Zoloft: Advanced SSRI Therapy for Major Depressive Disorder
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Zoloft (sertraline HCl) is a selective serotonin reuptake inhibitor (SSRI) 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 functions by increasing serotonin levels in the central nervous system, which helps restore chemical balance and improve mood, sleep, appetite, and energy levels. Its well-established efficacy, extensive clinical data, and generally favorable tolerability profile make it a cornerstone in modern psychiatric pharmacotherapy for millions of patients 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%)
- Pregnancy category: C (requires careful risk-benefit assessment)
Benefits
- Effectively reduces core symptoms of major depressive disorder, including low mood, anhedonia, and fatigue
- Demonstrates significant anxiolytic properties for comorbid anxiety disorders
- Lower risk of anticholinergic effects, cardiotoxicity, and weight gain compared to older antidepressants
- Once-daily dosing regimen supports treatment adherence and simplifies management
- Suitable for long-term maintenance therapy to prevent relapse and recurrence
- Evidence-supported efficacy across a broad range of anxiety and mood disorders
Common use
Zoloft is indicated for the acute and maintenance treatment of major depressive disorder in adults and pediatric patients aged 6 years and older. It is also approved for obsessive-compulsive disorder (adults and children), panic disorder (with or without agoraphobia), posttraumatic stress disorder, social anxiety disorder, and premenstrual dysphoric disorder. Off-label uses may include generalized anxiety disorder, bulimia nervosa, and certain pain syndromes, though these should only be prescribed following thorough clinical evaluation.
Dosage and direction
Dosage must be individualized based on diagnosis, patient response, and tolerability. For major depressive disorder and OCD in adults, initiate at 50 mg once daily, with increases in 50 mg increments at intervals of no less than one week. Maximum recommended dose is 200 mg/day. For panic disorder, PTSD, and social anxiety disorder, start at 25 mg once daily to minimize initial anxiety, increasing to 50 mg after one week. For PMDD, dosing may be continuous throughout the menstrual cycle or limited to the luteal phase. Administer with or without food; evening dosing may mitigate initial activation or insomnia. Dosage adjustments are necessary in hepatic impairment.
Precautions
Monitor patients closely for clinical worsening, suicidality, or unusual changes in behavior, particularly during initiation and dosage adjustments. Use caution in patients with a history of seizures. May cause hyponatremia, especially in elderly patients or those taking diuretics. Screen for bipolar disorder prior to initiation, as antidepressants can precipitate manic episodes. May increase the risk of bleeding, especially when used with NSAIDs, aspirin, or other anticoagulants. Discontinuation should be gradual to avoid withdrawal symptoms. Not recommended during pregnancy unless potential benefit justifies potential risk.
Contraindications
Zoloft is contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing MAOI therapy due to risk of serotonin syndrome. Contraindicated with pimozide due to QT prolongation risk. Hypersensitivity to sertraline or any component of the formulation. Avoid use with disulfiram if using the oral concentrate (contains alcohol).
Possible side effect
Common adverse reactions (≥5% and twice placebo) include: nausea, diarrhea/loose stools, insomnia, drowsiness, dry mouth, fatigue, dizziness, increased sweating, tremor, dyspepsia, decreased libido, ejaculation failure. Serious side effects may include: serotonin syndrome, abnormal bleeding, angle-closure glaucoma, hyponatremia, manic episodes, seizures, QT prolongation. Sexual dysfunction (anorgasmia, erectile dysfunction) is frequently underreported.
Drug interaction
Potent inhibitors of CYP2C19 (e.g., fluconazole, fluvoxamine) may increase sertraline levels. CYP2D6 inhibitors may increase levels of co-administered drugs metabolized by CYP2D6. Serotonin syndrome risk with other serotonergic drugs (tramadol, triptans, linezolid). Increased bleeding risk with anticoagulants, antiplatelets, and NSAIDs. May increase levels of tricyclic antidepressants, phenytoin, and warfarin. Use with caution with drugs that prolong QT interval.
Missed dose
If a dose is missed, take it as soon as remembered unless it is close to the next scheduled dose. Do not double the dose to make up for a missed one. Maintain regular dosing schedule to ensure stable plasma concentrations.
Overdose
Symptoms may include serotonin syndrome, drowsiness, nausea, vomiting, tachycardia, dizziness, agitation, tremor. Fatalities have been reported with mixed overdoses (especially with other drugs). No specific antidote exists; provide supportive care and symptomatic treatment. Gastric lavage with activated charcoal may be considered if presented early. Monitor ECG for QT prolongation.
Storage
Store at 20–25°C (68–77°F); excursions permitted to 15–30°C (59–86°F). Keep tightly closed in original container. Protect from light and moisture. Keep out of reach of children and pets. Oral concentrate must be diluted before use and may be stored for up to 6 weeks after dilution.
Disclaimer
This information is for educational purposes and does not replace professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider before starting, changing, or discontinuing any medication. Individual response to therapy may vary. Not all uses, precautions, or interactions are listed here.
Reviews
Clinical trials and meta-analyses consistently demonstrate Zoloft’s efficacy in reducing Hamilton Depression Rating Scale (HAM-D) scores by approximately 50% in responsive patients. It is regarded as a well-tolerated SSRI with a lower discontinuation rate due to adverse events compared to some older antidepressants. Many clinicians appreciate its flexibility in dosing and broad spectrum of action across depressive and anxiety disorders. Long-term studies support its use in maintenance therapy, showing significant relapse prevention benefits over placebo.