Anesthesiology APPLIED Exam › Pharmacology, equipment and physics

MAOIs, lithium, antidepressants and herbal supplements

Pharmacology, equipment and physics·~4 min read· Physician-reviewed✓ Sourced · 4

Stem

A 54-year-old woman, 68 kg, is scheduled for an elective laparoscopic hysterectomy. She has treatment-resistant depression controlled for three years on phenelzine after several failed SSRIs, and she has added over-the-counter St. John's wort "for mood" for the last two months. Her blood pressure is 128/76 and she is otherwise healthy. Her psychiatrist has not been contacted.

Question

How do her medications change your anesthetic plan?

Ideal answer

HeadlineTwo interactions matter: serotonin syndrome, and hypertensive crisis from indirect sympathomimetics. The phenelzine is her psychiatrist's call with me; the St. John's wort means postponing.

Name the mechanism. Phenelzine irreversibly blocks monoamine oxidase, so norepinephrine and serotonin accumulate.¹
Phenelzine: decided with her psychiatrist. Traditional teaching stops an MAOI at least ten days before elective general anesthesia,¹ but her depression is hard to control; my anesthetic is MAOI-safe either way.
Stop St. John's wort two weeks; postpone. It adds serotonergic risk and induces CYP3A4, speeding midazolam, alfentanil and lidocaine metabolism; SPAQI recommends stopping it two weeks before surgery.²
No meperidine, tramadol, methadone, dextromethorphan or methylene blue. All contraindicated with MAOIs;¹ propofol, a volatile and a non-depolarizing relaxant are fine, with infiltration, acetaminophen, an NSAID and titrated morphine or hydromorphone.
Hypotension: phenylephrine, not ephedrine,³ starting small because her response is exaggerated.

Breaking down the answer

Direct versus indirect — accumulated norepinephrine explains why indirect agents such as ephedrine release a surge and cause a crisis, while direct agents act predictably; accumulated serotonin explains the opioid list; morphine and hydromorphone have no serotonin reuptake activity. Mechanism first is the rationale examiners grade.
Stopping the MAOI is a shared decision — irreversible inhibition means stopping it takes weeks to restore the enzyme, and relapse of severe depression has its own risk; involving the psychiatrist shows judgment beyond the textbook rule.
Methylene blue is an MAOI too — the MAOI review lists IV methylene blue as contraindicated with these drugs,¹ which matters if the urologist asks for it to check ureteral integrity.
Herbal supplements have their own list — garlic, ginseng and kava are stopped two weeks before surgery, ginkgo increases bleeding, ephedra should be stopped altogether, and valerian is continued to avoid withdrawal.² Asking about supplements by name finds them.
Switching takes a washout — at least 14 days between an MAOI and another antidepressant.¹

Follow-up question

She proceeds with the phenelzine continued and the St. John's wort stopped. In recovery a covering clinician gives tramadol for pain. An hour later she is agitated and sweating, with heart rate 128, blood pressure 182/104, temperature 38.9 °C, and inducible ankle clonus. What is happening and what do you do?

Follow-up answer

HeadlineSerotonin syndrome: serotonergic exposure plus inducible clonus, agitation and diaphoresis meets the Hunter criteria.³ I tell the team tramadol is contraindicated with her MAOI.

I stop every serotonergic drug, give oxygen and IV fluids, and sedate her with a benzodiazepine, avoiding physical restraints because muscle activity drives the fever. Short-acting esmolol or nicardipine for the pressure. Cyproheptadine 12 mg orally, then 2 mg every 2 hours until she improves.³ If her temperature reaches 41.1 °C, I sedate, paralyze with a nondepolarizing relaxant, intubate and move her to the ICU.³ Clonus, temperature and vital signs every 15 minutes, CK and renal function, and an event report.

Pitfalls that cost points

Choosing meperidine for shivering after the case.
Treating serotonin syndrome with acetaminophen and restraints.
Never asking about over-the-counter supplements; patients often do not count them as medications.

Rapid-fire

Q: What is the therapeutic lithium level? A: 0.8–1.2 mEq/L for acute treatment; above 2 mEq/L is toxic.⁴

Q: Which perioperative drugs raise lithium levels? A: Thiazide diuretics, NSAIDs and renin-angiotensin antagonists.⁴

Q: Does lithium add serotonergic risk? A: Yes; combining it with serotonergic agents raises the risk of serotonin syndrome.⁴

Q: How does serotonin syndrome differ in time course from neuroleptic malignant syndrome? A: Serotonin syndrome usually appears within 24 hours of a drug change; neuroleptic malignant syndrome develops over days to weeks.³

Q: What does St. John's wort do to warfarin? A: It reduces warfarin's anticoagulant effect, so the INR needs closer watching if she needs anticoagulation after surgery.²

Numbers to know

Item	Value
MAOI stop before elective GA (traditional)	≥10 days¹
MAOI to another antidepressant	≥14-day washout¹
St. John's wort, garlic, ginseng, kava	Stop 2 weeks before (SPAQI)²
Lithium range / toxic	0.8–1.2 / >2 mEq/L⁴
Cyproheptadine	12 mg, then 2 mg every 2 h³
Intubate for temperature	≥41.1 °C³

Sources

1.Monoamine Oxidase Inhibitors (MAOI) (StatPearls) · StatPearls Publishing (NCBI Bookshelf) · ncbi.nlm.nih.gov
2.Herbal supplements and anesthesia (keyword) · OpenAnesthesia · openanesthesia.orgDiscontinuation intervals from the SPAQI consensus statement (Cummings, Mayo Clin Proc 2021).
3.Serotonin Syndrome (StatPearls) · StatPearls Publishing (NCBI Bookshelf) · ncbi.nlm.nih.govHunter criteria; treatment including cyproheptadine and direct-acting sympathomimetics for MAOI-related hypotension.
4.Lithium (StatPearls) · StatPearls Publishing (NCBI Bookshelf), 2024 · ncbi.nlm.nih.gov

Facts on this page were checked against these sources on Oct 16, 2026. Guidelines change; confirm doses against current institutional protocols.