Question 1

A 74-year-old man with chronic schizophrenia on clozapine 300mg/day presents with his daughter, who is concerned about worsening memory and confusion. She says "he used to be sharp for his age, but over the past 6 months he's been forgetting things and sometimes seems confused." His other medications include lisinopril and metformin. On your medication reconciliation, you ask about OTC medications and he says "just Benadryl, 50mg every night for sleep. I've taken it for years." What is the most likely cause of his cognitive decline, and what is your first intervention?

Accepted Answer

Answer A jumps to a dementia diagnosis without first addressing the reversible cause. Answer C may eventually be considered but reducing a clozapine dose in a stable patient risks psychotic relapse, and the diphenhydramine is the more easily modifiable variable. Answer D normalizes a potentially reversible problem. The teaching point: always assess for reversible causes of cognitive decline before attributing it to neurodegeneration. In elderly patients on psychiatric medications, anticholinergic burden is the most common reversible cause, and OTC diphenhydramine is the most common unrecognized contributor.

Question 2

A 45-year-old woman tells you she takes Tylenol PM every night for sleep and has for 2 years. She says it "used to work great but doesn't really help anymore." She also reports dry mouth, constipation, and occasional blurred vision. She asks for a "stronger sleep medication." What do you explain?

Accepted Answer

Answer A adds a controlled substance without addressing the existing problem or attempting evidence-based insomnia treatment first. Answer C ignores the tolerance, the ongoing anticholinergic burden, and the acetaminophen exposure. Answer D solves only the acetaminophen problem while perpetuating the diphenhydramine tolerance and anticholinergic burden. The teaching point: the tolerance/anticholinergic dissociation (sedation fades, anticholinergic effects persist) is the pharmacological basis for recommending against chronic diphenhydramine use for insomnia.

Question 3

An ER nurse calls you: "I gave haloperidol IM to a patient for agitation and now he's got his eyes stuck looking up and his neck is twisted. I don't have Cogentin in the Pyxis but I have Benadryl. What do I do?" How do you respond?

Accepted Answer

Answer A delays treatment of a painful, frightening emergency when an effective alternative is immediately available. Answer C uses an inadequate route (oral) for an acute emergency requiring rapid onset. IM or IV is needed. Answer D misidentifies the condition (dystonia presents with sustained involuntary muscle contraction; NMS presents with rigidity, hyperthermia, altered mental status, and autonomic instability, different presentation, different timeline). The teaching point: know that diphenhydramine IM is an effective substitute for benztropine IM in acute dystonia. In many clinical settings, it will be the only anticholinergic available.

Diphenhydramine

Side Effects Worth Knowing

Sedation/drowsiness: the marketed "benefit" and the primary problem

Anticholinergic effects: the persistent burden

Cognitive impairment: clinically significant, especially in elderly

Next-day impairment: underrecognized

Weight gain: with chronic use

Cardiotoxicity: at supratherapeutic doses / overdose

Paradoxical excitation: reported in children and elderly

See This Medication in Action

References & Further Reading