Sertraline

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.
• Dizziness and Fatigue: Patients may feel lightheaded or unusually tired during the initial phase of treatment.
• Sexual Dysfunction: This is a significant concern for many patients and may include decreased libido (sex drive), erectile dysfunction, or delayed ejaculation/orgasm. Unlike other side effects, sexual dysfunction may persist throughout treatment.

• Increased Sweating (Hyperhidrosis): Especially noticeable at night.
• Tremor: Fine shaking, usually in the hands.
• Agitation or Anxiety: Some patients may feel 'wired' or more anxious when first starting the medication.
• Decreased Appetite: This can sometimes lead to initial weight loss, though weight changes vary by individual.
• Vision Changes: Blurred vision or difficulty focusing.

• Hyponatremia: Low sodium levels in the blood, which can cause headaches, confusion, and in severe cases, seizures. This is more common in elderly patients taking diuretics.
• Bruising and Bleeding: SSRIs can interfere with platelet aggregation, leading to easier bruising or prolonged bleeding from cuts.
• Angle-Closure Glaucoma: Sertraline can cause slight pupillary dilation, which may trigger an acute glaucoma attack in susceptible individuals.

> Warning: Stop taking Sertraline and call your doctor immediately if you experience any of these serious symptoms.

1. 1Serotonin Syndrome: A potentially life-threatening condition caused by excessive serotonin. Symptoms include high fever, hallucinations, rapid heart rate, severe muscle stiffness, and loss of coordination.
2. 2Suicidal Thoughts or Behaviors: Especially in children, adolescents, and young adults. Monitor for worsening depression or sudden changes in behavior.
3. 3Seizures (Convulsions): Sertraline should be used with caution in patients with a history of seizure disorders.
4. 4Manic Episodes: In patients with undiagnosed Bipolar Disorder, sertraline can trigger a transition into mania, characterized by racing thoughts, extreme energy, and reckless behavior.
5. 5Severe Allergic Reactions: Symptoms include rash, hives, swelling of the face or throat, and difficulty breathing.

With prolonged use (months to years), some patients may experience:

• Weight Gain: While some lose weight initially, long-term use of SSRIs is sometimes associated with gradual weight gain.
• Bone Fractures: Some studies suggest a link between long-term SSRI use and a slight increase in the risk of bone fractures, possibly due to effects on bone density.
• Emotional Blunting: A feeling of being 'numb' or unable to experience intense emotions, both positive and negative.

Sertraline carries an FDA Black Box Warning regarding the risk of suicidal thoughts and behaviors in children, adolescents, and young adults (up to age 24). Clinical trials have shown that SSRIs can increase this risk during the early stages of treatment. Families and caregivers should closely observe patients for any new or worsening symptoms of depression, irritability, or unusual changes in behavior. This medication is not approved for use in pediatric patients for MDD, only for OCD.

Report any unusual symptoms or persistent side effects to your healthcare provider to discuss management strategies or dosage adjustments.

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.

• Serotonin Syndrome: The risk of serotonin syndrome is increased when sertraline is co-administered with other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's Wort) and with drugs that impair metabolism of serotonin (particularly MAOIs). Symptoms include mental status changes, autonomic instability, and neuromuscular abnormalities.
• Abnormal Bleeding: SSRIs, including sertraline, may increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs like ibuprofen or naproxen), warfarin, and other anticoagulants may add to this risk. Patients should be cautious about internal bleeding, such as gastrointestinal bleeds.
• Activation of Mania/Hypomania: In patients with bipolar disorder, treating a depressive episode with an antidepressant alone can trigger a manic episode. A thorough screening for bipolar disorder is necessary before starting sertraline.
• Seizures: Like other antidepressants, sertraline should be introduced with care in patients with a history of seizures or other conditions that lower the seizure threshold.
• QTc Prolongation: Some cases of QTc prolongation (a heart rhythm condition) and Torsade de Pointes have been reported. Use with caution in patients with risk factors for QT prolongation.

Healthcare providers may require periodic monitoring, including:

• Mental Status: Regular checks for worsening depression or suicidal ideation.
• Sodium Levels: Especially in elderly patients or those on diuretics, to check for hyponatremia.
• Liver Function Tests (LFTs): Since the drug is processed by the liver, baseline and periodic liver enzyme checks may be performed in patients with known hepatic issues.
• Weight and Growth: In pediatric patients, height and weight should be monitored regularly.

Sertraline may cause drowsiness, dizziness, or blurred vision. Do not drive, operate heavy machinery, or engage in potentially dangerous activities until you know how this medication affects you.

It is strongly recommended to avoid alcohol while taking sertraline. Alcohol can worsen the side effects of the medication, such as drowsiness and dizziness, and can also interfere with the medication's ability to treat your underlying condition.

Abruptly stopping sertraline can result in 'SSRI Discontinuation Syndrome.' Symptoms include 'brain zaps' (electrical-like sensations), dizziness, nausea, headache, irritability, and paresthesia (tingling). To avoid these, your doctor will provide a tapering schedule to gradually reduce the dose over several weeks.

> Important: Discuss all your medical conditions, including heart, liver, or kidney problems, with your healthcare provider before starting Sertraline.

• 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).

• Other Serotonergic Drugs: Combining sertraline with other drugs that increase serotonin (e.g., Duloxetine, Venlafaxine, Lithium, Tramadol, or Triptans for migraines) increases the risk of Serotonin Syndrome.
• Antiplatelets and Anticoagulants: Drugs like Warfarin, Heparin, or Clopidogrel, when taken with sertraline, significantly increase the risk of serious gastrointestinal bleeding.
• NSAIDs and Aspirin: Common pain relievers like Ibuprofen (Advil/Motrin) and Naproxen (Aleve) interfere with platelet function. When combined with SSRIs, the risk of stomach ulcers and bleeding increases.

• CYP2D6 Substrates: Sertraline is a weak to moderate inhibitor of the CYP2D6 enzyme. It may increase the blood levels of drugs metabolized by this enzyme, such as certain beta-blockers (metoprolol) or other antidepressants (tricyclics).
• Cimetidine: This heartburn medication can increase the concentration of sertraline in the blood, potentially increasing side effects.

• Grapefruit Juice: While the interaction is less severe than with other medications, large amounts of grapefruit juice may slightly increase sertraline levels by inhibiting CYP3A4 enzymes in the gut.
• Caffeine: Some patients may find that sertraline increases their sensitivity to caffeine, leading to increased jitteriness or insomnia.
• High-Fat Meals: As noted in the pharmacokinetic section, food increases the absorption of sertraline. It is best to be consistent—either always take it with food or always take it on an empty stomach.

• St. John's Wort: This herbal supplement has serotonergic properties and should be avoided, as it significantly increases the risk of serotonin syndrome.
• 5-HTP and L-Tryptophan: These precursors to serotonin should not be taken with sertraline due to the risk of serotonin toxicity.
• Ginkgo Biloba: May increase the risk of bleeding when combined with SSRIs.

Sertraline can cause false-positive results in urine drug screens for benzodiazepines and hallucinogens (like LSD) depending on the specific testing method used. If you are undergoing a drug test, inform the laboratory that you are taking sertraline.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking. Even over-the-counter medications can have significant interactions.

• 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.

These are conditions where the medication may be used, but only with extreme caution and careful risk-benefit analysis by a physician:

• Uncontrolled Seizure Disorder: Since SSRIs can lower the seizure threshold, patients with active epilepsy must be monitored closely.
• Severe Hepatic Impairment: The liver's inability to clear the drug can lead to toxic accumulation.
• Narrow-Angle Glaucoma: The slight pupillary dilation (mydriasis) caused by sertraline can trigger an attack of angle-closure glaucoma in patients with anatomically narrow angles.
• Bleeding Diathesis: Patients with known bleeding disorders (like hemophilia) or active peptic ulcers should use sertraline with caution due to the anti-platelet effects of SSRIs.

While there is no direct cross-sensitivity between sertraline and other SSRIs (like fluoxetine or paroxetine) in terms of chemical structure, patients who have experienced severe adverse reactions (like serotonin syndrome) to one SSRI are at an increased risk of experiencing similar reactions with another. However, many patients who do not tolerate one SSRI may successfully switch to another under medical supervision.

> Important: Your healthcare provider will evaluate your complete medical history, including any history of mania or liver disease, before prescribing Sertraline.

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 is generally considered one of the preferred SSRIs for breastfeeding mothers. Data indicates that sertraline passes into breast milk in very small amounts, and blood levels in nursing infants are typically very low or undetectable. No adverse effects on nursing infants are usually observed, though providers still recommend monitoring the infant for agitation or poor feeding.

As previously noted, sertraline is FDA-approved for OCD in children aged 6 and older. It is not approved for pediatric depression. Clinical trials have shown that the safety profile in children is generally similar to that in adults, though growth (weight and height) should be monitored throughout treatment to ensure the medication is not interfering with development.

Elderly patients (age 65+) are at a higher risk of developing hyponatremia (low blood sodium) while taking SSRIs. This condition can be subtle, presenting as headache, confusion, or weakness, and can lead to falls. Doctors may recommend regular blood tests to monitor sodium levels. Additionally, the risk of drug-drug interactions is higher in the elderly due to polypharmacy (taking multiple medications).

Since only a tiny fraction of sertraline is excreted unchanged by the kidneys, renal impairment does not significantly alter the drug's concentration. No dosage adjustment is typically required for patients with kidney disease, including those on dialysis.

In patients with mild liver impairment (Child-Pugh Class A), the half-life of sertraline is prolonged. These patients should receive approximately half the standard dose or be dosed every other day. Sertraline is not recommended for use in patients with more severe liver dysfunction (Child-Pugh Class B or C).

> Important: Special populations require individualized medical assessment. Always inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding.

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.

| Parameter | Value |

|---|---|

| Bioavailability | Approximately 44% (Oral) |

| Protein Binding | 98% (Primarily Albumin) |

| Half-life | 26 hours (Parent drug); 62-104 hours (Metabolite) |

| Tmax | 4.5 to 8.4 hours |

| Metabolism | Hepatic (CYP2B6, 2C19, 3A4) |

| Excretion | Renal (40-45%), Fecal (40-45%) |

• Molecular Formula: C17H17Cl2N•HCl
• Molecular Weight: 342.7 g/mol
• Solubility: Slightly soluble in water and isopropyl alcohol; soluble in ethanol.
• Structure: Sertraline is a (1S,4S)-enantiomer. It is a bicyclic compound, specifically a derivative of naphthylamine. The presence of two chlorine atoms on the phenyl ring is critical for its selective binding to the serotonin transporter.

Sertraline is a Selective Serotonin Reuptake Inhibitor (SSRI). It is grouped with other medications such as Fluoxetine (Prozac), Paroxetine (Paxil), Citalopram (Celexa), and Escitalopram (Lexapro). While they share a similar primary mechanism, they differ in their secondary receptor affinities, metabolic pathways, and half-lives.