A 38-year-old man with schizophrenia has been on risperidone 6 mg/day for 2 years with good symptom control. He now presents with gynecomastia, galactorrhea, and erectile dysfunction. Which of the following is NOT a recognized mechanism by which atypical antipsychotics cause hyperprolactinemia?

Explanation

## Mechanism of Antipsychotic-Induced Hyperprolactinemia ### Correct Pathophysiology Antipsychotics elevate prolactin primarily through **dopamine D2 antagonism** in the tuberoinfundibular axis. Dopamine normally acts as prolactin-inhibiting factor (PIF); blocking this removes the brake on lactotroph cells. **Key Point:** The tuberoinfundibular pathway is unique — it lies outside the blood–brain barrier and is highly sensitive to dopamine blockade. This is why hyperprolactinemia is one of the most common endocrine side effects of antipsychotics. ### Secondary Mechanisms 1. **Serotonergic disinhibition**: Atypical antipsychotics block 5-HT2A receptors. Because serotonin normally *inhibits* prolactin release (via TRH suppression), blocking 5-HT2A removes this inhibition, allowing prolactin to rise. 2. **Direct lactotroph blockade**: Dopamine antagonism at the lactotroph cell surface itself prevents dopamine-mediated suppression of prolactin secretion. ### Why Option B Is Wrong There is **no PRH (prolactin-releasing hormone)** in human physiology. Prolactin release is controlled by: - **Negative control**: Dopamine (PIF) — the dominant mechanism - **Positive control**: TRH (thyrotropin-releasing hormone) — a minor contributor No endogenous "PRH" exists. This is a decoy option that invokes a non-existent hormone. **High-Yield:** Remember: dopamine = prolactin inhibition. Anything that blocks dopamine (or removes dopamine's inhibitory tone) raises prolactin. ### Clinical Correlates | Antipsychotic | Hyperprolactinemia Risk | Mechanism Prominence | |---|---|---| | Risperidone | **Very high** | Strong D2 blockade + 5-HT2A antagonism | | Paliperidone | **Very high** | Active metabolite of risperidone | | Amisulpride | **High** | Selective D2/D3 antagonism | | Aripiprazole | **Low** | D2 partial agonist (maintains dopamine tone) | | Quetiapine | **Low** | Weak D2 affinity, rapid dissociation | | Clozapine | **Low** | Weak D2 affinity | **Clinical Pearl:** If a patient on risperidone develops hyperprolactinemia-related symptoms (gynecomastia, galactorrhea, sexual dysfunction, amenorrhea), consider switching to aripiprazole or quetiapine, which have minimal prolactin elevation. **Tip:** In NEET PG exams, when asked about antipsychotic side effect mechanisms, always verify that the proposed mechanism involves a **real physiological pathway**. Invented hormones or receptors are common distractors.