Question 1

A 62-year-old postmenopausal woman with breast cancer is taking tamoxifen. She develops moderate depression and her oncologist requests an antidepressant recommendation. Which SSRI is the most appropriate choice?

Accepted Answer

This is the tamoxifen-CYP2D6 question, identical in concept to the one on the fluoxetine page but approached from the paroxetine direction. Both paroxetine (answer A) and fluoxetine (answer B) are strong CYP2D6 inhibitors that should be avoided. Citalopram (answer D) has mild CYP2D6 inhibition and is sometimes considered acceptable, but it also carries the most QTc prolongation concern among SSRIs, which may be relevant in an oncology patient on other medications. Escitalopram is the cleanest choice: minimal CYP2D6 inhibition, minimal QTc risk at standard doses, and strong efficacy data.

Question 2

A 35-year-old man has been taking paroxetine 30mg daily for 2 years for generalized anxiety disorder. He and his psychiatrist decide to discontinue the medication because his anxiety is well-controlled with therapy alone. His psychiatrist tells him to stop taking it. Three days later, he presents to urgent care with dizziness, nausea, electric shock sensations in his head, irritability, vivid dreams, and a "flu-like" feeling. What is the most likely diagnosis, and what should be done?

Accepted Answer

This tests recognition of SSRI discontinuation syndrome and the specific knowledge that paroxetine is the worst offender. Serotonin syndrome (answer A) presents with hyperthermia, clonus, hyperreflexia, and agitation, not "brain zaps" and flu-like symptoms, and occurs from serotonergic excess, not withdrawal. Anxiety relapse (answer B) would not explain the neurological symptoms (electric shocks, dizziness) or flu-like presentation. A viral illness (answer D) would not explain the brain zaps. The critical teaching point: paroxetine should never be stopped abruptly. This error could have been prevented by prescribing a slow taper from the start.

Question 3

A 78-year-old woman in an assisted living facility is started on paroxetine 20mg for depression. She is also taking oxybutynin for overactive bladder, diphenhydramine at bedtime for insomnia, and donepezil for mild Alzheimer's disease. Two weeks later, her family reports increased confusion, a fall, worsening urinary retention, and dry mouth so severe she has stopped eating. What is the most important pharmacological concept to identify?

Accepted Answer

This question builds directly on the anticholinergic burden concept taught on the hydroxyzine page but adds a layer: the pharmacological antagonism between an anticholinergic medication (paroxetine) and a cholinesterase inhibitor (donepezil). Prescribing an anticholinergic SSRI to a patient on a cholinesterase inhibitor for dementia is a prescribing conflict that is testable and clinically dangerous. Answer A is partially true (paroxetine does inhibit CYP2D6, and donepezil is partially CYP2D6-metabolized), but the CYP interaction is not the primary driver of the clinical picture. Answer C should be considered (check sodium in any elderly patient with new confusion on an SSRI) but does not explain the full symptom constellation. Answer D is incorrect because donepezil is not serotonergic. The key teaching point: paroxetine is the wrong SSRI for elderly patients, particularly those with existing anticholinergic burden or on cholinesterase inhibitors.

Paroxetine

Side Effects Worth Knowing

Discontinuation Syndrome

Weight Gain

Sexual Dysfunction

Sedation / Fatigue

Dry Mouth, Constipation, Urinary Retention

Hyponatremia / SIADH

Nausea

Suicidality Risk in Young Adults

See This Medication in Action

References & Further Reading