Sertraline - Drug Monograph

Introduction

Sertraline is a selective serotonin reuptake inhibitor (SSRI) antidepressant medication widely prescribed for the treatment of various psychiatric disorders. First approved by the FDA in 1991, sertraline has become one of the most commonly prescribed antidepressants worldwide due to its established efficacy, generally favorable side effect profile, and broad range of approved indications.

Mechanism of Action

Sertraline exerts its therapeutic effects primarily through potent inhibition of serotonin reuptake at the presynaptic neuronal membrane. The drug selectively blocks the serotonin transporter (SERT), increasing synaptic concentrations of serotonin in the central nervous system. This enhanced serotonergic activity is believed to mediate its antidepressant and anxiolytic effects. Sertraline has minimal effects on norepinephrine and dopamine reuptake and shows very low affinity for muscarinic, histaminergic, and adrenergic receptors.

Indications

• Major depressive disorder (MDD) in adults and pediatric patients (ages 6-17)
• Obsessive-compulsive disorder (OCD) in adults and pediatric patients (ages 6-17)
• Panic disorder with or without agoraphobia
• Social anxiety disorder (social phobia)
• Post-traumatic stress disorder (PTSD)
• Premenstrual dysphoric disorder (PMDD)

Dosage and Administration

• Depression/OCD: 50 mg once daily
• Panic/PTSD/Social Anxiety: 25 mg once daily
• PMDD: 50 mg daily (either throughout menstrual cycle or luteal phase only)

• Hepatic impairment: Use lower doses or less frequent dosing
• Geriatric patients: Consider lower starting doses (25 mg daily)
• Pediatric patients (6-17 years): Start with 25 mg daily

Pharmacokinetics

Contraindications

• Hypersensitivity to sertraline or any component of the formulation
• Concomitant use with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI therapy
• Concomitant use with pimozide
• Use of MAOIs intended to treat psychiatric disorders within 14 days of stopping sertraline

Warnings and Precautions

• Serotonin syndrome: Risk particularly with concomitant serotonergic drugs
• Activation of mania/hypomania: Screen for bipolar disorder
• Seizures: Use caution in patients with seizure disorders
• Abnormal bleeding: SSRIs may increase risk of bleeding events
• SIADH/hyponatremia: Monitor sodium levels, particularly in elderly patients
• Discontinuation syndrome: Taper gradually when discontinuing treatment
• QTc prolongation: Monitor in patients with risk factors for QTc prolongation

Drug Interactions

• MAOIs: Risk of serotonin syndrome (contraindicated)
• Other serotonergic agents: Increased risk of serotonin syndrome
• Warfarin: Increased anticoagulant effect (monitor INR)
• Drugs metabolized by CYP2D6: Sertraline may inhibit metabolism of substrates
• Pimozide: Increased risk of QTc prolongation (contraindicated)
• NSAIDs/aspirin: Increased bleeding risk

• CYP2B6, CYP2C9, CYP2C19, CYP3A4 substrates: Sertraline may inhibit metabolism
• Lithium: Enhanced serotonergic effects
• Triptans: Increased serotonergic effects

Adverse Effects

• Nausea (26%)
• Diarrhea (18%)
• Insomnia (16%)
• Dry mouth (14%)
• Fatigue (12%)
• Dizziness (12%)
• Increased sweating (8%)

• Serotonin syndrome
• Suicidal ideation/behavior
• Seizures
• Mania/hypomania
• Hyponatremia/SIADH
• Abnormal bleeding
• Angle-closure glaucoma
• QTc prolongation

Monitoring Parameters

• Mental status and suicidal ideation: Particularly during initial treatment and dose adjustments
• Therapeutic response: Regular assessment of target symptoms
• Adverse effects: Monitor for emergence of side effects
• Electrolytes: Sodium levels in elderly patients and those on diuretics
• Bleeding parameters: In patients on anticoagulants or with bleeding tendencies
• Liver function: Periodic monitoring in patients with hepatic impairment
• Weight: Monitor for significant changes
• Sexual function: Assess for sexual side effects

Patient Education

• Take medication at the same time each day, preferably in the morning
• Do not abruptly discontinue medication without medical supervision
• Therapeutic effects may take 4-6 weeks to become apparent
• Report any worsening depression, suicidal thoughts, or unusual behavior changes
• Avoid alcohol consumption during treatment
• Use caution when operating machinery until effects are known
• Inform all healthcare providers about sertraline use, particularly before surgical procedures
• Use effective contraception as sertraline may cause fetal harm
• Report any signs of serotonin syndrome (agitation, hallucinations, fever, sweating)
• Notify provider if pregnancy is planned or occurs

References

1. FDA Prescribing Information: Zoloft (sertraline hydrochloride) 2. Stahl SM. Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 4th ed. Cambridge University Press; 2013. 3. Hirsch M, Birnbaum RJ. Selective serotonin reuptake inhibitors: Pharmacology, administration, and side effects. In: UpToDate; 2023. 4. Kennedy SH, Lam RW, McIntyre RS, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder. Can J Psychiatry. 2016;61(9):540-560. 5. Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018;391(10128):1357-1366. 6. Hiemke C, Bergemann N, Clement HW, et al. Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017. Pharmacopsychiatry. 2018;51(1-02):9-62.