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
Autoreceptors and Antidepressant Onset
Stem
A 28-year-old woman with major depressive disorder has been
taking an SSRI for 7 days with partial anxiogenic activation and
no mood improvement. She reports prior good response to an
SSRI years ago. Her clinician contemplates adding low-dose
buspirone versus waiting. Which neurobiological explanation
best supports continuing the SSRI alone rather than immediate
augmentation?
,Options
A. Early anxiogenic activation reflects postsynaptic 5-HT2A
supersensitivity that will rapidly reverse with buspirone.
B. Initial increased synaptic serotonin activates somatodendritic
5-HT1A autoreceptors, transiently reducing serotonergic neuron
firing; waiting allows autoreceptor desensitization and clinical
benefit.
C. Buspirone will block SERT and immediately increase synaptic
serotonin, accelerating antidepressant effect.
D. Early activation indicates MAO inhibition is needed; switching
to an MAOI will produce faster symptom relief.
Correct answer
B
Rationales
Correct (B): Early SSRI treatment raises synaptic 5-HT, which
activates somatodendritic 5-HT1A autoreceptors and decreases
firing of serotonergic neurons, producing transient reduced
downstream serotonin release. Stahl explains that therapeutic
onset commonly requires autoreceptor desensitization over
days–weeks; thus continuation (rather than immediate
pharmacologic augmentation that targets other mechanisms) is
often justified.
Incorrect (A): Early anxiogenic effects are more consistent with
autoreceptor-mediated changes than postsynaptic 5-HT2A
supersensitivity, which does not reverse “rapidly” with
buspirone.
,Incorrect (C): Buspirone is a 5-HT1A partial agonist/ agonist at
somatodendritic receptors and does not block SERT; it would
not immediately increase synaptic serotonin via transporter
blockade.
Incorrect (D): MAOI initiation is not indicated for early SSRI
activation and carries dietary/interaction risks; MAOIs do not
bypass autoreceptor dynamics to produce a faster onset.
Teaching Point
Somatodendritic autoreceptor desensitization explains SSRI
delayed onset and transient activation.
Citation
Stahl, S. M. (2021). Essential Psychopharmacology (5th ed.). Ch.
1.
2
Reference
Ch. 1 — Chemical Neurotransmission — Vesicular Storage and
VMAT Inhibitors
Stem
A 62-year-old man with Parkinsonian features and depressive
symptoms is prescribed a noradrenergic reuptake inhibitor. He
has a history of labile blood pressure and is taking a medication
that depletes vesicular monoamine storage. Which presynaptic
mechanism best explains exaggerated orthostatic hypotension
, if combined with a drug that increases synaptic norepinephrine
release?
Options
A. Blockade of VMAT reduces vesicular NE storage, increasing
cytosolic NE and enhancing nonvesicular reverse transport.
B. VMAT inhibition increases vesicular NE, leading to greater
exocytotic release and pressor effects.
C. VMAT inhibition reduces vesicular NE stores, causing
impaired evoked release and reduced sympathetic tone;
combined release agents therefore cause unpredictable
autonomic collapse.
D. VMAT inhibitors directly block postsynaptic alpha-1 receptors
causing orthostatic hypotension.
Correct answer
C
Rationales
Correct (C): VMAT inhibition depletes vesicular monoamine
stores, reducing stimulus-evoked exocytotic release and
baseline sympathetic neurotransmission—this can lower blood
pressure. If a drug attempts to increase synaptic NE (e.g., via
NET inhibition or amphetamine-type release), the mismatch
between depleted vesicular pools and presynaptic dysfunction
can produce unstable autonomic responses and orthostatic
hypotension. Stahl details how vesicular storage is essential for
regulated release.
Incorrect (A): While VMAT blockade can increase cytosolic
NEUROSCIENTIFIC BASIS AND PRACTICAL
APPLICATIONS
5TH EDITION
AUTHOR(S)STEPHEN M. STAHL
TEST BANK
1
Reference
Ch. 1 — Chemical Neurotransmission — Presynaptic
Autoreceptors and Antidepressant Onset
Stem
A 28-year-old woman with major depressive disorder has been
taking an SSRI for 7 days with partial anxiogenic activation and
no mood improvement. She reports prior good response to an
SSRI years ago. Her clinician contemplates adding low-dose
buspirone versus waiting. Which neurobiological explanation
best supports continuing the SSRI alone rather than immediate
augmentation?
,Options
A. Early anxiogenic activation reflects postsynaptic 5-HT2A
supersensitivity that will rapidly reverse with buspirone.
B. Initial increased synaptic serotonin activates somatodendritic
5-HT1A autoreceptors, transiently reducing serotonergic neuron
firing; waiting allows autoreceptor desensitization and clinical
benefit.
C. Buspirone will block SERT and immediately increase synaptic
serotonin, accelerating antidepressant effect.
D. Early activation indicates MAO inhibition is needed; switching
to an MAOI will produce faster symptom relief.
Correct answer
B
Rationales
Correct (B): Early SSRI treatment raises synaptic 5-HT, which
activates somatodendritic 5-HT1A autoreceptors and decreases
firing of serotonergic neurons, producing transient reduced
downstream serotonin release. Stahl explains that therapeutic
onset commonly requires autoreceptor desensitization over
days–weeks; thus continuation (rather than immediate
pharmacologic augmentation that targets other mechanisms) is
often justified.
Incorrect (A): Early anxiogenic effects are more consistent with
autoreceptor-mediated changes than postsynaptic 5-HT2A
supersensitivity, which does not reverse “rapidly” with
buspirone.
,Incorrect (C): Buspirone is a 5-HT1A partial agonist/ agonist at
somatodendritic receptors and does not block SERT; it would
not immediately increase synaptic serotonin via transporter
blockade.
Incorrect (D): MAOI initiation is not indicated for early SSRI
activation and carries dietary/interaction risks; MAOIs do not
bypass autoreceptor dynamics to produce a faster onset.
Teaching Point
Somatodendritic autoreceptor desensitization explains SSRI
delayed onset and transient activation.
Citation
Stahl, S. M. (2021). Essential Psychopharmacology (5th ed.). Ch.
1.
2
Reference
Ch. 1 — Chemical Neurotransmission — Vesicular Storage and
VMAT Inhibitors
Stem
A 62-year-old man with Parkinsonian features and depressive
symptoms is prescribed a noradrenergic reuptake inhibitor. He
has a history of labile blood pressure and is taking a medication
that depletes vesicular monoamine storage. Which presynaptic
mechanism best explains exaggerated orthostatic hypotension
, if combined with a drug that increases synaptic norepinephrine
release?
Options
A. Blockade of VMAT reduces vesicular NE storage, increasing
cytosolic NE and enhancing nonvesicular reverse transport.
B. VMAT inhibition increases vesicular NE, leading to greater
exocytotic release and pressor effects.
C. VMAT inhibition reduces vesicular NE stores, causing
impaired evoked release and reduced sympathetic tone;
combined release agents therefore cause unpredictable
autonomic collapse.
D. VMAT inhibitors directly block postsynaptic alpha-1 receptors
causing orthostatic hypotension.
Correct answer
C
Rationales
Correct (C): VMAT inhibition depletes vesicular monoamine
stores, reducing stimulus-evoked exocytotic release and
baseline sympathetic neurotransmission—this can lower blood
pressure. If a drug attempts to increase synaptic NE (e.g., via
NET inhibition or amphetamine-type release), the mismatch
between depleted vesicular pools and presynaptic dysfunction
can produce unstable autonomic responses and orthostatic
hypotension. Stahl details how vesicular storage is essential for
regulated release.
Incorrect (A): While VMAT blockade can increase cytosolic
