NSG 533 ADVANCED PHARMACOLOGY –
COMPREHENSIVE EXAM STUDY GUIDE
2026/2027 Questions with Verified Correct Answers &
Detailed Rationales | Graded A+
Question 1
Which of the following SSRIs requires up to a 5-week washout period because of
the long half-life of its potent active metabolite?
A) Escitalopram
B) Fluvoxamine
C) Fluoxetine
D) Sertraline
Answer: C) Fluoxetine
Rationale: Fluoxetine has the longest half-life among SSRIs (2-4 days) and its
active metabolite, norfluoxetine, has a half-life of 7-15 days. This necessitates a 5-
week washout period when switching to or from MAOIs to prevent serotonin
syndrome. Other SSRIs like sertraline, paroxetine, and fluvoxamine have shorter
half-lives requiring only 2-week washouts.
Question 2
Which symptom is most likely to improve within approximately 1 week of starting
antidepressant treatment?
A) Depressed mood
B) Suicidal thoughts
C) Anhedonia
D) Sleep disturbances
Answer: D) Sleep disturbances
Rationale: Sleep disturbances often improve within the first week of
antidepressant therapy, even before mood elevation occurs. This is due to the
sedating properties of many antidepressants and early effects on sleep architecture.
,Core depressive symptoms like mood, anhedonia, and suicidal ideation typically
take 2-6 weeks to respond.
Question 3
Which of the following medication combinations would you want to AVOID?
A) Fluoxetine-lithium
B) Fluoxetine-phenelzine
C) Citalopram-valproic acid
D) Citalopram-aripiprazole
Answer: B) Fluoxetine-phenelzine
Rationale: Combining an SSRI (fluoxetine) with an MAOI (phenelzine) is
contraindicated due to the risk of serotonin syndrome, hypertensive crisis, and
death. A 5-week washout period is required when switching from fluoxetine to an
MAOI. The other combinations may require monitoring but are not absolutely
contraindicated.
Question 4
A 26-year-old man with depression has been taking sertraline 200 mg/day for 12
weeks with no response. The patient has no other complications. The most
reasonable recommendation would be to:
A) Increase sertraline
B) Add fluoxetine
C) Switch to amitriptyline
D) Change to venlafaxine
E) Decrease sertraline
Answer: D) Change to venlafaxine
Rationale: The patient has failed an adequate trial of sertraline (200 mg/day for 12
weeks). Switching to a different class of antidepressant, such as venlafaxine
(SNRI), is recommended. Venlafaxine has a different mechanism of action and
may be effective in treatment-resistant depression. Increasing sertraline above 200
mg is not recommended, and adding fluoxetine would be duplicative.
,Question 5
Which combination is dangerously contraindicated?
A) MAOI-lorazepam
B) MAOI-acetaminophen
C) MAOI-meperidine
D) MAOI-ziprasidone
Answer: C) MAOI-meperidine
Rationale: MAOIs combined with meperidine (Demerol) can cause severe
serotonin syndrome, hyperthermia, seizures, and death. This is a classic and
dangerous drug interaction. MAOIs with other opioids like fentanyl or morphine
are also risky but meperidine is particularly dangerous due to its serotonergic
properties.
Question 6
A 23-year-old woman presents with decreased sleep, decreased appetite, decreased
concentration, depressed mood, thoughts of death, and anhedonia for 6 weeks. She
takes Ortho-Tri Cyclen daily. What is the BEST medication?
A) Nefazodone 100 mg PO BID
B) Paroxetine 20 mg PO daily
C) St. John's wort 300 mg PO TID
D) Amitriptyline 25 mg at bedtime
Answer: B) Paroxetine 20 mg PO daily
Rationale: The patient meets criteria for major depressive disorder. Paroxetine is a
first-line SSRI for depression. SSRIs have the best efficacy and safety profile.
Nefazodone has hepatotoxicity concerns, St. John's wort has drug interactions
(including with oral contraceptives), and amitriptyline is a TCA with more side
effects.
Question 7
, A 36-year-old man on linezolid and paroxetine develops agitation, confusion,
diaphoresis, and myoclonic jerks. What is the most likely diagnosis?
A) Metformin overdose
B) Bacterial meningitis
C) Neuroleptic malignant syndrome
D) Serotonin syndrome
Answer: D) Serotonin syndrome
Rationale: The patient is on linezolid (an antibiotic with weak MAOI properties)
and paroxetine (an SSRI). This combination increases serotonin risk. Serotonin
syndrome is characterized by agitation, confusion, diaphoresis, myoclonic jerks,
hyperthermia, and autonomic instability. This is a classic presentation of serotonin
syndrome.
Question 8
A 46-year-old woman on paroxetine 10 mg for 2 months says it's not working and
has started drinking 8-10 beers daily. She was sober for 4 years. What is the
appropriate treatment strategy?
A) Stop paroxetine and start nefazodone
B) Increase paroxetine to 20 mg
C) Stop paroxetine and start duloxetine
D) Continue paroxetine at the same dose
Answer: B) Increase paroxetine to 20 mg
Rationale: The patient is on a subtherapeutic dose of paroxetine (10 mg). The
starting therapeutic dose for depression is typically 20 mg. Before switching
medications, the dose should be optimized. The alcohol use is likely due to
inadequate treatment of depression. Nefazodone and duloxetine would be
considered after adequate dose optimization fails.
Question 9
Which is a flaw in the monoamine hypothesis of depression?
COMPREHENSIVE EXAM STUDY GUIDE
2026/2027 Questions with Verified Correct Answers &
Detailed Rationales | Graded A+
Question 1
Which of the following SSRIs requires up to a 5-week washout period because of
the long half-life of its potent active metabolite?
A) Escitalopram
B) Fluvoxamine
C) Fluoxetine
D) Sertraline
Answer: C) Fluoxetine
Rationale: Fluoxetine has the longest half-life among SSRIs (2-4 days) and its
active metabolite, norfluoxetine, has a half-life of 7-15 days. This necessitates a 5-
week washout period when switching to or from MAOIs to prevent serotonin
syndrome. Other SSRIs like sertraline, paroxetine, and fluvoxamine have shorter
half-lives requiring only 2-week washouts.
Question 2
Which symptom is most likely to improve within approximately 1 week of starting
antidepressant treatment?
A) Depressed mood
B) Suicidal thoughts
C) Anhedonia
D) Sleep disturbances
Answer: D) Sleep disturbances
Rationale: Sleep disturbances often improve within the first week of
antidepressant therapy, even before mood elevation occurs. This is due to the
sedating properties of many antidepressants and early effects on sleep architecture.
,Core depressive symptoms like mood, anhedonia, and suicidal ideation typically
take 2-6 weeks to respond.
Question 3
Which of the following medication combinations would you want to AVOID?
A) Fluoxetine-lithium
B) Fluoxetine-phenelzine
C) Citalopram-valproic acid
D) Citalopram-aripiprazole
Answer: B) Fluoxetine-phenelzine
Rationale: Combining an SSRI (fluoxetine) with an MAOI (phenelzine) is
contraindicated due to the risk of serotonin syndrome, hypertensive crisis, and
death. A 5-week washout period is required when switching from fluoxetine to an
MAOI. The other combinations may require monitoring but are not absolutely
contraindicated.
Question 4
A 26-year-old man with depression has been taking sertraline 200 mg/day for 12
weeks with no response. The patient has no other complications. The most
reasonable recommendation would be to:
A) Increase sertraline
B) Add fluoxetine
C) Switch to amitriptyline
D) Change to venlafaxine
E) Decrease sertraline
Answer: D) Change to venlafaxine
Rationale: The patient has failed an adequate trial of sertraline (200 mg/day for 12
weeks). Switching to a different class of antidepressant, such as venlafaxine
(SNRI), is recommended. Venlafaxine has a different mechanism of action and
may be effective in treatment-resistant depression. Increasing sertraline above 200
mg is not recommended, and adding fluoxetine would be duplicative.
,Question 5
Which combination is dangerously contraindicated?
A) MAOI-lorazepam
B) MAOI-acetaminophen
C) MAOI-meperidine
D) MAOI-ziprasidone
Answer: C) MAOI-meperidine
Rationale: MAOIs combined with meperidine (Demerol) can cause severe
serotonin syndrome, hyperthermia, seizures, and death. This is a classic and
dangerous drug interaction. MAOIs with other opioids like fentanyl or morphine
are also risky but meperidine is particularly dangerous due to its serotonergic
properties.
Question 6
A 23-year-old woman presents with decreased sleep, decreased appetite, decreased
concentration, depressed mood, thoughts of death, and anhedonia for 6 weeks. She
takes Ortho-Tri Cyclen daily. What is the BEST medication?
A) Nefazodone 100 mg PO BID
B) Paroxetine 20 mg PO daily
C) St. John's wort 300 mg PO TID
D) Amitriptyline 25 mg at bedtime
Answer: B) Paroxetine 20 mg PO daily
Rationale: The patient meets criteria for major depressive disorder. Paroxetine is a
first-line SSRI for depression. SSRIs have the best efficacy and safety profile.
Nefazodone has hepatotoxicity concerns, St. John's wort has drug interactions
(including with oral contraceptives), and amitriptyline is a TCA with more side
effects.
Question 7
, A 36-year-old man on linezolid and paroxetine develops agitation, confusion,
diaphoresis, and myoclonic jerks. What is the most likely diagnosis?
A) Metformin overdose
B) Bacterial meningitis
C) Neuroleptic malignant syndrome
D) Serotonin syndrome
Answer: D) Serotonin syndrome
Rationale: The patient is on linezolid (an antibiotic with weak MAOI properties)
and paroxetine (an SSRI). This combination increases serotonin risk. Serotonin
syndrome is characterized by agitation, confusion, diaphoresis, myoclonic jerks,
hyperthermia, and autonomic instability. This is a classic presentation of serotonin
syndrome.
Question 8
A 46-year-old woman on paroxetine 10 mg for 2 months says it's not working and
has started drinking 8-10 beers daily. She was sober for 4 years. What is the
appropriate treatment strategy?
A) Stop paroxetine and start nefazodone
B) Increase paroxetine to 20 mg
C) Stop paroxetine and start duloxetine
D) Continue paroxetine at the same dose
Answer: B) Increase paroxetine to 20 mg
Rationale: The patient is on a subtherapeutic dose of paroxetine (10 mg). The
starting therapeutic dose for depression is typically 20 mg. Before switching
medications, the dose should be optimized. The alcohol use is likely due to
inadequate treatment of depression. Nefazodone and duloxetine would be
considered after adequate dose optimization fails.
Question 9
Which is a flaw in the monoamine hypothesis of depression?
