sertraline
Last reviewed 2025-12-28
Reviewed by PsychMed Editorial Team.
Brands: ZOLOFT
Sources updated 2025 • 4 references
General Information
Sertraline (Zoloft) is a first-line SSRI for depression, PTSD, OCD, and anxiety disorders, favored in patients with serious mental illness because of modest interaction liability and metabolic neutrality.
Often paired with antipsychotics to target comorbid anxiety or depressive symptoms without exacerbating weight or prolactin issues.
Common early limitations include gastrointestinal upset, activation, and insomnia.
The contrast view and the Sertraline evidence feed can help highlight activation, discontinuation, and metabolic trade-offs alongside the bipolar disorder hub when evaluating augmentation or switch strategies.
U.S. approvals
- Major depressive disorder (1991)
- Obsessive-compulsive disorder (1996)
- Panic disorder (1996)
- Post-traumatic stress disorder (1999)
- Social anxiety disorder (2003)
Formulations & strengths
- Tablets (sertraline hydrochloride / sertraline HCl) 25 mg, 50 mg, 100 mg; oral concentrate 20 mg/mL (requires dilution prior to ingestion).
Generic availability
- Multiple manufacturers produce generic tablets and oral concentrate.
Low CYP inhibition and once-daily dosing support use alongside antipsychotics; monitor GI tolerability and sodium in older adults.
View labelExactMechanism of Action
Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.
Potent serotonin transporter inhibition with minimal direct activity at other receptors; weak dopamine transporter inhibition at high doses may contribute to activation.
- High-affinity SERT blocker; negligible M1/H1/α1 binding.
Metabolism and Pharmacokinetics
- Peak concentration 4.5–8.4 h post-dose; food increases exposure ~25% but not required.
- Extensively metabolized via CYP2B6/2C19/2C9/3A4/2D6 to weakly active desmethylsertraline.
- Parent half-life ~26 h (metabolite 62–104 h); eliminated mainly in feces with minimal unchanged drug in urine.
Dosing and Administration
- Start 50 mg once daily for major depressive disorder (clinical depression) or anxiety; titrate by 25–50 mg increments every ≥1 week to 100–200 mg/day (max 200 mg/day).
- For PTSD, OCD, or panic disorder, consider 25 mg daily for 1 week before increasing to reduce activation.
- Use lower starting doses or extended titration in hepatic impairment; avoid abrupt discontinuation when possible.
Monitoring & Labs
- Suicidality and psychiatric activation during initiation and dose changes, especially in younger patients and in bipolar-spectrum illness.
- Sodium in older adults or patients on diuretics if symptoms suggest hyponatremia (confusion, fatigue, falls).
- Bleeding/bruising risk when combined with NSAIDs, antiplatelets, or anticoagulants; reinforce early symptom reporting.
- Medication reconciliation when TCAs, antipsychotics, or other serotonergic agents are co-prescribed; anticipate switching washout needs when regimens change.
Sertraline’s most common early barrier is GI upset; reassurance and supportive dosing strategies can prevent premature discontinuation before benefit emerges. Discontinuation symptoms can occur with abrupt stopping; tapering tends to be better tolerated than sudden discontinuation, especially after long-term use.
Adverse Effects
FDA boxed warnings
- Antidepressants increase suicidality risk in children, adolescents, and young adults; monitor during initiation and titration.
Common side effects (≥10%)
- Gastrointestinal upset: Nausea or diarrhea common early; taking with food can improve tolerability.
- Sleep disturbance: Insomnia or somnolence—adjust dosing time based on patient response.
- Sexual dysfunction: Discuss expectations and management strategies up front.
- Tremor/activation: Usually transient; consider slower titration if problematic.
- Headache: Generally self-limited; reassure patients during first weeks.
Other notable effects
- Hyponatremia/SIADH risk in older adults or diuretic users—check sodium when symptomatic and counsel patients to report confusion or falls.
- Serotonin syndrome possible with other serotonergic agents.
- Discontinuation symptoms (dizziness, irritability) possible—taper gradually and coordinate with the compare view when planning cross-tapers.
Interactions
- Moderate CYP2D6/CYP2C19 inhibition—monitor narrow therapeutic index substrates (e.g., TCAs, metoprolol).
- Contraindicated with MAOIs, linezolid, methylene blue; enforce appropriate washout periods.
- Additive bleeding risk with NSAIDs, antiplatelets, anticoagulants; counsel on easy bruising.
Other Useful Information
- Oral concentrate must be diluted in water, ginger ale, lemonade, or orange juice immediately before administration.
- Encourage adherence through first 4–6 weeks before assessing nonresponse.
- Sertraline is commonly used alongside antipsychotics and mood stabilizers because metabolic effects are modest; clarify the target symptoms so augmentation does not become open-ended polypharmacy.
- Taking with food can improve early nausea/diarrhea; dose timing can be individualized (morning for insomnia, evening for sedation) based on tolerability.
- For patients using the oral concentrate, document dilution instructions clearly and confirm understanding; administration errors are a common cause of “nonresponse.”
References
- ZOLOFT (sertraline) prescribing information — DailyMed (2025)
- APA Clinical Practice Guideline for the Treatment of Depression — American Psychiatric Association (2023)Guidelinedepressionclinical
- CANMAT 2024 Clinical Guidelines for Major Depressive Disorder — Canadian Journal of Psychiatry (2024)