Clozapine

1. Class
   1. Atypical Antipsychotic (Second Generation agent)
   2. Neuroleptic
   3. Dibenzodiazepine Antipsychotic
2. Precautions
   1. Not a first line Antipsychotic: See Disadvantages below
   2. Agranulocytosis, Seizure risk, Myocarditis, Orthostatic Hypotension, and increased mortality in elderly are all FDA black box warnings
3. Indications
   1. Refractory Schizophrenia
   2. Suicidal behavior in Schizophrenia
   3. Psychosis in the elderly (not FDA approved)
   4. Bipolar Disorder (not FDA approved)
4. Dosing
   1. Adults
      1. Initial: 12.5 mg PO qd or bid
      2. Titrate slowly upwards in increments of 25-50 mg/day
      3. Target dosing: 300-450 mg/day
      4. Maximum dose: 900 mg/day
   2. Elderly
      1. Initial: 6.5 PO qd
      2. Titrate slowly upwards in increments of 25 mg/day
      3. Maximum dose: 450 mg/day
5. Cost
   1. Even generic costs >$250 per month
6. Disadvantages
   1. Agranulocytosis has high mortality
   2. Higher risk of Diabetes Mellitus and weight gain
   3. Hypertriglyceridemia
7. Adverse Effects
   1. Anticholinergic Symptoms
   2. Agranulocytosis
   3. Hypotension (alpha-Adrenergic Receptor blockade)
   4. Tachycardia
   5. Hyperthermia
   6. Hyperglycemia including development of Diabetes Mellitus
   7. Seizures
   8. Sialorrhea
   9. Weight gain
   10. Sedation
8. Drug Interactions
   1. Increase Antipsychotic levels (toxicity risk): Monitor for toxicity
      1. Grapefruit juice
      2. Caffeine
      3. Cimetidine
      4. Ciprofloxacin
      5. Citalopram
      6. Erythromycin
      7. Fluoxetine
      8. Fluvoxamine
      9. Paroxetine
      10. Sertraline
   2. Decrease Antipsychotic levels (lower efficacy)
      1. Barbiturates
      2. Carbamazepine
      3. Phenytoin
      4. Nicotine
      5. Rifampin
9. Monitoring
   1. See Antipsychotic