Atypical/second-generation

• Atypical antipsychotics:

  • Second-generation antipsychotics
  • Unlike typical antipsychotics, they are effective against both positive and negative symptoms of schizophrenia
  • Often preferred to typical antipsychotics for long-term treatment due to lower risk of EPSEs
• Common atypical antipsychotics:

  • Aripiprazole
  • Clozapine
  • Olanzapine
  • Quetiapine
  • Risperidone
• Common indications:

  • Schizophrenia
  • Bipolar affective disorder - both acute and maintenance
  • Adjunctive therapy for major depressive disorder, anxiety disorders and PTSD
• MOA:

  • Dopamine and serotonin antagonists
  • Block the D2 receptors and the 5-HT2A subtype of serotonin receptor
• The primary difference between typical and atypical antipsychotics is that EPSEs are rarer with atypical antipsychotics. But they are more associated with weight gain and metabolic syndrome, characterised by:

  • Obesity
  • Hypertension
  • Impaired fasting glucose
  • Hypertriglyceridemia
  • Low HDL cholesterol
• Cautions and contraindications:

  • Caution in Parkinson's disease due to EPSEs
  • Clozapine should be used with caution in cardiovascular disease
  • Avoid in dementia - increased incidence of stroke
  • Caution prescribing alongside agents that prolong the QTc interval
• Side effects associated with specific agents:

  • Olanzapine: highest association with weight gain, increased appetite and sedation
  • Risperidone: dizziness, anxiety, sedation and EPSEs
  • Paliperidone: temperature sensitivity and QTc prolongation
  • Quetiapine: least likely to cause EPSEs, most likely to cause drowsiness, orthostatic hypotension and dizziness
  • Aripiprazole: agitation, headache and restlessness - least associated with weight gain
• Atypical antipsychotics can be administered in oral or parenteral forms:

  • Risperidone, aripiprazole, olanzapine and paliperidone are available as extended-release or long-acting injectable form
  • Clozapine and olanzapine are available in sublingual formulation
• Clozapine is the agent of choice when the patient has failed multiple trials of standard antipsychotic therapies. Patients on clozapine need regular monitoring for white cell count to screen for agranulocytosis, a rare but fatal complication.
• Patients should be educated about the side effects and counselled on the importance of regular exercise, discontinuation of smoking, and eating a healthy diet. The following should also be regularly monitored:

  • Personal and family history of diabetes
  • Weight and height
  • Waist circumference
  • Blood pressure
  • Fasting plasma glucose
  • Lipid profile
• Cessation of smoking can increase serum concentration of antipsychotic (especially clozapine) so dose may need to be reduced to decrease risk of toxicity