factor for haloperidol and
hence possibly for delirium. The increased risk of need for haloperidol in patients
administered dopamine is evident in every age group after age 20.
CONCLUSIONS: The retrospective nature of this study, the inexact method to
assess acuity, and, most of all, the use of haloperidol as an indicator of the
presence of delirium preclude concluding that dopamine is directly a risk factor
for delirium, much less a causal risk factor. However, the association is potent
enough to suggest this possibility strongly and thus supports the need for
prospective studies to examine the relationship between dopamine and delirium
and to consider possible prophylactic treatment against delirium in those given
dopamine.
Sykes, N. and A. Thorns (2003). "Sedative use in the last week of life and the
implications for end-of-life decision making." Archives of Internal Medicine 163(3): 3414.
BACKGROUND: The use of sedation at the end of life has aroused ethical
controversy, attracting accusations of hastening death by gradually increasing
sedative doses. The doctrine of double effect has been introduced as an ethical
defense. This study aimed to determine how sedative doses change at the end of
life and how often the doctrine of double effect might be relevant. METHODS:
Case note review was performed of 237 consecutive patients who died in a
specialist palliative care unit. Sedative dose changes during the last week of life
were noted and survival from admission was compared between groups of
patients receiving no sedation, sedation for 7 days, or a commencement of
sedation in the last 48 hours of life. There was detailed review of notes from
patients who received a marked increase in sedative dose to explore the
applicability of the doctrine of double effect. RESULTS: Sedation was given to
48% of patients. Of these, 13% received sedatives for 7 days or more, while 56%
commenced sedative use only in the last 48 hours of life. The groups receiving
no sedation or sedation for less than 48 hours had the shortest survival from
admission (mean, 14.3 and 14.2 days), whereas the 7-day sedation group
survived for a mean of 36.6 days (P<.001). Sedative use and dose increased
toward the end of life, but the detailed case note review disclosed only 2 cases
where the doctrine of double effect may have been implicated. CONCLUSION:
Sedative dose increases in the last hours of life were not associated with
shortened survival overall, suggesting that the doctrine of double effect rarely has
to be invoked to excuse sedative prescribing in end-stage care.
Tabet, N. and R. Howard (2001). "Optimising management of delirium. Patients with
delirium should be treated with care.[comment]." BMJ 322(7302): 1602-3.
Tei, Y., T. Morita, et al. (2004). "Torsades de pointes caused by a small dose of
risperidone in a terminally ill cancer patient." Psychosomatics 45(5): 450-1.
Temple, M. J. (2003). "Use of atypical anti-psychotics in the management of posttraumatic confusional states in traumatic brain injury." Journal of the Royal Army
Medical Corps 149(1): 54-5.
The use of atypical anti-psychotics (AAP) in the treatment of organic
neuropsychiatric syndromes is little reported. We present a case of posttraumatic delirium with delusions treated with Risperidone and discuss the use of
AAP's in this situation.
Torres, R., D. Mittal, et al. (2001). "Use of quetiapine in delirium: case reports."
Psychosomatics 42(4): 347-9.
Tune, L. (2002). "The role of antipsychotics in treating delirium." Current Psychiatry
Reports 4(3): 209-12.
The mainstay of the pharmacologic management of delirium remains typical
antipsychotics, primarily haloperidol. Typical antipsychotics are associated with
significant side effects, particularly in the elderly. This article reviews the
literature on the use of both typical and atypical antipsychotics in the
management of acute delirium, with a focus on the elderly. In this population,
typical antipsychotics are associated with substantially more drug induce side
effects--either extrapyramidal side effects or anticholinergic effects from the
antipsychotics alone or in combination with benztropine or trihexyphenidyl.
Anticholinergic toxicity is especially problematic in delirious, demented patients,
because most dementias are associated with pre-existing deficiencies in
cholinergic neurotransmission.These issues will be reviewed for typical
antipsychotics as well as the emerging literature on the use of atypical
antipsychotics-- risperidone, olanzapine, and quetiapine--for pharmacologic
management of acute delirium. Data from two studies conducted at the Wesley
Woods Center at Emory University will be briefly reviewed as they constitute the
largest series to date investigating the pharmacologic management of delirious
demented patients.
Tune, L. E. (2000). "Serum anticholinergic activity levels and delirium in the elderly."
Seminars in Clinical Neuropsychiatry 5(2): 149-53.
This article will briefly review the clinical studies focusing on measurement of
serum levels of anticholinergic activity in delirious states. Three experimental
approaches have been taken. First, to identify medications currently prescribed
that have subtle anticholinergic effects. The current "list" includes 48 commonly
prescribed medications. Second, to associate serum anticholinergic activity with
delirium in various clinical states including postcardiotomy delirium,
postelectroconvulsive delirium, delirious elderly medical inpatients, and nursing
home patients. Third, to intervene in patients with elevated anticholinergic activity
by reducing known anticholinergics and correlating this reduction with clinical
measures of cognition and delirium. Our most recent data investigate the impact
of anticholinergics on demented patients. Prevalence of delirium was significantly
higher in patients receiving larger numbers of anticholinergics. [References: 25]
Tune, L. E. (2001). "Anticholinergic effects of medication in elderly patients." Journal of
Clinical Psychiatry 62 Suppl 21: 11-4.
Anticholinergic toxicity is a common problem in the elderly. It has many effects
ranging from dry mouth, constipation, and visual impairments to confusion,
delirium, and severe cognitive decline. The toxicity is often the result of the
cumulative anticholinergic burden of multiple prescription medications and
metabolites rather than of a single compound. The management of elderly
patients, particularly those suffering from dementia, should therefore aim to
reduce the use of medications with anticholinergic effects. [References: 19]
Tune, L. E. and S. Egeli (1999). "Acetylcholine and delirium." Dementia & Geriatric
Cognitive Disorders 10(5): 342-4.
The neurotransmitter acetylcholine has been implicated in animal and human
studies of delirium. This chapter will briefly review the clinical studies focussing
on measurement of serum levels of anticholinergic activity in delirious states.
Three approaches have been taken. First, to identify medications currently
prescribed that have subtle anticholinergic effects. The current 'list' includes 48
commonly prescribed medications. Second, to associate serum anticholinergic
activity with delirium in various clinical states including postcardiotomy delirium,
postelectroconvulsive delirium, delirious elderly medical inpatients, and nursing
home patients. Third, to intervene in patients with elevated anticholinergic activity
by reducing known anticholinergics and correlating this reduction with clinical
measures of cognition and delirium. Our most recent data investigates the impact
of anticholinergics on demented patients. Rates of delirium were significantly
higher in patients receiving larger numbers of anticholinergics. [References: 9]
Ueki, H. and N. Ogawa (2004). "Resolution of delusional depression after recovery from
delirium." Comprehensive Psychiatry 45(3): 230-4.
Little attention has been given to the effects of delirium on the course of
depression. In clinical practice, we sometimes observe delirium brought on
incidentally by severe physical illness or therapeutic drugs such as tricyclic
antidepressants. Recently, investigators have discussed whether delirium can in
fact have a beneficial effect on the course of depression. We present three cases
of delusional depression in which depressive symptoms resolved after patients
recovered from incidental delirium caused in two cases by medication, and by
respiratory distress leading to asphyxiation in the third. We surmise that delirium
may create a biological effect similar to that of electroconvulsive therapy (ECT),
which is widely hailed as an effective treatment for delusional depression.
Retrograde amnesia caused by delirium and the supportive milieu during
treatment of the delirium may have a beneficial psychological effect on recovery
from delusional depression. [References: 22]
Vatsavayi, V., S. Malhotra, et al. (2003). "Agitated delirium with posterior cerebral artery
infarction." Journal of Emergency Medicine 24(3): 263-6.
Infarction of the posterior cerebral artery may present only with signs of agitated
delirium and an acute confusional state. In the absence of other prominent
neurological deficits, this can be easily mistaken for toxic-metabolic
encephalopathy, head trauma, post-ictal confusion, or a psychiatric disorder.
Appropriate head imaging studies are important to detect an illness that might
otherwise be missed and left untreated.
Vilke, G. M. and T. C. Chan (2002). "Agitated delirium and sudden death.[comment]."
Prehospital Emergency Care 6(2): 259; author reply 259-60.
Weintraub, D. and S. Lippmann (2001). "Delirious mania in the elderly." International
Journal of Geriatric Psychiatry 16(4): 374-7.
Delirious mania is a clinical syndrome in which the signs and symptoms of
delirium manifest themselves in the context of a manic episode. Though there
have been numerous descriptions and case reports of this syndrome, all have
described mania as the presenting feature, with signs of delirium developing
subsequently, and none of the vignettes have involved elderly patients. We
report two cases of elderly individuals with mania who initially presented as in a
delirium. Both of them experienced clear manic episodes, which were confirmed
by their psychiatric histories and clinical responses to mood stabilizers. Mania
needs to be in the differential diagnosis of elderly people presenting with
confusion, disorientation, and perceptual changes, particularly in those with a
history of bipolar disorder. Copyright 2001 John Wiley & Sons, Ltd.
Weiss, A. P. and G. B. Murray (2001). "Abuse of topical analgesic.[comment]."
American Journal of Psychiatry 158(4): 651-2.
Wengel, S. P., W. J. Burke, et al. (1999). "Donepezil for postoperative delirium
associated with Alzheimer's disease." Journal of the American Geriatrics Society 47(3):
379-80.
Winell, J. and A. J. Roth (1497). "Psychiatric assessment and symptom management in
elderly cancer patients." Oncology (Huntington) 19(11): 1479-90; discussion 1492.
The number of older adults in the general population continues to grow. As their
numbers rise, the elderly and the management of their medical problems must be
of increasing concern for health-care professionals. Within this older population,
cancer is a leading cause of morbidity and mortality. Although many studies have
looked at the psychiatric implications of cancer in the general population, few
studies tackle the issues that may face the older adult with cancer. This article
focuses on the detection and treatment of depression, anxiety, fatigue, pain,
delirium, and dementia in the elderly cancer patient. [References: 65]
Wolters, E. C. and H. W. Berendse (2001). "Management of psychosis in Parkinson's
disease." Current Opinion in Neurology 14(4): 499-504.
Psychosis is quite common in Parkinson's disease (approximately 25% of
patients) and therefore constitutes a serious public health problem. All patients
suffering from idiopathic Parkinson's disease, and especially elderly and
demented patients, are at risk of developing delusions or hallucinations. The
most prominent psychotogenic factors are dopaminomimetic agents, which may
induce dopamine hypersensitivity in the frontal and limbic dopamine projection
regions, and consequently, either directly or indirectly, elicit psychotic signs and
symptoms. A Parkinson's disease-related cholinergic deficit in combination with
an age-related further loss of cholinergic integrity also plays a prominent role.
Psychosis in Parkinson's disease patients appears to be a more important
contributor to caregiver distress than motor parkinsonism. Psychosis therefore
probably represents the single greatest risk factor for nursing home placement.
Typical antipsychotic drugs, because of their selective dopamine receptor
antagonistic effects, can reduce psychotic signs but at the cost of an increase in
parkinsonism. As a consequence of a non-selective antagonism at both
serotonergic and dopaminergic receptors, atypical antipsychotic drugs are
associated with fewer extrapyramidal side-effects. On the other hand,
hypersensitivity to these agents may induce delirium or a malignant neuroleptic
syndrome. Atypical antipsychotic agents such as clozapine, quetiapine and
olanzapine should therefore be started at very low doses that are increased
gradually. Cholinomimetic therapy may prove to be helpful in the prevention and
treatment of psychotic manifestations in Parkinson's disease patients, given the
effects observed in patients suffering from dementia with Lewy bodies.
[References: 43]
Young, C. C. and E. Lujan (2004). "Intravenous ziprasidone for treatment of delirium in
the intensive care unit." Anesthesiology 101(3): 794-5.