A 32-year-old man with schizophrenia has been on risperidone 6 mg/day for 8 months. He presents to the psychiatry clinic with complaints of progressive difficulty in concentration, memory lapses, and tremor in both hands. His wife reports that he has gained 12 kg over the past 6 months. On examination, he has a resting tremor, cogwheel rigidity, and bradykinesia. His fasting blood glucose is 128 mg/dL (normal <100 mg/dL) and prolactin level is 45 ng/mL (normal <15 ng/mL). What is the most likely explanation for his tremor and rigidity?

Explanation

## Drug-Induced Parkinsonism (DIP) in Antipsychotic Use ### Clinical Presentation This patient exhibits the classic triad of drug-induced parkinsonism: 1. **Resting tremor** (pill-rolling type) 2. **Rigidity** (cogwheel type on examination) 3. **Bradykinesia** (slowed movement, concentration difficulties) **Key Point:** Drug-induced parkinsonism occurs in 20–30% of patients on typical antipsychotics and 5–10% on atypical antipsychotics like risperidone. It typically manifests within days to weeks of starting or increasing the dose, though this patient's 8-month timeline is also consistent (can occur at any point during treatment). ### Mechanism **High-Yield:** Antipsychotics block dopamine D2 receptors in the **substantia nigra and striatum** of the basal ganglia. This disrupts the normal balance between dopaminergic and cholinergic activity, leading to relative cholinergic excess and extrapyramidal symptoms. ### Distinguishing Features from Other Extrapyramidal Side Effects | Feature | Drug-Induced Parkinsonism | Neuroleptic Malignant Syndrome | Tardive Dyskinesia | |---------|---------------------------|--------------------------------|-------------------| | **Onset** | Days to weeks (or months) | Hours to days | Weeks to months (or years) | | **Temperature** | Normal | **Fever (>38.5°C)** | Normal | | **Rigidity type** | Cogwheel | Lead-pipe (uniform) | Absent | | **Tremor** | Resting, pill-rolling | Absent | Hyperkinetic (choreiform) | | **Consciousness** | Alert | **Altered/confused** | Normal | | **CK level** | Normal | **Markedly elevated (>1000)** | Normal | | **Reversibility** | Yes (with anticholinergic) | Requires ICU, dantrolene | Often irreversible | **Clinical Pearl:** This patient's normal temperature, alert mental status, and normal CK make NMS unlikely. His hyperkinetic involuntary movements are absent, ruling out tardive dyskinesia. ### Management of DIP 1. **First-line:** Anticholinergic agents (benztropine 1–2 mg BD or trihexyphenidyl 2–5 mg BD) 2. **Alternative:** Beta-blockers (propranolol) for tremor-predominant DIP 3. **Dose reduction or switch:** To atypical antipsychotic with lower D2 affinity (e.g., quetiapine, clozapine) **Tip:** Always assess for NMS first (fever, rigidity, altered mental status, elevated CK) before attributing symptoms to simple DIP, as NMS is a medical emergency. ### Additional Findings in This Case - **Weight gain + hyperglycemia:** Common metabolic side effects of risperidone (atypical antipsychotic) - **Elevated prolactin:** Risperidone has high D2 blockade in the tuberoinfundibular pathway, causing hyperprolactinemia [cite:Stahl's Essential Psychopharmacology 6e Ch 5]