Olanzapine (Zyprexa)

Mechanism of Action
​Olanzapine is an atypical antipsychotic that works by modulating neurotransmitter activity in the brain. Its mechanism of action includes:
  1. Dopamine D2 Receptor Antagonism:
    • Reduces overactive dopamine signaling, which is associated with psychosis and manic symptoms.
  2. Serotonin 5-HT2A Receptor Antagonism:
    • Enhances dopamine release in certain brain regions, which can improve negative and cognitive symptoms in schizophrenia and bipolar disorder.
  3. Other Receptor Interactions:
    • Binds to histamine H1, muscarinic, and adrenergic receptors, contributing to both its therapeutic effects and side effect profile.
Sources:
  • American Psychiatric Association Guidelines
  • Mechanisms of Action in Atypical Antipsychotics (Journal of Clinical Psychiatry)
Clinical Benefits
  1. Schizophrenia:
    • Reduces positive symptoms (e.g., hallucinations, delusions) and helps manage negative symptoms (e.g., social withdrawal).
  2. Bipolar Disorder:
    • Effective in acute manic or mixed episodes.
    • Often used for maintenance therapy to prevent relapse.
  3. Adjunct in Depression:
    • Approved in combination with fluoxetine for treatment-resistant depression or depressive episodes in bipolar disorder.
  4. Other Uses:
    • May be used off-label for agitation in dementia or borderline personality disorder.
Sources:
  • NICE Guidelines for Bipolar Disorder and Schizophrenia
  • FDA Prescribing Information

Dosage
  1. Schizophrenia and Bipolar Mania:
    • Starting Dose: 5–10 mg/day, increased by 5 mg/day every few days as needed.
    • Maintenance Dose: 10–20 mg/day.
  2. Bipolar Depression (with Fluoxetine):
    • Olanzapine 6–12 mg/day combined with fluoxetine 25–50 mg/day.
  3. Maximum Dose: 20 mg/day for most indications, though higher doses are sometimes used under close monitoring.
Important:
  • Dosage should be individualized based on patient response and tolerability.
  • Available in oral tablets, orally disintegrating tablets, and long-acting injectable forms.
Sources:
  • FDA Guidelines
  • APA Practice Parameters

Prevalence of Side EffectsCommon Side Effects (10–30%):
  • Metabolic Effects:
    • Weight gain, increased appetite, hyperlipidemia, and elevated blood glucose levels.
  • Sedation:
    • Common due to histamine receptor blockade.
  • Anticholinergic Effects:
    • Dry mouth, constipation, and blurred vision.
Serious Side Effects (Rare):
  1. Metabolic Syndrome:
    • Includes significant weight gain, insulin resistance, and dyslipidemia.
    • Risk is dose-dependent and more common in long-term use.
  2. Extrapyramidal Symptoms (EPS):
    • Less common compared to typical antipsychotics but can include tremors or akathisia (restlessness).
  3. Neuroleptic Malignant Syndrome (NMS):
    • Rare but life-threatening condition characterized by muscle rigidity, fever, and autonomic instability.
  4. Cardiac Effects:
    • QT prolongation, which can lead to arrhythmias in predisposed individuals.
Sources:
  • BMJ: Olanzapine Risk Profile
  • FDA Black Box Warnings

SummaryOlanzapine is a versatile antipsychotic with robust efficacy for schizophrenia and bipolar disorder. Its benefits are tempered by a high risk of metabolic side effects, necessitating regular monitoring of weight, blood sugar, and lipid profiles. Its tolerability and effectiveness often make it a cornerstone treatment for severe mental illnesses.