Schizophrenia: Treatment

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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).

  • Dopamine receptors before and after antipsychotics

  • ⭐ 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.

Dopamine pathways in the brainoka

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.

Clozapine ANC Monitoring and Treatment Decisions

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.

Practice Questions: Schizophrenia: Treatment

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A 72 year old lady is severely depressed. For the past 2 days she has suicidal thoughts with an actual intent to die. Which of the following is best suitable to alleviate the symptoms?

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Flashcards: Schizophrenia: Treatment

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If a patient of psychosis has failed treatment twice, consider adding the drug _____

TAP TO REVEAL ANSWER

If a patient of psychosis has failed treatment twice, consider adding the drug _____

clozapine

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