Quetiapine

Dosage for quetiapine is highly individualized based on the condition being treated, the patient's response, and their tolerability.

• Schizophrenia (Adults): The typical starting dose is 25 mg twice daily (IR) or 300 mg once daily (XR). The dose is usually titrated (increased gradually) to a target range of 400 mg to 800 mg per day. The maximum recommended dose is 800 mg/day.
• Bipolar Mania (Adults): When used alone or with mood stabilizers, the dose usually starts at 100 mg on day 1 and increases to 400 mg by day 4. The effective range is typically 400 mg to 800 mg per day.
• Bipolar Depression (Adults): The dosing schedule is usually more specific: 50 mg (Day 1), 100 mg (Day 2), 200 mg (Day 3), and 300 mg (Day 4). Most patients find relief at 300 mg once daily at bedtime.
• Major Depressive Disorder (Adjunct): Lower doses are typically used, starting at 50 mg daily and increasing to a target dose of 150 mg to 300 mg once daily.

Quetiapine is approved for specific uses in children and adolescents, but use must be monitored closely due to the risk of weight gain and metabolic changes.

• Schizophrenia (Ages 13-17): Starting dose is 25 mg twice daily, titrated to a target of 400 mg to 800 mg per day.
• Bipolar Mania (Ages 10-17): Starting dose is 25 mg twice daily, titrated to a target of 400 mg to 600 mg per day.
• Bipolar Depression: Quetiapine is NOT currently FDA-approved for treating bipolar depression in patients under the age of 18.

Renal Impairment

Dosage adjustments are generally not required for patients with kidney disease, as renal clearance of quetiapine is a minor pathway. However, patients should still be monitored for general tolerability.

Hepatic Impairment

Because quetiapine is extensively metabolized by the liver, patients with known liver impairment (e.g., cirrhosis) should start at a lower dose, typically 25 mg per day. The dose should be increased slowly, by 25 mg to 50 mg increments daily, until an effective dose is reached.

Elderly Patients

Older adults (65+) are often more sensitive to the sedative and hypotensive effects of quetiapine. Healthcare providers typically start elderly patients at 25 mg per day and titrate more slowly than in younger adults.

• Consistency: Take the medication at the same time(s) each day to maintain steady blood levels.
• Administration: Swallow tablets whole. Do not crush, chew, or break extended-release (XR) tablets, as this will release the entire dose at once, increasing the risk of severe side effects.
• Food: IR tablets can be taken with or without food. XR tablets should be taken on an empty stomach or with a very light meal (under 300 calories).
• Storage: Store at room temperature (68°F to 77°F) away from moisture and heat.

If you miss a dose, take it as soon as you remember. If it is almost time for your next scheduled dose, skip the missed dose and resume your regular schedule. Do not 'double up' or take two doses at once to make up for a missed one, as this increases the risk of toxicity.

Signs of a quetiapine overdose may include severe drowsiness, rapid heartbeat (tachycardia), low blood pressure (hypotension), seizures, or fainting. In severe cases, coma or death can occur. If an overdose is suspected, contact your local poison control center or seek emergency medical attention immediately.

> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop the medication without medical guidance, as sudden discontinuation can lead to withdrawal symptoms or a relapse of your condition.

Many patients starting quetiapine will experience some degree of side effects, particularly during the first few weeks of treatment as the body adjusts.

• Somnolence (Drowsiness): This is the most frequently reported side effect. It can range from mild tiredness to profound sedation. It is often most intense during the first week of titration.
• Dry Mouth (Xerostomia): A common anticholinergic-like effect that can be managed by staying hydrated or using sugar-free lozenges.
• Weight Gain: Quetiapine is known to cause significant weight gain in many patients. This is often due to increased appetite (hyperphagia) caused by the drug's effect on histamine and serotonin receptors.
• Headache: Usually transient and resolves as treatment continues.
• Dizziness: Particularly when standing up quickly (orthostatic hypotension).

• Dyspepsia (Indigestion): Stomach upset or discomfort after eating.
• Constipation: Slowing of the digestive tract.
• Tachycardia: A noticeable fast or pounding heartbeat.
• Blurred Vision: Difficulty focusing, often related to the drug's effect on the autonomic nervous system.
• Peripheral Edema: Mild swelling of the hands, ankles, or feet.

• Priapism: A painful, prolonged erection lasting more than 4 hours, which requires immediate surgical intervention to prevent permanent damage.
• Seizures: Quetiapine may lower the seizure threshold, especially in patients with a history of epilepsy.
• Hypothyroidism: A decrease in thyroid hormone levels (T4), which may require thyroid replacement therapy.
• Somnambulism: Sleep-walking or performing other complex behaviors while asleep (e.g., 'sleep-eating').

> Warning: Stop taking Quetiapine and call your doctor immediately or seek emergency care if you experience any of the following:

1. 1Neuroleptic Malignant Syndrome (NMS): A potentially fatal reaction characterized by high fever, muscle rigidity (stiffness), altered mental status, and irregular pulse or blood pressure.
2. 2Tardive Dyskinesia (TD): A movement disorder involving involuntary, repetitive body movements, such as grimacing, sticking out the tongue, or smacking the lips. This condition can become permanent even after stopping the drug.
3. 3Severe Hyperglycemia (High Blood Sugar): Symptoms include extreme thirst, frequent urination, fruity-smelling breath, and blurred vision. In extreme cases, this can lead to ketoacidosis or coma.
4. 4Agranulocytosis: A dangerous drop in white blood cell count, making you highly susceptible to infections. Symptoms include fever, sore throat, and mouth sores.
5. 5QT Prolongation: An alteration in the heart's electrical activity that can lead to a dangerous heart rhythm called Torsade de Pointes.

• Metabolic Syndrome: Long-term use is associated with a 'metabolic triad' of weight gain, increased blood sugar (Type 2 Diabetes), and increased cholesterol/triglycerides (dyslipidemia). Regular blood work is mandatory.
• Cataracts: There have been reports of lens changes in patients taking quetiapine over long periods. The FDA recommends eye examinations every 6 months during long-term therapy.
• Tardive Dyskinesia Risk: The risk of developing TD increases with the total cumulative dose and the duration of treatment, especially in elderly women.

Quetiapine carries two significant FDA Black Box Warnings:

1. 1Increased Mortality in Elderly Patients with Dementia-Related Psychosis: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Quetiapine is NOT approved for the treatment of patients with dementia-related psychosis.
2. 2Suicidal Thoughts and Behaviors: Antidepressants and certain antipsychotics (like quetiapine when used for depression) increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults (up to age 24) in short-term studies. Patients of all ages starting therapy should be monitored closely for worsening of symptoms or emergence of suicidal ideation.

Report any unusual symptoms or changes in mood to your healthcare provider immediately.

Quetiapine is a potent medication that affects the central nervous system. It requires careful medical supervision and regular monitoring to ensure safety. Patients should never share this medication with others, even if they have similar symptoms.

Dementia-Related Psychosis: Clinical trials have shown that elderly patients with dementia who take atypical antipsychotics have a higher rate of death, primarily due to cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) causes. Quetiapine is not indicated for this population.

Suicidality in Young Adults: While quetiapine can treat depression, it may also increase suicidal thoughts in those under 25 during the initial months of treatment. Families and caregivers should watch for agitation, irritability, or unusual changes in behavior.

• Metabolic Changes: Quetiapine can cause significant increases in blood glucose, lipids (cholesterol), and body weight. Patients with diabetes or those at risk for diabetes should have their blood sugar monitored regularly.
• Orthostatic Hypotension: This drug may cause a sudden drop in blood pressure when rising from a sitting or lying position, leading to dizziness or fainting (syncope). This is most common during the initial dose titration.
• Neuroleptic Malignant Syndrome (NMS): This is a rare but life-threatening emergency. If you develop a high fever and stiff muscles, seek help immediately.
• Extrapyramidal Symptoms (EPS): Although less common than with older drugs, quetiapine can cause restlessness (akathisia), tremors, or muscle spasms.
• QT Prolongation: Caution is advised in patients with a history of heart rhythm disorders or those taking other medications that affect the heart's electrical interval.

To ensure your safety while taking quetiapine, your healthcare provider will likely order the following tests:

• Weight and BMI: Measured at baseline and frequently thereafter.
• Blood Glucose/HbA1c: To monitor for the development of diabetes.
• Lipid Panel: To check cholesterol and triglyceride levels.
• Complete Blood Count (CBC): To monitor white blood cell levels, especially in the first few months.
• Eye Exams: Slit-lamp exams every 6 months are recommended by some guidelines to check for cataracts.
• Thyroid Function: Periodic checks of T4 levels.

Quetiapine causes significant sedation and can impair judgment, thinking, and motor skills. Do not drive a car, operate heavy machinery, or engage in dangerous activities until you know how the medication affects you. For many, this impairment is most severe in the first two weeks of treatment.

Alcohol should be strictly avoided while taking quetiapine. Alcohol increases the sedative effects of the drug, which can lead to dangerous levels of respiratory depression, extreme dizziness, and an increased risk of falls or accidents.

Do not stop taking quetiapine abruptly. Sudden discontinuation can cause 'discontinuation syndrome,' with symptoms including nausea, vomiting, insomnia, headache, diarrhea, dizziness, and irritability. Furthermore, stopping the drug suddenly can cause a rapid return of psychotic or manic symptoms. Your doctor will provide a tapering schedule to slowly reduce the dose over several weeks.

> Important: Discuss all your medical conditions, especially heart problems, liver disease, or a history of low white blood cell counts, with your healthcare provider before starting Quetiapine.

There are several drugs that should never be combined with quetiapine due to the risk of severe, life-threatening interactions:

• Strong CYP3A4 Inhibitors (e.g., Ketoconazole, Itraconazole, Ritonavir): These drugs block the enzyme that breaks down quetiapine. Taking them together can increase quetiapine levels in the blood by more than 500%, leading to extreme toxicity and sedation.
• Strong CYP3A4 Inducers (e.g., Phenytoin, Carbamazepine, Rifampin): These drugs speed up the metabolism of quetiapine, causing its levels to drop so low that the medication becomes completely ineffective. For example, phenytoin can decrease quetiapine concentrations by up to 80%.

• Antihypertensive Drugs: Since quetiapine can lower blood pressure, combining it with blood pressure medications (like lisinopril or amlodipine) can cause dangerously low blood pressure and fainting.
• CNS Depressants: Combining quetiapine with benzodiazepines (like Xanax or Valium), opioids (like oxycodone), or sleep medications can lead to severe respiratory depression and excessive sedation.
• Drugs that Prolong the QT Interval: Medications such as amiodarone, sotalol, moxifloxacin, and certain other antipsychotics should be used with extreme caution as they increase the risk of fatal heart arrhythmias.

• Dopamine Agonists: Since quetiapine blocks dopamine receptors, it may reduce the effectiveness of drugs used to treat Parkinson’s disease, such as levodopa or ropinirole.
• Anticholinergic Drugs: Drugs used for overactive bladder or COPD may have additive effects with quetiapine, leading to severe constipation, blurred vision, and urinary retention.

• Grapefruit and Grapefruit Juice: Grapefruit contains compounds that inhibit the CYP3A4 enzyme. Consuming grapefruit while taking quetiapine can lead to increased drug levels and a higher risk of side effects. It is best to avoid grapefruit entirely.
• High-Fat Meals: As noted, high-fat meals can significantly increase the absorption of the Extended-Release (XR) formulation. Always follow the specific food instructions for the version you are prescribed.

• St. John’s Wort: This herbal supplement is a potent inducer of CYP3A4 and can significantly reduce the amount of quetiapine in your system, making it less effective.
• Kava and Valerian Root: These supplements have sedative properties and can worsen the drowsiness caused by quetiapine.
• CBD (Cannabidiol): CBD can inhibit the metabolism of many drugs, potentially increasing quetiapine levels. Consult your doctor before using CBD products.

Quetiapine can cause false-positive results on urine drug screens for methadone or tricyclic antidepressants (TCAs). If you are required to take a drug test, inform the laboratory that you are taking quetiapine so that a more specific confirmatory test (like GC/MS) can be performed.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking. A complete list is essential to prevent dangerous interactions.

Quetiapine is strictly contraindicated in the following circumstances:

• Known Hypersensitivity: Patients who have had a documented severe allergic reaction to quetiapine fumarate or any of the inactive ingredients in the tablet (such as lactose or magnesium stearate) must not take the drug. Symptoms of hypersensitivity include rash, hives, swelling of the face or throat (angioedema), and difficulty breathing.
• Coadministration with Strong CYP3A4 Inhibitors: Due to the risk of profound sedation and cardiovascular collapse, the use of quetiapine with drugs like ketoconazole is considered an absolute contraindication in many clinical guidelines.

These are conditions where the drug should generally be avoided unless the potential benefits clearly outweigh the risks:

• Severe Hepatic Impairment: Because the liver is the primary site of metabolism, patients with end-stage liver disease may accumulate toxic levels of the drug.
• History of Severe Neutropenia: Patients who have previously experienced a dangerously low white blood cell count (neutropenia) due to other medications should be treated with extreme caution, as quetiapine can worsen this condition.
• Cardiovascular Disease: Patients with a history of recent heart attack (myocardial infarction), heart failure, or unstable heart disease are at higher risk for the hypotensive and tachycardic effects of the drug.
• Seizure Disorders: Quetiapine should be used cautiously in those with a history of epilepsy or conditions that lower the seizure threshold (e.g., Alzheimer's disease).

While quetiapine is chemically distinct, patients who have had severe adverse reactions to other dibenzothiazepine derivatives (like clozapine) should be monitored closely for similar reactions, although direct cross-allergy is rare.

> Important: Your healthcare provider will evaluate your complete medical history, including any previous drug reactions, before determining if Quetiapine is safe for you.

Quetiapine is classified as Pregnancy Category C (under the old FDA system). There are no adequate and well-controlled studies in pregnant women.

• Neonatal Risks: Infants exposed to antipsychotic drugs during the third trimester are at risk for Extrapyramidal Symptoms (EPS) and withdrawal symptoms after birth. These may include agitation, hypertonia (stiff muscles), hypotonia (floppy muscles), tremor, somnolence, and respiratory distress.
• Registry: Pregnant women taking quetiapine are encouraged to enroll in the National Pregnancy Registry for Atypical Antipsychotics to help monitor the safety of the drug during pregnancy.

Quetiapine is excreted into human breast milk in very small amounts. While the levels are generally considered low (less than 1% of the mother's weight-adjusted dose), the long-term effects on the developing infant's nervous system are unknown. If a mother must take quetiapine while breastfeeding, the infant should be monitored for excessive drowsiness, irritability, and developmental milestones.

Quetiapine is FDA-approved for schizophrenia in adolescents (13-17) and for bipolar mania in children (10-17). It is NOT approved for use in children under 10.

• Growth and Development: Long-term effects on growth and sexual maturation have not been fully studied.
• Metabolic Sensitivity: Children and adolescents are more prone to significant weight gain and increases in prolactin levels than adults.

• Dementia Warning: As noted in the Black Box Warning, quetiapine increases the risk of death in elderly patients with dementia.
• Fall Risk: Due to sedation and orthostatic hypotension, the risk of falls and resulting fractures is significantly higher in the elderly.
• Clearance: Older patients often have a 30% to 50% lower clearance of the drug, requiring much lower starting doses and slower titration.

In patients with renal impairment (CrCl < 30 mL/min), the clearance of quetiapine is not significantly altered. No specific dose adjustment is required, but clinical monitoring for side effects is always advised.

Quetiapine is extensively metabolized by the liver. In patients with liver impairment (Child-Pugh Class A or B), the plasma concentration of quetiapine can be 30% higher than in healthy individuals.

• Adjustment: Start at 25 mg/day and increase by 25-50 mg/day until the target dose is reached. Use in Child-Pugh Class C (severe) has not been studied and should be approached with extreme caution.

> Important: Special populations require individualized medical assessment and more frequent monitoring by a specialist.

Quetiapine's therapeutic effect is primarily attributed to its dual antagonism of Serotonin (5-HT2A) and Dopamine (D2) receptors. It has a significantly higher affinity for 5-HT2A receptors than for D2 receptors, which is a hallmark of atypical antipsychotics.

Furthermore, its active metabolite, norquetiapine, has high affinity for the Norepinephrine Transporter (NET). By inhibiting the reuptake of norepinephrine, norquetiapine increases the availability of this neurotransmitter in the synaptic cleft, which is believed to be the primary driver of quetiapine's effectiveness in treating depression.

• Receptor Profile: Quetiapine also acts as an antagonist at Histamine H1 (causing sedation), Alpha-1 adrenergic (causing hypotension), and Alpha-2 adrenergic receptors. It has little to no affinity for muscarinic cholinergic or benzodiazepine receptors.
• Dose-Response: The antipsychotic effect typically requires higher doses (400-800 mg), while the antidepressant effect is seen at moderate doses (150-300 mg), and sedative effects can occur at very low doses (25-50 mg).

| Parameter | Value |

|---|---|

| Bioavailability | 100% (relative to oral solution) |

| Protein Binding | 83% |

| Half-life | 6-7 hours (Quetiapine); 12 hours (Norquetiapine) |

| Tmax | 1.5 hours (IR); 6 hours (XR) |

| Metabolism | Hepatic (Primarily CYP3A4) |

| Excretion | Renal 73%, Fecal 20% |

• Molecular Formula: C21H25N3O2S (as quetiapine base)
• Molecular Weight: 383.5 g/mol (base); 883.1 g/mol (as fumarate salt)
• Solubility: Soluble in water; slightly soluble in alcohol.
• Structure: A dibenzothiazepine derivative consisting of a tricyclic core with a side chain containing an ethoxyethanol group.

Quetiapine is a Second-Generation Antipsychotic (SGA). It is chemically related to clozapine and olanzapine but has a distinct side-effect profile, particularly regarding its lower risk of extrapyramidal symptoms compared to first-generation agents like chlorpromazine.