Olanzapine exerts its therapeutic effects through its action on multiple neurotransmitter systems in the brain. Its key mechanisms include:

1. Dopamine Receptor Antagonism:
   • Olanzapine primarily blocks dopamine D2 receptors in the mesolimbic pathway, reducing positive symptoms of schizophrenia such as hallucinations and delusions.
   • It has a lower affinity for D2 receptors compared to first-generation antipsychotics, which contributes to its reduced risk of extrapyramidal side effects (EPS).
2. Serotonin Receptor Antagonism:
   • Olanzapine strongly blocks serotonin 5-HT2A receptors, which is thought to improve negative symptoms (e.g., social withdrawal, apathy) and cognitive symptoms of schizophrenia.
   • This action also contributes to its efficacy in mood stabilization.
3. Other Receptor Interactions:
   • Olanzapine has affinity for muscarinic M1, histamine H1, and adrenergic α1 receptors, which contributes to its side effect profile (e.g., sedation, weight gain, orthostatic hypotension).
4. Mood Stabilization:
   • By modulating dopamine and serotonin activity, olanzapine helps stabilize mood in bipolar disorder, particularly in manic or mixed episodes.

Olanzapine is approved for a variety of clinical conditions, including:

1. Schizophrenia:
   • Treatment of acute and chronic schizophrenia, including both positive and negative symptoms.
2. Bipolar Disorder:
   • Management of acute manic or mixed episodes.
   • Maintenance treatment to prevent recurrence of manic or depressive episodes.
3. Treatment-Resistant Depression:
   • Adjunctive therapy with antidepressants for major depressive disorder (MDD) that has not responded to other treatments.
4. Other Uses:
   • Agitation and aggression in dementia (off-label use, with caution due to increased mortality risk in elderly patients).
   • Anorexia nervosa (off-label use in some cases).

The dosage of olanzapine varies depending on the indication, patient age, and clinical response. The following dosing guidelines are based on the British National Formulary (BNF) and clinical pharmacology references:

1. Schizophrenia:
   • Adults: Start with 5–10 mg once daily, increasing gradually to a maintenance dose of 10–20 mg daily.
   • Elderly: Lower starting doses (2.5–5 mg daily) are recommended due to increased sensitivity to side effects.
2. Bipolar Disorder:
   • Adults: Start with 10–15 mg once daily, adjusted based on response. The maintenance dose is typically 5–20 mg daily.
3. Treatment-Resistant Depression:
   • Adults: Start with 2.5–5 mg once daily as an adjunct to antidepressants, increasing gradually if needed.

Important Considerations:

• Olanzapine is available in oral tablets, orally disintegrating tablets, and intramuscular (IM) formulations for acute agitation.
• Dose adjustments may be necessary for patients with hepatic impairment.
• Regular monitoring of weight, blood glucose, and lipid levels is recommended due to the risk of metabolic side effects.

Olanzapine is associated with a range of side effects, some of which can be serious. Common side effects include:

1. Metabolic Effects:
   • Weight gain, hyperglycemia, and dyslipidemia, which increase the risk of metabolic syndrome and type 2 diabetes.
2. Central Nervous System:
   • Sedation, dizziness, and somnolence.
   • Extrapyramidal symptoms (EPS) are less common than with first-generation antipsychotics but can still occur.
3. Cardiovascular:
   • Orthostatic hypotension and tachycardia.
4. Gastrointestinal:
   • Constipation, dry mouth, and increased appetite.
5. Other:
   • Elevated prolactin levels, leading to gynecomastia, galactorrhea, or menstrual irregularities.

Serious Side Effects:

• Neuroleptic Malignant Syndrome (NMS): A rare but life-threatening condition characterized by fever, muscle rigidity, and autonomic instability.
• Tardive Dyskinesia: A potentially irreversible movement disorder associated with long-term use of antipsychotics.
• Increased Mortality in Elderly Patients with Dementia: Olanzapine is associated with an increased risk of stroke and death in elderly patients with dementia-related psychosis.

Olanzapine requires careful monitoring and adherence to specific precautions to ensure patient safety:

1. Metabolic Monitoring:
   • Regular monitoring of weight, blood glucose, and lipid levels is essential to detect and manage metabolic side effects.
2. Pregnancy and Lactation:
   • Olanzapine should be used during pregnancy only if the potential benefits outweigh the risks. It is excreted in breast milk, so breastfeeding is generally not recommended.
3. Elderly Patients:
   • Lower doses are recommended due to increased sensitivity to side effects, particularly sedation and orthostatic hypotension.
4. Cardiovascular Risk:
   • Use with caution in patients with a history of cardiovascular disease or risk factors for QT prolongation.
5. Suicidal Risk:
   • Monitor for worsening depression or suicidal thoughts, particularly in patients with mood disorders.

Olanzapine has a moderate potential for drug interactions due to its metabolism via cytochrome P450 enzymes (primarily CYP1A2). Key interactions include:

1. CYP1A2 Inhibitors:
   • Fluvoxamine and ciprofloxacin can increase olanzapine levels, increasing the risk of side effects.
2. CYP1A2 Inducers:
   • Smoking and carbamazepine can decrease olanzapine levels, reducing its efficacy.
3. Central Nervous System Depressants:
   • Alcohol, benzodiazepines, and opioids can enhance sedation and respiratory depression.
4. Antihypertensives:
   • Olanzapine may enhance the hypotensive effects of antihypertensive medications.
5. Other Interactions:
   • Levodopa and dopamine agonists: Reduced efficacy due to dopamine receptor antagonism.

Olanzapine is the generic name for this medication. It is marketed under various brand names, depending on the country and manufacturer. Some examples include:

• Zyprexa (a well-known brand in the United States and other regions).
• Oleanz.
• Zalasta.
• Olance.