STAHL'S ESSENTIAL PSYCHOPHARMACOLOGY
NEUROSCIENTIFIC BASIS AND PRACTICAL
APPLICATIONS
5TH EDITION
AUTHOR(S)STEPHEN M. STAHL
TEST BANK
1
Reference
Ch. 1 — Synaptic Vesicle Release & Exocytosis
Stem
A 34-year-old patient with MDD reports early morning
worsening of mood and fatigue after starting an SSRI 5 days
ago. They also have orthostatic lightheadedness. You recall
Stahl’s description of presynaptic mechanisms. Which
immediate synaptic mechanism best explains the transient
worsened activation and autonomic symptoms shortly after
SSRI initiation?
A. Rapid blockade of postsynaptic 5-HT₂A receptors producing
acute autonomic instability.
,B. Increased synaptic serotonin leading to activation of
somatodendritic 5-HT₁A autoreceptors that transiently reduce
serotonergic neuronal firing.
C. Immediate upregulation of postsynaptic 5-HT₁A receptors
causing overinhibition of mood circuits.
D. Rapid depletion of vesicular serotonin stores from
continuous exocytosis.
Correct answer
B
Rationales
Correct: SSRI blockade of SERT increases extracellular 5-HT,
which acutely activates somatodendritic 5-HT₁A autoreceptors
reducing firing and serotonin release to terminals — explaining
early transient worsening and autonomic effects. This is exactly
the autoreceptor-mediated feedback Stahl emphasizes.
A (incorrect): Postsynaptic 5-HT₂A blockade is not immediate
with SSRIs and would not explain reduced serotonergic firing or
early activation symptoms.
C (incorrect): Postsynaptic 5-HT₁A upregulation occurs slowly
with chronic treatment; acute overinhibition from postsynaptic
receptor upregulation is inconsistent with timing.
D (incorrect): Vesicular serotonin depletion from exocytosis is
not the primary acute mechanism after SERT blockade
described by Stahl.
,Teaching point
Acute SSRI increases activate 5-HT₁A autoreceptors, transiently
reducing serotonergic output.
Citation
Stahl, S. M. (2021). Essential Psychopharmacology (5th ed.). Ch.
1.
2
Reference
Ch. 1 — Ionotropic vs Metabotropic Receptors
Stem
A 58-year-old with psychotic depression is severely sedated by
an antipsychotic but still has prominent negative symptoms and
cognitive slowing. Considering receptor types described by
Stahl, which pharmacologic strategy most directly preserves fast
excitatory transmission while modulating slower
neuromodulatory tone to reduce sedation?
A. Use a high-affinity H1 inverse agonist antipsychotic to block
histamine receptors.
B. Prefer a drug with low affinity for H1 and M1 receptors but
with selective modulation of metabotropic monoaminergic
receptors.
C. Switch to an NMDA antagonist to increase ionotropic
glutamate signalling.
, D. Add a GABA-A positive allosteric modulator to counteract
sedation.
Correct answer
B
Rationales
Correct: Ionotropic receptors mediate fast transmission;
sedation often stems from H1 (histamine) and M1 (muscarinic)
receptor antagonism (both metabotropic). Selecting a drug with
low H1/M1 affinity spares fast ionotropic signalling while still
modulating metabotropic monoamine receptors. Stahl
highlights receptor-specific side-effect profiles.
A (incorrect): High-affinity H1 inverse agonism increases
sedation, not reduce it.
C (incorrect): NMDA antagonists alter ionotropic glutamatergic
transmission but introduce psychotomimetic risks and are not
the targeted way to preserve fast transmission while
modulating monoamines.
D (incorrect): Adding a GABA-A modulator would increase, not
reduce, sedation.
Teaching point
Minimize H1/M1 blockade to reduce sedation while targeting
metabotropic monoamine receptors.
Citation
Stahl, S. M. (2021). Essential Psychopharmacology (5th ed.). Ch.
1.
NEUROSCIENTIFIC BASIS AND PRACTICAL
APPLICATIONS
5TH EDITION
AUTHOR(S)STEPHEN M. STAHL
TEST BANK
1
Reference
Ch. 1 — Synaptic Vesicle Release & Exocytosis
Stem
A 34-year-old patient with MDD reports early morning
worsening of mood and fatigue after starting an SSRI 5 days
ago. They also have orthostatic lightheadedness. You recall
Stahl’s description of presynaptic mechanisms. Which
immediate synaptic mechanism best explains the transient
worsened activation and autonomic symptoms shortly after
SSRI initiation?
A. Rapid blockade of postsynaptic 5-HT₂A receptors producing
acute autonomic instability.
,B. Increased synaptic serotonin leading to activation of
somatodendritic 5-HT₁A autoreceptors that transiently reduce
serotonergic neuronal firing.
C. Immediate upregulation of postsynaptic 5-HT₁A receptors
causing overinhibition of mood circuits.
D. Rapid depletion of vesicular serotonin stores from
continuous exocytosis.
Correct answer
B
Rationales
Correct: SSRI blockade of SERT increases extracellular 5-HT,
which acutely activates somatodendritic 5-HT₁A autoreceptors
reducing firing and serotonin release to terminals — explaining
early transient worsening and autonomic effects. This is exactly
the autoreceptor-mediated feedback Stahl emphasizes.
A (incorrect): Postsynaptic 5-HT₂A blockade is not immediate
with SSRIs and would not explain reduced serotonergic firing or
early activation symptoms.
C (incorrect): Postsynaptic 5-HT₁A upregulation occurs slowly
with chronic treatment; acute overinhibition from postsynaptic
receptor upregulation is inconsistent with timing.
D (incorrect): Vesicular serotonin depletion from exocytosis is
not the primary acute mechanism after SERT blockade
described by Stahl.
,Teaching point
Acute SSRI increases activate 5-HT₁A autoreceptors, transiently
reducing serotonergic output.
Citation
Stahl, S. M. (2021). Essential Psychopharmacology (5th ed.). Ch.
1.
2
Reference
Ch. 1 — Ionotropic vs Metabotropic Receptors
Stem
A 58-year-old with psychotic depression is severely sedated by
an antipsychotic but still has prominent negative symptoms and
cognitive slowing. Considering receptor types described by
Stahl, which pharmacologic strategy most directly preserves fast
excitatory transmission while modulating slower
neuromodulatory tone to reduce sedation?
A. Use a high-affinity H1 inverse agonist antipsychotic to block
histamine receptors.
B. Prefer a drug with low affinity for H1 and M1 receptors but
with selective modulation of metabotropic monoaminergic
receptors.
C. Switch to an NMDA antagonist to increase ionotropic
glutamate signalling.
, D. Add a GABA-A positive allosteric modulator to counteract
sedation.
Correct answer
B
Rationales
Correct: Ionotropic receptors mediate fast transmission;
sedation often stems from H1 (histamine) and M1 (muscarinic)
receptor antagonism (both metabotropic). Selecting a drug with
low H1/M1 affinity spares fast ionotropic signalling while still
modulating metabotropic monoamine receptors. Stahl
highlights receptor-specific side-effect profiles.
A (incorrect): High-affinity H1 inverse agonism increases
sedation, not reduce it.
C (incorrect): NMDA antagonists alter ionotropic glutamatergic
transmission but introduce psychotomimetic risks and are not
the targeted way to preserve fast transmission while
modulating monoamines.
D (incorrect): Adding a GABA-A modulator would increase, not
reduce, sedation.
Teaching point
Minimize H1/M1 blockade to reduce sedation while targeting
metabotropic monoamine receptors.
Citation
Stahl, S. M. (2021). Essential Psychopharmacology (5th ed.). Ch.
1.
