CASE 1: BEWARE ‘OLD MAN KIPLING’
Mrs. A, age 87, has Alzheimer’s disease. About 1 month before presentation, she entered a nursing home because of increasing agitation, paranoia, auditory and visual hallucinations, and decreased ability to care for herself. Her doctor started risperidone, 0.5 mg bid, to treat her agitation and psychosis.
Two days later, Mrs. A barricaded herself in her room. She told staff that “Old Man Kipling” was trying to break in, steal her money, and kill her and her son. She was sent to the emergency room; psychiatric consultation was ordered.
Mrs. A also has hypertension, renal cell carcinoma, anemia, and chronic renal failure. She had seen a psychiatrist for worsening cognitive function but has no other psychiatric history. Brain CT without contrast revealed generalized atrophy with no acute cerebral events. Workup showed decreased potassium (3.1 mEq/L), which returned to normal after Mrs. A was given potassium chloride, 20 mEq/d for 5 days. Other lab results were normal. Hydrochlorothiazide, 25 mg/d for hypertension, was stopped to prevent potassium depletion. No neurologic deficits were found.
Upon admission to the geriatric psychiatry unit, Mrs. A was paranoid and agitated. She talked to an imaginary person, continued to fear “Old Man Kipling,” and again tried to barricade herself.
ECG at admission—done because of Mrs. A’s age, cardiac history, and hydrochlorothiazide use—showed a corrected QT (QTc) interval of 494 msec, nearly 50 msec above the high-normal range for women. The interval was 460 msec at baseline (before risperidone treatment). Mrs. A was switched to olanzapine, 5 mg at bedtime, but her QTc intervals stayed between 494 and 495 msec, and her psychotic symptoms continued unabated.
Table 1
Mean antipsychotic-induced QTc interval change from baseline to steady state
| Antipsychotic | Mean QTc interval change |
|---|---|
| Haloperidol | 4.7 msec |
| Olanzapine | 6.4 msec |
| Risperidone | 10.0 msec |
| Quetiapine | 14.5 msec |
| Ziprasidone | 20.6 msec |
| Thioridazine | 35.8 msec |
| Source: reference 2. | |
The authors’ observations
Antipsychotics, used to treat behavioral disturbances in older patients, can prolong QTc intervals. Although often asymptomatic, a prolonged interval can lead to torsade de pointes, a polymorphic ventricular arrhythmia that can progress to ventricular fibrillation and cause sudden death.
Reilly et al1 suggest that antipsychotic-induced QTc prolongation may be dose-dependent. Age >65 is also a risk factor.
Start low and go slow when prescribing antipsychotics to patients with QTc intervals 450 msec. If prolonged intervals persist, switch antipsychotics and consult a cardiologist to help manage the patient’s care.
Switching agents will not entirely eliminate the risk, however. Mrs. A’s QTc interval remained elevated despite the switch to olanzapine, which is less likely than most antipsychotics to increase the interval.
Among mostly healthy men, haloperidol was shown to cause a lower mean QTc interval increase than other antipsychotics (Table 1), although QTc prolongations >60 msec were reported in 4% of those who took haloperidol.2 The agent also may cause tardive dyskinesia, and that risk is multiplied in patients >age 65.3 For Mrs. A, however, persistent psychosis and declining function outweighed the risks.
With haloperidol, start low and titrate slowly to reduce the risk of extrapyramidal symptoms (EPS). Decrease the dosage if involuntary movements develop. If a haloperidol decrease would lead to decompensation, add an anticholinergic agent such as benztropine, but be careful because anticholinergics can worsen cognitive function.
Test for involuntary movements before starting an antipsychotic. Retest every 4 to 6 months, when changing dosages or switching antipsychotics, and when patients complain of EPS.
CASE 1 CONTINUED: GOODBYE MR. KIPLING
Mrs. A was switched to haloperidol, 0.5 mg bid titrated over 3 weeks to 2 mg every morning and 3 mg nightly. Daily ECGs across 10 days showed QTc intervals 467 msec. Abnormal Involuntary Movement Scale testing showed no EPS. Her blood pressure was stable, ranging from 110 to 130 mm Hg (systolic) and 70 to 80 mm Hg (diastolic).
The patient became calmer and her paranoid delusions and hallucinations disappeared. Her Folstein Mini-Mental Status Examination score during her third and final week of hospitalization was 16, indicating moderate dementia. She was discharged to her son’s care; outpatient psychiatric care was also arranged. The psychiatrist started donepezil, 5 mg/d titrated to 10 mg/d after 6 weeks, to treat her memory impairments.
More than 1 year later, Mrs. A lives at home with her son. She has not needed psychiatric hospitalization. Her primary care physician monitors her cardiac health.
CASE 2: SUICIDALITY AND SEXUAL BEHAVIOR
Mr. B, age 50, has battled schizoaffective disorder for more than 30 years. Upon presenting to the ER, he told clinicians he planned to jump from his seventh-floor apartment after arguing with his neighbor.
The patient had been taking gabapentin, 300 mg bid; olanzapine, 10 mg at bedtime; citalopram, 20 mg/d; clonazepam, 1 mg at bedtime for panic symptoms; atorvastatin, 10 mg/d for hyperlipidemia; and esomeprazole, 40 mg/d, for ongoing GI problems. He also has bradycardia.