Schizophrenia: Treatment

Antipsychotics: The Basics - Brain Balancers

• Cornerstone of schizophrenia treatment.

• Mechanism: Primarily modulate dopamine pathways; most are $D_2$ receptor antagonists.

• Classification:

• FGAs (1st Gen): Effective for positive symptoms (hallucinations, delusions). Risk of Extrapyramidal Symptoms (EPS).

• SGAs (2nd Gen): Broader efficacy, including some negative symptoms. Lower EPS risk, but higher risk of metabolic side effects (weight gain, diabetes).

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• ⭐ All antipsychotics require 60-80% $D_2$ receptor occupancy for optimal efficacy; higher occupancy increases EPS risk without improving efficacy.

FGAs: Side Effect Profiles - Classic Dopamine Blockers

• Mechanism: $D_2$ receptor blockade.
• Extrapyramidal Symptoms (EPS): Nigrostriatal $D_2$ block.
  • Acute Dystonia: Spasms, torticollis. Tx: Anticholinergics.
  • Akathisia: Restlessness. Tx: $\beta$-blockers, Benzodiazepines (BZDs).
  • Parkinsonism: Tremor, rigidity, bradykinesia. Tx: Anticholinergics.
  • Tardive Dyskinesia (TD): Orofacial dyskinesia. Often irreversible. 📌 TD: Time Dependent.
• Neuroleptic Malignant Syndrome (NMS):
  • FEVER: Fever, Encephalopathy, Vitals unstable, Enzymes $\uparrow$ (CK), Rigidity.
  • Tx: Stop FGA, Dantrolene, Bromocriptine.
• Hyperprolactinemia: Tuberoinfundibular $D_2$ block.
  • Galactorrhea, amenorrhea, gynecomastia, sexual dysfunction.
• Other Side Effects (Potency-dependent):
  • Low Potency (e.g., Chlorpromazine): $\uparrow$Anticholinergic, $\uparrow$Sedation (H1 block), $\uparrow$Orthostatic Hypotension ($\alpha_1$ block).
  • High Potency (e.g., Haloperidol): $\uparrow$EPS, $\downarrow$Sedation/Hypotension/Anticholinergic effects.

  ⭐ NMS is a medical emergency: fever, muscle rigidity, autonomic dysfunction, altered mental status; requires immediate FGA discontinuation and supportive care.

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SGAs: Metabolic Concerns - Modern Mind Menders

• SGAs (Atypical Antipsychotics): D2 & 5-HT2A antagonists.
• Benefits: ↓EPS, better for negative symptoms vs FGAs.
• Key Issue: Metabolic Syndrome (MetS) - ↑Weight/BMI, ↑Waist, Dyslipidemia (↑TG, ↓HDL), ↑BP, ↑FBG.
• Metabolic Risk Profile:
  • High: Clozapine, Olanzapine (📌 Old Clothes = fat & sleepy)
  • Moderate: Risperidone, Quetiapine, Paliperidone
  • Low/Neutral: Aripiprazole, Ziprasidone, Lurasidone (📌 A Zippy Lura = Atypical & Lean)
• Monitoring: Essential!
  • Baseline & regular: Weight, BMI, Waist, BP, FPG, Lipids.
  • ⚠️ FPG ≥ 126 mg/dL (Diabetes), TG ≥ 150 mg/dL.
• Management: Lifestyle modification, switch SGA, consider Metformin.

⭐ Clozapine and Olanzapine have the highest propensity for inducing significant weight gain and new-onset diabetes.

TRS & Clozapine - Strategy & Special Ops

• TRS Definition: Failure of ≥2 antipsychotics (≥1 atypical) at adequate dose & duration (e.g., 6-8 weeks).
• Clozapine Strategy:
  • The ONLY proven drug for TRS; also for persistent suicidality, severe TD.
  • Dosing: Start 12.5-25 mg/day, titrate slowly to 300-600 mg/day (max 900 mg).
  • ⚠️ Critical Monitoring "AMC-S":
    • Agranulocytosis: ANC weekly (18wks) → bi-weekly (18wks) → monthly.
      • Stop: ANC < 1000/µL (or < 500/µL in BEN).
      • Interrupt: ANC 1000-1500/µL.
    • Myocarditis/Cardiomyopathy: Baseline & monitor ECG, troponin, CRP.
    • Constipation (severe).
    • Seizures (dose-dependent).
  • Other SEs: Hypersalivation, weight gain, sedation.
• Augmentation (if Clozapine partial response): ECT, lamotrigine, another AP (cautiously).
• Long-Term Strategy:
  • LAIs: Consider for adherence post-stabilization.
  • Psychosocial therapies (CBTp, family therapy): Essential adjunct.

⭐ Clozapine requires mandatory blood monitoring (ANC) due to potentially fatal agranulocytosis risk.

High‑Yield Points - ⚡ Biggest Takeaways

• Antipsychotics are the cornerstone of schizophrenia management.
• Second-Generation Antipsychotics (SGAs) are typically first-line due to better tolerability (fewer EPS).
• Clozapine is uniquely effective for Treatment-Resistant Schizophrenia (TRS).
• Regular WBC monitoring is mandatory with Clozapine due to agranulocytosis risk.
• Long-Acting Injectable (LAI) antipsychotics significantly improve treatment adherence.
• Psychosocial interventions, like CBT and family therapy, are crucial adjuncts.
• ECT is a valuable option for catatonia, severe suicidality, or resistant cases.