EXAM REVIEW FOR PSYCHOPHARMACOLOGY PMHNP
WITH QUESTIONS AND CORRECT ANSWERS
2026/2027
1. A 34-year-old with major depressive disorder has failed two SSRIs at adequate
doses and durations. Which receptor profile would most favor augmentation with
low-dose aripiprazole?
A. High 5-HT2A antagonism, partial D2 agonism
B. High D2 antagonism, low 5-HT1A affinity
C. High NET inhibition, low 5-HT2C affinity
D. High MAO-A inhibition, low D3 affinity
Correct Answer: A
*Explanation: Aripiprazole’s partial D2 agonism stabilizes dopamine transmission,
and its 5-HT2A antagonism enhances serotonin release; this combination is
evidence-based for SSRI augmentation in TRD. Options B, C, and D describe
typical antipsychotics (D2 antagonism), NRI, or MAOI profiles, not aripiprazole’s
mechanism.*
2. A patient on clozapine develops new-onset tachycardia, hypersalivation, and
fever. Which additional finding is most critical to rule out immediately?
A. Eosinophilia
B. Elevated creatine kinase
C. Neutropenia
D. Hyperglycemia
Correct Answer: B
Explanation: Fever, tachycardia, and hypersalivation in a clozapine-treated patient
raise concern for NMS or inflammatory syndrome; elevated creatine kinase
supports NMS. Neutropenia (C) is common but not acutely life-threatening without
infection. Eosinophilia (A) suggests DRESS, less acute. Hyperglycemia (D) is a
chronic concern.
,3. Which cytochrome P450 enzyme is primarily responsible for the conversion of
tamoxifen to its active metabolite, and which antidepressant most inhibits this
enzyme?
A. CYP3A4; sertraline
B. CYP2D6; paroxetine
C. CYP1A2; fluvoxamine
D. CYP2C19; escitalopram
Correct Answer: B
*Explanation: Tamoxifen requires CYP2D6 for bioactivation; paroxetine is a potent
CYP2D6 inhibitor, reducing endoxifen levels and potentially increasing breast
cancer recurrence risk. Sertraline (A) weakly inhibits CYP2D6. Fluvoxamine (C)
inhibits CYP1A2/2C19. Escitalopram (D) minimally inhibits CYP2D6.*
4. A 48-year-old with bipolar I disorder on lithium 1200 mg/day presents with
coarse tremor, ataxia, and nausea. Lithium level is 2.0 mEq/L. Which acute
management step is contraindicated?
A. Intravenous normal saline
B. Hemodialysis
C. Intravenous furosemide
D. Holding lithium
Correct Answer: C
Explanation: Furosemide can worsen lithium toxicity by causing volume depletion
and reducing renal clearance. IV saline (A) enhances excretion. Hemodialysis (B) is
indicated for severe toxicity (level >2.5 or symptoms). Holding lithium (D) is
standard. Loop diuretics are avoided in acute toxicity.
5. Which statement best describes the effect of valproate on lamotrigine
pharmacokinetics?
A. Valproate doubles lamotrigine half-life by glucuronidation inhibition
B. Valproate reduces lamotrigine levels via CYP3A4 induction
C. Valproate has no significant interaction with lamotrigine
D. Valproate increases lamotrigine renal excretion by protein binding
displacement
Correct Answer: A
, *Explanation: Valproate inhibits lamotrigine glucuronidation, roughly doubling
lamotrigine half-life and requiring a 50% dose reduction of lamotrigine when
added. B and C are incorrect; D is partially true but not the primary mechanism—
displacement is transient, inhibition of metabolism dominates.*
6. A patient with generalized anxiety disorder on venlafaxine 225 mg daily reports
severe nausea, headache, and dizziness within 24 hours of a missed dose. Which
mechanism best explains this phenomenon?
A. Serotonin syndrome from rapid autoreceptor upregulation
B. Cholinergic rebound due to venlafaxine’s weak anticholinergic effect
C. Noradrenergic and serotonergic withdrawal due to short half-life
D. Dopamine hypersensitivity from VMAT2 inhibition
Correct Answer: C
*Explanation: Venlafaxine has a short half-life (~5 hours) and both SNRI effects;
abrupt discontinuation causes rapid drop in synaptic NE/5-HT, leading to
“discontinuation syndrome.” A (serotonin syndrome) occurs with excess, not
withdrawal. B: venlafaxine has minimal anticholinergic effects. D: VMAT2
inhibition is not venlafaxine’s action.*
7. A PMHNP is considering switching from phenelzine to selegiline transdermal
patch. What minimum washout period is required to avoid hypertensive crisis?
A. 3 days
B. 7 days
C. 14 days
D. 21 days
Correct Answer: C
*Explanation: Phenelzine is an irreversible MAOI; selegiline transdermal (even at 6
mg/24h) still requires MAO-A inhibition at higher doses. Standard washout from
an irreversible MAOI to another MAOI is 14 days (or 5 half-lives). B (7 days)
insufficient; D (21 days) overly cautious but not required.*
, 8. Which anticonvulsant is associated with dose-dependent hyponatremia due to
ADH-like effect on renal collecting ducts?
A. Lamotrigine
B. Oxcarbazepine
C. Topiramate
D. Gabapentin
Correct Answer: B
Explanation: Oxcarbazepine (and carbamazepine) cause hyponatremia via
enhanced ADH action or renal tubular sensitivity. Lamotrigine (A) rarely causes
hyponatremia. Topiramate (C) can cause metabolic acidosis but not ADH-mediated
hyponatremia. Gabapentin (D) has no significant effect on sodium.
9. A 22-year-old with first-episode psychosis is started on risperidone 2 mg daily.
Three weeks later, she develops severe muscle rigidity, fever, and elevated
creatine kinase (2000 U/L). The most appropriate next step is:
A. Add benztropine 2 mg IM
B. Increase risperidone to 4 mg
C. Switch to aripiprazole
D. Administer dantrolene IV and discontinue risperidone
Correct Answer: D
Explanation: This presentation is neuroleptic malignant syndrome (NMS).
Dantrolene or bromocriptine and immediate antipsychotic discontinuation are
standard. Benztropine (A) is for EPS, not NMS. Increasing dose (B) worsens outcome.
Aripiprazole (C) can also cause NMS; switch is not acute management.
10. Which medication is most likely to cause a false-positive urine amphetamine
screen due to cross-reactivity on immunoassays?
A. Quetiapine
B. Bupropion
C. Trazodone
D. Lamotrigine
Correct Answer: B
Explanation: Bupropion (and some other phenethylamines) cross-reacts with
amphetamine immunoassays. Quetiapine (A) may cause false-positive for
WITH QUESTIONS AND CORRECT ANSWERS
2026/2027
1. A 34-year-old with major depressive disorder has failed two SSRIs at adequate
doses and durations. Which receptor profile would most favor augmentation with
low-dose aripiprazole?
A. High 5-HT2A antagonism, partial D2 agonism
B. High D2 antagonism, low 5-HT1A affinity
C. High NET inhibition, low 5-HT2C affinity
D. High MAO-A inhibition, low D3 affinity
Correct Answer: A
*Explanation: Aripiprazole’s partial D2 agonism stabilizes dopamine transmission,
and its 5-HT2A antagonism enhances serotonin release; this combination is
evidence-based for SSRI augmentation in TRD. Options B, C, and D describe
typical antipsychotics (D2 antagonism), NRI, or MAOI profiles, not aripiprazole’s
mechanism.*
2. A patient on clozapine develops new-onset tachycardia, hypersalivation, and
fever. Which additional finding is most critical to rule out immediately?
A. Eosinophilia
B. Elevated creatine kinase
C. Neutropenia
D. Hyperglycemia
Correct Answer: B
Explanation: Fever, tachycardia, and hypersalivation in a clozapine-treated patient
raise concern for NMS or inflammatory syndrome; elevated creatine kinase
supports NMS. Neutropenia (C) is common but not acutely life-threatening without
infection. Eosinophilia (A) suggests DRESS, less acute. Hyperglycemia (D) is a
chronic concern.
,3. Which cytochrome P450 enzyme is primarily responsible for the conversion of
tamoxifen to its active metabolite, and which antidepressant most inhibits this
enzyme?
A. CYP3A4; sertraline
B. CYP2D6; paroxetine
C. CYP1A2; fluvoxamine
D. CYP2C19; escitalopram
Correct Answer: B
*Explanation: Tamoxifen requires CYP2D6 for bioactivation; paroxetine is a potent
CYP2D6 inhibitor, reducing endoxifen levels and potentially increasing breast
cancer recurrence risk. Sertraline (A) weakly inhibits CYP2D6. Fluvoxamine (C)
inhibits CYP1A2/2C19. Escitalopram (D) minimally inhibits CYP2D6.*
4. A 48-year-old with bipolar I disorder on lithium 1200 mg/day presents with
coarse tremor, ataxia, and nausea. Lithium level is 2.0 mEq/L. Which acute
management step is contraindicated?
A. Intravenous normal saline
B. Hemodialysis
C. Intravenous furosemide
D. Holding lithium
Correct Answer: C
Explanation: Furosemide can worsen lithium toxicity by causing volume depletion
and reducing renal clearance. IV saline (A) enhances excretion. Hemodialysis (B) is
indicated for severe toxicity (level >2.5 or symptoms). Holding lithium (D) is
standard. Loop diuretics are avoided in acute toxicity.
5. Which statement best describes the effect of valproate on lamotrigine
pharmacokinetics?
A. Valproate doubles lamotrigine half-life by glucuronidation inhibition
B. Valproate reduces lamotrigine levels via CYP3A4 induction
C. Valproate has no significant interaction with lamotrigine
D. Valproate increases lamotrigine renal excretion by protein binding
displacement
Correct Answer: A
, *Explanation: Valproate inhibits lamotrigine glucuronidation, roughly doubling
lamotrigine half-life and requiring a 50% dose reduction of lamotrigine when
added. B and C are incorrect; D is partially true but not the primary mechanism—
displacement is transient, inhibition of metabolism dominates.*
6. A patient with generalized anxiety disorder on venlafaxine 225 mg daily reports
severe nausea, headache, and dizziness within 24 hours of a missed dose. Which
mechanism best explains this phenomenon?
A. Serotonin syndrome from rapid autoreceptor upregulation
B. Cholinergic rebound due to venlafaxine’s weak anticholinergic effect
C. Noradrenergic and serotonergic withdrawal due to short half-life
D. Dopamine hypersensitivity from VMAT2 inhibition
Correct Answer: C
*Explanation: Venlafaxine has a short half-life (~5 hours) and both SNRI effects;
abrupt discontinuation causes rapid drop in synaptic NE/5-HT, leading to
“discontinuation syndrome.” A (serotonin syndrome) occurs with excess, not
withdrawal. B: venlafaxine has minimal anticholinergic effects. D: VMAT2
inhibition is not venlafaxine’s action.*
7. A PMHNP is considering switching from phenelzine to selegiline transdermal
patch. What minimum washout period is required to avoid hypertensive crisis?
A. 3 days
B. 7 days
C. 14 days
D. 21 days
Correct Answer: C
*Explanation: Phenelzine is an irreversible MAOI; selegiline transdermal (even at 6
mg/24h) still requires MAO-A inhibition at higher doses. Standard washout from
an irreversible MAOI to another MAOI is 14 days (or 5 half-lives). B (7 days)
insufficient; D (21 days) overly cautious but not required.*
, 8. Which anticonvulsant is associated with dose-dependent hyponatremia due to
ADH-like effect on renal collecting ducts?
A. Lamotrigine
B. Oxcarbazepine
C. Topiramate
D. Gabapentin
Correct Answer: B
Explanation: Oxcarbazepine (and carbamazepine) cause hyponatremia via
enhanced ADH action or renal tubular sensitivity. Lamotrigine (A) rarely causes
hyponatremia. Topiramate (C) can cause metabolic acidosis but not ADH-mediated
hyponatremia. Gabapentin (D) has no significant effect on sodium.
9. A 22-year-old with first-episode psychosis is started on risperidone 2 mg daily.
Three weeks later, she develops severe muscle rigidity, fever, and elevated
creatine kinase (2000 U/L). The most appropriate next step is:
A. Add benztropine 2 mg IM
B. Increase risperidone to 4 mg
C. Switch to aripiprazole
D. Administer dantrolene IV and discontinue risperidone
Correct Answer: D
Explanation: This presentation is neuroleptic malignant syndrome (NMS).
Dantrolene or bromocriptine and immediate antipsychotic discontinuation are
standard. Benztropine (A) is for EPS, not NMS. Increasing dose (B) worsens outcome.
Aripiprazole (C) can also cause NMS; switch is not acute management.
10. Which medication is most likely to cause a false-positive urine amphetamine
screen due to cross-reactivity on immunoassays?
A. Quetiapine
B. Bupropion
C. Trazodone
D. Lamotrigine
Correct Answer: B
Explanation: Bupropion (and some other phenethylamines) cross-reacts with
amphetamine immunoassays. Quetiapine (A) may cause false-positive for
