Zoloft (sertraline HCl) is a selective serotonin reuptake inhibitor (SSRI) approved by the FDA for the management 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 cornerstone of modern psychopharmacology, it functions by increasing serotonin levels in the brain, a neurotransmitter critically involved in mood regulation, emotional stability, and anxiety response. Its well-established efficacy, extensive clinical data, and generally favorable tolerability profile make it a first-line pharmacological intervention for these conditions, offering patients a pathway toward sustained symptom relief and improved daily functioning.

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: Exhibits linear and proportional pharmacokinetics over the recommended dosing range
• Half-life: Approximately 26 hours, supporting once-daily dosing
• Metabolism: Primarily hepatic, via CYP450 isoenzymes (notably CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4)
• Excretion: Equally via feces and urine

Benefits

• Proven Efficacy in Multiple Indications: Clinically demonstrated to significantly reduce the core symptoms of depression and anxiety disorders, leading to improved mood and reduced fear.
• Restoration of Functional Capacity: By alleviating debilitating psychological symptoms, it enables patients to regain engagement in social, occupational, and daily activities.
• Long-Term Maintenance Therapy: Supports sustained remission and helps prevent relapse of major depressive episodes when used as directed.
• Generally Favorable Side Effect Profile: Compared to older antidepressant classes (e.g., TCAs, MAOIs), it is associated with fewer anticholinergic effects and less sedation.
• Dosing Flexibility: Available in multiple strengths, allowing for precise titration to an individual’s therapeutic needs and tolerability.

Common use

Zoloft (sertraline) is indicated for the treatment of:

• Major Depressive Disorder (MDD): For the acute and maintenance treatment of MDD in adults, and for the acute treatment of MDD in pediatric patients aged 6-17 years.
• Obsessive-Compulsive Disorder (OCD): For the acute and maintenance treatment of OCD in adults and pediatric patients aged 6-17 years.
• Panic Disorder: For the treatment of panic disorder, with or without agoraphobia, in adults.
• Posttraumatic Stress Disorder (PTSD): For the treatment of PTSD in adults.
• Social Anxiety Disorder: For the treatment of social anxiety disorder in adults.
• Premenstrual Dysphoric Disorder (PMDD): For the treatment of PMDD in adults.

Its use is based on a comprehensive psychiatric diagnosis. Treatment should be part of a total therapeutic program that often includes psychotherapy and other supportive measures.

Dosage and direction

Administration: Zoloft is administered orally, once daily, either in the morning or evening, with or without food. The oral concentrate must be diluted before administration; use only with the supplied dropper and mix with 4 oz (½ cup) of water, ginger ale, lemon/lime soda, lemonade, or orange juice ONLY. Do not mix with any other liquids.

Initial Dose and Titration:

• Adults (MDD, OCD, Panic, PTSD, SAD): The recommended starting dose is 50 mg once daily. Depending on therapeutic response and tolerability, doses may be increased in increments of 50 mg at intervals of no less than one week, up to a maximum dose of 200 mg/day.
• Pediatric Patients (OCD, aged 6-12): Start at 25 mg once daily. After one week, increase to 50 mg once daily. Subsequent weekly increments can be made up to a maximum of 200 mg/day.
• Pediatric Patients (OCD, aged 13-17): Start at 50 mg once daily. Doses can be increased weekly up to a maximum of 200 mg/day.
• PMDD: The recommended dosage for PMDD is 50 mg per day throughout the menstrual cycle or limited to the luteal phase (the 14 days prior to the onset of menses). Dosing may be increased up to 100 mg/day or decreased to 25 mg/day based on response.

Dosage adjustments are necessary for patients with hepatic impairment. A lower or less frequent dose should be used. Zoloft is not recommended for patients with severe hepatic impairment.

Precautions

• Suicidal Thoughts and Behaviors: Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. All patients starting therapy should be monitored closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber.
• Serotonin Syndrome: Risk is increased, particularly with concomitant use of other serotonergic drugs. Symptoms include mental status changes, autonomic instability, neuromuscular aberrations, and gastrointestinal symptoms. This is a potentially life-threatening condition requiring immediate medical attention.
• Abnormal Bleeding: SSRIs and SNRIs may increase the risk of bleeding events. Patients should be cautioned about the risk, especially when co-administered with aspirin, NSAIDs, warfarin, or other drugs that affect coagulation.
• Activation of Mania/Hypomania: May occur in patients with bipolar disorder. Screen patients for bipolar disorder prior to initiating treatment; Zoloft is not approved for treating bipolar depression.
• Angle-Closure Glaucoma: Can occur in patients with anatomically narrow angles who do not have a patent iridectomy.
• Hyponatremia: Can occur as a result of treatment, potentially due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Elderly patients and those taking diuretics are at greater risk.
• Long-Term Use and Discontinuation: Abrupt discontinuation can lead to withdrawal symptoms. A gradual taper is recommended to minimize these effects.

Contraindications

• Hypersensitivity to sertraline or any component of the formulation.
• Use of Monoamine Oxidase Inhibitors (MAOIs): Concomitant use with MAOIs intended to treat psychiatric disorders is contraindicated due to the risk of serious, sometimes fatal, drug interactions. Zoloft must not be started within 14 days of stopping an MAOI. Similarly, an MAOI should not be started until at least 14 days after discontinuing Zoloft.
• Use of Pimozide: Concomitant use is contraindicated.
• Use of Disulfiram (for oral concentrate only): The concentrate contains alcohol and is contraindicated with disulfiram.

Possible side effect

Side effects are generally dose-related and may decrease in intensity with continued therapy. Common adverse reactions (incidence ≥5% and at least twice that of placebo) include:

• Gastrointestinal: Nausea, diarrhea/loose stools, dyspepsia, dry mouth, constipation
• Nervous System: Insomnia, somnolence, dizziness, fatigue, headache, tremor
• Psychiatric: Agitation, decreased libido
• Other: Increased sweating, male sexual dysfunction (ejaculation failure, delayed ejaculation)

Other important side effects to monitor include:

• Weight changes (loss or gain)
• Visual disturbances
• Palpitations
• Rash
• Symptoms of serotonin syndrome

Drug interaction

Zoloft is metabolized by multiple CYP450 enzymes and is also an inhibitor of CYP2D6, leading to a significant potential for drug-drug interactions.

• MAOIs: Contraindicated due to risk of serotonin syndrome (see Contraindications).
• Pimozide: Contraindicated. Increased pimozide levels can prolong the QTc interval.
• Other Serotonergic Drugs: Use with triptans, tramadol, tryptophan, other SSRIs/SNRIs, or St. John’s Wort increases the risk of serotonin syndrome.
• Drugs Metabolized by CYP2D6: Zoloft inhibits CYP2D6. Concomitant use with drugs that are metabolized by CYP2D6 and have a narrow therapeutic index (e.g., tricyclic antidepressants, flecainide, propafenone, thioridazine) requires dosage adjustment or consideration of an alternative medication.
• Warfarin: May potentiate anticoagulant effect; closely monitor prothrombin time and INR.
• CNS-Acting Drugs: Use with caution with other CNS drugs (e.g., antipsychotics, benzodiazepines) due to additive effects.
• Drugs Highly Bound to Plasma Protein: May be displaced from protein binding sites (e.g., warfarin, digitoxin).

Missed dose

If a dose is missed, it should be taken as soon as remembered. However, if it is almost time for the next scheduled dose, the missed dose should be skipped and the regular dosing schedule resumed. Do not double the dose to make up for a missed one.

Overdose

Symptoms: Overdose experience includes serotonin syndrome-related symptoms, somnolence, vomiting, tachycardia, nausea, dizziness, agitation, tremor, and rarely, bradycardia, bundle branch block, coma, delirium, ECG changes, hypertension, hypotension, manic reaction, pancreatitis, seizures, and syncope. Management: There is no specific antidote. Provide supportive and symptomatic treatment. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. Gastric lavage with a protected airway may be indicated if performed soon after ingestion. Activated charcoal may be useful. Consider the prolonged half-life (26 hours) and sustained-release properties when managing overdose.

Storage

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F). Keep the bottle tightly closed to protect from moisture and light. Keep out of reach of children. The oral concentrate should be stored in the original bottle; after dilution, the mixture may be stored at room temperature but must be used within 24 hours.

Disclaimer

This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any new treatment. Never disregard professional medical advice or delay in seeking it because of something you have read here. The content has been compiled from various sources and may not be entirely error-free or encompass all possible uses, directions, precautions, or interactions.

Reviews

Clinical studies and meta-analyses consistently demonstrate Zoloft’s efficacy. In an 8-week double-blind study of major depression, 62% of patients on sertraline (50-200 mg/day) showed significant improvement vs. 33% on placebo. For OCD, a 12-week study showed a mean improvement of 40% on the Y-BOCS scale for sertraline patients versus 10% for placebo. Long-term maintenance studies show a significant reduction in relapse rates compared to placebo over 44 weeks. Patient-reported outcomes often highlight a gradual but meaningful improvement in mood, energy, and reduction in anxiety and intrusive thoughts, though many also report initial side effects like nausea which often subside. “After 8 weeks on a 100mg dose, the constant fog of depression finally lifted. The initial nausea was challenging but manageable.” - Verified Patient, 42 “As a clinician, I find sertraline to be a reliable and effective first-line SSRI. Its predictable pharmacokinetics and extensive evidence base make it a cornerstone of my practice for MDD and anxiety disorders.” - Psychiatrist, 15 years experience