Schizophrenia — Clinical Features MCQ — NEET PG Practice Question | NEETPGAI
Schizophrenia — Clinical Features
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brain Psychiatry
A 35-year-old man with a 10-year history of schizophrenia has failed adequate trials of risperidone (6 mg/day × 8 weeks) and olanzapine (15 mg/day × 8 weeks) with persistent positive symptoms (hallucinations, delusions). He has no history of seizures or cardiac arrhythmias. What is the drug of choice for treatment-resistant schizophrenia?
A. Quetiapine
B. Aripiprazole
C. Clozapine
D. Paliperidone
Explanation
Treatment-Resistant Schizophrenia: Clozapine as Gold Standard
Key Point
Clozapine is the only antipsychotic with proven efficacy in treatment-resistant schizophrenia (TRS) and is the gold standard for patients who fail ≥2 adequate trials of different antipsychotics at therapeutic doses and durations.
Definition of Treatment-Resistant Schizophrenia
Failure to achieve adequate response (≥20% reduction in positive symptoms) despite:
1.
Two or more adequate antipsychotic trials (therapeutic dose for ≥4–8 weeks each)
2.
Different pharmacological classes preferred
3.
Documented poor adherence excluded
Why Clozapine in TRS?
Efficacy:
30–50% of TRS patients respond to clozapine (vs. <10% to other agents)
Effective against both positive and negative symptoms
Reduces suicidality and aggression in schizophrenia
Mechanism of Superior Efficacy:
Rapid dissociation from D2 receptors ("hit-and-run" hypothesis)
Preferential limbic > striatal dopamine blockade
Glutamatergic and GABAergic effects
Monitoring Requirements for Clozapine
Table
Parameter
Baseline
Frequency
Action
WBC/ANC
Required
Weekly × 6 mo, then biweekly
Stop if ANC <1500
ECG
Required
If symptoms warrant
Exclude QTc >500 ms
Metabolic panel
Required
Quarterly
Monitor glucose, lipids
Seizure threshold
Assess
Observe clinically
Risk increases at >600 mg/day
High-YieldNEET PG
Clozapine-induced agranulocytosis occurs in ~0.8–1% of patients (highest in first 3 months). Regular WBC monitoring is mandatory and non-negotiable. Myocarditis (rare but serious) can occur within first 2 weeks.
Warning
Common misconceptions:
Clozapine is contraindicated in all cardiac disease → Only uncontrolled arrhythmias/active myocarditis are absolute contraindications
Clozapine causes seizures in all patients → Dose-dependent risk; manageable with anticonvulsants if needed
Clozapine is first-line → Reserved for TRS only due to toxicity profile
Clinical Pearl
Clozapine is the only antipsychotic with anti-suicidal efficacy in schizophrenia, making it particularly valuable in high-risk TRS patients.
Tip
In NEET PG, if the stem explicitly states "failed ≥2 antipsychotic trials" or "treatment-resistant," the answer is clozapine unless contraindicated (active myocarditis, WBC <3500, uncontrolled seizures).
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