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Sertraline is a potent selective serotonin reuptake inhibitor (SSRI) primarily prescribed for major depressive disorder, anxiety disorders, and obsessive-compulsive disorder. It works by increasing serotonin levels in the brain to improve mood and emotional balance.

Dosage for sertraline is highly individualized and depends on the condition being treated, the severity of symptoms, and the patient's response to the medication. Healthcare providers typically start with a low dose and gradually increase it (titrate) to minimize side effects.

• Major Depressive Disorder and OCD: The typical starting dose is 50 mg once daily. If necessary, the dose may be increased in 50 mg increments at intervals of at least one week, up to a maximum of 200 mg per day.
• Panic Disorder, PTSD, and Social Anxiety Disorder: Treatment usually begins with a lower dose of 25 mg once daily for the first week to reduce the risk of initial anxiety or agitation. After one week, the dose is typically increased to 50 mg once daily. Further increases may occur up to 200 mg per day.
• Premenstrual Dysphoric Disorder (PMDD): Sertraline may be taken continuously (every day) or intermittently (only during the 14 days prior to the start of menstruation). The starting dose is 50 mg daily, which may be increased to 100 mg daily for continuous dosing or 150 mg daily for intermittent dosing.

Sertraline is FDA-approved for the treatment of Obsessive-Compulsive Disorder (OCD) in pediatric patients. It is not currently approved for MDD in children due to concerns regarding suicidality risks in younger populations.

• Children (Ages 6–12): The recommended starting dose is 25 mg once daily. After one week, the dose may be increased to 50 mg once daily. Further adjustments can be made up to 200 mg per day if required.
• Adolescents (Ages 13–17): The starting dose is 50 mg once daily, with titration up to 200 mg per day based on clinical response.

Renal Impairment

Because sertraline is primarily metabolized by the liver and excreted as inactive metabolites, significant dosage adjustments are generally not required for patients with mild to severe renal (kidney) impairment. However, these patients should still be monitored closely.

Hepatic Impairment

In patients with hepatic (liver) impairment, the clearance of sertraline is reduced, leading to higher levels of the drug in the bloodstream. For patients with mild liver disease (Child-Pugh Class A), a lower dose or less frequent dosing schedule is recommended. Sertraline is generally not recommended for patients with moderate to severe hepatic impairment.

Elderly Patients

Older adults may be more sensitive to the effects of SSRIs, particularly the risk of hyponatremia (low blood sodium). While the standard adult dose is often used, healthcare providers may choose to titrate the dose more slowly in the geriatric population.

• Consistency: Take sertraline at the same time every day, either in the morning or evening. Consistency helps maintain stable levels of the medication in your system.
• With or Without Food: Tablets can be taken with or without food. However, taking it with food may help reduce gastrointestinal side effects like nausea.
• Oral Solution: If using the liquid concentrate, use the provided dropper to measure the dose. Mix the dose with 4 ounces (1/2 cup) of water, ginger ale, lemon/lime soda, lemonade, or orange juice. Do not mix it with other liquids. Drink the mixture immediately after mixing.
• Storage: Store at room temperature (68°F to 77°F or 20°C to 25°C), away from moisture and heat.

If you miss a dose, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and return to your regular schedule. Do not take two doses at once to make up for a missed one, as this increases the risk of side effects.

Symptoms of a sertraline overdose may include extreme drowsiness, nausea, vomiting, rapid heart rate, tremors, agitation, and dizziness. In severe cases, it can lead to coma or serotonin syndrome. If an overdose is suspected, contact emergency medical services or a poison control center immediately.

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

Most patients taking sertraline will experience some side effects, particularly during the first two weeks of treatment as the body adjusts to the medication. Common side effects include:

• Nausea: This is the most frequently reported side effect. It often subsides after the first week. Taking the medication with food can help.
• Diarrhea and Loose Stools: Sertraline can affect the serotonin receptors in the gut, leading to increased motility.
• Insomnia: Some patients find sertraline stimulating, making it difficult to fall or stay asleep. Taking the dose in the morning may alleviate this.
• Dry Mouth (Xerostomia): A common effect of many antidepressants, which can be managed by staying hydrated or using sugar-free gum.

Sertraline is a powerful psychiatric medication that requires careful monitoring. Patients should be aware that it may take 4 to 6 weeks to feel the full therapeutic benefits. It is vital not to stop the medication abruptly, as this can lead to Discontinuation Syndrome. Always maintain open communication with your healthcare team regarding your progress and any concerns.

Suicidality and Antidepressant Drugs: Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older. In patients of all ages who are started on antidepressant therapy, monitor closely for worsening and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber.

• Monoamine Oxidase Inhibitors (MAOIs): Do not use sertraline within 14 days of taking an MAOI (such as phenelzine, selegiline, or tranylcypromine). Combining these can cause a fatal 'hypertensive crisis' or severe serotonin syndrome. At least 14 days must pass after stopping an MAOI before starting sertraline, and at least 14 days must pass after stopping sertraline before starting an MAOI.
• Pimozide: Sertraline can increase the levels of pimozide, an antipsychotic, which significantly increases the risk of dangerous heart rhythm problems (QT prolongation).
• Disulfiram: The oral solution form of sertraline contains 12% alcohol and should not be used with disulfiram (Antabuse), as it can cause a severe reaction (vomiting, flushing, headache).

• Hypersensitivity: Sertraline is strictly contraindicated in patients with a known allergy to sertraline hydrochloride or any of the inactive ingredients in the formulation. Anaphylaxis and severe skin reactions (like Stevens-Johnson Syndrome) are rare but possible.
• Concurrent MAOI Use: Use of Monoamine Oxidase Inhibitors (MAOIs) intended to treat psychiatric disorders with sertraline or within 14 days of stopping treatment with sertraline is contraindicated because of an increased risk of serotonin syndrome. The use of sertraline within 14 days of stopping an MAOI is also contraindicated.
• Pimozide Co-administration: Due to the narrow therapeutic index of pimozide and its known effect on the QT interval, the use of these two drugs together is strictly forbidden.
• Disulfiram (for Oral Solution): Because the liquid concentrate contains alcohol, it must not be used in patients taking disulfiram.

Sertraline is classified as a Pregnancy Category C medication (under the old FDA system). This means that animal studies have shown an adverse effect on the fetus, but there are no adequate and well-controlled studies in humans.

• First Trimester: Some studies have suggested a very slight increase in the risk of heart defects, though the absolute risk remains low.
• Third Trimester: Infants exposed to SSRIs late in the third trimester may develop complications requiring prolonged hospitalization, respiratory support, and tube feeding. This is often referred to as 'Neonatal Adaptation Syndrome' and includes symptoms like irritability, tremor, and respiratory distress.
• PPHN: There is an association between SSRI use in pregnancy and Persistent Pulmonary Hypertension of the Newborn (PPHN), a serious lung condition.
• Decision Making: Untreated depression during pregnancy also carries significant risks for both the mother and the baby. The decision to continue or stop sertraline must be made collaboratively between the patient and her doctors.

Sertraline's primary action is the potent inhibition of the serotonin reuptake pump (SERT) on the presynaptic neuronal membrane. By binding to the SERT, sertraline prevents the reabsorption of serotonin (5-HT) into the cell. This leads to a sustained increase in serotonin levels within the synaptic cleft, enhancing the activation of postsynaptic serotonin receptors.

Unlike other SSRIs, sertraline also exhibits a low-affinity binding to the dopamine transporter (DAT). While this effect is 10-20 times weaker than its effect on serotonin, it distinguishes sertraline from drugs like paroxetine. Furthermore, sertraline has a high affinity for sigma-1 receptors, which may play a role in its anxiolytic (anti-anxiety) and antidepressant effects, although the exact clinical significance of sigma-1 binding is still being researched.

The pharmacodynamic effects of sertraline are characterized by a 'lag time.' While the inhibition of serotonin reuptake occurs within hours of the first dose, the clinical antidepressant effect typically takes 2 to 4 weeks to manifest. This is believed to be due to the time required for the 'downregulation' or desensitization of inhibitory autoreceptors (like 5-HT1A), which eventually allows for a more robust release of serotonin. Tolerance to the antidepressant effects is rare, but some patients may experience 'tachyphylaxis' (a sudden decrease in response) over long-term treatment.