,NRNP 6665 PMHNP Care Across the Lifespan I
– Academic Year 2026/2027 – Midterm
Comprehensive Examination with Verified
Questions and Correct Answer Rationales | with
complete solutions.
SECTION 1: PHARMACODYNAMICS,
PHARMACOKINETICS, AND
PSYCHOPHARMACOLOGY (Questions 1-20)
1. A patient with major depressive disorder and comorbid chronic
kidney disease stage 3 (eGFR 40 mL/min) requires antidepressant
therapy. Which agent is safest without dose adjustment?
A) Duloxetine 30 mg daily
B) Sertraline 50 mg daily
C) Venlafaxine 75 mg daily
D) Mirtazapine 15 mg at bedtime
Answer: B – Sertraline 50 mg daily
Rationale: Sertraline is primarily hepatically metabolized and does not
require dose adjustment in renal impairment. Duloxetine is contraindicated
when CrCl < 30 mL/min. Venlafaxine and its active metabolite are renally
cleared, requiring dose reduction. Mirtazapine is renally cleared and may
accumulate in CKD .
2. A patient with generalized anxiety disorder and comorbid alcohol
use disorder is prescribed a first-line pharmacotherapy. Which
agent is most appropriate?
,A) Buspirone
B) Duloxetine
C) Gabapentin
D) Paroxetine
Answer: B – Duloxetine
Rationale: Duloxetine is FDA-approved for GAD and has no significant
interaction with alcohol. Buspirone has modest efficacy and is not first-line.
Gabapentin is off-label and has abuse potential. Paroxetine is effective but
has withdrawal symptoms and may interact with alcohol .
3. A patient with treatment-resistant schizophrenia has failed
adequate trials of two antipsychotics. Which augmentation strategy
has the strongest evidence?
A) Adding a benzodiazepine such as clonazepam
B) Switching to clozapine monotherapy
C) Adding valproate to current antipsychotic
D) Augmenting with lamotrigine
Answer: B – Switching to clozapine monotherapy
Rationale: Clozapine is the gold standard for treatment-resistant
schizophrenia, with superior efficacy over other antipsychotics.
Augmentation with benzodiazepines, valproate, or lamotrigine has limited
evidence and is not first-line after inadequate response to two
antipsychotics .
4. A patient on long-term lithium therapy develops polyuria and
polydipsia. Which intervention is most appropriate?
A) Switch to sustained-release lithium formulation
B) Add hydrochlorothiazide 25 mg daily
C) Discontinue lithium and start valproate
D) Reduce lithium dose and monitor serum levels
Answer: D – Reduce lithium dose and monitor serum levels
, Rationale: Lithium-induced nephrogenic diabetes insipidus is dose-related.
The first step is to reduce the dose if therapeutic levels allow. Thiazides can
paradoxically reduce urine volume but may increase lithium levels and
require close monitoring. Switching or changing formulation is not first-line .
5. Which genetic polymorphism is associated with increased risk of
serotonin syndrome when using SSRIs?
A) CYP2D6 poor metabolizer status
B) CYP2C19 ultrarapid metabolizer status
C) 5-HTTLPR short allele homozygosity
D) COMT Val158Met polymorphism
Answer: A – CYP2D6 poor metabolizer status
Rationale: CYP2D6 poor metabolizers have reduced clearance of many SSRIs
(e.g., paroxetine, fluoxetine), leading to higher drug concentrations and
increased risk of serotonin syndrome. CYP2C19 ultrarapid metabolizers may
have reduced efficacy. 5-HTTLPR and COMT polymorphisms affect response
but not directly toxicity .
6. Which neurobiological finding best explains the therapeutic lag of
SSRIs in major depressive disorder despite immediate increases in
synaptic serotonin?
A) Downregulation of presynaptic 5-HT1A autoreceptors
B) Upregulation of postsynaptic 5-HT2A receptors
C) Inhibition of serotonin transporter (SERT) within hours
D) Desensitization of somatodendritic 5-HT1A autoreceptors
Answer: D – Desensitization of somatodendritic 5-HT1A
autoreceptors
Rationale: SSRIs rapidly block SERT, increasing extracellular serotonin, but
clinical response requires weeks because somatodendritic 5-HT1A
autoreceptors in the raphe nuclei must desensitize to allow sustained
serotonin release. SERT inhibition occurs immediately but does not explain
the lag .
– Academic Year 2026/2027 – Midterm
Comprehensive Examination with Verified
Questions and Correct Answer Rationales | with
complete solutions.
SECTION 1: PHARMACODYNAMICS,
PHARMACOKINETICS, AND
PSYCHOPHARMACOLOGY (Questions 1-20)
1. A patient with major depressive disorder and comorbid chronic
kidney disease stage 3 (eGFR 40 mL/min) requires antidepressant
therapy. Which agent is safest without dose adjustment?
A) Duloxetine 30 mg daily
B) Sertraline 50 mg daily
C) Venlafaxine 75 mg daily
D) Mirtazapine 15 mg at bedtime
Answer: B – Sertraline 50 mg daily
Rationale: Sertraline is primarily hepatically metabolized and does not
require dose adjustment in renal impairment. Duloxetine is contraindicated
when CrCl < 30 mL/min. Venlafaxine and its active metabolite are renally
cleared, requiring dose reduction. Mirtazapine is renally cleared and may
accumulate in CKD .
2. A patient with generalized anxiety disorder and comorbid alcohol
use disorder is prescribed a first-line pharmacotherapy. Which
agent is most appropriate?
,A) Buspirone
B) Duloxetine
C) Gabapentin
D) Paroxetine
Answer: B – Duloxetine
Rationale: Duloxetine is FDA-approved for GAD and has no significant
interaction with alcohol. Buspirone has modest efficacy and is not first-line.
Gabapentin is off-label and has abuse potential. Paroxetine is effective but
has withdrawal symptoms and may interact with alcohol .
3. A patient with treatment-resistant schizophrenia has failed
adequate trials of two antipsychotics. Which augmentation strategy
has the strongest evidence?
A) Adding a benzodiazepine such as clonazepam
B) Switching to clozapine monotherapy
C) Adding valproate to current antipsychotic
D) Augmenting with lamotrigine
Answer: B – Switching to clozapine monotherapy
Rationale: Clozapine is the gold standard for treatment-resistant
schizophrenia, with superior efficacy over other antipsychotics.
Augmentation with benzodiazepines, valproate, or lamotrigine has limited
evidence and is not first-line after inadequate response to two
antipsychotics .
4. A patient on long-term lithium therapy develops polyuria and
polydipsia. Which intervention is most appropriate?
A) Switch to sustained-release lithium formulation
B) Add hydrochlorothiazide 25 mg daily
C) Discontinue lithium and start valproate
D) Reduce lithium dose and monitor serum levels
Answer: D – Reduce lithium dose and monitor serum levels
, Rationale: Lithium-induced nephrogenic diabetes insipidus is dose-related.
The first step is to reduce the dose if therapeutic levels allow. Thiazides can
paradoxically reduce urine volume but may increase lithium levels and
require close monitoring. Switching or changing formulation is not first-line .
5. Which genetic polymorphism is associated with increased risk of
serotonin syndrome when using SSRIs?
A) CYP2D6 poor metabolizer status
B) CYP2C19 ultrarapid metabolizer status
C) 5-HTTLPR short allele homozygosity
D) COMT Val158Met polymorphism
Answer: A – CYP2D6 poor metabolizer status
Rationale: CYP2D6 poor metabolizers have reduced clearance of many SSRIs
(e.g., paroxetine, fluoxetine), leading to higher drug concentrations and
increased risk of serotonin syndrome. CYP2C19 ultrarapid metabolizers may
have reduced efficacy. 5-HTTLPR and COMT polymorphisms affect response
but not directly toxicity .
6. Which neurobiological finding best explains the therapeutic lag of
SSRIs in major depressive disorder despite immediate increases in
synaptic serotonin?
A) Downregulation of presynaptic 5-HT1A autoreceptors
B) Upregulation of postsynaptic 5-HT2A receptors
C) Inhibition of serotonin transporter (SERT) within hours
D) Desensitization of somatodendritic 5-HT1A autoreceptors
Answer: D – Desensitization of somatodendritic 5-HT1A
autoreceptors
Rationale: SSRIs rapidly block SERT, increasing extracellular serotonin, but
clinical response requires weeks because somatodendritic 5-HT1A
autoreceptors in the raphe nuclei must desensitize to allow sustained
serotonin release. SERT inhibition occurs immediately but does not explain
the lag .
