Dosing and uses of Zoloft (sertraline)
Adult dosage forms and strengths
tablet
- 25mg
- 50mg
- 100mg
oral concentrate
- 20mg/mL
Major Depressive Disorder
Initial: 50 mg PO qDay
May increase by 25 mg at 1-week intervals; not to exceed 200 mg qDay
Obsessive-Compulsive Disorder
Initial: 50 mg PO qDay
May increase by 25 mg at 1-week intervals; not to exceed 200 mg qDay
Panic Disorder, Posttraumatic Stress Disorder
Initial: 25 mg PO qDay
May increase by 25 mg at 1-week intervals; not to exceed 200 mg qDay
Social Anxiety Disorder
Initial: 25 mg PO qDay
May increase by 25 mg at 1-week intervals not to exceed 200 mg qDay
Premenstrual Dysphoric Disorder
Initial: 50 mg qDay PO given continuously throughout menstrual cycle or given during luteal phase only
May increase by 50 mg at the onset of each new menstrual cycle; no more than 150 mg qDay when administered continuously or 100 mg qDay when administered during luteal phase only
Pruritus (Off-label)
25-100 mg daily for up to 5 years; 75-100 mg doses found to be most effective
Dosing Modifications
Renal impairment: Dose adjustment not necessary
Hepatic impairment: Not studied; use caution; administer lower or less frequent dosing
Discontinuation of therapy: Gradually taper dose over at least several weeks to limit possibilities of withdrawal symptoms and detection of re-emerging symptoms; consider half-life of antidepressant when tapering; shorter half-life may require longer and more conservative dose reductions
Administration
Oral solution: Measure with calibrated dropper; dilute in water or juice; slight haze normaL
Pediatric dosage forms and strengths
tablet
- 25mg
- 50mg
- 100mg
oral concentrate
- 20mg/mL
Obsessive-Compulsive Disorder
<6 years: Safety and efficacy not established
6-12 years: 25 mg PO qDay initially
12-17 years: 50 mg PO qDay initially
May increase by 50 mg qDay at 1-week intervals to no more than 200 mg qDay; give qHS if somnolence experienced
Geriatric dosage forms and strengths
The elderly are prone to SSRI/SNRI-induced hyponatremia; monitor closely
Major Depressive Disorder
25 mg PO qDay initially; may increase by 25 mg every 2-3 days; not to exceed 200 mg qDay
Alzheimer dementia related depression: Start at 12.5 mg/day and titrate every 1-2 weeks to response; not to exceed 150-200 mg
Zoloft (sertraline) adverse (side) effects
>10%
Diarrhea (13-24%)
Nausea (13-30%)
Headache (20-25%)
Insomnia (12-28%)
Ejaculation disorder (7-19%)
Dizziness (6-17%)
Dry mouth (6-16%)
Fatigue (10-16%)
Drowsiness (2-15%)
1-10%
Agitation (1-6%)
Anorexia (5-10%)
Anxiety (4%)
Constipation (5-8%)
Paresthesia (2%)
Impotence (5-10%)
Sweating (< 1%)
Malaise (7-9%)
Vomiting (4%)
Pain (3-6%)
Frequency not defined
Asthenia
Back pain
Chest pain
Hypoesthesia
Increased appetite
Myalgia
Palpitations
Rhinitis
Tinnitus
Weight gain
Yawning
Warnings
Black box warnings
In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 years) taking antidepressants for major depressive disorders and other psychiatric illnesses
This increase was not seen in patients over age 24 years; a slight decrease in suicidal thinking was seen in adults over age 65 years
In children and young adults, risks must be weighed against the benefits of taking antidepressants
Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies; this should be done during initial 1-2 months of therapy and dosage adjustments
The patient’s family should communicate any abrupt changes in behavior to the healthcare provider
Worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of therapy
This drug is not approved for use in pediatric patients for major depressive disorder but it is approved for obsessive compulsive disorder in children >6 years
Not approved for the treatment of bipolar depression
Contraindications
Hypersensitivity
Do not use disulfiram concomitantly with oral solution due to alcohol in preparation
Concomitant pimozide: Risk of long QT syndrome
Coadministration with serotonergic drugs
- Do not use MAOIs concomitantly or within 14 days before initiating sertraline or within 14 days after discontinuing sertraline
- Reactions to concomitant administration with MAO inhibitors include tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia with features resembling neuroleptic malignant syndrome, seizures, rigidity, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma
- Starting sertraline in a patient who is being treated with linezolid or IV methylene blue is contraindicated because of an increased risk of serotonin syndrome
- If linezolid or IV methylene blue must be administered, discontinue SSRI immediately and monitor for CNS toxicity; may resume 24 hr after last linezolid or methylene blue dose, or after 2 weeks of monitoring (5 weeks for fluoxetine), whichever comes first
Cautions
Clinical worsening and suicide ideation may occur despite medication
Use caution in patients with seizure disorders
May worsen mania symptoms or precipitate mania in patients with bipolar disorder
Increases risk of hyponatremia and impairment of cognitive/motor functions in the elderly
Increases risk of bleeding in patients taking anticoagulants/antiplatelets concomitantly
Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy
Pregnancy: Conflicting evidence regarding use of SSRIs during pregnancy and increased risk of persistent pulmonary hypertension of the newborn (see Pregnancy)
In neonates exposed to SNRIs/SSRIs late in third trimester: Risk of complications such as feeding difficulties, irritability, and respiratory problems
Avoid abrupt withdrawaL
Bone fractures reported with antidepressant therapy; consider the possibility if patient presents with bone pain, bruising, or point of tenderness
Coadministration with other drugs that enhance the effects of serotonergic neurotransmission (eg, tryptophan, fenfluramine, fentanyl, 5-HT agonists, St. John’s Wort) should be undertaken with caution and avoided whenever possible due to the potential for pharmacodynamic interaction (see Contraindications)
May cause false-positive urine immunoassay screening tests for benzodiazepines
SSRIs and SNRIs are associated with development of SIADH; hyponatremia reported
Pregnancy and lactation
Pregnancy
Pregnancy category: C
Use late in the third trimester associated with complications in newborns and may require prolonged hospitalization, respiratory support, and tube feeding
Persistent pulmonary hypertension of the newborn
- Potential risk of persistent pulmonary hypertension of the newborn (PPHN) when used during pregnancy
- Initial public health advisory in 2006 was based on a single published study; since then, there have been conflicting findings from new studies, making it unclear whether use of SSRIs during pregnancy can cause PPHN
- FDA has reviewed the additional new study results and has concluded that, given the conflicting results from different studies, it is premature to reach any conclusion about a possible link between SSRI use in pregnancy and PPHN
- FDA recommendation: FDA advises healthcare professionals not to alter their current clinical practice of treating depression during pregnancy and to report any adverse events to the FDA MedWatch program
- A meta-analysis of 7 observational studies, found exposure to SSRIs in late pregnancy (ie, >20 weeks' gestation) more than doubled the risk of PPHN that could not be explained by other etiologies (eg, congenital malformations, meconium aspiration) (BMJ 2014;348:f6932)
Lactation
Distributed into milk; use caution (AAP states effect on nursing infants is unknown but may be of concern)
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Zoloft (sertraline)
Mechanism of action
Selective serotonin reuptake inhibitor; little or no affinity for alpha-adrenergic histamine or cholinergic receptor
Absorption
Bioavailability: Absorption increased by food
Peak plasma time: 4.5-8.4 hr
Distribution
Protein bound: 98%
Metabolism
Metabolized by hepatic cytochrome P450 enzymes
Metabolites: Minimal potency
Elimination
Half-life: 26 hr
Dialyzable: No
Excretion: Urine (12-14% unchanged); feces (40-45%)
Pharmacogenomics
Several SSRIs (eg, fluoxetine, fluvoxamine, paroxetine, sertraline) are metabolized by CYP2D6
CYP2D6 is involved in the metabolism of approximately 20% of drugs in clinical use and displays large individual-to-individual variability in activity due to genetic polymorphisms
More than 80 CYP2D6 variant alleles have been identified; however, 4 of the most prevalent alleles, CYP2D6*3, *4, *5, and *6, account for 93-97% of CYP2D6 poor metabolizers
CYP2D6*4, the most common variant (~25% frequency in whites), causes a splicing defect; CYP2D6*3 (2.7% frequency) causes a frameshift mutation; and CYP3D6*5 (2.6%) is an entire deletion of the CYP2D6 gene; individuals homozygous for these alleles have no CYP2D6 activity
The impact of CYP2D6 activity is further complicated in some SSRIs (eg, fluoxetine, fluvoxamine, paroxetine, sertraline) because in addition to being substrates for CYP2D6, they are also known to moderately inhibit CYP2D6 activity
Genetic testing laboratories
- Genotyping tests for CYP2D6 variants are commercially available through the following companies
- Applied Biosystems (https://www.appliedbiosystems.com/)
- GenPath Diagnostics (https://www.genpathdiagnostics.com/)
