STAHL'S ESSENTIAL PSYCHOPHARMACOLOGY
NEUROSCIENTIFIC BASIS AND PRACTICAL
APPLICATIONS
5TH EDITION
AUTHOR(S)STEPHEN M. STAHL
TEST BANK
1.
Reference
Ch. 1 — Chemical Neurotransmission — Vesicular storage and
VMAT
PMHNP-Level Question Stem
A 58-year-old woman with recurrent major depressive disorder
and prominent psychomotor retardation has failed two SSRIs.
She reports severe daytime sedation and weight gain on
mirtazapine. You are considering a drug that increases synaptic
monoamines by blocking vesicular monoamine transporter
(VMAT) function. Which strategy best matches VMAT-targeted
pharmacology for augmenting synaptic monoamines while
minimizing prolonged postsynaptic receptor blockade?
,Options
A. Add low-dose amphetamine to increase cytosolic
monoamine release via reverse transport.
B. Start a reversible VMAT inhibitor that prevents vesicular
uptake, increasing cytosolic availability.
C. Switch to a high-affinity postsynaptic monoamine receptor
antagonist to up-regulate presynaptic release.
D. Add an MAO-A inhibitor to block enzymatic breakdown of
cytosolic monoamines.
Correct Answer
B
Rationales
Correct (B) — Reversible VMAT inhibition reduces vesicular
sequestration, increasing cytosolic monoamine available for
non-vesicular release and reuptake into the synapse, enhancing
extracellular monoamines without directly blocking
postsynaptic receptors. Stahl explains that VMAT manipulation
alters presynaptic storage and can increase available
transmitter. This strategy targets presynaptic storage
mechanisms aligning with the patient’s poor response to SSRIs
and need for activation without heavy sedation.
Incorrect (A) — Amphetamine promotes reverse transport and
massive release; it risks agitation, insomnia, and cardiovascular
side effects, and is not a selective VMAT reversible inhibitor per
Stahl’s presynaptic mechanisms.
Incorrect (C) — Postsynaptic antagonists do not increase
,synaptic monoamine availability; they reduce postsynaptic
signaling and can worsen depression.
Incorrect (D) — MAO-A inhibition increases monoamines by
preventing enzymatic breakdown, but carries dietary and drug
interaction risks and is not a VMAT-targeted approach.
Teaching Point
Targeting VMAT modulates presynaptic storage to increase
extracellular monoamines without direct postsynaptic blockade.
Citation
Stahl, S. M. (2021). Essential Psychopharmacology (5th ed.). Ch.
1.
2.
Reference
Ch. 1 — Chemical Neurotransmission — Reuptake transporters
(SERT, NET, DAT)
PMHNP-Level Question Stem
A 34-year-old man with major depressive disorder reports
residual anergia and poor concentration on an SSRI that
resolved his core sad mood. He has a history of controlled
hypertension. You consider adding an agent that preferentially
inhibits norepinephrine reuptake to target motivational
symptoms. Based on transporter pharmacology, which choice
best balances efficacy and cardiovascular safety?
, Options
A. Add a selective NET inhibitor with minimal peripheral
adrenergic effect.
B. Switch to a potent NET inhibitor with strong peripheral
norepinephrine elevation.
C. Add a dopamine reuptake inhibitor (DAT) alone to improve
motivation.
D. Augment with a low-dose alpha-1 agonist to increase frontal
cortical arousal.
Correct Answer
A
Rationales
Correct (A) — A selective NET inhibitor that preferentially
targets central NET over peripheral adrenergic receptors will
increase cortical norepinephrine availability improving energy
and concentration while minimizing peripheral vasoconstrictive
effects. Stahl emphasizes transporter selectivity and central vs
peripheral distribution in predicting clinical effects and safety.
Incorrect (B) — A potent nonselective NET agent raises
peripheral NE, risking hypertension; Stahl notes peripheral
adrenergic activation as a cardiovascular safety concern.
Incorrect (C) — Isolated DAT inhibition may improve motivation
but may be less effective for noradrenergic deficits and can
increase stimulant-like adverse effects; transporter targeting
should match symptom biology.
Incorrect (D) — Alpha-1 agonists act postsynaptically and risk
NEUROSCIENTIFIC BASIS AND PRACTICAL
APPLICATIONS
5TH EDITION
AUTHOR(S)STEPHEN M. STAHL
TEST BANK
1.
Reference
Ch. 1 — Chemical Neurotransmission — Vesicular storage and
VMAT
PMHNP-Level Question Stem
A 58-year-old woman with recurrent major depressive disorder
and prominent psychomotor retardation has failed two SSRIs.
She reports severe daytime sedation and weight gain on
mirtazapine. You are considering a drug that increases synaptic
monoamines by blocking vesicular monoamine transporter
(VMAT) function. Which strategy best matches VMAT-targeted
pharmacology for augmenting synaptic monoamines while
minimizing prolonged postsynaptic receptor blockade?
,Options
A. Add low-dose amphetamine to increase cytosolic
monoamine release via reverse transport.
B. Start a reversible VMAT inhibitor that prevents vesicular
uptake, increasing cytosolic availability.
C. Switch to a high-affinity postsynaptic monoamine receptor
antagonist to up-regulate presynaptic release.
D. Add an MAO-A inhibitor to block enzymatic breakdown of
cytosolic monoamines.
Correct Answer
B
Rationales
Correct (B) — Reversible VMAT inhibition reduces vesicular
sequestration, increasing cytosolic monoamine available for
non-vesicular release and reuptake into the synapse, enhancing
extracellular monoamines without directly blocking
postsynaptic receptors. Stahl explains that VMAT manipulation
alters presynaptic storage and can increase available
transmitter. This strategy targets presynaptic storage
mechanisms aligning with the patient’s poor response to SSRIs
and need for activation without heavy sedation.
Incorrect (A) — Amphetamine promotes reverse transport and
massive release; it risks agitation, insomnia, and cardiovascular
side effects, and is not a selective VMAT reversible inhibitor per
Stahl’s presynaptic mechanisms.
Incorrect (C) — Postsynaptic antagonists do not increase
,synaptic monoamine availability; they reduce postsynaptic
signaling and can worsen depression.
Incorrect (D) — MAO-A inhibition increases monoamines by
preventing enzymatic breakdown, but carries dietary and drug
interaction risks and is not a VMAT-targeted approach.
Teaching Point
Targeting VMAT modulates presynaptic storage to increase
extracellular monoamines without direct postsynaptic blockade.
Citation
Stahl, S. M. (2021). Essential Psychopharmacology (5th ed.). Ch.
1.
2.
Reference
Ch. 1 — Chemical Neurotransmission — Reuptake transporters
(SERT, NET, DAT)
PMHNP-Level Question Stem
A 34-year-old man with major depressive disorder reports
residual anergia and poor concentration on an SSRI that
resolved his core sad mood. He has a history of controlled
hypertension. You consider adding an agent that preferentially
inhibits norepinephrine reuptake to target motivational
symptoms. Based on transporter pharmacology, which choice
best balances efficacy and cardiovascular safety?
, Options
A. Add a selective NET inhibitor with minimal peripheral
adrenergic effect.
B. Switch to a potent NET inhibitor with strong peripheral
norepinephrine elevation.
C. Add a dopamine reuptake inhibitor (DAT) alone to improve
motivation.
D. Augment with a low-dose alpha-1 agonist to increase frontal
cortical arousal.
Correct Answer
A
Rationales
Correct (A) — A selective NET inhibitor that preferentially
targets central NET over peripheral adrenergic receptors will
increase cortical norepinephrine availability improving energy
and concentration while minimizing peripheral vasoconstrictive
effects. Stahl emphasizes transporter selectivity and central vs
peripheral distribution in predicting clinical effects and safety.
Incorrect (B) — A potent nonselective NET agent raises
peripheral NE, risking hypertension; Stahl notes peripheral
adrenergic activation as a cardiovascular safety concern.
Incorrect (C) — Isolated DAT inhibition may improve motivation
but may be less effective for noradrenergic deficits and can
increase stimulant-like adverse effects; transporter targeting
should match symptom biology.
Incorrect (D) — Alpha-1 agonists act postsynaptically and risk
