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DOMAIN 1: ANTIDEPRESSANTS & MOOD STABILIZERS (Q1-15)
1. A 38-year-old patient with treatment-resistant major depressive disorder (MDD) has
failed adequate trials of two SSRIs. The patient also has significant psychomotor
retardation and hypersomnia. The PMHNP considers augmenting with a medication
that has both noradrenergic/dopaminergic activity and evidence for improving energy
and concentration. The MOST appropriate augmenting agent is:
A. Bupropion (due to dopamine/norepinephrine reuptake inhibition)
B. Mirtazapine (for its serotonergic/noradrenergic effects and sedating properties)
C. Aripiprazole (FDA-approved adjunct for MDD with dopamine partial agonism)
D. Benzodiazepine (to address anxiety component of depression)
Correct Answer: C
Rationale: C is correct. Aripiprazole is FDA-approved as adjunctive treatment for MDD
when SSRIs provide insufficient response. Its mechanism as a dopamine D2 partial
agonist and serotonin 5-HT1A partial agonist can address residual symptoms like
fatigue and poor concentration through enhanced dopaminergic transmission in
mesocortical pathways. While bupropion (A) has noradrenergic/dopaminergic activity, it
is typically used as monotherapy or switch strategy rather than augmentation per
STAR*D trial evidence. Mirtazapine (B) would worsen hypersomnia due to potent
antihistaminic (H1) sedating effects. Benzodiazepines (D) are not indicated for
depressive core symptoms and carry significant dependence and cognitive risks.
,2. A 29-year-old patient with bipolar II disorder presents with rapid cycling (4 mood
episodes in 12 months) and prominent depressive symptoms. The patient has a history
of nonadherence to complex medication regimens. The PMHNP selects a mood
stabilizer with the STRONGEST evidence for reducing rapid cycling and depressive
relapse prevention in bipolar disorder:
A. Lithium carbonate (first-line for classic bipolar disorder with mania)
B. Carbamazepine (effective for mixed states and ultradian cycling)
C. Lamotrigine (superior for bipolar depression and rapid cycling prevention)
D. Valproic acid (broad efficacy for mania but less for depression)
Correct Answer: C
Rationale: C is correct. Lamotrigine demonstrates superior efficacy for bipolar
depression and rapid cycling prevention compared to other mood stabilizers, with a
favorable side effect profile supporting adherence. Its mechanism involves inhibition of
voltage-gated sodium channels and modulation of glutamate release, stabilizing mood
without cognitive dulling. Lithium (A), while first-line for classic bipolar I with mania,
shows inferior response in rapid cycling and requires monitoring that may challenge
adherence. Carbamazepine (B) has limited evidence for rapid cycling specifically and
problematic drug interactions. Valproic acid (D) is more effective for manic episodes
than depressive phases in rapid cycling patterns.
3. A 45-year-old patient with MDD and comorbid fibromyalgia is started on duloxetine.
After 6 weeks at 60 mg daily, the patient reports improved mood but persistent
neuropathic pain and sleep disturbance. The PMHNP considers dose optimization
based on dual reuptake inhibition kinetics and pain pathway modulation:
A. Maintain 60 mg as this is the maximum recommended antidepressant dose
B. Switch to venlafaxine for superior SNRI efficacy in pain conditions
C. Increase to 90-120 mg to achieve greater noradrenergic reuptake inhibition for
analgesia
D. Add pregabalin immediately as duloxetine lacks pain indication
Correct Answer: C
Rationale: C is correct. Duloxetine demonstrates dose-dependent noradrenergic
reuptake inhibition, with the 60 mg dose being primarily serotonergic and higher doses
, (90-120 mg) required for substantial norepinephrine transporter occupancy necessary
for neuropathic pain modulation. The FDA approves up to 120 mg daily for fibromyalgia.
Maintaining 60 mg (A) leaves the patient undertreated for pain. Venlafaxine (B) actually
shows inferior noradrenergic reuptake inhibition at moderate doses compared to
duloxetine and lacks fibromyalgia indication. Duloxetine (D) has explicit FDA indications
for diabetic peripheral neuropathic pain and fibromyalgia, making pregabalin addition
premature before dose optimization.
4. A 34-year-old patient with treatment-resistant OCD has failed sertraline 200 mg and
fluoxetine 60 mg trials. The PMHNP considers clomipramine based on its unique
pharmacologic properties in OCD pathophysiology:
A. Selective serotonin reuptake inhibition without significant metabolite activity
B. Primarily noradrenergic reuptake inhibition for comorbid ADHD
C. Potent serotonin reuptake inhibition plus active metabolite desmethylclomipramine
with balanced SRI/NRI activity
D. Dopamine antagonism for obsessional thoughts
Correct Answer: C
Rationale: C is correct. Clomipramine, a tricyclic antidepressant, and its active
metabolite desmethylclomipramine provide potent serotonin reuptake inhibition
combined with norepinephrine reuptake inhibition, which may enhance efficacy in
severe OCD through dual monoamine modulation. This pharmacologic profile
distinguishes it from SSRIs and explains its superior efficacy in some
treatment-resistant OCD cases despite side effect burden. Clomipramine is not
selective (A), nor primarily noradrenergic (B), and lacks significant dopamine
antagonism (D).
5. A 52-year-old patient with bipolar I disorder presents with acute mania, psychotic
features, and severe aggression requiring rapid stabilization. The patient has QTc
prolongation (520 ms) on ECG. The PMHNP avoids which antipsychotic due to
significant QTc prolongation risk:
A. Olanzapine (metabolic risks but minimal QTc effect)
B. Risperidone (prolactin elevation but modest QTc risk)