Sertraline

Generic Name: Sertraline
Brand Names: Zoloft, Lustral (UK and some Commonwealth countries)
Drug Class: Selective Serotonin Reuptake Inhibitor (SSRI)
Formulations: Oral tablets (25 mg, 50 mg, 100 mg), Oral concentrate solution (20 mg/mL)
Route of Administration: Oral

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Therapeutic Indications and Clinical Use

Sertraline is a widely prescribed SSRI used for the treatment of multiple psychiatric conditions. It is FDA- and EMA-approved for several primary indications and used off-label in others.

Approved Indications:

1. Major Depressive Disorder (MDD) – Adults

2. Obsessive-Compulsive Disorder (OCD) – Adults and children ≥6 years

3. Panic Disorder – Adults

4. Post-Traumatic Stress Disorder (PTSD) – Adults

5. Social Anxiety Disorder (SAD) – Adults

6. Premenstrual Dysphoric Disorder (PMDD) – Adults

Off-Label Uses:

• Generalized Anxiety Disorder (GAD)

• Binge Eating Disorder

• Body Dysmorphic Disorder

• Premature Ejaculation

• Bulimia Nervosa

• Alcohol Use Disorder (as adjunct)

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Mechanism of Action

Sertraline is a selective serotonin reuptake inhibitor (SSRI). It increases serotonin (5-hydroxytryptamine, 5-HT) concentrations in the synaptic cleft by inhibiting its reuptake into presynaptic neurons.

• Primary Action: Inhibits serotonin transporter (SERT)

• Secondary Binding (Weak): Dopamine transporter (DAT), sigma-1 receptors (possible clinical implications in mood regulation)

• Result: Enhanced serotonergic neurotransmission, which improves mood and reduces anxiety and obsessive symptoms

Sertraline does not exhibit significant affinity for muscarinic, histaminergic, or adrenergic receptors, contributing to a relatively favorable side effect profile compared to tricyclic antidepressants.

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Dosing and Administration

Adults:

• Depression and OCD:

  • Starting dose: 50 mg once daily

  • Titration: Increase in 25–50 mg increments at intervals ≥1 week

  • Maximum: 200 mg/day

• Panic Disorder, PTSD, SAD:

  • Start with 25 mg/day, increase to 50 mg/day after one week

  • Adjust based on tolerability and response

• PMDD:

  • Continuous: 50 mg/day throughout cycle

  • Intermittent: 50 mg/day during luteal phase only (last 14 days of menstrual cycle)

  • May increase to 100 mg/day

Pediatrics (OCD):

• 6–12 years: Start with 25 mg/day, max 200 mg/day

• 13–17 years: Start with 50 mg/day, max 200 mg/day

Administration Notes:

• Can be taken with or without food

• For oral concentrate: must be diluted before use (in water, ginger ale, lemon/lime soda, orange juice, or lemonade)

• Dose titration should be done gradually to reduce side effects

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Pharmacokinetics

• Absorption: 100% absorbed orally; significant first-pass effect

• Time to peak plasma level: 4.5–8.4 hours

• Bioavailability: ~44% due to first-pass metabolism

• Protein Binding: ~98%

• Metabolism: Hepatic via CYP2B6, CYP2D6, CYP3A4

• Active Metabolite: Desmethylsertraline (less potent, longer half-life)

• Half-Life:

  • Sertraline: ~26 hours

  • Desmethylsertraline: 62–104 hours

• Excretion: Urine (40–45%), feces (40–45%)

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Contraindications

• Concurrent use with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing an MAOI (risk of serotonin syndrome)

• Concurrent use with pimozide (risk of QT prolongation and arrhythmias)

• Known hypersensitivity to sertraline or its components

• Concomitant use of disulfiram with the oral concentrate (contains alcohol)

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Warnings and Precautions

• Suicidality: Antidepressants increase the risk of suicidal thoughts in children, adolescents, and young adults (boxed warning by FDA)

• Serotonin Syndrome: Risk when combined with serotonergic drugs (e.g., triptans, other SSRIs, SNRIs, tramadol)

• QT Prolongation: Caution in patients with cardiac disease or taking QT-prolonging agents

• Hyponatremia: Especially in elderly; related to SIADH

• Bleeding Risk: SSRIs impair platelet aggregation; increased risk with NSAIDs, aspirin, anticoagulants

• Seizure Risk: Use with caution in patients with seizure disorders

• Mania: Can induce mania/hypomania in patients with bipolar disorder; screen before initiating

• Hepatic Impairment: Reduce dose or frequency in severe hepatic dysfunction

• Discontinuation Syndrome: Taper gradually to avoid withdrawal symptoms (dizziness, insomnia, irritability, headache)

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Adverse Effects

Very Common (≥10%)

• Nausea

• Diarrhea

• Insomnia

• Dry mouth

• Sexual dysfunction (delayed ejaculation, anorgasmia)

• Somnolence

Common (1–10%)

• Tremor

• Dizziness

• Headache

• Increased sweating

• Fatigue

• Agitation

• Anxiety

• Appetite changes

• Weight changes

• Ejaculatory failure

Less Common (<1%) / Serious

• Hyponatremia

• Seizures

• Suicidal ideation

• Serotonin syndrome

• Hepatotoxicity

• QT prolongation and arrhythmias

• Extrapyramidal symptoms (rare)

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Drug Interactions

1. MAO Inhibitors – Contraindicated; risk of serotonin syndrome

2. Pimozide – Contraindicated; increases pimozide levels and QT risk

3. NSAIDs/Anticoagulants – Increased bleeding risk

4. Other serotonergic drugs – Increases serotonin syndrome risk (e.g., triptans, fentanyl, lithium, tramadol)

5. CYP2D6 substrates (e.g., metoprolol, codeine) – May increase plasma concentrations

6. Benzodiazepines (e.g., diazepam) – Possible increased sedation

7. Digoxin – Risk of reduced efficacy or increased toxicity

8. Alcohol – Though not contraindicated, caution is advised due to CNS effects

9. St. John’s Wort – Increases serotonergic effects; avoid concurrent use

10. CYP enzyme inducers/inhibitors – May alter sertraline metabolism (e.g., carbamazepine, erythromycin)

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Monitoring Parameters

• Clinical response: mood, sleep, appetite, energy, suicidal thoughts

• Adverse effects: GI symptoms, sexual dysfunction, agitation

• Suicidal ideation: especially in young adults and during dose changes

• Electrolytes: sodium levels in older adults

• ECG: in patients with risk of QT prolongation

• Liver function tests: in long-term therapy or hepatic risk

• Body weight: monitor for gain/loss

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Pregnancy and Lactation

• Pregnancy Category C (US)

  • Some evidence of risk in late pregnancy (e.g., neonatal adaptation syndrome, persistent pulmonary hypertension of the newborn)

  • Benefits may outweigh risks in moderate/severe depression

• Lactation:

  • Sertraline is one of the SSRIs most studied and considered compatible with breastfeeding

  • Infant plasma levels are low to undetectable

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Discontinuation Strategy

• Avoid abrupt discontinuation

• Taper gradually over several weeks

• Withdrawal symptoms: nausea, dizziness, paresthesia, irritability, insomnia, “electric shock” sensations

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Use in Special Populations

• Elderly: Increased risk of hyponatremia and falls; start at lower dose

• Pediatrics: Approved for OCD only (≥6 years); not approved for pediatric depression in most regions

• Hepatic impairment: Use half of the normal dose

• Renal impairment: No dose adjustment typically required

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Comparative Aspects Among SSRIs

• Half-life: Intermediate (longer than paroxetine, shorter than fluoxetine)

• Sedation: Less than paroxetine, more activating than fluoxetine

• Weight impact: Neutral to mild weight loss in short-term; possible gain long-term

• Sexual dysfunction: High incidence (like all SSRIs)

• Withdrawal risk: Moderate (less than paroxetine but more than fluoxetine)

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Counseling Points for Patients

• May take 1–4 weeks to see initial improvement; full effects may take 6–8 weeks

• Take once daily, preferably at the same time each day

• Do not stop medication abruptly

• Report worsening depression, unusual behavior, or suicidal thoughts immediately

• Avoid alcohol during therapy

• Inform physician of all other medications (including OTC and herbal products)

• Discuss any concerns related to sexual dysfunction, weight changes, or sleep disturbances

• For oral concentrate: dilute correctly and consume immediately

• Avoid hazardous activities until the drug’s effect on the individual is known

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Availability and Regulatory Information

• Prescription-only medication

• Widely available globally in generic form

• Listed on WHO Essential Medicines list

• No controlled substance classification