Usage
Sertraline is prescribed for the treatment of various mental health conditions including:
- Major Depressive Disorder (MDD)
- Obsessive-Compulsive Disorder (OCD)
- Panic Disorder (PD)
- Post-Traumatic Stress Disorder (PTSD)
- Social Anxiety Disorder (SAD)
- Premenstrual Dysphoric Disorder (PMDD)
Pharmacological Classification: Sertraline is classified as a Selective Serotonin Reuptake Inhibitor (SSRI).
Mechanism of Action: Sertraline primarily works by increasing the extracellular level of serotonin in the brain by inhibiting its reuptake into presynaptic neurons. This leads to enhanced serotonergic neurotransmission, which is believed to be the key mechanism in alleviating symptoms of the above-mentioned conditions.
Alternate Names
Sertraline hydrochloride is the chemical name. It’s often marketed internationally under various brand names, most notably Zoloft.
How It Works
Pharmacodynamics: Sertraline’s primary effect is to increase serotonin levels in the synaptic cleft, leading to enhanced serotonergic neurotransmission. It has weak effects on norepinephrine and dopamine reuptake and does not inhibit monoamine oxidase.
Pharmacokinetics:
- Absorption: Sertraline is well-absorbed orally, and its bioavailability is enhanced when taken with food.
- Metabolism: Sertraline undergoes extensive first-pass metabolism in the liver, primarily by CYP450 enzymes (CYP2C19, CYP3A4, CYP2B6, and CYP2D6), to form N-desmethylsertraline, an inactive metabolite.
- Elimination: Sertraline has an elimination half-life of approximately 26 hours, while its metabolite, N-desmethylsertraline, has a longer half-life of around 62-104 hours. Elimination occurs primarily through hepatic metabolism, with a small portion excreted unchanged in urine and feces.
Mode of Action: Sertraline binds to the serotonin transporter protein (SERT) on the presynaptic neuron, inhibiting the reuptake of serotonin.
Receptor Binding/Enzyme Inhibition: Sertraline selectively inhibits SERT, with little to no affinity for other receptors such as GABA, dopamine, or other serotonin receptor subtypes (5HT1A, 5HT1B, 5HT2).
Dosage
Standard Dosage
Adults:
- MDD, OCD: Initial dose is 50 mg once daily, which can be increased in 25-50 mg increments at weekly intervals, as needed. The maximum dose is 200 mg daily.
- PD, PTSD, SAD: Initial dose is 25 mg once daily, increased to 50 mg once daily after one week. Subsequent increases can be made in 50 mg increments at weekly intervals, as needed. The maximum dose is 200 mg daily.
- PMDD: Continuous dosing: 50 mg daily. Intermittent dosing: 50 mg daily during the luteal phase (starting 14 days before expected menses until the onset of menstruation).
Children (OCD):
- 6-12 years: Initial dose is 25 mg once daily, which can be increased to 50 mg daily after one week.
- 13-17 years: Initial dose is 50 mg once daily.
Subsequent increases can be made in 50 mg increments at weekly intervals, as needed, up to a maximum of 200 mg daily.
Special Cases:
- Elderly Patients: Start at a lower dose (e.g., 25 mg/day) and titrate cautiously, considering potential age-related decreases in hepatic, renal, or cardiac function and the higher risk of hyponatremia.
- Patients with Renal Impairment: No dosage adjustment is typically necessary.
- Patients with Hepatic Dysfunction:
- Mild impairment: Reduce the initial and therapeutic dose by half.
- Moderate to severe impairment: Not recommended.
- Patients with Comorbid Conditions: Careful monitoring and dose adjustments may be needed for patients with conditions like diabetes, cardiovascular disease, or a history of seizures.
Clinical Use Cases
Sertraline’s clinical use is focused on outpatient management of the previously mentioned mental health disorders. It does not have specific applications for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dosage adjustments should be based on individual patient response and tolerability. Gradual dose increases at weekly intervals are recommended.
Side Effects
Common Side Effects:
Nausea, diarrhea, dry mouth, insomnia, somnolence, dizziness, headache, tremor, sexual dysfunction, sweating.
Rare but Serious Side Effects:
Serotonin syndrome (fever, rigidity, mental status changes, autonomic instability), hyponatremia (especially in elderly), bleeding disorders, mania/hypomania, seizures, QTc prolongation, angle-closure glaucoma, Steven-Johnson syndrome.
Long-Term Effects:
Potential for sexual dysfunction, weight changes, and discontinuation syndrome upon abrupt cessation.
Adverse Drug Reactions (ADR):
Serotonin syndrome, severe hyponatremia, allergic reactions, abnormal bleeding.
Contraindications
- Hypersensitivity to sertraline
- Concomitant use of MAOIs (or within 14 days of discontinuing MAOIs)
- Concomitant use of pimozide
Drug Interactions
- MAOIs: Risk of serotonin syndrome.
- Pimozide: Increased risk of cardiac arrhythmias.
- CYP450 inhibitors/inducers: May alter sertraline levels.
- CNS depressants: Additive effects.
- Serotonergic drugs (e.g., triptans, other SSRIs): Increased risk of serotonin syndrome.
- Anticoagulants/antiplatelet drugs: Increased bleeding risk.
- Alcohol: May enhance sedative effects.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C. While some studies suggest a potential increased risk of certain birth defects, the overall risk is considered low.
- Breastfeeding: Sertraline is present in breast milk. Monitor infants for potential side effects like irritability or feeding difficulties.
Drug Profile Summary
- Mechanism of Action: SSRI, inhibits serotonin reuptake.
- Side Effects: Nausea, insomnia, sexual dysfunction, dizziness; rarely, serotonin syndrome.
- Contraindications: MAOIs, pimozide, hypersensitivity.
- Drug Interactions: MAOIs, pimozide, CYP450 modulators, serotonergic drugs, anticoagulants.
- Pregnancy & Breastfeeding: Category C; use with caution.
- Dosage: See detailed dosage section above.
- Monitoring Parameters: Monitor for clinical worsening, suicidal thoughts, and adverse effects.
Popular Combinations
Sertraline is sometimes used in combination with other medications to address specific symptoms or comorbid conditions. However, combination therapy should always be carefully considered due to the potential for drug interactions.
Precautions
- Monitor for suicidality, especially in young adults.
- Screen for bipolar disorder before starting treatment.
- Taper dose gradually upon discontinuation.
- Caution in patients with liver disease, epilepsy, bleeding disorders, glaucoma, and diabetes.
- Avoid alcohol.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Sertraline?
A: See detailed dosage section above.
Q2: What are the common side effects of sertraline?
A: The most common side effects include nausea, diarrhea, dry mouth, insomnia, somnolence, dizziness, headache, tremor, sexual dysfunction, and sweating.
Q3: How should sertraline be discontinued?
A: Sertraline should be tapered gradually over several weeks to minimize withdrawal symptoms.
Q4: Can sertraline be used during pregnancy?
A: Sertraline is a Pregnancy Category C drug. Consult with a specialist to weigh the risks and benefits.
Q5: What are the signs of serotonin syndrome?
A: Symptoms include agitation, confusion, tachycardia, hypertension, muscle rigidity, tremor, hyperthermia, and sweating.
Q6: Does sertraline interact with other medications?
A: Yes, sertraline can interact with MAOIs, pimozide, CYP450 modulators, other serotonergic drugs, and anticoagulants.
Q7: How long does it take for sertraline to work?
A: It can take several weeks for sertraline to reach full therapeutic effect.
Q8: Can sertraline be used in children?
A: Sertraline is approved for use in children aged 6 years and older for OCD.
Q9: What should patients avoid while taking Sertraline?
A: Patients should avoid alcohol and grapefruit juice, which can interact with sertraline. They should inform their doctors about all medications and supplements they’re taking.
Q10: Is sertraline addictive?
A: Sertraline is not considered addictive, but withdrawal symptoms can occur if it’s stopped abruptly.
