Schizophrenia is a mental illness that severely impairs social and mental functioning.

Epidemiology

• Incidence - 2-4/1000
  • Lifetime prevalence of 1%
• Age -  onset in 20’s; younger age for men
• Sex - equal distribution

Risk Factors

• Family history is strongly correlated
• Other, less-correlated, factors
  • Cannabis use
  • CNS infection in childhood
  • Maternal obstetrical complications

Pathophysiology

• Neurotransmitter is likely involved in dopamine transmission
  • Drugs that induce states similar to schizophrenia increase dopaminergic transmission
  • Drugs that treat schizophrenia decrease dopaminergic transmission

Clinical Presentation

• Hallucinations, delusions
• Disorganized speech
• Disorganized behavior
• Signs and symptoms must be present >30 days in the absence of treatment

Treatment

• Antipsychotic drugs are the mainstay of therapy
• Dopamine D2 antagonists - chlorpromazine, clozapine, fluphenazine, fluphenazine decanoate, haloperidol, haloperidol decanoate, loxapine, molindone, perphenazine, thioridazine, thiothixene, trifluoperazine
• Atypical mixed neuroreceptor antagonists (low affinity D2 antagonists, high-affinity 5-HT2A antagonists) - aripiprazole, chlorpromazine, clozapine, olanzapine, quetiapine, risperidone, thioridazine, ziprasidone
• Hepatic phase 1 oxidation is catalyzed by cytochrome P450 (CYP)
  • Inheritance of clinically significant CYP2D6 variants alter drug metabolism

Diagnosis

• Based on clinical presentation

Treatment Monitoring

• Important to be aware of drug interactions  (see CYPs with Major Roles in the In-Vivo Clearance of Antipsychotic Agents table below)
  • Hepatic phase 1 oxidation is catalyzed by cytochrome P450 (CYP)
  • Inheritance of clinically significant CYP2D6 variants alter drug metabolism
• Pharmacogenetic testing may guide drug and dose selection
• Periodic drug monitoring is useful to assure compliance, identify drug-drug interactions or other reasons to adjust dosing, and may establish optimal therapeutic ranges for an individual patient.  Suggested therapeutic ranges and toxic thresholds are available for some but not all commonly used antipsychotic drugs  (see Pharmacokinetics of Antischizophrenic Therapeutics table below)
• Additional clinical testing (such as complete blood count, liver enzyme testing) is required for some drugs to detect toxicity

Differential Diagnosis

• Brief psychotic episode
• Delirium
• Acute or chronic medical illness
• Substance abuse
• Schizophreniform disorders
• Medication-induced disorder
• Pervasive developmental disorder