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Sertraline

From Pharmacopedia
Revision as of 03:31, 14 May 2026 by MDElliottMD (talk | contribs) (Pharmacopedia: add <pharmaInteractions/>)
SSRI, Antidepressant, Anxiolytic
Sertraline
Zoloft, Lustral
Sertraline is a selective serotonin reuptake inhibitor (SSRI) commonly prescribed for depression, anxiety disorders, OCD, PTSD, and panic disorder. In the US, it is one of the most frequently utilized SSRIs at this time.

Experience

👥 No personal reports yet
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Problems

  • Major depressive disorder
  • Generalized anxiety disorder
  • Obsessive-compulsive disorder
  • Post-traumatic stress disorder
  • Panic disorder
  • Premenstrual dysphoric disorder
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Titration strategies

Start 25–50 mg PO daily. Titrate by 25–50 mg every 1–2 weeks based on response. Typical effective dose 50–200 mg/day; max 200 mg/day.

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Effects

  • Improved mood👤 no reports yet⚕️ no reports yet
    Onset typically 2–4 weeks.
  • Anxiolysis👤 no reports yet⚕️ no reports yet
    Onset typically 2–4 weeks.
  • Reduced obsessive thoughts👤 no reports yet⚕️ no reports yet
    Delayed onset; full benefit often takes 4+ weeks.
  • Nausea👤 no reports yet⚕️ no reports yet
    Often improves over the first 1–2 weeks.
  • Diarrhea👤 no reports yet⚕️ no reports yet
  • Sexual dysfunction👤 no reports yet⚕️ no reports yet
    Decreased libido, delayed orgasm, anorgasmia. Can persist long-term in some patients (PSSD).
  • Insomnia👤 no reports yet⚕️ no reports yet
  • Somnolence / sedation👤 no reports yet⚕️ no reports yet
  • Sweating / diaphoresis👤 no reports yet⚕️ no reports yet
  • Serotonin syndrome👤 no reports yet⚕️ no reports yet
    Especially with other serotonergic agents (triptans, tramadol, MAOIs, linezolid).
  • QT prolongation👤 no reports yet⚕️ no reports yet
    Dose-dependent; check ECG in cardiac risk.
  • Hyponatremia / SIADH👤 no reports yet⚕️ no reports yet
    Especially in elderly patients.
  • Bleeding risk👤 no reports yet⚕️ no reports yet
    Particularly with concurrent NSAIDs or anticoagulants.
  • Suicidality👤 no reports yet⚕️ no reports yet
    Black box warning in patients under 25; close monitoring in first 4 weeks.
  • Discontinuation syndrome👤 no reports yet⚕️ no reports yet
    "Brain zaps," dizziness, irritability, flu-like symptoms with abrupt cessation. Taper to avoid.
    Serotonin syndrome (especially with other serotonergic agents), QT prolongation at high doses, hyponatremia (SIADH, esp. elderly), bleeding risk, suicidality warning in young adults, discontinuation syndrome.

+ Add an effect

Pharmacokinetics

Well-absorbed orally, ~44% bioavailability. Metabolized hepatically via CYP3A4/CYP2C19/CYP2D6 to N-desmethylsertraline (less active). Half-life ~26h; steady state in ~1 week.

Pharmacodynamics

Highly selective inhibitor of the serotonin reuptake transporter (SERT). Mild dopamine reuptake inhibition at higher doses. Minimal affinity for muscarinic, histaminic, or adrenergic receptors — hence cleaner adverse effect profile than TCAs.

Interactions

MAOIs (serotonin syndrome — contraindicated), triptans, tramadol, linezolid, lithium, NSAIDs/anticoagulants (bleeding), CYP2D6 substrates.

Pharmacogenomic + mechanism interactions23 edges
Pharmacogenomic guideline recommendationsCPIC and Dutch Pharmacogenetics Working Group clinical guidelines
Phenotype:CYP2C19 ultrarapid metabolizer monitor CPIC A 70 / 100
CPIC rec 8094883 [Strong]: Initiate therapy with recommended starting dose. CPIC pair-level A (CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants) [PMID 25974703, 37032427]
Phenotype:cyp2b6 rm monitor CPIC Strong 70 / 100
CPIC rec 8094940 [Strong]: Initiate therapy with recommended starting dose. CPIC pair-level B (CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants) [PMID 37032427]
Phenotype:cyp2b6 nm monitor CPIC Strong 70 / 100
CPIC rec 8094886 [Strong]: Initiate therapy with recommended starting dose. CPIC pair-level B (CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants) [PMID 37032427]
Phenotype:CYP2C19 rapid metabolizer monitor CPIC A 70 / 100
CPIC rec 8094890 [Strong]: Initiate therapy with recommended starting dose. CPIC pair-level A (CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants) [PMID 25974703, 37032427]
Phenotype:CYP2C19 normal metabolizer monitor CPIC A 70 / 100
CPIC rec 8094897 [Strong]: Initiate therapy with recommended starting dose CPIC pair-level A (CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants) [PMID 25974703, 37032427]
Phenotype:cyp2c19 lpm dose reduce 50 CPIC A 55 / 100
CPIC rec 8094918 [Moderate]: Consider a lower starting dose, slower titration schedule and 50% reduction of standard maintenance dose as compared to CYP2C19 normal metabolizers or select a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19. CPIC pair-level A (CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants) [PMID 25974703, 37032427]
Phenotype:cyp2b6 nm dose reduce 50 CPIC B 55 / 100
CPIC rec 8094921 [Moderate]: Consider a lower starting dose, slower titration schedule and 50% reduction of standard maintenance dose as compared to CYP2C19 normal metabolizers or select a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19. CPIC pair-level B (CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants) [PMID 37032427]
Phenotype:cyp2b6 im dose reduce 50 CPIC B 55 / 100
CPIC rec 8094922 [Moderate]: Consider a lower starting dose, slower titration schedule and 50% reduction of standard maintenance dose as compared to CYP2C19 normal metabolizers or select a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19. CPIC pair-level B (CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants) [PMID 37032427]
Phenotype:CYP2C19 poor metabolizer dose reduce 50 CPIC A 55 / 100
CPIC rec 8094925 [Moderate]: Consider a lower starting dose, slower titration schedule and 50% reduction of standard maintenance dose as compared to CYP2C19 normal metabolizers or select a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19. CPIC pair-level A (CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants) [PMID 25974703, 37032427]
Phenotype:cyp2b6 um monitor CPIC B 45 / 100
CPIC rec 8094898 [Moderate]: Initiate therapy with recommended starting dose. CPIC pair-level B (CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants) [PMID 37032427]
Phenotype:cyp2b6 im monitor CPIC B 45 / 100
CPIC rec 8094887 [Moderate]: Initiate therapy with recommended starting dose. CPIC pair-level B (CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants) [PMID 37032427]
Phenotype:cyp2c19 lim monitor CPIC A 45 / 100
CPIC rec 8094904 [Moderate]: Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose than normal metabolizers. CPIC pair-level A (CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants) [PMID 25974703, 37032427]
Phenotype:CYP2C19 intermediate metabolizer monitor CPIC A 45 / 100
CPIC rec 8094911 [Moderate]: Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose than CYP2C19 normal metabolizers. CPIC pair-level A (CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants) [PMID 25974703, 37032427]
Phenotype:cyp2b6 pm dose reduce 50 CPIC B 30 / 100
CPIC rec 8094909 [Optional]: Consider a lower starting dose, slower titration schedule and 50% reduction of standard maintenance dose as compared to CYP2B6 normal metabolizers CPIC pair-level B (CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants) [PMID 37032427]
Phenotype:cyp2c19 lim dose reduce 50 CPIC A 30 / 100
CPIC rec 8094909 [Optional]: Consider a lower starting dose, slower titration schedule and 50% reduction of standard maintenance dose as compared to CYP2B6 normal metabolizers CPIC pair-level A (CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants) [PMID 25974703, 37032427]
Phenotype:CYP2C19 intermediate metabolizer dose reduce 50 CPIC A 30 / 100
CPIC rec 8094916 [Optional]: Consider a lower starting dose, slower titration schedule and 50% reduction of standard maintenance dose as compared to CYP2B6 normal metabolizers CPIC pair-level A (CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants) [PMID 25974703, 37032427]
Phenotype:cyp2b6 um dose reduce 50 CPIC B 30 / 100
CPIC rec 8094919 [Optional]: Consider a lower starting dose, slower titration schedule and 50% reduction of standard maintenance dose as compared to CYP2C19 normal metabolizers or select a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19. CPIC pair-level B (CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants) [PMID 37032427]
Phenotype:cyp2b6 rm dose reduce 50 CPIC B 30 / 100
CPIC rec 8094920 [Optional]: Consider a lower starting dose, slower titration schedule and 50% reduction of standard maintenance dose as compared to CYP2C19 normal metabolizers or select a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19. CPIC pair-level B (CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants) [PMID 37032427]
Phenotype:cyp2b6 pm dose reduce 25 CPIC B 25 / 100
CPIC rec 8094902 [Optional]: Consider a lower starting dose, slower titration schedule and 25% reduction of standard maintenance dose as compared to CYP2B6 normal metabolizers or select a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2B6. CPIC pair-level B (CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants) [PMID 37032427]
Phenotype:CYP2C19 normal metabolizer dose reduce 25 CPIC A 25 / 100
CPIC rec 8094902 [Optional]: Consider a lower starting dose, slower titration schedule and 25% reduction of standard maintenance dose as compared to CYP2B6 normal metabolizers or select a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2B6. CPIC pair-level A (CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants) [PMID 25974703, 37032427]
Phenotype:cyp2b6 pm monitor CPIC B 20 / 100
CPIC rec 8094888 [Optional]: Initiate therapy with recommended starting dose. CPIC pair-level B (CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants) [PMID 37032427]
Phenotype:cyp2c19 lpm monitor CPIC A 20 / 100
CPIC rec 8094923 [Optional]: Select an alternative antidepressant not primarily metabolized by CYP2C19 or CYP2B6. CPIC pair-level A (CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants) [PMID 25974703, 37032427]
Phenotype:CYP2C19 poor metabolizer monitor CPIC A 20 / 100
CPIC rec 8094930 [Optional]: Select an alternative antidepressant not primarily metabolized by CYP2C19 or CYP2B6. CPIC pair-level A (CYP2D6, CYP2C19, CYP2B6, SLC6A4, HTR2A and Serotonin Reuptake Inhibitor Antidepressants) [PMID 25974703, 37032427]

Patient experience

Fluoxetine via Category:Antidepressants👤 exp n/a/5 outcome n/a (n=1)⚕️ exp 1.0/5 outcome +33.0 (n=1)

Pregnancy and lactation

Category C. SSRIs in third trimester associated with persistent pulmonary hypertension of the newborn (PPHN) and neonatal adaptation syndrome. Risk-benefit decision; sertraline often preferred in pregnancy among SSRIs.

Monitoring

Mood/suicidality (especially first 4 weeks), sodium (elderly), QT in cardiac risk, response and side effects.

Patient counseling

Take with or without food. Effect emerges over 2–4 weeks. Don't stop abruptly — taper to avoid withdrawal. Report serotonin-syndrome symptoms.

Relevant anecdote

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Relevant Literature

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See also

Fluoxetine, Paroxetine, Citalopram, Escitalopram
Structure of Sertraline
Summary
Classes
SSRI, Antidepressant, Anxiolytic
Common uses
+ 4 more uses →
Pharmacy
Pharmacology
Routes
Oral
Onset
2–4 weeks for full effect
Half-life
26 hours (parent); norsertraline 62–104 hours
Bioavailability
~44%
Pregnancy
Category C
Legal status
Rx-only
Purported mechanism
SSRI; weak DRI

Pharmacokinetics

Well-absorbed orally, ~44% bioavailability. Metabolized hepatically via CYP3A4/CYP2C19/CYP2D6 to N-desmethylsertraline (less active). Half-life ~26h; steady state in ~1 week.

Pharmacodynamics

Highly selective inhibitor of the serotonin reuptake transporter (SERT). Mild dopamine reuptake inhibition at higher doses. Minimal affinity for muscarinic, histaminic, or adrenergic receptors — hence cleaner adverse effect profile than TCAs.

Indications

  • Major depressive disorder
  • Generalized anxiety disorder
  • Obsessive-compulsive disorder
  • Post-traumatic stress disorder
  • Panic disorder
  • Premenstrual dysphoric disorder

    Dosing and titration

Start 25–50 mg PO daily. Titrate by 25–50 mg every 1–2 weeks based on response. Typical effective dose 50–200 mg/day; max 200 mg/day.

Effects

Therapeutic: improved mood, reduced anxiety, fewer obsessive thoughts (delayed 2–4 weeks).

Common adverse: nausea, diarrhea, sexual dysfunction, insomnia, somnolence, sweating.

Adverse effects

Serotonin syndrome (especially with other serotonergic agents), QT prolongation at high doses, hyponatremia (SIADH, esp. elderly), bleeding risk, suicidality warning in young adults, discontinuation syndrome.

Contraindications

MAOIs (within 14 days), pimozide, severe hepatic impairment. Caution: bipolar disorder (mood switching risk), seizure disorders.

Interactions

MAOIs (serotonin syndrome — contraindicated), triptans, tramadol, linezolid, lithium, NSAIDs/anticoagulants (bleeding), CYP2D6 substrates.

Pregnancy and lactation

Category C. SSRIs in third trimester associated with persistent pulmonary hypertension of the newborn (PPHN) and neonatal adaptation syndrome. Risk-benefit decision; sertraline often preferred in pregnancy among SSRIs.

Monitoring

Mood/suicidality (especially first 4 weeks), sodium (elderly), QT in cardiac risk, response and side effects.

Patient counseling

Take with or without food. Effect emerges over 2–4 weeks. Don't stop abruptly — taper to avoid withdrawal. Report serotonin-syndrome symptoms.

See also

Fluoxetine, Paroxetine, Citalopram, Escitalopram

Pharmacokinetics

Well-absorbed orally, ~44% bioavailability. Metabolized hepatically via CYP3A4/CYP2C19/CYP2D6 to N-desmethylsertraline (less active). Half-life ~26h; steady state in ~1 week.

Pharmacodynamics

Highly selective inhibitor of the serotonin reuptake transporter (SERT). Mild dopamine reuptake inhibition at higher doses. Minimal affinity for muscarinic, histaminic, or adrenergic receptors — hence cleaner adverse effect profile than TCAs.

Indications

  • Major depressive disorder
  • Generalized anxiety disorder
  • Obsessive-compulsive disorder
  • Post-traumatic stress disorder
  • Panic disorder
  • Premenstrual dysphoric disorder

    Dosing and titration

Start 25–50 mg PO daily. Titrate by 25–50 mg every 1–2 weeks based on response. Typical effective dose 50–200 mg/day; max 200 mg/day.

Effects

Therapeutic: improved mood, reduced anxiety, fewer obsessive thoughts (delayed 2–4 weeks).

Common adverse: nausea, diarrhea, sexual dysfunction, insomnia, somnolence, sweating.

Adverse effects

Serotonin syndrome (especially with other serotonergic agents), QT prolongation at high doses, hyponatremia (SIADH, esp. elderly), bleeding risk, suicidality warning in young adults, discontinuation syndrome.

Contraindications

MAOIs (within 14 days), pimozide, severe hepatic impairment. Caution: bipolar disorder (mood switching risk), seizure disorders.

Interactions

MAOIs (serotonin syndrome — contraindicated), triptans, tramadol, linezolid, lithium, NSAIDs/anticoagulants (bleeding), CYP2D6 substrates.

Pregnancy and lactation

Category C. SSRIs in third trimester associated with persistent pulmonary hypertension of the newborn (PPHN) and neonatal adaptation syndrome. Risk-benefit decision; sertraline often preferred in pregnancy among SSRIs.

Monitoring

Mood/suicidality (especially first 4 weeks), sodium (elderly), QT in cardiac risk, response and side effects.

Patient counseling

Take with or without food. Effect emerges over 2–4 weeks. Don't stop abruptly — taper to avoid withdrawal. Report serotonin-syndrome symptoms.

See also

Fluoxetine, Paroxetine, Citalopram, Escitalopram