Medicine & USMLE

Atypical Antipsychotics

Mental Health Drugs
  1. Tricyclic Antidepressants
  2. SSRIs
  3. SNRIs
  4. Benzodiazepines
  5. Barbiturates
  6. Typical Antipsychotics
  7. Atypical Antipsychotics
  8. Extrapyramidal Symptoms
  9. Lithium
  10. MAOIs
  11. Bupropion
  12. Buspirone
  13. Trazodone
  14. Zolpidem
  15. Amphetamines
  16. Mirtazapine


Atypical antipsychotics are a drug class used to treat psychosis in schizophrenia and other psychotic conditions, and are also used as mood stabilizers for bipolar disorder. Drugs in this category include clozapine, olanzapine, aripiprazole, risperidone, quetiapine, and ziprasidone. Side effects of these drugs include extrapyramidal symptoms, abbreviated EPS, which refers to a constellation of movement problems, like tremors, muscle spasms, and restlessness. Atypical antipsychotics are also well known for causing metabolic syndrome and weight gain. Other side effects include sedation, anticholinergic effects, and neuroleptic malignant syndrome, abbreviated NMS. NMS is a medical emergency characterized by muscle rigidity, fever, confusion, and unstable vitals. Clozapine can cause agranulocytosis, or a rapid fall in white blood cells, and ziprasidone can cause QT prolongation and the abnormal heart rhythm of torsades de pointes.

Key Points

  • Atypical Antipsychotics
    • Also called second-generation antipsychotics
    • Key Drugs
      • Clozapine
      • Risperidone
      • Olanzapine
      • Quetiapine
      • Aripiprazole
      • Ziprasidone
    • Mechanism
      • Blocks serotonin and dopamine receptors
    • Clinical Use
      • Schizophrenia
        • First line treatment
        • Treats both positive AND negative symptoms
        • Clozapine is only used to treat schizophrenia that has not responded to traditional antipsychotics. This is because it has some serious adverse effects (e.g. agranulocytosis)
      • Psychosis
        • Atypical antipsychotics like quetiapine and aripiprazole may be used to treat acute psychosis and delusions, especially in the context of dementia
      • Bipolar Disorder
        • Has mood-stabilizing effects
    • Side Effects and Adverse Reactions
      • Neuroleptic Malignant Syndrome (NMS)
        • Life threatening, a medical emergency
        • Manifests with high fever, muscle rigidity, altered mental status, and unstable vital signs
        • All antipsychotics should be held and provider notified immediately
      • Extrapyramidal Symptoms (EPS)
        • More commonly seen in typical antipsychotics than atypical
        • Drug-induced movement disorders
          • Dystonia
            • Muscle contraction, spasm, stiffness
          • Pseudoparkinsonism
            • Mimics Parkinson’s disease with a shuffling gait, bradykinesia, tremor, rigidity
          • Akathisia
            • Restlessness
          • Tardive Dyskinesia (TD)
            • Involuntary repetitive movements, often of the mouth, face, and neck (e.g. lip smacking, sticking out tongue, grimacing)
            • Appears with long-term use
        • Can be treated with the drug benztropine
        • EPS is common, but still an adverse effect that should receive medical attention. Notify the provider if EPS is noticed.
      • Agranulocytosis (clozapine)
        • Drop in granulocyte (e.g. neutrophil) count after starting clozapine can lead to severe infections
        • Call the provider immediately if sore throat or fever develop
        • Closely monitor WBC
      • QT prolongation (ziprasidone)
        • Patients taking ziprasidone are at risk of developing Torsades de Pointes and should be monitored for cardiac effects
      • Sedation / Drowsiness
        • This is a normal and expected side effect
        • Avoid alcohol and other CNS depressants to prevent oversedation
      • Anticholinergic effects
        • Urinary retention, constipation, dry mouth, blurred vision, tachycardia
        • Patients should be advised that they may experience side effects like dry mouth
      • Metabolic Syndrome
        • Weight gain
        • Hyperglycemia
          • May turn into diabetes mellitus
          • Monitor blood glucose levels
        • High cholesterol
      • Headaches
        • This is a normal and expected side effect
      • Orthostatic Hypotension
      • Seizures (clozapine)