NYACP Board Review Question of the Week
Every other Tuesday, NYACP members are sent a Board Review Question from ACP's MKSAP 18 to test professional knowledge and help prepare for the exam. Participant totals and answer percentages are distributed on the first Thursday of the month in IM Connected, the Chapter's eNewsletter, and are also published on this page.
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November 4, 2025
MKSAP 19 General Internal Medicine 1, Question 13
A 59-year-old man undergoes follow-up evaluation for persistent major depressive disorder of several years' duration. He is currently being treated with venlafaxine; he previously took fluoxetine titrated to the maximum dosage before it was tapered off owing to lack of response and intolerable sexual side effects. He also takes aripiprazole and receives psychotherapy. He reports no improvement in his symptoms, which do not include mania or hypomania. He has not had suicidal ideation. He has no other medical conditions and takes no other medications.
On physical examination, vital signs are normal. He appears tired, with a sad, blunted affect. Score on the PHQ-9 is 17, unchanged from his previous score.
Which of the following is the most appropriate treatment?
A. Add intranasal esketamine
B. Add lithium
C. Discontinue aripiprazole and initiate risperidone
D. Discontinue venlafaxine and initiate sertraline
Responses Received from Members (Graph is uploaded on Thursday afternoon):
The Correct Answer is: A. Add intranasal esketamine
Educational Objective:
Treat resistant depression with esketamine.
The most appropriate treatment is the addition of intranasal esketamine (Option A). This patient, who has severe major depressive disorder that is unresponsive to maximal combination oral therapy with a second-generation antidepressant (SGA) and an antipsychotic agent as well as psychotherapy, is a candidate for intranasal esketamine. Intranasal esketamine is approved as an adjunct to oral antidepressant agents for treatment-resistant major depressive disorder and major depressive disorder with suicidal ideation. Esketamine is a glutamate receptor modulator, which offers a novel mechanism of action for depression treatment. Unlike most other antidepressant therapies, treatment effect is almost immediate; however, there are several barriers to its use. Labeling indications restrict the drug to patients whose symptoms have failed to respond to two courses of appropriately prescribed antidepressant therapy, and patients cannot drive or operate machinery for 24 hours after administration. Esketamine must be administered intranasally in a physician's office under direct supervision, and physicians must be enrolled in an FDA-mandated Risk Evaluation and Mitigation Strategies (REMS) program. Esketamine carries a black box warning for dissociation, sedation, and suicidal thoughts. The cost of the month-long induction is very expensive.
Lithium (Option B) is indicated for the treatment of bipolar 1 disorder and schizoaffective disorder. It is not an approved therapy for major depressive disorder. This patient reports no symptoms of mania that would justify the use of this therapy.
Risperidone (Option C), an antipsychotic agent, is not indicated for the treatment of major depressive disorder. However, the addition of other antipsychotic medications to SGAs is an appropriate strategy for treatment failure. Approved regimens include olanzapine plus fluoxetine, and aripiprazole or quetiapine plus any SGA.
Selective serotonin reuptake inhibitors (SSRIs) are one of four classes of SGAs considered first-line therapy for major depressive disorder. Other SGAs include serotonin-norepinephrine reuptake inhibitors, serotonin modulators, and atypical antidepressants. Sertraline (Option D) is an SSRI. This patient's symptoms have already failed to respond to treatment with one SSRI (fluoxetine) at
maximum doses. In addition, the sexual side effects he experienced can occur with all SSRIs and are likely to recur with sertraline; therefore, this drug is not a good option for the patient.
Key Point
Intranasal esketamine can be added to oral antidepressant agents for treatment-resistant major depressive disorder.
Unlike most other antidepressant therapies, esketamine has an almost immediate effect on depression symptoms.
Bibliography
Daly EJ, Singh JB, Fedgchin M, et al. Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry. 2018;75:139-48. PMID: 29282469 doi:10.1001/jamapsychiatry.2017.3739
Copyright 2019, American College of Physicians.
October 21, 2025
MKSAP 18 Neurology, Question 71
A 39-year-old woman is evaluated for a 4-year history of headaches that typically occur twice weekly and last 8 to 12 hours when not treated early. The pain is bilateral, frontotemporal, vice-like, and aggravated by physical activity. Approximately half of the episodes have become severe and are associated with combined photophobia and phonophobia. She has had no associated nausea, vomiting, or visual or neurologic symptoms and reports no cranial autonomic features. Stress is the only clear trigger. Naproxen resolves the headache when administered early in the headache course. She takes no other medication.
On physical examination, vital signs are normal; BMI is 23. All other physical examination findings, including those from a neurologic examination, are unremarkable.
Which of the following is the most likely diagnosis?
A. Medication-overuse headache
B. Migraine
C. Sinus headache
D. Tension-type headache
Responses Received from Members (549 Responses):
The Correct Answer is: B. Migraine
Educational Objective:
Diagnose migraine.
The patient's headaches meet the diagnostic criteria for migraine. The International Classification of Headache Disorders (third edition [beta version]) (ICHD-3) criteria require at least five episodes lasting 4 to 72 hours when untreated (or unsuccessfully treated) for this diagnosis. Pain should exhibit two of the following four characteristics: unilateral location, throbbing nature, moderate to severe intensity, and worsening with physical activity. Associated features must include either nausea or a combination of photophobia and phonophobia. Neurologic symptoms reflective of aura are described by 30% of patients with migraine. There must be no evidence of a secondary pathologic cause of the headache. Patients with chronic migraine may report milder attacks meeting tension-type headache criteria with at least some attacks meeting full migraine criteria. This patient described 8- to 12-hour severe attacks aggravated by activity with associated combined photophobia and phonophobia; her neurologic examination findings are normal. Neuroimaging is unnecessary in typical migraine presentations such as hers.
Medication overuse headache may result from overtreatment with acute medication in patients with underlying migraine or tension-type headache. Use of triptans, ergot alkaloids, opioids, or combination analgesics for 10 or more days per month or simple analgesics for 15 or more days per month constitutes medication overuse. Naproxen sodium used 8 days per month does not constitute medication overuse.
Over 90% of self- and clinician-diagnosed “sinus” headaches fulfill criteria for migraine. Acute rhinosinusitis may cause discomfort in the head or face, but headache is late in the disease course and typically a minor feature. Correlation of chronic or recurrent headaches with sinonasal pathology is without solid evidence. Weekly episodes of headache without nasal or sinus symptoms have no origins in the sinus cavities.
Episodic tension-type headache (TTH) is characterized by attacks of a nondisabling headache that lacks the typical features of migraine. Episodes may last from 30 minutes to 1 week. The pain of TTH typically is not severe or aggravated by routine physical activity. Photophobia or phonophobia may be present, but not both, according to ICHD-3 criteria. Mild nausea sometimes is noted with chronic TTH (≥15 days/mo) but not episodic TTH (<15 days/mo). Moderate to severe nausea and aura are not found with either TTH subtype.
Key Point
The diagnosis of migraine requires at least five episodes lasting 4 to 72 hours when untreated (or unsuccessfully treated), with pain exhibiting two of the following characteristics: unilateral location, throbbing nature, moderate to severe intensity, and worsening with physical activity; associated features must include either nausea or a combination of photophobia and phonophobia.
Bibliography
MacGregor EA. Migraine. Ann Intern Med. 2017;166:ITC49-ITC64. PMID: 28384749
Copyright 2018, American College of Physicians.