STAHL'S ESSENTIAL PSYCHOPHARMACOLOGY
NEUROSCIENTIFIC BASIS AND PRACTICAL
APPLICATIONS
5TH EDITION
AUTHOR(S)STEPHEN M. STAHL
TEST BANK
1
Reference
Ch. 1 — Chemical Neurotransmission — Presynaptic Regulation
& Autoreceptors
Stem
A 34-year-old woman with major depressive disorder has had
partial improvement after 10 days on an SSRI; she reports
transient worsening of anxiety and mild nausea. She previously
responded to an SSRI years ago. Which presynaptic mechanism
best explains the early increase in anxiety and the typical
delayed antidepressant response?
,A. Immediate down-regulation of postsynaptic 5-HT2A
receptors increasing excitatory drive.
B. Acute blockade of SERT elevating synaptic 5-HT and
activating somatodendritic 5-HT1A autoreceptors, reducing
serotonergic firing.
C. Rapid desensitization of 5-HT1A autoreceptors leading to
immediate increased serotonergic tone.
D. Enhanced VMAT2 activity causing increased vesicular 5-HT
release.
Correct answer
B
Rationales
Correct (B): SSRIs acutely block SERT, raising synaptic 5-HT.
Increased 5-HT activates somatodendritic 5-HT1A
autoreceptors, which transiently reduce firing of serotonergic
neurons and terminal 5-HT release, often worsening anxiety
and delaying full antidepressant effect until autoreceptors
desensitize. Stahl emphasizes autoreceptor-mediated delays in
therapeutic onset.
Incorrect (A): Postsynaptic 5-HT2A down-regulation is not
immediate; early anxiety is better explained by presynaptic
autoreceptor effects.
Incorrect (C): Desensitization of 5-HT1A autoreceptors is a slow
adaptive change (weeks), not the immediate mechanism for
early anxiety.
,Incorrect (D): VMAT2 activity is not acutely enhanced by SSRIs;
increased vesicular loading would not explain early anxiety.
Teaching point
Acute SSRI → ↑synaptic 5-HT → 5-HT1A autoreceptor
activation → transient ↓firing; therapeutic lag follows
autoreceptor desensitization.
Citation
Stahl, S. M. (2021). Essential Psychopharmacology (5th ed.). Ch.
1.
2
Reference
Ch. 1 — Chemical Neurotransmission — Vesicular Transport &
VMAT
Stem
A 57-year-old man with treatment-resistant hypertension and
depression receives a medication that produces marked
depressive symptoms over weeks. Mechanistic review shows
depletion of vesicular monoamines. Which agent and
mechanism most likely produced his depression?
A. Reserpine — irreversible VMAT2 inhibition causing
monoamine depletion.
B. Amphetamine — VMAT2 activation causing increased
vesicular monoamine storage.
C. Phenelzine — MAO inhibition leading to monoamine
, depletion.
D. Methylphenidate — SERT blockade decreasing synaptic 5-HT.
Correct answer
A
Rationales
Correct (A): Reserpine inhibits VMAT2, preventing vesicular
storage of monoamines; cytoplasmic monoamines are
degraded, producing monoamine depletion and depressive
symptoms — a classic mechanistic example discussed in Stahl.
Incorrect (B): Amphetamine causes monoamine release
(reverse transport) and depletion with chronic use, but it does
not activate VMAT2 to increase vesicular storage.
Incorrect (C): Phenelzine inhibits MAO, increasing monoamines,
not depleting them.
Incorrect (D): Methylphenidate inhibits DAT/NET (and has
modest SERT effects) increasing synaptic catecholamines; it
does not block SERT to decrease 5-HT.
Teaching point
VMAT2 inhibition (reserpine) → failure to store monoamines →
cytosolic degradation → clinical depression.
Citation
Stahl, S. M. (2021). Essential Psychopharmacology (5th ed.). Ch.
1.
3
NEUROSCIENTIFIC BASIS AND PRACTICAL
APPLICATIONS
5TH EDITION
AUTHOR(S)STEPHEN M. STAHL
TEST BANK
1
Reference
Ch. 1 — Chemical Neurotransmission — Presynaptic Regulation
& Autoreceptors
Stem
A 34-year-old woman with major depressive disorder has had
partial improvement after 10 days on an SSRI; she reports
transient worsening of anxiety and mild nausea. She previously
responded to an SSRI years ago. Which presynaptic mechanism
best explains the early increase in anxiety and the typical
delayed antidepressant response?
,A. Immediate down-regulation of postsynaptic 5-HT2A
receptors increasing excitatory drive.
B. Acute blockade of SERT elevating synaptic 5-HT and
activating somatodendritic 5-HT1A autoreceptors, reducing
serotonergic firing.
C. Rapid desensitization of 5-HT1A autoreceptors leading to
immediate increased serotonergic tone.
D. Enhanced VMAT2 activity causing increased vesicular 5-HT
release.
Correct answer
B
Rationales
Correct (B): SSRIs acutely block SERT, raising synaptic 5-HT.
Increased 5-HT activates somatodendritic 5-HT1A
autoreceptors, which transiently reduce firing of serotonergic
neurons and terminal 5-HT release, often worsening anxiety
and delaying full antidepressant effect until autoreceptors
desensitize. Stahl emphasizes autoreceptor-mediated delays in
therapeutic onset.
Incorrect (A): Postsynaptic 5-HT2A down-regulation is not
immediate; early anxiety is better explained by presynaptic
autoreceptor effects.
Incorrect (C): Desensitization of 5-HT1A autoreceptors is a slow
adaptive change (weeks), not the immediate mechanism for
early anxiety.
,Incorrect (D): VMAT2 activity is not acutely enhanced by SSRIs;
increased vesicular loading would not explain early anxiety.
Teaching point
Acute SSRI → ↑synaptic 5-HT → 5-HT1A autoreceptor
activation → transient ↓firing; therapeutic lag follows
autoreceptor desensitization.
Citation
Stahl, S. M. (2021). Essential Psychopharmacology (5th ed.). Ch.
1.
2
Reference
Ch. 1 — Chemical Neurotransmission — Vesicular Transport &
VMAT
Stem
A 57-year-old man with treatment-resistant hypertension and
depression receives a medication that produces marked
depressive symptoms over weeks. Mechanistic review shows
depletion of vesicular monoamines. Which agent and
mechanism most likely produced his depression?
A. Reserpine — irreversible VMAT2 inhibition causing
monoamine depletion.
B. Amphetamine — VMAT2 activation causing increased
vesicular monoamine storage.
C. Phenelzine — MAO inhibition leading to monoamine
, depletion.
D. Methylphenidate — SERT blockade decreasing synaptic 5-HT.
Correct answer
A
Rationales
Correct (A): Reserpine inhibits VMAT2, preventing vesicular
storage of monoamines; cytoplasmic monoamines are
degraded, producing monoamine depletion and depressive
symptoms — a classic mechanistic example discussed in Stahl.
Incorrect (B): Amphetamine causes monoamine release
(reverse transport) and depletion with chronic use, but it does
not activate VMAT2 to increase vesicular storage.
Incorrect (C): Phenelzine inhibits MAO, increasing monoamines,
not depleting them.
Incorrect (D): Methylphenidate inhibits DAT/NET (and has
modest SERT effects) increasing synaptic catecholamines; it
does not block SERT to decrease 5-HT.
Teaching point
VMAT2 inhibition (reserpine) → failure to store monoamines →
cytosolic degradation → clinical depression.
Citation
Stahl, S. M. (2021). Essential Psychopharmacology (5th ed.). Ch.
1.
3
