Olanzapine is a synthetic derivative of thienobenzodiazepine with antipsychotic, antinausea, and antiemetic activities. As a selective monoaminergic antagonist, olanzapine binds with high-affinity binding to the following receptors: serotoninergic, dopaminergic, muscarinic M1-5, histamine H1, and alpha-1-adrenergic receptors; it binds weakly to gamma-aminobutyric acid type A, benzodiazepine, and beta-adrenergic receptors. The antinausea and antiemetic effects of this agent appear to be due to the blockade of 5-HT2 and 5-HT3 receptors for serotonin. Although its exact mechanism of action in schizophrenia is unknown, it has been proposed that olanzapine’s antipsychotic activity is mediated through antagonism to dopamine D2 receptors with rapid ligand-receptor dissociation kinetics that help to minimize extrapyramidal symptoms (EPS). Olanzapine may also stimulate appetite.
Olanzapine is an atypical antipsychotic that is used currently in the treatment of schizophrenia and bipolar illness. Olanzapine is not infrequently associated with serum aminotransferase elevations during therapy and there have been rare instances of clinically apparent acute liver injury linked to its use.
Olanzapine is an antipsychotic medication used to treat schizophrenia and bipolar disorder. It is usually classed with the atypical antipsychotics, the newer generation of antipsychotics.
Mechanism of Action of Olanzapine
Olanzapine’s antipsychotic activity is likely due to a combination of antagonism at D2 receptors in the mesolimbic pathway and 5HT2A receptors in the frontal cortex. Antagonism at D2 receptors relieves positive symptoms while antagonism at 5HT2A receptors relieves negative symptoms of schizophrenia. Structurally and pharmacologically similar to clozapine, olanzapine binds to alpha(1), dopamine, histamine H1, muscarinic, and serotonin type 2 (5-HT2) receptors.
Indications of Olanzapine
- Acute agitation
- Acute depressive episode
- Delirium
- Bipolar disorder
- Major depressive disorder
- Anorexia
- Depression
- Schizophrenia
- Anorexia Nervosa
- Asperger Syndrome
- Body Dysmorphic Disorder
- Borderline Personality Disorder
- Insomnia
- Nausea/Vomiting, chemotherapy induced
- Obsessive compulsive disorder
- Paranoid disorder
- Schizoaffective disorder
- Tourette’s syndrome
- Delusional Parasitosis
- Gilles de la tourette’s syndrome
- Major depressive disorder, recurrent episode
- Mixed manic depressive episode
- Post-traumatic stress disorder
- Psychosis
- Schizophrenic disorders
- Acute manic episode
Contra-Indications of Olanzapine
- High cholesterol
- High amount of triglyceride in the blood
- Excessive fat in the blood
- Extreme loss of body water
- Overweight
- Decreased white blood cells
- Decreased neutrophils a type of white blood cell
- Having thoughts of suicide
- Parkinson symptoms
- Abnormal movements of face muscles and tongue
- Neuroleptic malignant syndrome
- Lower seizure threshold
- Closed angle glaucoma
- Heart attack
- Disease of Inadequate Blood Flow to the Heart Muscle
- Slow Heartbeat
- Sinus Tachycardia
- Abnormal heart rhythm
- Chronic heart failure
- Abnormal EKG with QT changes from Birth
- Transient Ischemic Attack
- Stroke
- Disorder of the Blood Vessels of the Brain
- Blood Pressure Drop Upon Standing
- Abnormally low blood pressure
- Paralysis of the Intestines
- Severe liver disease
- Enlarged prostate with urination problem
- Seizures
- Weight gain
- High Blood Sugar
- abnormal liver function tests
- Susceptible to Breathing Fluid Into Lungs
- Decreased Blood Volume
- Problems with Food Passing Through the Esophagus
- Tobacco smoking
- Dementia in an Elderly Person
Dosage of Olanzapine
Strengths: 2.5 mg; 5 mg; 7.5 mg; 10 mg; 15 mg; 20 mg; 210 mg; 300 mg; 405 mg
Bipolar Disorder
Monotherapy
- Initial dose: 10 or 15 mg orally once a day
- Dose adjustments: If indicated, dose adjustments should occur at intervals of at least 24 hours in 5 mg increments/decrements.
- Maintenance dose: 5 to 20 mg orally once a day
- Maximum dose: 20 mg/day
Adjunctive Treatment with Lithium or Valproate
- Initial dose: 10 mg orally once a day
- Maintenance dose: 5 to 20 mg orally once a day
- Maximum dose: 20 mg/day
Treatment of Depressive Episodes Associated with Bipolar I Disorder
- Initial dose: 5 mg orally once a day (with fluoxetine)
- Dose adjustments: Should be made with the individual components within the dose range of 5 to 12.5 mg as indicated according to efficacy and tolerability.
- Maximum dose: 18 mg/day (with fluoxetine)
Schizophrenia
Oral
- Initial dose: 5 to 10 mg orally once a day
- Target dose: 10 mg orally once a day within the first several days; further dose adjustments, if needed, should occur at intervals of not less than 1 week in 5 mg increments/decrements.
- Maximum dose: 20 mg orally once a day
Depression
Treatment of Depressive Episodes Associated with Bipolar I Disorder
- Initial dose: 5 mg orally once a day (with fluoxetine)
- Dose adjustments: Should be made with the individual components within the dose range of 5 to 20 mg as indicated according to efficacy and tolerability
- Maximum dose: 18 mg/day (with fluoxetine)
Agitated State
Immediate-release Injection
- Initial dose: 10 mg IM once
- Dose range: 2.5 to 10 mg
- Subsequent doses up to 10 mg may be given every 2 hours for agitation that persists following the initial dose
- Maximum number of doses: 3 doses in 24 hours; additional doses in patients with clinically significant postural hypotension are not recommended
Pediatric Schizophrenia
13 to 17 years
- Initial dose: 2.5 to 5 mg orally once a day
- Target dose: 10 mg orally once a day; further dose adjustments, if needed, should occur at intervals of not less than 1 week in 2.5 to 5 mg increments/decrements.
- Maximum dose: 20 mg orally/day
Pediatric Dose for Depression
Treatment of Depressive Episodes Associated with Bipolar I Disorder
10 to 17 years
- Initial dose: 2.5 mg orally once a day (with fluoxetine)
- Dose adjustments: Should be made with the individual components within the dose range of 3 to 12 mg as indicated according to efficacy and tolerability
- Maximum dose: 12 mg/day (with fluoxetine)
Side Effects of Olanzapine
The most common
- Extrapyramidal side effects including:
- Akathisia (motor restlessness)
- Dystonia (continuous spasms and muscle contractions)
- Muscle rigidity
- Parkinsonism (characteristic symptoms such as rigidity)
- Hypotension
- Anticholinergic side effects such as (These adverse effects are more common than with lower-potency typical antipsychotics, such as chlorpromazine and thioridazine.)
- Blurred vision
- Constipation
- Dry mouth
More common
- The difficulty with speaking or swallowing
- inability to move the eyes
- loss of balance control
- mask-like face
- muscle spasms, especially of the neck and back
- restlessness or need to keep moving (severe)
- shuffling walk
- the stiffness of the arms and legs
- trembling and shaking of the fingers and hands
- twisting movements of the body
- the weakness of the arms and legs
Less common
- Decreased thirst
- difficulty in urination
- dizziness, lightheadedness, or fainting
- hallucinations (seeing or hearing things that are not there)
- lip smacking or puckering
- puffing of the cheeks
- rapid or worm-like movements of the tongue
- skin rash
- uncontrolled chewing movements
Drug Interactions of Olanzapine
Olanzapine may interact with following drug, suppliments, & may change the efficasy of drug
- alpha blockers (e.g., alfuzosin, doxazosin, tamsulosin)
- amphetamines (e.g., dextroamphetamine, lisdexamphetamine)
- antihistamines (e.g,. cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine)
- anti-Parkinsons medications (e.g., amantadine, apomorphine, bromocriptine, levodopa, pramipexole, ropinirole)
- antipsychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone)
- antiseizure medications (e.g., clobazam, ethosuximide, felbamate, levetiracetam, phenobarbital, phenytoin, primidone, topiramate, valproic acid, zonisamide)
- aripiprazole
- “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
- baclofen
- barbiturates (e.g., butalbital, pentobarbital, phenobarbital)
- benzodiazepines (e.g., alprazolam, diazepam, lorazepam)
- beta-adrenergic blockers (e.g., atenolol, propranolol, sotalol)
- bupropion
- calcitriol
- calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
- captopril
- celecoxib
- chloroquine
- cholecalciferol
- cyclosporine
- dantrolene
- domperidone
- “gliptin” diabetes medications (e.g., linagliptin, saxagliptin, sitagliptin)
- gabapentin
- H2 antagonists (e.g., famotidine, ranitidine)
- metronidazole
- mirabegron
- montelukast
- non-steroidal anti-inflammatory medications (NSAIDs; e.g., diclofenac, ibuprofen, naproxen)
- phosphodiesterase 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil)
- potassium chloride (potassium supplements)
- proton pump inhibitors (e.g., lansoprazole, omeprazole)
- quinolone antibiotics (e.g., levofloxacin, norfloxacin, moxifloxacin)
- selective serotonin reuptake inhibitors (SSRIs; e.g., paroxetine, fluoxetine,citalopram)
- serotonin antagonists (anti-emetic medications; e.g., granisetron, ondansetron)
- “statin” anti-cholesterol medications (e.g., atorvastatin, lovastatin,simvastatin)
- tapentadol
- tetracycline
- theophylline
- thiazide diuretics (water pills; e.g., hydrochlorothiazide, indapamide, metolazone)
- tramadol
- tricyclic antidepressants (e.g., amitriptyline, clomipramine, desipramine, trimipramine)
- zafirlukast
Pregnancy & Lactation of Olanzapine
FDA Pregnancy Category C
Pregnancy
This drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. AU TGA pregnancy category: C US FDA pregnancy category: C Comment-A pregnancy exposure registry is available. -Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk of experiencing extrapyramidal neurological disturbances and/or withdrawal symptoms following delivery.
Lactation
Maternal doses of olanzapine up to 20 mg daily produce low levels in milk and undetectable levels in the serum of breastfed infants. In most cases, short-term side effects have not been reported, but sedation has occurred. Limited long-term follow-up of infants exposed to olanzapine indicates that infants generally developed normally. Systematic reviews of second-generation antipsychotics concluded that olanzapine seemed to be a first-line agent during breastfeeding.
References
