One month after starting the fentanyl patch, Mrs. M complained of sudden forgetfulness, low energy, poor concentration, and increased sleep. The physician suspected depression with possible comorbid anxiety and prescribed sertraline, 50 mg/d, and alprazolam, 0.5 mg bid. Mrs. M stopped sertraline after 3 days because it was causing diarrhea but kept taking alprazolam.
Mrs. M saw her primary care physician once after starting alprazolam and sertraline but missed her most recent appointment last month. The physician says he inadvertently approved at least 1 premature request for an alprazolam refill.
Six days after admission, Mrs. M’s sedation, cognitive impairment, and lethargy persist. She reports no mood and anxiety problems, and we have not restarted alprazolam.
The authors’ observations
The fentanyl patch most likely began to diminish Mrs. M’s alertness soon after she started using it. The doctor, however, mistook cognitive slowing for new-onset depression or anxiety. Depressive symptoms can imitate dementia, but Mrs. M’s severe sedation and denial of depressive symptoms suggest a medication side effect.
The primary care physician’s reconstruction of Mrs. M’s history explained her positive benzodiazepine reading, and her use of the short-acting benzodiazepine alprazolam could account for her sudden-onset paranoia and cognitive decline (Box). Benzodiazepines can cause behavioral side effects such as disinhibition, agitation, or paranoia, and patients age ≥65 are at increased risk for these side effects.4 In particular, benzodiazepines with half-lives ≥6 to 8 hours such as clonazepam and oxazepam can cause short-term memory impairment, confusion, and delirium.5-7
Reconstructing a patient history: What to ask for, and how to ask
Because alprazolam’s mean plasma half-life can be as short as 8 hours, 3 to 4 daily doses usually are necessary for day-long therapeutic effect. Multiple dosing of benzodiazepines, however, can cause withdrawal symptoms such as rebound anxiety and insomnia. To quell these symptoms, patients often take higher or additional benzodiazepine doses without a doctor’s permission, leading to potential overuse, addiction, or overdose.Reconstructing treatment history is critical if the patient or family members cannot recall past treatments or if the patient cannot communicate.
Get permission from the patient or family as required under the Health Insurance Portability and Accountability Act. Then contact the primary care or other prescribing physician to obtain:
- a copy of the physician’s last progress note and initial evaluation
- notes about adverse reactions to current or past medications
- trials of medications and other treatments relevant to the current complaint.
In emergent cases when the patient is unresponsive or mentally incapacitated and no family members are available, follow the above steps and initiate treatment. Carefully document that the patient was incoherent, his life was in danger, and you could not reach a family member for permission to treat.
If you cannot communicate with the patient or contact a family member but care is less emergent, consult the hospital’s ethics committee to see if a guardian has been appointed. Contact the primary care physician only after the guardian grants permission.
When prescribing benzodiazepines (especially in older patients) watch for signs of overuse or abuse, such as early requests for refills, unkempt appearance, excessive sleepiness, or agitation (Table 1).
Warning signs of opioid, benzodiazepine overuse
| Frequent requests for early refills |
| Patient exceeds prescribed dosage without authorization |
| Patient reports lost/stolen prescription; if patient has history of substance abuse/dependence or legal problems, even 1 report should raise a red flag |
| Patient increasingly unkempt or impaired |
| Negative mood change |
| Agitation |
| Patient involved in car or other accidents |
| Sedation |
| Purposeful oversedation, particularly when patient has an apparent secondary gain from opioid use (such as qualifying for disability benefits or escaping from work) |
| New-onset cognitive impairment |
| Patient abusing alcohol or other illicit CNS depressants |
The authors’ observations
Persistent chronic pain in the elderly can diminish health and quality of life, resulting in depression, social isolation, immobility, and sleep disturbance.
Managing an older patient’s pain can be challenging (Table 2). Opioids are effective painkillers, but even at relatively low dosages they can diminish function and cognition and increase risk of delirium. Also, patients’ ability to tolerate different opioids at different dosages varies widely.
Mrs. M’s opioid regimen was intolerable and numerous other treatments did not alleviate her pain. At this point, replacing fentanyl with another opioid was our best option.8
We decided to try methadone, which is indicated for moderate to severe pain that does not respond to nonnarcotic treatments. Methadone often is used for chronic pain associated with arthritis or malignancy.
Methadone is less sedating, more tolerable, and carries a lower risk of cognitive side effects than other opioids. Methadone also is fast- and long-acting—its analgesic effects begin within 30 minutes to 1 hour of oral administration9 and last approximately 12 hours, thus reducing the risk of breakthrough pain. Methadone also: