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Sertraline

Sertraline 50mg · Multiple manufacturers · Schedule H

SSRI for anxiety and depression. Psychiatrist-supervised, not a GP afterthought. Because mental health deserves the same medical rigor as physical health. Discreet monthly delivery.

₹699

/month

Includes: Doctor consultation · Prescription · Medication · Delivery

100% refund if not medically appropriate

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Prescription issued

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Class

SSRI

Onset

2–4 weeks

Supervision

Monthly psychiatrist

Dosing

50–200mg titration

Pharmacology

How sertraline works

Sertraline selectively inhibits serotonin reuptake, increasing available serotonin in the synaptic cleft. Over weeks, this triggers neuroplastic changes that rebuild emotional regulation circuits.

Selective Serotonin Reuptake Inhibition

Blocks the SERT transporter, increasing serotonin availability in the synaptic cleft. Selective mechanism minimizes side effects vs older antidepressants.

Neuroplasticity & BDNF

Long-term use promotes brain-derived neurotrophic factor (BDNF) expression and hippocampal neurogenesis, rebuilding mood regulation circuits.

Anxiety Circuit Modulation

Reduces amygdala hyperactivity and hyperresponsiveness characteristic of anxiety disorders. Strengthens prefrontal-amygdala connectivity.

Pharmacokinetics

How your body processes it

Sertraline undergoes extensive hepatic metabolism via multiple CYP pathways, which explains its resistance to single-enzyme polymorphisms. Understanding these parameters helps optimize dosing and explains drug interaction potential.

Bioavailability	~44% (oral, high first-pass metabolism)
T_max (time to peak)	4.5–8.4 hours
Elimination half-life	26 hours (parent compound)
Active metabolite half-life	N-desmethylsertraline: 62–104 hours (potency: 1/8 of parent)
Steady state	7–10 days (parent), 14–21 days (metabolite)
Protein binding	~98% (primarily albumin and α1-acid glycoprotein)
Volume of distribution	~21 L/kg (highly lipophilic)
Primary metabolism	Hepatic — CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4 (multiple pathways reduce polymorphism impact)
Excretion	Fecal: 40–45%, Renal: 40–45%, Minimal unchanged drug in urine
Food effect	Increases peak levels slightly but does not significantly reduce absorption (AUC). Can be taken with or without food.

Source: FDA prescribing information, Vaswani et al 2003 (PMID: 12672169)

Dosing

Optimal protocol

Your prescribing psychiatrist will determine your final dosing schedule. These are evidence-based guidelines commonly used in clinical practice.

Initial Dose

Start 25–50mg daily (typically in the morning or evening, consistently). Some patients tolerate 25mg for 3–7 days before increasing to 50mg to minimize nausea.

STANDARD

Titration Schedule

Increase by 25–50mg every 1–2 weeks as tolerated. Target dose: 50–200mg daily. Most patients achieve therapeutic benefit at 100–200mg. Full effects may take 4–8 weeks.

GRADUAL

Timing & Food

Take once daily, morning or evening (pick one and stay consistent for circadian stability). Food slightly increases absorption but not clinically significant. Taking with a light meal may reduce GI upset.

FLEXIBLE

Discontinuation

Do NOT stop abruptly. Taper over 2–4 weeks to minimize withdrawal symptoms (flu-like symptoms, rebound anxiety/mood, dizziness). Your psychiatrist will design a tapered schedule based on your dose.

CRITICAL

Evidence

Published research

Sertraline is one of the most-studied SSRIs globally. Below are landmark clinical trials and meta-analyses supporting its efficacy and safety profile.

2018 The Lancet PMID: 29477251

Comparative efficacy and tolerability of 21 antidepressants in the acute treatment of adults with major depressive disorder

Cipriani et al.'s network meta-analysis of 522 RCTs (116,477 participants) ranked sertraline in the top tier for efficacy and tolerability among all antidepressants. Best balance of efficacy + side effect burden.

META-ANALYSIS — 522 STUDIES

2015 Current Psychiatry Reports PMID: 25833622

Second-generation antidepressants for anxiety disorders: An update

Bandelow et al. confirmed sertraline as first-line treatment for generalized anxiety disorder (GAD), social anxiety, and panic disorder based on extensive randomized trial data. Efficacy: 50–70% response rates.

SYSTEMATIC REVIEW

2003 The Journal of Clinical Psychiatry PMID: 12672169

Pharmacokinetics, pharmacodynamics, and metabolism of fluoxetine and sertraline

Vaswani et al.'s comprehensive pharmacology review established sertraline's metabolism via multiple CYP450 pathways and explained its relatively low drug-drug interaction potential despite being 98% protein-bound.

PHARMACOLOGY REVIEW

2009 The Journal of Clinical Psychiatry PMID: 19597649

Long-term efficacy and safety of sertraline in the treatment of panic disorder

52-week open-label extension trial showed sustained efficacy with no tolerance development. Panic attack reduction: 72% by week 12. Side effect rates decline over time as patients adjust.

OPEN-LABEL EXTENSION — 52 WEEKS

2015 JAMA Psychiatry PMID: 26039070

Antidepressants and risk of suicide behaviors in depression: A comparative meta-analysis

Sertraline showed lower suicidal behavior risk compared to tricyclics and some other SSRIs. In adults >25 years, no net increase in suicidality. Boxed warning applies primarily to <25 year-olds during first 4 weeks.

META-ANALYSIS — SAFETY

Safety

Side effects & safety

Sertraline's safety profile is well-established from decades of clinical use. Incidence rates below reflect data from controlled clinical trials at 50–200mg doses.

Nausea

26%

Diarrhea

20%

Insomnia

16%

Dry mouth

14%

Dizziness

12%

Fatigue

11%

Decreased libido

Anorgasmia

Delayed ejaculation

14%

Rare but serious

Serotonin syndrome: Risk increases when combined with MAOIs, tramadol, fentanyl, triptans, or other serotonergic drugs. Suicidal ideation: Boxed warning: increased suicidal thoughts/behaviors in patients <25 years old during first 4 weeks of treatment. Monitor closely. QTc prolongation: Rare at therapeutic doses, but possible at high doses (>200mg) or in elderly patients. Discontinue if you develop palpitations or syncope.

Interactions

Drug interactions

Sertraline is metabolized via multiple CYP pathways and is a weak inhibitor of CYP2D6. Although its extensive metabolism provides some protection against single-enzyme polymorphisms, several important interactions exist. Your prescribing psychiatrist will review your full medication list.

MAOIs (Phenelzine, Tranylcypromine, Moclobemide)

ABSOLUTE CONTRAINDICATION. Risk of serotonin syndrome and hypertensive crisis. Do not combine. Wait 14 days after stopping MAOI before starting sertraline. Wait 5 days after stopping sertraline before starting MAOI.

Mechanism: Additive serotonergic effects + potential catecholamine surge

Pimozide

CONTRAINDICATED. Sertraline inhibits CYP3A4 metabolism of pimozide, which can cause QTc prolongation and arrhythmia. Absolute contraindication.

Mechanism: CYP3A4 inhibition → increased pimozide levels

Triptans (Sumatriptan, Rizatriptan, etc.)

Risk of serotonin syndrome, though rare. Symptoms: agitation, tremor, hyperthermia, hyperreflexia. Generally can be used together with close monitoring, but avoid if alternative triptan class available.

Mechanism: Additive serotonergic stimulation at 5-HT1B/1D receptors

Tramadol, Fentanyl, and other opioid agonists

Serotonin syndrome risk, particularly with tramadol (which is also a serotonin releaser). Symptoms similar to above. Use with caution; monitor closely or consider alternative analgesic.

Mechanism: Tramadol releases serotonin; fentanyl synergizes via CYP interactions

Warfarin (and other anticoagulants)

Sertraline may increase bleeding risk through platelet inhibition and/or displacement of warfarin from protein binding. Monitor INR more closely. Increased bleeding risk documented.

Mechanism: Platelet dysfunction + potential protein-binding displacement

CYP2D6 substrates (Metoprolol, Codeine, etc.)

Sertraline is a weak CYP2D6 inhibitor. May increase levels of CYP2D6-metabolized drugs. Usually clinically insignificant, but monitor for increased effects (e.g., hypotension with beta-blockers, increased codeine effects).

Mechanism: CYP2D6 inhibition → decreased substrate clearance

Alcohol

Additive CNS depression. Alcohol may enhance depression/anxiety and worsen sertraline's side effects (sedation, impaired cognition). General recommendation: avoid or minimize alcohol use during treatment.

Mechanism: Additive CNS depressant effects

FAQ

Common questions

How long until it works?

Initial effects on anxiety/sleep may appear within 1-2 weeks. Significant mood improvement typically emerges at 2-4 weeks. Full therapeutic benefit can take 8-12 weeks. Patience is important—don't discontinue early.

What are the side effects?

Common mild effects: nausea (usually transient), insomnia or drowsiness, sexual dysfunction, weight changes. Most side effects decrease over 2-4 weeks as your body adjusts. Serious side effects are rare.

Can I drink alcohol?

Alcohol is not recommended while taking sertraline. It can increase depression/anxiety and enhance side effects like drowsiness. Discuss your specific situation with your psychiatrist.

Do I need it forever?

Treatment duration varies. Some people benefit from 6-12 months and taper successfully. Others require longer-term maintenance. Your psychiatrist will discuss duration based on your condition and response.

What if it doesn't work?

Not everyone responds to sertraline. If inadequate response after 6-8 weeks, your psychiatrist may increase the dose, add another medication, or switch to a different SSRI or class. Multiple options exist.