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Ms. B, age 48, is admitted to our hospital after overdosing on unknown amounts of amitriptyline, diphenhydramine, and laxatives. Three days after admission, the psychiatry service is consulted to assess her for “bipolar disorder.” Although Ms. B does not have a psychiatric history, her internist believes her pressured speech and psychomotor agitation warrant investigation.
During the initial psychiatric interview, Ms. B is disoriented, with fluctuating alertness and cognition. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU)1 is positive for delirium. We perform a delirium workup while we start Ms. B on olanzapine, 5 mg/d orally and 5 mg intramuscular (IM) every 8 hours as needed.
Ms. B’s laboratory results (complete blood count, complete metabolic profile, urinalysis, chest roentgenogram, vitamin B12 level, blood alcohol level, urine drug screen, arterial blood gas, and head CT) are unremarkable except for her amitriptyline/nortriptyline level, which is in the toxic range. On physical examination, Ms. B’s heart rate and temperature are elevated, her pupils are dilated and sluggish, and her skin is hot and dry. Based on these findings, we determine that Ms. B’s delirium most likely is an anticholinergic syndrome from amitriptyline/diphenhydramine toxicity.2 We discontinue olanzapine after only 2 doses because of its potential anticholinergic effects.3
In hospitalized patients, delirium is one of the most frequently encountered mental disorders, but because of its variable presentation the condition often is underrecognized and undertreated, which leads to longer hospitalizations and increased mortality.4,5 Ms. B’s case illustrates the classical delirium presentation (Table 1),6 highlighting 2 hallmark features of the disorder: inattention and an acute fluctuating course.4 Unfortunately, delirium is a diverse disorder that may present with numerous nonclassical symptoms—including lethargy, emotionality, sleep irregularities, and neurologic abnormalities—in lieu of more commonly recognized symptoms.4,5
In addition to recommending identifying and addressing the underlying acute illness, American Psychiatric Association guidelines suggest prescribing psychotropic medications to treat delirium symptoms.5,7 Antipsychotics are considered first-line pharmacotherapy because they have been shown to lower hospital mortality rates8 and improve delirium symptoms even before underlying medical etiologies are treated.5 Haloperidol is the mainstay of delirium treatment.8 Compared with atypical antipsychotics in delirium treatment, haloperidol doses <3.5 mg/d have not been associated with an increase in extrapyramidal symptoms (EPS).9
Although not devoid of side effects, atypical antipsychotics are an alternative to haloperidol.8,10 This article briefly summarizes the current evidence on the use of atypicals for treating delirium.
Table 1
Delirium: Diagnostic criteria
| Delirium describes a group of related disorders with variable clinical presentations and differing causation. Regardless of the etiology, all types of delirium share a set of common symptoms that include: |
| Disturbances of consciousness and attention |
| Changes in cognition such as memory deficit, language disturbance, or disorientation |
| Perceptual disturbances not better accounted for by dementia |
| Abrupt onset (usually hours to days) |
| Fluctuating symptoms throughout the course of the day |
| Source: Adapted from reference 6 |
CASE CONTINUED: IM ziprasidone
After reassessing our treatment options, we prescribe ziprasidone, 10 mg IM twice a day, and an additional 10 mg IM every 12 hours as needed. Ziprasidone’s minimal anticholinergic and sedative effects3 seem favorable for Ms. B’s delirium; however, this medication has several drawbacks, including IM administration, greater expense compared with intravenous haloperidol, and risk of adverse cardiac affects, specifically prolonged corrected QT (QTc) interval.11 Bioavailability of oral ziprasidone is markedly less than the IM preparation (~60% vs 100%, respectively), and oral bioavailability decreases to approximately 30% when taken without food.12 Given Ms. B’s her current mental state, we feel that IM ziprasidone is a more reliable means to achieve therapeutic efficacy.13
With respect to cardiac concerns, we evaluate Ms. B’s predisposing and precipitating risk factors.11 Family members confirm that she had no cardiac history. We obtain baseline ECGs and continually monitor her QTc interval, which remained at <500 msec during ziprasidone treatment.
Ms. B tolerates ziprasidone and we note modest improvement in her mental status after 2 days of treatment; her vigilant-A portion of the CAM-ICU improves, but she still screens positive for delirium. During the next week Ms. B develops several medical comorbidities, including ileus, urinary tract infection, and methicillin-resistant Staphylococcus aureus infection. Despite these complications her mental status continues to improve. Within 6 days, Ms. B’s attention and cognition improve dramatically. She is oriented and able to engage in medical decision-making, and she screens negative for delirium on the CAM-ICU. We begin to assess her for psychiatric disorders that may have contributed to her hospitalization.
Evidence for antipsychotics