- USES: Sertraline is used for depressive disorders, panic attacks, anxiety, obsessive-compulsive disorders and posttraumatic stress disorders. EPIDEMIOLOGY: Sertraline overdose is fairly common, but only rarely results in serious toxicity. However, deaths have occasionally been reported. PHARMACOLOGY: It is a selective serotonin reuptake inhibitor (SSRI). TOXICOLOGY: Typically, sertraline overdose is mainly associated with CNS depression. Seizures have rarely been reported. Serotonergic toxicity, especially after congestions with other serotonergic agents (MAO inhibitors, serotonin releasers, and other serotonin reuptake inhibitors) may be observed. QTc prolongation, but not torsade de pointes has been reported. MILD TO MODERATE TOXICITY: Somnolence, dizziness, agitation, nausea, vomiting, constipation, diarrhea, tachycardia, palpitations, hypertension, mydriasis, elevated liver enzymes, and cutaneous vasodilation. SEVERE TOXICITY: Marked CNS depression. Serotonergic toxicity, such as hyperreflexia, clonus, altered mental status, or hemodynamic instability may be seen, usually when sertraline is taken in combination with other serotonergic agents, but serotonin syndrome has been reported after sertraline overdose. Seizures have been reported. Hyponatremia secondary to SIADH has been reported following overdose and has been severe enough to cause seizures. ADVERSE EFFECTS: Agitation, insomnia, headache, dizziness, somnolence, and fatigue are among the most frequently reported adverse effects of sertraline. Other effects include: NEUROLOGIC/PSYCHIATRIC: Ataxia, incoordination, vertigo, abnormal dreams, aggressive behavior, delusions, hallucinations, emotional lability, paranoia, suicidal ideation, akathisia, tingling, extrapyramidal symptoms, dystonia, exacerbation of tics, mania, and depersonalization, and feelings of panic. CARDIOVASCULAR: Palpitations, chest pain, hypertension, hypotension, edema, peripheral ischemia, syncope, and tachycardia. GASTROINTESTINAL: Nausea, diarrhea, dysphagia, gastritis, glossitis, gum hyperplasia, hiccups, stomatitis, tenesmus, constipation, indigestion, anorexia, flatulence, abdominal pain, increased appetite, eructation, and tongue ulceration. GENITOURINARY: Incontinence, urinary frequency, dysuria, urinary retention, urinary incontinence, dysmenorrhea, intermenstrual bleeding, amenorrhea, menorrhagia, leukorrhea, atrophic vaginitis, gynecomastia, galactorrhea, breast pain, and breast enlargement. and renal pain. OCULAR: Exophthalmos, xerophthalmia, blurred vision, diplopia, photophobia, tearing, conjunctivitis, eye pain, and mydriasis. MUSCULOSKELETAL: Myalgia, arthralgia, and dystonia. RESPIRATORY: Bronchospasm, dyspnea, cough, and hyperventilation. OTHER: Diaphoresis, dermatitis, hyponatremia secondary to SIADH, and elevated liver enzymes.
Range of Toxicity:
- TOXICITY: Expect mild toxicity in sertraline naive patients even at therapeutic dosages. Ingestion of up to 250 mg is not expected to result in more than mild toxicity. SEVERE: Serious toxicity is not expected after an overdose of up to 2 g of sertraline. Complete recovery after an ingestion of 8 g and 13.5 g of sertraline, respectively has been reported, however, in another case, 2.5 g of sertraline was fatal. Adding sertraline to an established therapy with serotonergic agents may lead to serotonin toxicity. THERAPEUTIC DOSE: ADULT: DEPRESSION and PANIC DISORDER: 50 mg orally once daily; may increase the dosage up to a maximal dose of 200 mg daily. ANXIETY: 50 mg orally once daily. POSTTRAUMATIC STRESS DISORDER: 25 mg orally once daily up to 200 mg/day. PEDIATRIC: OBSESSIVE COMPULSIVE DISORDER: Ages 6 to 12 years: Initial dose: 25 mg once daily; and 50 mg once daily in adolescents (ages 13 to 17 years); maximum dose 200 mg daily. The safety and efficacy of sertraline for other conditions in children under 18 years has not been studied.
- Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Primarily supportive care; activated charcoal may be helpful in patients presenting shortly after ingestion. Give benzodiazepines titrated to effect for anxiety and seizures. MANAGEMENT OF SEVERE TOXICITY: Consider activated charcoal if patients present early after ingestion. If significant CNS depression occurs, intubate the patient for airway protection before giving charcoal. Consider intravenous lipid therapy early for patients with ventricular dysrhythmias or hypotension. Give benzodiazepines for seizures. Treat serotonin toxicity with benzodiazepine, and consider cyproheptadine, if symptoms persist. Severe cases may require neuromuscular paralysis.
- Decontamination: PREHOSPITAL: Activated charcoal may be considered if the patient is alert and able to protect their airway. HOSPITAL: Activated charcoal, gastric lavage may be considered if a large ingestion.
- Airway management: Early orotracheal intubation in patients with signs of severe intoxication (CNS depression, seizures, agitation).
- Antidote: There is no specific antidote.
- Fat emulsion: Patients who develop significant cardiovascular toxicity should be treated with intravenous lipids. Administer 1.5 mL/kg of 20% lipid emulsion over 2 to 3 minutes as an IV bolus, followed by an infusion of 0.25 mL/kg/min. If possible, discontinue after 30 to 60 minutes. Longer periods of lipid therapy should be considered if the patient’s hemodynamic stability is dependent on continued lipid infusion.
- Serotonin syndrome: Treat initially with benzodiazepines. Cyproheptadine is sometimes used for moderate cases (ADULT: 12 mg orally then 2 mg every 2 hours until symptoms improve; maximum 24 mg/day. CHILD: 0.25 mg/kg/day divided every 6 hours; maximum dose 12 mg/day). Patients with severe serotonin syndrome (ie, severe hyperthermia, agitation, rigidity, hypertension, tachycardia, acidosis) may require neuromuscular paralysis.
- Monitoring of patient: Monitor vital signs and mental status. Sertraline serum levels are not rapidly available and not helpful in managing overdose. No specific lab work is needed in most patients. Obtain an ECG and institute continuous cardiac monitoring in patients with moderate to severe toxicity (ie, CNS depression, seizures, coma, serotonin toxicity). Monitor serum electrolytes, creatinine phosphokinase and lactate levels in patients with serotonin toxicity, seizures, or coma.
- Enhanced elimination procedure: There is no role for repeat-dose activated charcoal. Hemodialysis is not useful given the large volume of distribution (20 L/kg) and high protein binding (99%).
- Patient disposition: HOME CRITERIA: Asymptomatic or mildly symptomatic (nausea, discrete somnolence, diaphoresis, mydriasis) patients can be managed at home, if the ingestion was inadvertent and 250 mg or less. OBSERVATION CRITERIA: Patients with deliberate ingestions, patients with more than mild symptoms, and those with inadvertent ingestions of more than 250 mg should be referred to a healthcare facility for evaluation and treatment. If symptoms resolve after 6 to 12 hours of observation the patient may be discharged. ADMISSION CRITERIA: Any patients experiencing more than mild effects that do not resolve after 6 to 12 hours of observation should be admitted to the hospital. CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity (ie, CNS depression, seizures, serotonin toxicity), or in whom the diagnosis is unclear.