Sertraline Toxic Dose
The toxic dose of sertraline is not precisely defined, but doses above 200 mg/day are considered maximum therapeutic doses, with reported overdoses ranging from 50 to 8,000 mg (mean 1,579 mg) typically resulting in only minor and short-duration symptoms. 1
Therapeutic Dosing vs. Toxicity
Therapeutic Dosing Range
- Standard therapeutic dosing of sertraline ranges from 50-200 mg/day 2
- 50 mg/day is considered the usual effective therapeutic dose for most patients 3
- For adolescents, the effective dose is typically 50 mg, with a maximum recommended dosage of 200 mg 2
Plasma Concentration Levels
- Therapeutic plasma concentration range for sertraline is 10-50 ng/mL 2, 4
- Dose-related steady-state plasma concentrations:
- 50 mg/day: 12±17 ng/mL
- 100 mg/day: 19±18 ng/mL
- 150 mg/day: 31±29 ng/mL
- 200 mg/day: 29±18 ng/mL 2
Overdose Presentation and Management
Clinical Manifestations of Overdose
- In isolated sertraline overdoses, the most common symptoms are:
- Tremor
- Lethargy
- Nausea 1
- Less common findings include:
- Agitation
- Confusion
- Vomiting 1
Important Observations from Overdose Studies
- In a prospective study of 40 sertraline overdoses:
- 17 patients took sertraline alone, and 10 of these had no signs or symptoms
- No significant morbidity was observed in isolated sertraline overdoses
- Mean ingested amount was 1,579 mg (range 50-8,000 mg)
- Mean presentation time was 3.0 hours after ingestion 1
Management of Overdose
- Treatment typically includes:
- Gastric lavage
- Activated charcoal
- Observation 1
- Most patients can be observed for 4-24 hours without adverse outcomes 1
Safety Profile and Considerations
Pharmacokinetic Factors
- Sertraline has an elimination half-life of approximately 24-26 hours 5, 6
- It follows first-order kinetics and is highly protein-bound 7
- Metabolism is primarily by demethylation to an inactive metabolite 6
Safety Advantages
- Sertraline has a wide therapeutic index compared to tricyclic antidepressants 5
- It has minimal anticholinergic activity and is essentially devoid of cardiovascular effects 5
- Deaths from sertraline alone are rare, though they have been reported following very large ingestions 2
Special Populations and Precautions
Pediatric and Adolescent Considerations
- All SSRIs, including sertraline, carry a boxed warning for suicidal thinking and behavior through age 24 years 2
- Close monitoring for suicidality is recommended by the FDA, especially in the first months of treatment and following dosage adjustments 2
- Behavioral activation/agitation may occur early in SSRI treatment, with dose increases, or with concomitant administration of drugs that inhibit SSRI metabolism 2
Drug Interactions
- Avoid combining with MAOIs due to risk of serotonin syndrome 2
- Caution is needed when sertraline is given with drugs having a low therapeutic ratio, such as corticosteroids, oral hypoglycemic agents, and warfarin 6
Clinical Implications
- Despite the relatively benign nature of most sertraline overdoses, any suspected overdose should be treated as a medical emergency
- The margin of safety of SSRIs in overdose is greater than for other antidepressants, but deaths have been reported following very large ingestions 2
- Sertraline overdoses are commonly taken with other medications or alcohol, which may significantly increase toxicity risk 1
While sertraline has a relatively wide therapeutic window compared to older antidepressants, any suspected overdose should be promptly evaluated in an emergency setting due to the potential for serious adverse effects in very large ingestions or when combined with other substances.