Sertraline (Zoloft)

Class

SSRI (Selective Serotonin Reuptake Inhibitor)

Mechanism

Selective serotonin reuptake inhibitor (SERT) with mild dopaminergic activity via dopamine transporter (DAT) inhibition, enhancing serotonergic and dopaminergic neurotransmission.

FDA-Approved Use

Major depressive disorder (MDD), obsessive-compulsive disorder (OCD), panic disorder, posttraumatic stress disorder (PTSD), social anxiety disorder (SoAD), premenstrual dysphoric disorder (PMDD)

Off-Label Use

Generalized anxiety disorder (GAD), binge eating disorder, bulimia nervosa, agitation and aggression in traumatic brain injury (TBI), post-stroke affective lability, post-stroke depression, depression in Parkinson’s disease (PD), depression in dementia

Formulation

Oral tablets and liquid solution (25 mg, 50 mg, 100 mg)

Titration

25–50 mg p.o. daily, titrating as clinically indicated

Dose Range

50–200 mg/day

Kinetics

Half-life ~26 hours; metabolized primarily by CYP3A4, CYP2B6, CYP2C19; steady state in ~7 days

Common AEs

Nausea, diarrhea, tremor, dizziness, insomnia, dry mouth, fatigue, sexual dysfunction

Serious/Rare AEs

Serotonin syndrome, hyponatremia, bleeding risk, withdrawal symptoms on abrupt discontinuation

Monitoring

Monitor for serotonin syndrome symptoms, suicidality, hyponatremia (especially in elderly), and withdrawal symptoms during discontinuation

Black Box Warning

Increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults with MDD and other psychiatric disorders

Considerations

Sertraline may be used in post-stroke depression with relatively low anticholinergic burden. It is preferred in patients with seizure disorders due to fewer CYP450 interactions compared to other SSRIs, reducing the risk of interactions with antiepileptic drugs. Use cautiously in hepatic dysfunction, and consider slower titration in elderly patients or those with multiple comorbidities.