, Question 1
A patient with treatment-resistant schizophrenia has failed adequate trials of
two second-generation antipsychotics. Which agent is supported by the
strongest evidence for clozapine-resistant illness?
A. Olanzapine augmentation with fluoxetine
B. Electroconvulsive therapy combined with clozapine
C. High-dose risperidone long-acting injection
D. Adjunctive lithium carbonate
Correct Answer: B - Electroconvulsive therapy combined with
clozapine
RATIONALE
The CUtLASS and subsequent evidence syntheses support ECT
augmentation of clozapine as the best-supported strategy for
clozapine-resistant schizophrenia. Olanzapine-fluoxetine targets
depressive symptoms, high-dose risperidone lacks efficacy beyond
standard dosing, and lithium has no established role in clozapine
resistance.
Question 2
Which CYP450 interaction most accurately explains the dangerous rise in TCA
levels when fluoxetine is co-prescribed?
A. Fluoxetine induces CYP3A4, accelerating TCA activation
B. Fluoxetine inhibits CYP2D6, reducing TCA clearance
C. Fluoxetine inhibits CYP1A2, increasing TCA absorption
D. Fluoxetine induces CYP2C19, converting TCAs to toxic metabolites
Correct Answer: B - Fluoxetine inhibits CYP2D6, reducing TCA
clearance
Page 2
, RATIONALE
Fluoxetine is a potent CYP2D6 inhibitor, and tertiary amine TCAs are
primarily metabolized by CYP2D6; inhibition raises parent drug
concentrations and toxicity risk. The other options misstate the
enzyme or the direction of the interaction.
Question 3
A patient with major depressive disorder and a history of narrow-angle
glaucoma requires an antidepressant with the least anticholinergic burden.
Which agent is most appropriate?
A. Amitriptyline
B. Paroxetine
C. Sertraline
D. Doxepin
Correct Answer: C - Sertraline
RATIONALE
Sertraline has minimal anticholinergic activity, making it safest in
narrow-angle glaucoma. Amitriptyline and doxepin are highly
anticholinergic, and paroxetine has moderate anticholinergic effects
that can worsen glaucoma.
Question 4
A patient on lithium reports new-onset coarse tremor, ataxia, and confusion.
Which serum level and management are most consistent with toxicity?
A. 0.6 mEq/L; continue current dose
B. 1.4 mEq/L; hold lithium and provide supportive care
C. 0.9 mEq/L; increase fluid intake
D. 1.1 mEq/L; add propranolol
Correct Answer: B - 1.4 mEq/L; hold lithium and provide
supportive care
Page 3
, RATIONALE
Lithium toxicity typically manifests above 1.2-1.5 mEq/L with
neurologic and gastrointestinal symptoms. Holding the drug and
supportive care are indicated; the other levels are therapeutic or too
low to explain toxicity.
Question 5
Which statement best reflects the current understanding of the 'delayed onset'
of antidepressant action?
A. It results from gradual serotonin transporter occupancy requiring 6-8
weeks
B. It reflects downstream neuroplastic changes such as BDNF-mediated
synaptogenesis
C. It is due to autoinduction of hepatic enzymes
D. It is an artifact of clinical trial design
Correct Answer: B - It reflects downstream neuroplastic changes
such as BDNF-mediated synaptogenesis
RATIONALE
Neuroplasticity hypotheses attribute the 2-4 week delay to
downstream changes including BDNF signaling and synaptic
remodeling rather than immediate transporter occupancy. The other
options misattribute the mechanism to pharmacokinetic or
methodological factors.
Question 6
A patient with PTSD and frequent nightmares is being considered for
pharmacotherapy. Which agent has the strongest evidence for reducing
trauma-related nightmares?
A. Prazosin
B. Sertraline
C. Hydroxyzine
Page 4
A patient with treatment-resistant schizophrenia has failed adequate trials of
two second-generation antipsychotics. Which agent is supported by the
strongest evidence for clozapine-resistant illness?
A. Olanzapine augmentation with fluoxetine
B. Electroconvulsive therapy combined with clozapine
C. High-dose risperidone long-acting injection
D. Adjunctive lithium carbonate
Correct Answer: B - Electroconvulsive therapy combined with
clozapine
RATIONALE
The CUtLASS and subsequent evidence syntheses support ECT
augmentation of clozapine as the best-supported strategy for
clozapine-resistant schizophrenia. Olanzapine-fluoxetine targets
depressive symptoms, high-dose risperidone lacks efficacy beyond
standard dosing, and lithium has no established role in clozapine
resistance.
Question 2
Which CYP450 interaction most accurately explains the dangerous rise in TCA
levels when fluoxetine is co-prescribed?
A. Fluoxetine induces CYP3A4, accelerating TCA activation
B. Fluoxetine inhibits CYP2D6, reducing TCA clearance
C. Fluoxetine inhibits CYP1A2, increasing TCA absorption
D. Fluoxetine induces CYP2C19, converting TCAs to toxic metabolites
Correct Answer: B - Fluoxetine inhibits CYP2D6, reducing TCA
clearance
Page 2
, RATIONALE
Fluoxetine is a potent CYP2D6 inhibitor, and tertiary amine TCAs are
primarily metabolized by CYP2D6; inhibition raises parent drug
concentrations and toxicity risk. The other options misstate the
enzyme or the direction of the interaction.
Question 3
A patient with major depressive disorder and a history of narrow-angle
glaucoma requires an antidepressant with the least anticholinergic burden.
Which agent is most appropriate?
A. Amitriptyline
B. Paroxetine
C. Sertraline
D. Doxepin
Correct Answer: C - Sertraline
RATIONALE
Sertraline has minimal anticholinergic activity, making it safest in
narrow-angle glaucoma. Amitriptyline and doxepin are highly
anticholinergic, and paroxetine has moderate anticholinergic effects
that can worsen glaucoma.
Question 4
A patient on lithium reports new-onset coarse tremor, ataxia, and confusion.
Which serum level and management are most consistent with toxicity?
A. 0.6 mEq/L; continue current dose
B. 1.4 mEq/L; hold lithium and provide supportive care
C. 0.9 mEq/L; increase fluid intake
D. 1.1 mEq/L; add propranolol
Correct Answer: B - 1.4 mEq/L; hold lithium and provide
supportive care
Page 3
, RATIONALE
Lithium toxicity typically manifests above 1.2-1.5 mEq/L with
neurologic and gastrointestinal symptoms. Holding the drug and
supportive care are indicated; the other levels are therapeutic or too
low to explain toxicity.
Question 5
Which statement best reflects the current understanding of the 'delayed onset'
of antidepressant action?
A. It results from gradual serotonin transporter occupancy requiring 6-8
weeks
B. It reflects downstream neuroplastic changes such as BDNF-mediated
synaptogenesis
C. It is due to autoinduction of hepatic enzymes
D. It is an artifact of clinical trial design
Correct Answer: B - It reflects downstream neuroplastic changes
such as BDNF-mediated synaptogenesis
RATIONALE
Neuroplasticity hypotheses attribute the 2-4 week delay to
downstream changes including BDNF signaling and synaptic
remodeling rather than immediate transporter occupancy. The other
options misattribute the mechanism to pharmacokinetic or
methodological factors.
Question 6
A patient with PTSD and frequent nightmares is being considered for
pharmacotherapy. Which agent has the strongest evidence for reducing
trauma-related nightmares?
A. Prazosin
B. Sertraline
C. Hydroxyzine
Page 4
