Introduction
Zoloft (sertraline) is a selective serotonin reuptake inhibitor (SSRI) antidepressant that has been a cornerstone in the treatment of depression and anxiety disorders for decades. It is one of the most widely prescribed antidepressants globally, known for its favorable safety profile and established efficacy.
Mechanism of Action
Zoloft exerts its therapeutic effects by selectively inhibiting the reuptake of serotonin (5-HT) in the central nervous system. By blocking the serotonin transporter (SERT), sertraline increases the availability of serotonin in the synaptic cleft, enhancing serotonergic neurotransmission. This action is believed to be responsible for its antidepressant, anxiolytic, and anti-obsessional effects. Unlike older antidepressants, sertraline has minimal affinity for muscarinic, histaminergic, and α1-adrenergic receptors, resulting in fewer anticholinergic and sedative side effects.
Indications
- Major Depressive Disorder (MDD)
- Obsessive-Compulsive Disorder (OCD)
- Panic Disorder
- Post-Traumatic Stress Disorder (PTSD)
- Social Anxiety Disorder
- Premenstrual Dysphoric Disorder (PMDD)
Dosage and Administration
Initial Dose: 50 mg once daily Dosage Range: 50-200 mg daily Maximum Dose: 200 mg daily Special Populations:- Elderly: Start with 25 mg daily
- Hepatic Impairment: Use lower doses and monitor closely
- Pediatric: Not approved for use in children under 6 years
- Pregnancy: Category C; risk-benefit assessment required
Pharmacokinetics
Absorption: Slowly absorbed with peak plasma concentrations occurring 4-8 hours after oral administration Distribution: 99% protein bound Metabolism: Extensively metabolized by CYP450 enzymes, primarily CYP2C19 and CYP3A4 Elimination: Half-life of approximately 26 hours, allowing once-daily dosingContraindications
- Concomitant use with MAOIs or within 14 days of MAOI use
- Known hypersensitivity to sertraline
- Pimozide use
- Uncontrolled narrow-angle glaucoma
Warnings and Precautions
- Suicidality: Increased risk in children, adolescents, and young adults
- Serotonin syndrome: Risk when combined with other serotonergic agents
- Bleeding risk: May increase risk of bleeding events
- QTc prolongation: Monitor in patients at risk for QTc prolongation
- Discontinuation syndrome: Taper gradually when discontinuing therapy
Drug Interactions
- MAOIs: Contraindicated
- Warfarin: Increased bleeding risk
- NSAIDs: Increased bleeding risk
Adverse Effects
Common:- Nausea
- Diarrhea
- Insomnia
- Sexual dysfunction
- Dry mouth
- Headache
- Fatigue
- Serotonin syndrome
- Suicidal ideation
- Seizures
- Hyponatremia
- Mania
- Angle-closure glaucoma
Monitoring Parameters
- Blood pressure
- Liver function tests
- Sodium levels in elderly patients
- Bleeding parameters
- QTc interval in at-risk patients
- Mood and behavior changes
- Weight changes
- Sexual function
Patient Education
- Take with food to reduce nausea
- Do not stop medication abruptly
- Report any new or worsening symptoms
- Avoid alcohol
- Use effective contraception
- Inform healthcare providers of all medications
- Allow 4-6 weeks for full therapeutic effect
References
1. Zoloft Prescribing Information, Pfizer Inc. 2. American Journal of Psychiatry 3. Journal of Clinical Psychiatry 4. New England Journal of Medicine 5. Cochrane Database of Systematic Reviews 6. FDA Drug Safety Communications 7. World Journal of Biological Psychiatry 8. British Journal of Psychiatry 9. Journal of Affective Disorders 10. Archives of General Psychiatry
This monograph is for educational purposes only and should not replace professional medical advice. Always consult with a healthcare provider for personalized medical guidance.