Atypical Anti-Psychotics



  • A subdivision of anti-psychotic group of drugs.
  • Mainly useful for schizophrenia.


  • Atypical antipsychotics (acting via other mechanisms – Low D2/5HT2A affinity).
  • Note: Another drug group – Typical (D2-blockers).


  • Acts by antagonistic to 5-HT2 & alpha receptors.

Drugs included:

  • Clozapine, Olanzapine, Quetiapine, Risperidone, Iloperidone, Paliperidone, Ziprasidone, Aripiprazole, Asenapine, Sertindole & Zotepine.

General adverse effects:

  • Most drugs cause extrapyramidal symptoms.
  • Weight gain.
  • Hyperlipidemia.
  • New-onset diabetes mellitus.
    • Last 3 effects not seen with ziprasidone & aripiprazole.

Individual drugs:

1. Clozapine:

  • Atypical antipsychotic drug with weak D2 blocking action.


  • Mainly acts by blocking 5-HT2, alpha-adrenergic & D4 receptors.
  • Powerful anticholinergic effects (equivalent to chlorpromazine & thioridazine).


  • 1st FDA approved drug for antisuicide indication of schizophrenia.
  • Suppresses both positive & negative symptoms.

Adverse effects:

  • Convulsions – Dose-dependent, only in high doses.
    • Only as a reserve drug.
    • Due to seizures precipitation risk, even in non-epileptics.
  • AgranulocytosisDose- independent.
  • Myocarditis – Hence, contra-indicated cardiac patients.
  • Specific risk of intestinal dysfunctionPotentially severe ileus & sialorrhea.
  • Least risk of extrapyramidal symptoms.

2. Risperidone:

  • Active metabolite – Paliperidone.
  • Paliperidone – Has lesser risk of causing metabolic adverse effects.
  • MOA:
    • Acts by blocking 5-HT2, alpha adrenergic & D2 receptors.
    • More potent D2 blocker than clozapine.
    • Risk of seizures precipitation is less than clozapine.
  • Adverse effects:
    • Hyperprolactinemia (more commonly)
    • Cause extrapyramidal symptoms at high dose.

3. Olanzapine:

  • Similar MOA as risperidone.
  • Potent anticholinergic drug.
  • Adverse effects:
    • Stroke & death in elderly patients (Significantly higher risk).
    • Dry mouth.
    • Constipation.
    • Seizures.
    • Weight gain.
  • Uses:
    • Schizophrenia.
    • Acute Mania.
    • Bipolar disorder.

4. Ziprasidone:

  • Causes QT prolongation.
  • Risk of arrhythmias.
  • Not associated with weight gain, hyperlipidemia or diabetes (Unlike other atypical antipsychotics)

5. Quetiapine:

  • Shortest half-life.
  • Cause cataract formation.

6. Aripiprazole:

  • Acts as partial agonist at 5-HT1A & D2 receptors and antagonist at 5-HT2A receptor.
  • Also known as “Dopamine- serotonin stabilizer”.
  • Longer half-life.
  • Uses: Approved for treatment of irritability associated with autistic disorders in children.

7. Asenapine:

  • Used sublingually for schizophrenia & acute mania.

8. Iloperidone:

  • Cause orthostatic hypotension.
  • QT interval prolongation.
  • Less risk of extrapyramidal effects.

Exam Important

  • Atypical antipsychotics act via other mechanisms due to their low D2/5HT2A affinity.
  • Clozapine, Olanzapine, Quetiapine, Risperidone, Iloperidone, Paliperidone, Ziprasidone, Aripiprazole, Asenapine, Sertindole & Zotepine are all atypical antipsychotics.
  • All atypical antipsychotics cause extrapyramidal symptoms, weight gain & hyperlipidemia, except ziprasidone & aripiprazole.
  • Clozapine is an atypical antipsychotic drug with weak D2 blocking action.
  • Clozapine mainly acts by blocking 5-HT2, alpha-adrenergic & D4 receptors.
  • Clozapine has powerful anticholinergic effects equivalent to chlorpromazine & thioridazine.
  • Clozapine is the 1st FDA approved drug for antisuicide indication of schizophrenia, suppressing both positive & negative symptoms.
  • Clozapine is used as a reserve drug due to risk of seizures precipitation even in non-epileptics.
  • Convulsions are dose-dependent adverse effect of clozapine, only in high doses.
  • Agranulocytosis is a dose-independent clozapine.
  • Specific risk of intestinal dysfunction severe ileus & sialorrhea is adverse effect of clozapine.
  • Active metabolite of risperidone is Paliperidone.
  • Paliperidone has lesser risk of causing metabolic adverse effects.
  • Risperidone acts by blocking 5-HT2, alpha adrenergic & D2 receptors.
  • Risperidone is more potent D2 blocker than clozapine.
  • For Risperidone risk of seizures precipitation is less than clozapine.
  • Risperidone more commonly causes hyperprolactinemia.
  • Risperidone causes extrapyramidal symptoms at high dose.
  • Olanzapine is a potent anticholinergic drug.
  • Olanzapine has significantly higher risk of stroke & death in elderly patients.
  • Ziprasidone causes QT prolongation & arrhythmia risk.
  • Quetiapine has shortest half-life & cause cataract formation.
  • partial agonist at 5-HT1A & D2 receptors and antagonist at 5-HT2A receptor, hence known as “Dopamine- serotonin stabilizer”.
  • Aripiprazole is approved for treatment of irritability associated with autistic disorders in children.
  • Asenapine is used sublingually for schizophrenia & acute mania.
  • Iloperidone cause orthostatic hypotension & QT interval prolongation.
Don’t Forget to Solve all the previous Year Question asked on ATYPICAL ANTI-PSYCHOTICS

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