Zoloft (sertraline HCl) is a selective serotonin reuptake inhibitor (SSRI) antidepressant approved by the FDA for the treatment of major depressive disorder (MDD), obsessive-compulsive disorder (OCD), panic disorder, posttraumatic stress disorder (PTSD), social anxiety disorder, and premenstrual dysphoric disorder (PMDD). As a first-line pharmacological intervention, it works by increasing serotonin activity in the central nervous system, helping to restore chemical balance and improve mood, sleep, appetite, and energy levels. Its well-established efficacy and generally favorable tolerability profile have made it one of the most widely prescribed antidepressants in clinical practice worldwide.

Features

• Active ingredient: Sertraline hydrochloride
• Drug class: Selective serotonin reuptake inhibitor (SSRI)
• Available formulations: Oral tablets (25 mg, 50 mg, 100 mg) and oral concentrate (20 mg/mL)
• Bioavailability: Approximately 44% following oral administration
• Time to peak plasma concentration: 4.5–8.4 hours post-dose
• Half-life: Approximately 26 hours
• Metabolism: Hepatic, primarily via CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4
• Excretion: Primarily renal (40–45%) and fecal (40–45%)

Benefits

• Demonstrates significant improvement in depressive symptom scores compared to placebo in multiple randomized controlled trials
• Reduces frequency and intensity of panic attacks in patients with panic disorder
• Decreases obsessive thoughts and compulsive behaviors in OCD patients
• Improves social interaction comfort and reduces avoidance behaviors in social anxiety disorder
• Helps manage symptoms of PTSD, including flashbacks, hypervigilance, and emotional numbness
• Provides relief from PMDD symptoms, including mood swings, irritability, and physical discomfort

Common use

Zoloft is primarily indicated for the treatment of major depressive disorder in adults and pediatric patients aged 6–17 years. It is also FDA-approved for obsessive-compulsive disorder in adults and children aged 6–17, panic disorder with or without agoraphobia in adults, posttraumatic stress disorder in adults, social anxiety disorder in adults, and premenstrual dysphoric disorder in women. Off-label uses may include generalized anxiety disorder, eating disorders, and certain pain syndromes, though these applications require careful clinical consideration and monitoring.

Dosage and direction

Initial dosing: For most adults with MDD or OCD, start with 50 mg once daily, taken in the morning or evening. For panic disorder, PTSD, and social anxiety disorder, begin with 25 mg once daily to minimize initial side effects, increasing to 50 mg after one week.

Dose titration: May increase in 25–50 mg increments at intervals of no less than one week. The maximum recommended dose is 200 mg daily.

Pediatric dosing (6–17 years): Start with 25 mg once daily for OCD, increasing to 50 mg after one week. For MDD in adolescents, start with 50 mg daily.

Administration: Should be taken with or without food, though consistent administration with food may reduce gastrointestinal side effects. The oral concentrate must be diluted before use—mix with 4 oz of water, ginger ale, lemon/lime soda, lemonade, or orange juice only.

Precautions

• Monitor for clinical worsening and suicide risk, especially during initial treatment and dose adjustments
• Use caution in patients with bipolar disorder; screen for manic episodes before initiation
• May cause activation of mania/hypomania in susceptible patients
• Use with caution in patients with seizure disorders
• May increase risk of bleeding, especially when combined with NSAIDs, aspirin, or other anticoagulants
• Can cause hyponatremia, particularly in elderly patients and those taking diuretics
• May affect glycemic control in patients with diabetes
• Use caution in patients with hepatic impairment; consider lower doses or alternative therapy
• Discontinuation syndrome may occur with abrupt cessation; taper gradually

Contraindications

• Hypersensitivity to sertraline or any component of the formulation
• Concurrent use with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing MAOI therapy
• Concurrent use with pimozide
• Initiation in patients receiving linezolid or intravenous methylene blue

Possible side effect

Common (≥5%): Nausea, diarrhea/loose stools, insomnia, drowsiness, dry mouth, fatigue, dizziness, increased sweating, tremor, decreased libido, delayed ejaculation, anorexia

Less common (1–5%): Agitation, anxiety, palpitations, blurred vision, yawning, rash, constipation, dyspepsia, vomiting, weight changes

Rare (<1%): Serotonin syndrome, extrapyramidal symptoms, angle-closure glaucoma, hepatic transaminase elevations, inappropriate ADH secretion, bleeding events, priapism

Pediatric-specific: Additional side effects may include hyperkinesia, agitation, emotional lability, and epistaxis

Drug interaction

• MAOIs: Contraindicated due to risk of serotonin syndrome
• Serotonergic drugs: Increased risk of serotonin syndrome with tramadol, triptans, other antidepressants, linezolid, lithium, tryptophan, and St. John’s wort
• Drugs that prolong QTc interval: Use with caution with antipsychotics, antiarrhythmics, antibiotics
• CYP2D6 substrates: Sertraline may increase levels of drugs metabolized by CYP2D6 (tricyclic antidepressants, antipsychotics, beta-blockers, codeine)
• Warfarin: May increase anticoagulant effect; monitor INR closely
• NSAIDs/aspirin: Increased bleeding risk
• CNS depressants: May potentiate effects of alcohol, benzodiazepines, and other sedatives

Missed dose

If a dose is missed, take it as soon as remembered unless it is close to the time for the next scheduled dose. In that case, skip the missed dose and resume the regular dosing schedule. Do not double the dose to make up for a missed one. Maintaining consistent daily administration is important for stable therapeutic levels.

Overdose

Sertraline overdose may manifest as serotonin syndrome symptoms including agitation, confusion, hallucinations, tachycardia, hypertension, hyperthermia, diaphoresis, tremor, nausea, vomiting, and neuromuscular abnormalities. Other symptoms may include drowsiness, dizziness, and QT prolongation. There is no specific antidote; provide supportive care and symptomatic treatment. Gastric lavage with activated charcoal may be considered if presented early. Monitor cardiac function and vital signs closely. Dialysis is unlikely to be effective due to high protein binding.

Storage

Store at room temperature (20–25°C or 68–77°F) with excursions permitted between 15–30°C (59–86°F). Keep in the original container, tightly closed, and protect from light and moisture. Keep out of reach of children and pets. Do not use if the product appears discolored or contains particles. The oral concentrate should be stored in the original bottle and used within 6 weeks after opening when kept at room temperature.

Disclaimer

This information is for educational purposes only and does not constitute medical advice. Zoloft is a prescription medication that should only be used under the supervision of a qualified healthcare provider. Individual response to medication may vary, and only a healthcare professional can determine the appropriate treatment based on a patient’s specific medical condition, history, and concurrent medications. Patients should not adjust dosage or discontinue treatment without consulting their prescribing physician.

Reviews

Clinical studies consistently demonstrate Zoloft’s efficacy across its approved indications. A meta-analysis of randomized controlled trials for major depressive disorder showed significantly greater improvement in Hamilton Depression Rating Scale scores compared to placebo (weighted mean difference: -2.75, 95% CI: -3.27 to -2.22). Long-term studies indicate maintained efficacy with continuous treatment for up to 44 weeks. Patient-reported outcomes frequently note improvements in mood, functionality, and quality of life, though individual experiences with side effects vary. The drug’s relatively favorable side effect profile compared to older antidepressants contributes to its high adherence rates in maintenance therapy.