NR 546 / NR546 Midterm Actual Exam (Latest
2026) Tested Questions with Revised Answers,
(A+ Guarantee)
Q001:
Type: NGN - Psychopharm
Scenario: A 34-year-old female with treatment-resistant major depressive disorder
(MDD) presents for evaluation. She has failed adequate trials of sertraline 200 mg/day (8
weeks), venlafaxine XR 225 mg/day (10 weeks), and bupropion XL 450 mg/day (8
weeks) due to persistent anhedonia, hypersomnia, and weight gain. She has no psychotic
features. Genotyping reveals CYP2D6 ultra-rapid metabolizer (UM) status and CYP2C19
poor metabolizer (PM) status. Current meds: sertraline 200 mg, propranolol 20 mg BID
for performance anxiety. Labs: TSH 2.8, B12 normal, vitamin D 18 ng/mL.
Question: What is the most appropriate next psychopharmacologic intervention based on
her pharmacogenomic profile and treatment history?
Options:
A. Increase sertraline to 250 mg daily
B. Switch to escitalopram 10 mg daily
C. Augment with aripiprazole 2 mg daily
D. Initiate ketamine infusion 0.5 mg/kg
(Correct: C)
Rationale:
● Answer: Augment with aripiprazole 2 mg daily
● Why (2026 Standard): In treatment-resistant MDD with inadequate response to 3
antidepressants, augmentation with atypical antipsychotics is first-line per 2023
APA guidelines. Aripiprazole's partial D2 agonism and 5-HT2A antagonism
enhance dopaminergic and serotonergic transmission in prefrontal cortex,
addressing anhedonia. Her CYP2D6 UM status accelerates aripiprazole
metabolism, requiring dose adjustment later, but initial 2 mg is safe. CYP2C19
PM status makes sertraline levels high (via CYP2C19 inhibition), but she's still
non-responsive, indicating non-CYP related resistance. Ketamine is reserved for
severe suicidal ideation or ≥4 failed trials.
, ● Errors: A is incorrect because increasing sertraline won't overcome resistance and
worsens metabolic side effects via CYP2D6 UM (increased active metabolite). B
is incorrect because escitalopram is metabolized by CYP2C19, and as a PM, she'd
have toxic accumulation. D is incorrect because ketamine is not indicated without
imminent suicide risk and after only 3 failed trials.
Q002:
Type: Expert MCQ
Scenario: A 24-year-old male with ADHD-combined type and generalized anxiety
disorder (GAD) is started on methylphenidate ER 36 mg daily. After 1 week, he reports
improved focus but worsened anxiety, insomnia, and palpitations. HR 92, BP 138/86. He
has CYP2D6 extensive metabolizer status.
Question: What is the most appropriate next step?
Options:
A. Switch to amphetamine-dextroamphetamine ER 20 mg daily
B. Add propranolol 10 mg BID
C. Reduce methylphenidate ER to 18 mg daily and add guanfacine ER 1 mg at bedtime
D. Discontinue methylphenidate and start atomoxetine 80 mg daily
(Correct: C)
Rationale:
● Answer: Reduce methylphenidate ER to 18 mg daily and add guanfacine ER 1 mg
at bedtime
● Why (2026 Standard): Methylphenidate-induced anxiety and autonomic activation
occurs via norepinephrine reuptake inhibition and dopamine increase in limbic
areas. Reducing dose mitigates this while preserving some benefit. Adding
guanfacine (alpha-2A agonist) reduces sympathetic outflow from locus coeruleus,
improves prefrontal cortex regulation, and treats ADHD via norepinephrine
modulation without stimulant side effects. 2024 AACAP guidelines support
alpha-2 agonist augmentation for stimulant-induced anxiety/insomnia.
● Errors: A is incorrect because amphetamine increases norepinephrine release,
worsening anxiety. B is incorrect because propranolol blocks β2 receptors, causing
fatigue and worsening ADHD symptoms via reduced PFC catecholamine
signaling. D is incorrect because atomoxetine (NRI) would similarly worsen
anxiety and requires 4-6 weeks for effect.
Q003:
Type: NGN - Psychopharm
,Scenario: A 56-year-old male with bipolar I disorder, currently hospitalized for acute
mania with psychotic features. He is refusing oral medications and requires acute
stabilization. Current meds: lithium 1200 mg daily (level 0.4 mEq/L), risperidone 3 mg
BID (recently started), lorazepam 2 mg q6h PRN. Labs: Cr 1.5 mg/dL (baseline 0.9), Na
134, WBC 8.5, TSH 2.1. ECG shows QTc 480 ms. He is agitated, threatening staff,
requiring 4-point restraints.
Question: What is the most appropriate immediate medication adjustment?
Options:
A. Switch risperidone to ziprasidone 40 mg BID
B. Increase lithium to 1500 mg daily
C. Initiate valproate ER 500 mg BID and obtain level
D. Add olanzapine IM 10 mg q4h PRN agitation
(Correct: C)
Rationale:
● Answer: Initiate valproate ER 500 mg BID and obtain level
● Why (2026 Standard): Lithium level is subtherapeutic for mania (target 0.8-1.0
mEq/L) but increasing dose is contraindicated with rising creatinine, indicating
nephrotoxicity. Risperidone at 6 mg/day combined with lorazepam increases
sedation and QTc prolongation risk (risperidone blocks IKr channels via
CYP2D6). Valproate is first-line for acute mania with psychosis, loading doses of
20-30 mg/kg can achieve therapeutic levels quickly. It stabilizes mood via GABA
enhancement and sodium channel blockade. 2023 ISBD guidelines recommend
valproate for mania with psychosis.
● Errors: A is incorrect because ziprasidone further prolongs QTc (mean increase
15-20 ms) and requires food for absorption. B is incorrect because lithium
nephrotoxicity is worsening with suboptimal response. D is incorrect because IM
olanzapine has black box warning for respiratory depression when combined with
benzodiazepines.
Q004:
Type: Expert MCQ
Scenario: A 62-year-old female with major depressive disorder and chronic neuropathic
pain from diabetic peripheral neuropathy is on duloxetine 60 mg daily for 6 weeks with
partial response (PHQ-9 reduced from 18 to 12) but reports persistent burning pain. She
has CYP1A2 normal metabolizer status.
Question: What is the most appropriate next step?
Options:
, A. Increase duloxetine to 120 mg daily
B. Add pregabalin 75 mg BID
C. Switch to amitriptyline 75 mg at bedtime
D. Add tramadol 50 mg BID PRN pain
(Correct: B)
Rationale:
● Answer: Add pregabalin 75 mg BID
● Why (2026 Standard): Duloxetine's SNRI mechanism (5-HT/NE reuptake
inhibition) provides analgesia at 60 mg, but maximum dose is 60 mg for
neuropathic pain (FDA indication). Adding pregabalin (α2-δ subunit ligand)
reduces calcium-dependent neurotransmitter release in hyperexcited neurons,
providing synergistic analgesia. 2024 ADA guidelines for diabetic neuropathy
recommend combination therapy if monotherapy fails. Pregabalin has no
significant CYP interactions.
● Errors: A is incorrect because 120 mg offers no added analgesia and increases
hepatotoxicity risk. C is incorrect because amitriptyline is metabolized by
CYP2D6/1A2, has anticholinergic burden in elderly, and combined with
duloxetine increases serotonin syndrome risk. D is incorrect because tramadol is
serotonergic (5-HT reuptake inhibition), risking serotonin syndrome with
duloxetine, and has opioid component.
Q005:
Type: NGN - Psychopharm
Scenario: A 29-year-old female with treatment-resistant depression and bulimia nervosa
is scheduled for Spravato (esketamine) treatment. She is currently on fluoxetine 60 mg
daily and lithium 600 mg BID (level 0.6 mEq/L). BMI 18.5, BP 108/68, HR 72. She has
CYP2C19 poor metabolizer status. Her depression involves severe suicidal ideation with
plan.
Question: What is the most critical monitoring parameter during Spravato induction
phase?
Options:
A. Suicidal ideation every 2 hours
B. Blood pressure every 40 minutes for 2 hours
C. Lithium level every 3 days
D. Weight daily
(Correct: B)
Rationale:
2026) Tested Questions with Revised Answers,
(A+ Guarantee)
Q001:
Type: NGN - Psychopharm
Scenario: A 34-year-old female with treatment-resistant major depressive disorder
(MDD) presents for evaluation. She has failed adequate trials of sertraline 200 mg/day (8
weeks), venlafaxine XR 225 mg/day (10 weeks), and bupropion XL 450 mg/day (8
weeks) due to persistent anhedonia, hypersomnia, and weight gain. She has no psychotic
features. Genotyping reveals CYP2D6 ultra-rapid metabolizer (UM) status and CYP2C19
poor metabolizer (PM) status. Current meds: sertraline 200 mg, propranolol 20 mg BID
for performance anxiety. Labs: TSH 2.8, B12 normal, vitamin D 18 ng/mL.
Question: What is the most appropriate next psychopharmacologic intervention based on
her pharmacogenomic profile and treatment history?
Options:
A. Increase sertraline to 250 mg daily
B. Switch to escitalopram 10 mg daily
C. Augment with aripiprazole 2 mg daily
D. Initiate ketamine infusion 0.5 mg/kg
(Correct: C)
Rationale:
● Answer: Augment with aripiprazole 2 mg daily
● Why (2026 Standard): In treatment-resistant MDD with inadequate response to 3
antidepressants, augmentation with atypical antipsychotics is first-line per 2023
APA guidelines. Aripiprazole's partial D2 agonism and 5-HT2A antagonism
enhance dopaminergic and serotonergic transmission in prefrontal cortex,
addressing anhedonia. Her CYP2D6 UM status accelerates aripiprazole
metabolism, requiring dose adjustment later, but initial 2 mg is safe. CYP2C19
PM status makes sertraline levels high (via CYP2C19 inhibition), but she's still
non-responsive, indicating non-CYP related resistance. Ketamine is reserved for
severe suicidal ideation or ≥4 failed trials.
, ● Errors: A is incorrect because increasing sertraline won't overcome resistance and
worsens metabolic side effects via CYP2D6 UM (increased active metabolite). B
is incorrect because escitalopram is metabolized by CYP2C19, and as a PM, she'd
have toxic accumulation. D is incorrect because ketamine is not indicated without
imminent suicide risk and after only 3 failed trials.
Q002:
Type: Expert MCQ
Scenario: A 24-year-old male with ADHD-combined type and generalized anxiety
disorder (GAD) is started on methylphenidate ER 36 mg daily. After 1 week, he reports
improved focus but worsened anxiety, insomnia, and palpitations. HR 92, BP 138/86. He
has CYP2D6 extensive metabolizer status.
Question: What is the most appropriate next step?
Options:
A. Switch to amphetamine-dextroamphetamine ER 20 mg daily
B. Add propranolol 10 mg BID
C. Reduce methylphenidate ER to 18 mg daily and add guanfacine ER 1 mg at bedtime
D. Discontinue methylphenidate and start atomoxetine 80 mg daily
(Correct: C)
Rationale:
● Answer: Reduce methylphenidate ER to 18 mg daily and add guanfacine ER 1 mg
at bedtime
● Why (2026 Standard): Methylphenidate-induced anxiety and autonomic activation
occurs via norepinephrine reuptake inhibition and dopamine increase in limbic
areas. Reducing dose mitigates this while preserving some benefit. Adding
guanfacine (alpha-2A agonist) reduces sympathetic outflow from locus coeruleus,
improves prefrontal cortex regulation, and treats ADHD via norepinephrine
modulation without stimulant side effects. 2024 AACAP guidelines support
alpha-2 agonist augmentation for stimulant-induced anxiety/insomnia.
● Errors: A is incorrect because amphetamine increases norepinephrine release,
worsening anxiety. B is incorrect because propranolol blocks β2 receptors, causing
fatigue and worsening ADHD symptoms via reduced PFC catecholamine
signaling. D is incorrect because atomoxetine (NRI) would similarly worsen
anxiety and requires 4-6 weeks for effect.
Q003:
Type: NGN - Psychopharm
,Scenario: A 56-year-old male with bipolar I disorder, currently hospitalized for acute
mania with psychotic features. He is refusing oral medications and requires acute
stabilization. Current meds: lithium 1200 mg daily (level 0.4 mEq/L), risperidone 3 mg
BID (recently started), lorazepam 2 mg q6h PRN. Labs: Cr 1.5 mg/dL (baseline 0.9), Na
134, WBC 8.5, TSH 2.1. ECG shows QTc 480 ms. He is agitated, threatening staff,
requiring 4-point restraints.
Question: What is the most appropriate immediate medication adjustment?
Options:
A. Switch risperidone to ziprasidone 40 mg BID
B. Increase lithium to 1500 mg daily
C. Initiate valproate ER 500 mg BID and obtain level
D. Add olanzapine IM 10 mg q4h PRN agitation
(Correct: C)
Rationale:
● Answer: Initiate valproate ER 500 mg BID and obtain level
● Why (2026 Standard): Lithium level is subtherapeutic for mania (target 0.8-1.0
mEq/L) but increasing dose is contraindicated with rising creatinine, indicating
nephrotoxicity. Risperidone at 6 mg/day combined with lorazepam increases
sedation and QTc prolongation risk (risperidone blocks IKr channels via
CYP2D6). Valproate is first-line for acute mania with psychosis, loading doses of
20-30 mg/kg can achieve therapeutic levels quickly. It stabilizes mood via GABA
enhancement and sodium channel blockade. 2023 ISBD guidelines recommend
valproate for mania with psychosis.
● Errors: A is incorrect because ziprasidone further prolongs QTc (mean increase
15-20 ms) and requires food for absorption. B is incorrect because lithium
nephrotoxicity is worsening with suboptimal response. D is incorrect because IM
olanzapine has black box warning for respiratory depression when combined with
benzodiazepines.
Q004:
Type: Expert MCQ
Scenario: A 62-year-old female with major depressive disorder and chronic neuropathic
pain from diabetic peripheral neuropathy is on duloxetine 60 mg daily for 6 weeks with
partial response (PHQ-9 reduced from 18 to 12) but reports persistent burning pain. She
has CYP1A2 normal metabolizer status.
Question: What is the most appropriate next step?
Options:
, A. Increase duloxetine to 120 mg daily
B. Add pregabalin 75 mg BID
C. Switch to amitriptyline 75 mg at bedtime
D. Add tramadol 50 mg BID PRN pain
(Correct: B)
Rationale:
● Answer: Add pregabalin 75 mg BID
● Why (2026 Standard): Duloxetine's SNRI mechanism (5-HT/NE reuptake
inhibition) provides analgesia at 60 mg, but maximum dose is 60 mg for
neuropathic pain (FDA indication). Adding pregabalin (α2-δ subunit ligand)
reduces calcium-dependent neurotransmitter release in hyperexcited neurons,
providing synergistic analgesia. 2024 ADA guidelines for diabetic neuropathy
recommend combination therapy if monotherapy fails. Pregabalin has no
significant CYP interactions.
● Errors: A is incorrect because 120 mg offers no added analgesia and increases
hepatotoxicity risk. C is incorrect because amitriptyline is metabolized by
CYP2D6/1A2, has anticholinergic burden in elderly, and combined with
duloxetine increases serotonin syndrome risk. D is incorrect because tramadol is
serotonergic (5-HT reuptake inhibition), risking serotonin syndrome with
duloxetine, and has opioid component.
Q005:
Type: NGN - Psychopharm
Scenario: A 29-year-old female with treatment-resistant depression and bulimia nervosa
is scheduled for Spravato (esketamine) treatment. She is currently on fluoxetine 60 mg
daily and lithium 600 mg BID (level 0.6 mEq/L). BMI 18.5, BP 108/68, HR 72. She has
CYP2C19 poor metabolizer status. Her depression involves severe suicidal ideation with
plan.
Question: What is the most critical monitoring parameter during Spravato induction
phase?
Options:
A. Suicidal ideation every 2 hours
B. Blood pressure every 40 minutes for 2 hours
C. Lithium level every 3 days
D. Weight daily
(Correct: B)
Rationale:
