Occurs when a high D2 affinity drug is replaced with a low D2 affinity drug.

Occurs when a high D2 affinity drug is replaced with a low D2 affinity drug.

• A. Cholinergic rebound
• B. Flu-like symptoms
• C. Acute withdrawal effects
• D. Dopaminergic rebound

Answer: (D)

When a very potent D2 antagonist is switched to a drug with lower D2 affinity, the brain’s dopamine blockade drops more quickly than the system can adapt. Chronic strong D2 blockade can lead to receptor changes and increased sensitivity to dopamine; once the blockade lessens, that sensitized system produces a surge of dopaminergic activity. The result is dopaminergic rebound—sudden return or worsening of symptoms driven by dopamine, such as agitation, restlessness, or a flare of psychosis. Clinically, this is more likely with abrupt switches, so cross-titration or gradual tapering helps maintain some D2 modulation during the transition. Cholinergic rebound, flu-like symptoms, and general acute withdrawal describe other withdrawal or physiological processes not specific to changing D2 receptor occupancy, so they don’t capture the mechanism at play here.

When a very potent D2 antagonist is switched to a drug with lower D2 affinity, the brain’s dopamine blockade drops more quickly than the system can adapt. Chronic strong D2 blockade can lead to receptor changes and increased sensitivity to dopamine; once the blockade lessens, that sensitized system produces a surge of dopaminergic activity. The result is dopaminergic rebound—sudden return or worsening of symptoms driven by dopamine, such as agitation, restlessness, or a flare of psychosis. Clinically, this is more likely with abrupt switches, so cross-titration or gradual tapering helps maintain some D2 modulation during the transition.

Cholinergic rebound, flu-like symptoms, and general acute withdrawal describe other withdrawal or physiological processes not specific to changing D2 receptor occupancy, so they don’t capture the mechanism at play here.