PSYCHOPHARMACOLOGY PMHNP EXAM STUDY GUIDE WITH
QUESTIONS AND CORRECT ANSWERS 2026/2027
1. A 45-year-old patient with major depressive disorder has been
treated with sertraline 200 mg daily for 8 weeks with only partial
response. Which of the following is the most evidence-based next
step according to current PMHNP guidelines?
A. Switch immediately to an MAOI
B. Add low-dose lithium augmentation
C. Increase sertraline to 300 mg daily
D. Add buspirone 30 mg daily
Correct Answer: B
Explanation: Lithium augmentation is a well-established,
evidence-based strategy for treatment-resistant depression after
inadequate response to SSRIs. MAOIs require a washout period
and have higher risk; sertraline max dose is 200 mg; buspirone is
more for anxiety than depressive symptom augmentation.
2. Which antipsychotic has the highest risk of causing
agranulocytosis and requires mandatory weekly blood monitoring
for the first 6 months?
A. Risperidone
B. Olanzapine
C. Clozapine
D. Quetiapine
Correct Answer: C
Explanation: Clozapine carries a black box warning for
agranulocytosis and requires enrollment in the REMS program
with weekly ANC monitoring initially. The other antipsychotics do
not require this level of hematologic monitoring.
,3. A 32-year-old pregnant woman (first trimester) with bipolar I
disorder presents with acute mania. Which medication is
CONTRAINDICATED due to high teratogenic risk?
A. Haloperidol
B. Valproate
C. Lamotrigine
D. Lithium
Correct Answer: B
Explanation: Valproate has the highest teratogenic risk (neural
tube defects up to 10-20%) and is absolutely contraindicated in
pregnancy. Lithium has Ebstein's anomaly risk but is sometimes
used; haloperidol and lamotrigine have lower risk profiles.
4. Which of the following best describes the mechanism of action of
varenicline in smoking cessation?
A. Full agonist at α4β2 nicotinic receptors
B. Partial agonist at α4β2 nicotinic receptors
C. Antagonist at dopamine D2 receptors
D. Reuptake inhibitor of norepinephrine and dopamine
Correct Answer: B
Explanation: Varenicline is a partial agonist at α4β2 nicotinic
acetylcholine receptors, providing modest dopamine release while
blocking nicotine binding. Bupropion is the norepinephrine-
dopamine reuptake inhibitor option.
5. A patient on long-term lithium therapy presents with polyuria,
polydipsia, and urine specific gravity of 1.005. What is the most
, likely diagnosis?
A. Syndrome of inappropriate antidiuretic hormone (SIADH)
B. Nephrogenic diabetes insipidus
C. Central diabetes insipidus
D. Psychogenic polydipsia
Correct Answer: B
Explanation: Lithium causes nephrogenic diabetes insipidus by
interfering with ADH action on collecting ducts, leading to dilute
urine and polyuria/polydipsia. SIADH would show concentrated
urine; psychogenic polydipsia has normal kidney function.
6. Which antidepressant is FDA-approved for obsessive-compulsive
disorder (OCD) at the highest required doses?
A. Fluoxetine
B. Sertraline
C. Fluvoxamine
D. All require similar doses
Correct Answer: A
Explanation: Fluoxetine is FDA-approved for OCD and often
requires doses up to 80 mg/day (higher than depression). While
sertraline and fluvoxamine are also used for OCD, fluoxetine has
the most robust evidence at high doses.
7. A 60-year-old patient with Parkinson's disease develops psychosis.
Which antipsychotic is preferred due to lowest risk of worsening
motor symptoms?
A. Risperidone
B. Haloperidol
C. Pimavanserin
, D. Olanzapine
Correct Answer: C
Explanation: Pimavanserin is a 5-HT2A inverse agonist/antagonist
approved specifically for Parkinson's disease psychosis with no
dopamine D2 blockade, thus not worsening motor symptoms.
Traditional antipsychotics worsen Parkinsonism.
8. Which medication requires monitoring of triglycerides and HbA1c
due to high metabolic side effect risk?
A. Aripiprazole
B. Ziprasidone
C. Olanzapine
D. Lurasidone
Correct Answer: C
Explanation: Olanzapine has the highest risk for metabolic
syndrome including weight gain, dyslipidemia, and insulin
resistance among second-generation antipsychotics. Aripiprazole,
ziprasidone, and lurasidone have lower metabolic risk.
9. What is the primary mechanism by which benzodiazepines exert
their anxiolytic effects?
A. Agonist at GABA-A receptor chloride channel
B. Antagonist at serotonin 5-HT2A receptors
C. Inhibitor of norepinephrine reuptake
D. Partial agonist at dopamine D2 receptors
Correct Answer: A
Explanation: Benzodiazepines are positive allosteric modulators
(agonists) at GABA-A receptors, enhancing chloride influx and
QUESTIONS AND CORRECT ANSWERS 2026/2027
1. A 45-year-old patient with major depressive disorder has been
treated with sertraline 200 mg daily for 8 weeks with only partial
response. Which of the following is the most evidence-based next
step according to current PMHNP guidelines?
A. Switch immediately to an MAOI
B. Add low-dose lithium augmentation
C. Increase sertraline to 300 mg daily
D. Add buspirone 30 mg daily
Correct Answer: B
Explanation: Lithium augmentation is a well-established,
evidence-based strategy for treatment-resistant depression after
inadequate response to SSRIs. MAOIs require a washout period
and have higher risk; sertraline max dose is 200 mg; buspirone is
more for anxiety than depressive symptom augmentation.
2. Which antipsychotic has the highest risk of causing
agranulocytosis and requires mandatory weekly blood monitoring
for the first 6 months?
A. Risperidone
B. Olanzapine
C. Clozapine
D. Quetiapine
Correct Answer: C
Explanation: Clozapine carries a black box warning for
agranulocytosis and requires enrollment in the REMS program
with weekly ANC monitoring initially. The other antipsychotics do
not require this level of hematologic monitoring.
,3. A 32-year-old pregnant woman (first trimester) with bipolar I
disorder presents with acute mania. Which medication is
CONTRAINDICATED due to high teratogenic risk?
A. Haloperidol
B. Valproate
C. Lamotrigine
D. Lithium
Correct Answer: B
Explanation: Valproate has the highest teratogenic risk (neural
tube defects up to 10-20%) and is absolutely contraindicated in
pregnancy. Lithium has Ebstein's anomaly risk but is sometimes
used; haloperidol and lamotrigine have lower risk profiles.
4. Which of the following best describes the mechanism of action of
varenicline in smoking cessation?
A. Full agonist at α4β2 nicotinic receptors
B. Partial agonist at α4β2 nicotinic receptors
C. Antagonist at dopamine D2 receptors
D. Reuptake inhibitor of norepinephrine and dopamine
Correct Answer: B
Explanation: Varenicline is a partial agonist at α4β2 nicotinic
acetylcholine receptors, providing modest dopamine release while
blocking nicotine binding. Bupropion is the norepinephrine-
dopamine reuptake inhibitor option.
5. A patient on long-term lithium therapy presents with polyuria,
polydipsia, and urine specific gravity of 1.005. What is the most
, likely diagnosis?
A. Syndrome of inappropriate antidiuretic hormone (SIADH)
B. Nephrogenic diabetes insipidus
C. Central diabetes insipidus
D. Psychogenic polydipsia
Correct Answer: B
Explanation: Lithium causes nephrogenic diabetes insipidus by
interfering with ADH action on collecting ducts, leading to dilute
urine and polyuria/polydipsia. SIADH would show concentrated
urine; psychogenic polydipsia has normal kidney function.
6. Which antidepressant is FDA-approved for obsessive-compulsive
disorder (OCD) at the highest required doses?
A. Fluoxetine
B. Sertraline
C. Fluvoxamine
D. All require similar doses
Correct Answer: A
Explanation: Fluoxetine is FDA-approved for OCD and often
requires doses up to 80 mg/day (higher than depression). While
sertraline and fluvoxamine are also used for OCD, fluoxetine has
the most robust evidence at high doses.
7. A 60-year-old patient with Parkinson's disease develops psychosis.
Which antipsychotic is preferred due to lowest risk of worsening
motor symptoms?
A. Risperidone
B. Haloperidol
C. Pimavanserin
, D. Olanzapine
Correct Answer: C
Explanation: Pimavanserin is a 5-HT2A inverse agonist/antagonist
approved specifically for Parkinson's disease psychosis with no
dopamine D2 blockade, thus not worsening motor symptoms.
Traditional antipsychotics worsen Parkinsonism.
8. Which medication requires monitoring of triglycerides and HbA1c
due to high metabolic side effect risk?
A. Aripiprazole
B. Ziprasidone
C. Olanzapine
D. Lurasidone
Correct Answer: C
Explanation: Olanzapine has the highest risk for metabolic
syndrome including weight gain, dyslipidemia, and insulin
resistance among second-generation antipsychotics. Aripiprazole,
ziprasidone, and lurasidone have lower metabolic risk.
9. What is the primary mechanism by which benzodiazepines exert
their anxiolytic effects?
A. Agonist at GABA-A receptor chloride channel
B. Antagonist at serotonin 5-HT2A receptors
C. Inhibitor of norepinephrine reuptake
D. Partial agonist at dopamine D2 receptors
Correct Answer: A
Explanation: Benzodiazepines are positive allosteric modulators
(agonists) at GABA-A receptors, enhancing chloride influx and
