Version November 2024
Antidepressants increased the risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors.
Dosage guidance:
Dosage form information: Two solid oral dosage forms are available (tablets and capsules); the capsules are available in two strengths (150 mg and 200 mg) and should not be used to initiate sertraline therapy. Capsules may be considered in patients who have received sertraline 100 or 125 mg daily for at least 1 week.
Depression: Limited data available:
Note: In the management of pediatric depression in children and adolescents, if pharmacotherapy deemed necessary with/without psychotherapeutic interventions, a selective serotonin reuptake inhibitor (SSRI) is recommended first line; sertraline is not typically recommended first line due to the availability of 2 SSRIs with FDA-approval for pediatric depression (fluoxetine, escitalopram); in practice, sertraline is often an alternative or subsequent medication early in pediatric depression treatment (Ref).
Children ≥6 years and Adolescents ≤17 years: Oral: Initial: 25 mg once daily; titrate in 12.5 to 25 mg increments at ≥1-week intervals; usual effective dose: 50 mg once daily; maximum daily dose: 200 mg/day; consider lower initial dose of 12.5 mg in patients who are sensitive to the higher 25 mg dose. For acute treatment in an inpatient setting and as an initial therapy, a more rapid dose titration may be considered with close monitoring (Ref).
Obsessive-compulsive disorder (OCD):
Note: In the management of OCD in children and adolescents, if pharmacotherapy deemed necessary it should be in combination with cognitive behavior therapy (CBT) and an SSRI should be used first line; a preferred agent has not been identified (Ref).
Children 6 to 12 years: Oral: Initial: 25 mg once daily; titrate dose upwards if clinically needed; increase by 25 to 50 mg/day increments at intervals of at least 1 week; range: 25 to 200 mg/day; maximum daily dose: 200 mg/day.
Adolescents 13 to 17 years: Oral: Initial: 50 mg once daily; titrate dose upwards if clinically needed; increase by 50 mg/day increments at intervals of at least 1 week; range: 25 to 200 mg/day; maximum daily dose: 200 mg/day.
When combined with CBT, the 12-week Pediatric OCD Treatment Study (POTS) Randomized Controlled Trial (Ref), which included 97 patients (age range: 7 to 17 years), reported mean highest daily sertraline doses of 133 ± 64 mg in the sertraline/CBT group, 170 ± 33 mg in the sertraline-only group, and 176 ± 40 mg for the group who received placebo equivalents; median doses were 150, 200, and 200 mg, respectively. Dosing used a fixed flexible upward titration from 25 mg/day to 200 mg/day over 6 weeks, after which the dosage could be adjusted based on adverse effects only.
Discontinuation of therapy: Consider planning antidepressant discontinuation for lower-stress times, recognizing non-illness-related factors could cause stress or anxiety and be misattributed to antidepressant discontinuation (Ref). Upon discontinuation of antidepressant therapy, gradually taper the dose to minimize the incidence of discontinuation syndromes (withdrawal) and allow for the detection of reemerging disease state symptoms (eg, relapse). Evidence supporting ideal taper rates after illness remission is limited. APA and NICE guidelines suggest tapering therapy over at least several weeks with consideration to the half-life of the antidepressant; antidepressants with a shorter half-life may need to be tapered more conservatively. After long-term (years) antidepressant treatment, WFSBP guidelines recommend tapering over 4 to 6 months, with close monitoring during and for 6 months after discontinuation. If intolerable discontinuation symptoms occur following a dose reduction, consider resuming the previously prescribed dose and/or decrease dose at a more gradual rate (Ref).
Switching antidepressants: Evidence for ideal antidepressant switching strategies in pediatric patients is sparse; strategies described in pediatric guidelines include a conservative approach (tapering and discontinuing the first SSRI before adding the second) and cross-titration (gradually discontinuing the first antidepressant while at the same time gradually increasing the new antidepressant). While consensus does not exist regarding which approach to utilize, it is important to note that the conservative approach runs the risk for exacerbation of symptoms or discontinuation syndrome; cross-titration may avoid these risks (Ref). Cross-titration (eg, over 1 to 4 weeks depending upon sensitivity to discontinuation symptoms and adverse effects) is standard for most switches, but is contraindicated when switching to or from a monamine oxidase inhibitors. While not as common of a strategy, a direct switch may be considered when switching to another agent in the same or similar class (eg, when switching between 2 SSRIs), when the antidepressant to be discontinued has been used for <1 week, or when the discontinuation is for adverse effects. When choosing the switch strategy, consider the risk of discontinuation symptoms, potential for drug interactions, other antidepressant properties (eg, half-life, adverse effects, pharmacodynamics), and the degree of symptom control desired (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in manufacturer's labeling; however, sertraline pharmacokinetics does not appear to be affected by renal impairment.
Children ≥6 years and Adolescents: Oral:
Mild impairment: Reduce dose to 50% of usual dose.
Moderate to severe impairment: Use is not recommended.
(For additional information see "Sertraline: Drug information")
Dosage guidance:
Dosing: Some experts suggest a lower starting dose of 12.5 to 25 mg daily and gradual titration in increments of ≤25 mg, particularly in patients with anxiety who are sensitive to antidepressant-associated overstimulation effects (eg, anxiety, insomnia) (Ref).
Dosage form information: Do not initiate treatment with capsules; administer other sertraline products for initial dosage, titration, and doses <150 mg once daily; however, capsules may be initiated in patients who have received sertraline 100 or 125 mg for ≥1 week or sertraline ≥150 mg/day.
Binge eating disorder (off-label use): Oral: Initial: 25 mg once daily after lunch; may increase dose based on response and tolerability in increments of 25 mg every 3 days. Usual dose range: 100 to 200 mg/day. Maximum dose: 200 mg/day (Ref). Based on limited data, some experts recommend doses used for major depressive disorder and slower titrations (eg, ≥1 week) (Ref).
Body dysmorphic disorder (off-label use): Oral: Some experts suggest an initial dose of 50 mg once daily; may increase dose gradually based on response and tolerability in increments of 50 mg at intervals of every 2 to 3 weeks up to a usual dose of 200 mg/day; doses up to 400 mg/day, if tolerated, may be necessary in some patients for optimal response (Ref). Note: An adequate trial for assessment of effect is 12 to 16 weeks, including a dose of 200 mg for at least 4 of those weeks, if needed and tolerated (Ref).
Generalized anxiety disorder (off-label use): Oral: Initial: 25 to 50 mg once daily; may gradually increase dose based on response and tolerability in increments of 25 to 50 mg per day at intervals ≥1 week. Doses may be increased every 3 to 4 days if warranted in inpatient settings. Some experts maintain the dose at 25 to 50 mg/day for 4 to 6 weeks to assess for efficacy before increasing further. Usual dose: 50 to 150 mg/day. Maximum dose: 200 mg/day (Ref).
Major depressive disorder (MDD) (unipolar):
Tablets, oral solution: Oral: Initial: 50 mg once daily; may increase dose based on response and tolerability in increments of 25 to 50 mg once weekly to a maximum of 200 mg/day (according to manufacturer's labeling); however, doses up to 300 mg/day have been used in clinical practice for MDD and may provide further benefit (Ref). More rapid titrations (every 3 days) in combination with an antipsychotic (eg, olanzapine) are used by some experts for patients with psychotic features (Ref).
Capsules:
Note: Capsules may be initiated in patients receiving sertraline 100 mg/day or 125 mg/day for ≥1 week or sertraline ≥150 mg/day.
Oral: Usual dose: 150 or 200 mg once daily. Maximum dose: 200 mg/day; however, doses up to 300 mg/day have been used in clinical practice for MDD and may provide further benefit (Ref).
Obsessive-compulsive disorder:
Tablets, oral solution: Oral: Initial: 50 mg once daily; may increase dose based on response and tolerability in increments of 25 to 50 mg once weekly to a maximum of 200 mg/day (according to the manufacturer's labeling). Doses up to 400 mg/day may have modest clinical benefit in patients with inadequate response to standard doses (Ref), but adverse effects may be increased.
Capsules:
Note: Capsules may be initiated in patients receiving sertraline 100 mg/day or 125 mg/day for ≥1 week or sertraline ≥150 mg/day.
Oral: Usual dose: 150 mg or 200 mg once daily. Maximum dose: 200 mg/day. Doses up to 400 mg/day may have modest clinical benefit in patients with inadequate response to standard doses (Ref), but adverse effects may be increased.
Panic disorder: Oral: Initial: 25 mg once daily for 3 to 7 days, then increase to 50 mg/day (Ref); thereafter, may increase dose based on response and tolerability in increments of 25 to 50 mg at intervals ≥1 week to a maximum of 200 mg/day. Some experts maintain dose at lower end of therapeutic range (ie, 50 to 75 mg) for 4 weeks before considering further dose increases. May require 6 weeks at maximally tolerated dose for adequate treatment trial (Ref).
Posttraumatic stress disorder (PTSD): Oral: Initial: 25 to 50 mg once daily (Ref); may increase dose based on response and tolerability in increments of 25 to 50 mg at intervals ≥1 week to a maximum of 200 mg/day (according to the manufacturer's labeling); however, doses up to 250 mg/day have been used in clinical practice and may provide further benefit (Ref).
Premature ejaculation (off-label use): Oral:
Daily dosing: Initial: 50 mg once daily; may increase dose based on response and tolerability at intervals of ~3 to 4 weeks in 50 mg increments up to 200 mg/day (Ref).
On-demand dosing: Based on limited evidence: 100 mg 6 to 8 hours before intercourse; maximum dose 2 times per week, with ≥3 days between doses (Ref).
Premenstrual dysphoric disorder (PMDD):
Continuous daily dosing regimen: Oral: Initial: 25 mg once daily; over the first month, increase to the usual effective dose of 50 mg once daily; in subsequent menstrual cycles, further increases in dose (eg, in 50 mg increments per menstrual cycle) up to 200 mg/day may be necessary in some patients for optimal response (Ref).
Intermittent regimens:
Luteal phase dosing regimen: Oral: Initial: 25 mg once daily during the luteal phase of menstrual cycle only (ie, beginning therapy 14 days before anticipated onset of menstruation and continued to the onset of menses); over the first month, increase to the usual effective dose of 50 mg/day; in subsequent menstrual cycles, further increases in dose (eg, in 50 mg increments per menstrual cycle) up to 150 mg/day during the luteal phase may be necessary in some patients for optimal response (Ref).
Symptom-onset dosing regimen (off-label dosing): Oral: Initial: 25 mg once daily from the day of symptom onset until a few days after the start of menses; over the first month, increase to the usual effective dose of 50 mg/day; in subsequent menstrual cycles, further increases in dose (eg, in 50 mg increments per menstrual cycle) up to 150 mg/day may be necessary for some patients for optimal response (Ref).
Note: If a daily dose ≥100 mg was established in previous cycles, may begin with 50 mg once daily for 2 to 3 days in subsequent cycles, then increase to previously established dose (Ref).
Social anxiety disorder: Oral: Initial: 25 to 50 mg once daily; after 4 to 6 weeks at this dose, may increase dose based on response and tolerability in increments of 25 to 50 mg at intervals ≥1 week to a maximum of 200 mg/day (Ref); however, doses up to 250 mg/day have been used in clinical practice and may provide further benefit (Ref).
Discontinuation of therapy: When discontinuing antidepressant treatment that has lasted for ≥4 weeks, gradually taper the dose (eg, over 2 to 4 weeks) to minimize withdrawal symptoms and detect reemerging symptoms (Ref). For brief treatment (eg, 2 to 3 weeks), may taper over 1 to 2 weeks; <2 weeks of treatment generally does not warrant tapering (Ref). Reasons for a slower taper (eg, over 4 weeks) include prior history of antidepressant withdrawal symptoms or high doses of antidepressants (Ref). If intolerable withdrawal symptoms occur, resume the previously prescribed dose and/or decrease dose at a more gradual rate (Ref). Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months (Ref). Evidence supporting ideal taper rates is limited (Ref). When tapering the dose of sertraline capsules, doses <150 mg will require the use of another sertraline product.
Switching antidepressants: Evidence for ideal antidepressant switching strategies is limited; strategies include cross-titration (gradually discontinuing the first antidepressant while at the same time gradually increasing the new antidepressant) and direct switch (abruptly discontinuing the first antidepressant and then starting the new antidepressant at an equivalent dose or lower dose and increasing it gradually). Cross-titration (eg, over 1 to 4 weeks depending upon sensitivity to discontinuation symptoms and adverse effects) is standard for most switches, but is contraindicated when switching to or from an MAOI. A direct switch may be an appropriate approach when switching to another agent in the same or similar class (eg, when switching between two SSRIs), when the antidepressant to be discontinued has been used for <1 week, or when the discontinuation is for adverse effects. When choosing the switch strategy, consider the risk of discontinuation symptoms, potential for drug interactions, other antidepressant properties (eg, half-life, adverse effects, and pharmacodynamics), and the degree of symptom control desired (Ref).
Switching to or from an MAOI:
Allow 14 days to elapse between discontinuing an MAOI and initiation of sertraline.
Allow 14 days to elapse between discontinuing sertraline and initiation of an MAOI.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: Mild to severe impairment: No dosage adjustment necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Not dialyzable (Ref): No dosage adjustment necessary (Ref).
Peritoneal dialysis: No dosage adjustment necessary (Ref).
CRRT: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).
The hepatic dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST, Jeong Park, PharmD, MS, BCTXP, FCCP, FAST, Arun Jesudian, MD, Sasan Sakiani, MD.
Note: Use of sertraline capsules is not recommended in the setting of hepatic impairment as dosage adjustments are not possible with the available strengths (Ref).
Hepatic impairment prior to treatment initiation:
Initial or dose titration in patients with preexisting liver cirrhosis:
Child-Turcotte-Pugh class A and B: Oral: Initial: Administer 50% of the usual recommended indication-specific dose; may increase based on response and tolerability in ≤25 mg increments at ≥2-week intervals (Ref). Maximum dose: 100 mg/day (Ref).
Child-Turcotte-Pugh class C: Use is not recommended (Ref).
Dosage adjustment in patients with chronic, worsening hepatic function during treatment (eg, progression from Child-Turcotte-Pugh class A to B):
Progression from baseline to Child-Turcotte-Pugh class A through B:
For patients currently taking ≤100 mg/day: No dosage adjustment necessary. May increase based on response and tolerability in ≤25 mg increments at ≥2-week intervals (Ref). Maximum dose: 100 mg/day (Ref).
For patients currently taking >100mg/day: Consider a 50% reduction in dose (Ref). May increase based on response and tolerability in ≤25 mg increments at ≥2-week intervals (Ref). Maximum dose: 100 mg/day (Ref).
Child-Turcotte-Pugh class C: Use is not recommended due to increased exposure and prolongation of half-life. If continuation of therapy is deemed necessary, consider a 50% reduction in dose with no further dose escalation in collaboration with and close monitoring from provider managing sertraline therapy (eg, psychiatrist) (Ref).
Acute worsening hepatic function (eg, requiring hospitalization):
Child-Turcotte-Pugh class A and B: Consider a 50% reduction in dose during acute worsening of hepatic function (Ref). May resume previous dose if hepatic function returns to pre-event baseline (Ref); if hepatic function does not improve to pre-event baseline consider dose reduction to ≤100 mg/day (Ref).
Child-Turcotte-Pugh class C: Use is not recommended due to increased exposure and prolongation of half-life. If continuation of therapy is deemed necessary, consider a 50% reduction in dose with no further dose escalation in collaboration with and close monitoring from provider managing sertraline therapy (eg, psychiatrist) (Ref).
Antidepressants (when used as monotherapy) may precipitate a mixed/manic episode in patients with bipolar disorder. Treatment-emergent mania or hypomania in patients with unipolar major depressive disorder (MDD) have been reported, as many cases of bipolar disorder present in episodes of MDD (Ref).
Mechanism: Non-dose-related; idiosyncratic. Unclear to what extent mood switches represent an uncovering of unrecognized bipolar disorder or a more direct pharmacologic effect independent of diagnosis (Ref).
Onset: Varied; a systematic review observed that the risk of switching increased significantly within the initial 2 years of antidepressant treatment in patients with unipolar MDD receiving an antidepressant as monotherapy, but not thereafter (up to 4.6 years) (Ref).
Risk factors:
• Family history of bipolar disorder (Ref)
• Depressive episode with psychotic symptoms (Ref)
• Younger age at onset of depression (Ref)
• Antidepressant resistance (Ref)
• Female sex (Ref)
Selective serotonin reuptake inhibitors (SSRIs), including sertraline, may increase the risk of bleeding, particularly if used concomitantly with antiplatelets and/or anticoagulants. Multiple observational studies have found an association with SSRI use and a variety of bleeding complications, ranging from bruising, hematomas, petechiae, purpuric disease and epistaxis to stroke, upper GI bleeding, intracranial hemorrhage, postpartum hemorrhage, and perioperative bleeding, although conflicting evidence also exists (Ref).
Mechanism: Possibly via inhibition of serotonin-mediated platelet activation (inhibition of the serotonin reuptake transporter) and subsequent platelet dysfunction. Sertraline is considered to display high affinity for the serotonin reuptake receptor (Ref). SSRIs may also increase gastric acidity, which can increase the risk of GI bleeding (Ref).
Onset: Varied; bleeding risk is likely delayed for several weeks until SSRI-induced platelet serotonin depletion becomes clinically significant (Ref), although the onset of bleeding may be more unpredictable if patients are taking concomitant antiplatelets, anticoagulants, or nonsteroidal anti-inflammatory agents (NSAIDs). For upper GI bleeding, some studies have found risk to be the highest in the first 28 to 30 days (Ref), whereas another study reported a median time of onset of 25 weeks (Ref).
Risk factors:
• Concomitant use of anticoagulants and/or antiplatelets (Ref)
• Preexisting platelet dysfunction or coagulation disorders (eg, von Willebrand factor) (Ref)
• Concomitant use of NSAIDs increases the risk for upper GI bleeding (Ref).
Limited data from observational studies involving mostly older adults (≥50 years) suggest selective serotonin reuptake inhibitors (SSRIs) are associated with an increased risk of bone fractures (Ref).
Mechanism: Time-related; mechanism not fully elucidated; postulated to be through a direct effect by SSRIs on bone metabolism via interaction with 5-HT and osteoblast, osteocyte, and/or osteoclast activity (Ref). An increased tendency for falls may also contribute to the increased risk of fractures associated with SSRIs (Ref).
Onset: Delayed; risk appears to increase after initiation and may continue to increase with long-term use. A meta-analysis found risk of fracture increased from 2.9% over 1 year to 5.4% over 2 years; within 5 years, risk increased to 13.4% (Ref).
Risk factors:
• Long-term use may be a risk factor (Ref)
Selective serotonin reuptake inhibitors are associated with syndrome of inappropriate antidiuretic hormone secretion (SIADH) and/or hyponatremia (including severe cases), predominantly in the elderly (Ref). Hyponatremia is reversible with discontinuation of therapy (Ref).
Mechanism: May cause SIADH via release of antidiuretic hormone (ADH) (Ref) or may cause nephrogenic SIADH by increasing the sensitivity of the kidney to ADH (Ref).
Onset: Intermediate; usually develops within the first few weeks of treatment (Ref).
Risk factors:
• Older age (Ref)
• Females (Ref)
• Concomitant use of diuretics (Ref)
• Low body weight (Ref)
• Lower baseline serum sodium concentration (Ref)
• Volume depletion (Ref)
• History of hyponatremia (potential risk factor) (Ref)
• Symptoms of psychosis (potential risk factor) (Ref)
Selective serotonin reuptake inhibitors (SSRIs) are associated with acute angle-closure glaucoma (AACG) in case reports and a case-controlled study. AACG may cause symptoms including eye pain, changes in vision, swelling, and redness, which can rapidly lead to permanent blindness if not treated (Ref). In addition, SSRIs may be associated with an increased risk of cataract development (Ref).
Mechanism: Unclear; hypothesized SSRIs may increase the intraocular pressure via serotonergic effects on ciliary body muscle activation and pupil dilation (Ref).
Risk factors:
For AACG:
• Females (Ref)
• ≥50 years of age (slight increase) (Ref)
• Hyperopia (slight increase) (Ref)
• Personal or family history of AACG (Ref)
• Inuit or Asian descent (Ref)
Serotonin syndrome has been reported and typically occurs with coadministration of multiple serotonergic drugs but can occur following a single serotonergic agent at therapeutic doses (Ref). The diagnosis of serotonin syndrome is made based on the Hunter Serotonin Toxicity Criteria (Ref) and may result in a spectrum of symptoms, such as anxiety, agitation, confusion, delirium, hyperreflexia, muscle rigidity, myoclonus, tachycardia, tachypnea, and tremor. Severe cases may cause hyperthermia, significant autonomic instability (ie, rapid and severe changes in blood pressure and pulse), coma, and seizures (Ref).
Mechanism: Dose-related; overstimulation of serotonin receptors by serotonergic agents (Ref).
Onset: Rapid; in the majority of cases (74%), onset occurred within 24 hours of treatment initiation, overdose, or change in dose (Ref).
Risk factors:
• Concomitant use of drugs that increase serotonin synthesis, block serotonin reuptake, and/or impair serotonin metabolism (eg, monamine oxidase inhibitors [MAOIs]). Of note, concomitant use of some serotonergic agents, such as MAOIs, are contraindicated.
Selective serotonin reuptake inhibitors (SSRIs) are commonly associated with sexual disorders in both men and women. The following adverse reactions have been associated with SSRI use: Ejaculatory delay, orgasm disturbance, erectile dysfunction, decreased libido (Ref). Priapism and decreased penile sensation have also been reported (Ref).
Mechanism: Increases in serotonin may affect other hormones and neurotransmitters involved in sexual function; in particular, testosterone's effect on sexual arousal and dopamine's role in achieving orgasm (Ref).
Risk factors:
• Depression (sexual dysfunction is commonly associated with depression; SSRI-associated sexual dysfunction may be difficult to differentiate in treated patients) (Ref)
Antidepressants are associated with an increased risk of suicidal ideation and suicidal tendencies in pediatric and young adult patients (18 to 24 years of age) in short-term studies. In adults >24 years of age, short-term studies did not show an increased risk of suicidal thinking and behavior, and in older adults (≥65 years of age) a decreased risk was observed. Although data have yielded inconsistent results regarding the association of antidepressants and risk of suicide, particularly among adults, collective evidence shows a trend of an elevated risk of suicidality in younger age groups (Ref). Of note, the risk of a suicide attempt is inherent in major depression and may persist until remission occurs.
Mechanism: Not established; one of several postulated mechanisms is antidepressants may energize suicidal patients to act on impulses; another suggests that antidepressants may produce a worsening of depressive symptoms leading to the emergence of suicidal thoughts and actions (Ref).
Onset: Varied; increased risk observed in short-term studies (ie, <4 months) in pediatric and young adults; it is unknown whether this risk extends to long-term use (ie, >4 months)
Risk factors:
• Children and adolescents (Ref)
• Depression (risk of suicide is associated with major depression and may persist until remission occurs)
Withdrawal syndrome, consisting of both somatic symptoms (eg, dizziness, chills, light-headedness, vertigo, electric-shock sensations, paresthesia, fatigue, headache, nausea, tremor, diarrhea, visual disturbances) and psychological symptoms (eg, anxiety, agitation, confusion, insomnia, irritability), has been reported, primarily following abrupt discontinuation. Withdrawal symptoms may also occur following gradual tapering (Ref).
Mechanism: Withdrawal; due to reduced availability of serotonin in the CNS with decreasing levels of the selective serotonin reuptake inhibitor (SSRI). Other neurotransmission systems, including increased glutamine and dopamine, may also be affected, as well as the hypothalamic-pituitary-adrenal axis (Ref).
Onset: Intermediate; expected onset is 1 to 10 days (following either abrupt or tapered discontinuation) (Ref).
Risk factors:
• Abrupt discontinuation (rather than dose taper) or tapering the antidepressant too quickly (Ref)
• Drugs with a half-life <24 hours (eg, paroxetine, venlafaxine) (Ref)
• Higher doses (Ref)
• Longer duration of treatment (eg, ≥4 weeks) (Ref)
• Prior history of antidepressant withdrawal symptoms (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Diarrhea (20%), nausea (26%), xerostomia (14%)
Nervous system: Dizziness (12%), drowsiness (adults: 11%; literature suggests incidence occurs less frequently in children and adolescents compared to adults [Safer 2006]), fatigue (12%), insomnia (20%)
1% to 10%:
Cardiovascular: Edema (<2%), hypertension (<2%), palpitations (4%), syncope (<2%), tachycardia (<2%), vasodilation (<2%)
Dermatologic: Alopecia (<2%), bullous dermatitis (<2%), dermatitis (<2%), diaphoresis (<2%), erythematous rash (<2%), follicular rash (<2%), hyperhidrosis (7%), maculopapular rash (<2%), pruritus (<2%), urticaria (<2%)
Endocrine & metabolic: Decreased libido (4% to 7%) (table 1), diabetes mellitus (<2%), galactorrhea not associated with childbirth (<2%), hypercholesterolemia (<2%), hypoglycemia (<2%), hypothyroidism (<2%), weight loss (>7% of body weight; children: 7%; adolescents: 2%)
|
Drug (Sertraline) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Sertraline) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
7% |
2% |
Males |
Mostly 50 mg to 200 mg per day |
Major depressive disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, social anxiety disorder, and premenstrual dysphoric disorder |
1,316 |
973 |
|
4% |
2% |
Females |
Mostly 50 mg to 200 mg per day |
Major depressive disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, social anxiety disorder, and premenstrual dysphoric disorder |
1,750 |
1,320 |
Gastrointestinal: Abdominal pain (≥5%), bruxism (<2%), constipation (6%), decreased appetite (7%), dyspepsia (8%), hematochezia (<2%), increased appetite (<2%), melena (<2%), rectal hemorrhage (<2%), vomiting (adults: 4%; literature suggests incidence is higher in adolescents compared to adults, and is two- to threefold higher in children compared to adults [Safer 2006])
Genitourinary: Ejaculation failure (8%) (table 2), ejaculatory disorder (3%) (table 3), erectile dysfunction (4%) (table 4), hematuria (<2%), priapism (<2%), sexual disorder (males: 2%; literature suggests an incidence ranging from 54% to 63% [Higgins 2010; Montejo 2001]) (table 5), urinary incontinence (≥2%), vaginal hemorrhage (<2%)
|
Drug (Sertraline) |
Placebo |
Dose |
Indication |
Number of Patients (Sertraline) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
8% |
1% |
Mostly 50 mg to 200 mg per day |
Major depressive disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, social anxiety disorder, and premenstrual dysphoric disorder |
1,316 |
973 |
|
Drug (Sertraline) |
Placebo |
Dose |
Indication |
Number of Patients (Sertraline) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
3% |
0% |
Mostly 50 mg to 200 mg per day |
Major depressive disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, social anxiety disorder, and premenstrual dysphoric disorder |
1,316 |
973 |
|
Drug (Sertraline) |
Placebo |
Dose |
Indication |
Number of Patients (Sertraline) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
4% |
1% |
Mostly 50 mg to 200 mg per day |
Major depressive disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, social anxiety disorder, and premenstrual dysphoric disorder |
1,316 |
973 |
|
Drug (Sertraline) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Sertraline) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
2% |
0% |
Males |
Mostly 50 mg to 200 mg per day |
Major depressive disorder, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, social anxiety disorder, and premenstrual dysphoric disorder |
1,316 |
973 |
Hematologic & oncologic: Hemorrhage (<2%)
Hepatic: Increased liver enzymes (<2%)
Hypersensitivity: Anaphylaxis (<2%)
Nervous system: Abnormal gait (<2%), agitation (8%), anxiety (children and adolescents: ≥2%), ataxia (<2%), coma (<2%), confusion (<2%), euphoria (<2%), hallucination (<2%), hypertonia (<2%), hypoesthesia (<2%), impaired consciousness (<2%), irritability (<2%), lethargy (<2%), malaise (≥5%), psychomotor agitation (<2%), seizure (<2%), tremor (9%), yawning (<2%)
Neuromuscular & skeletal: Hyperkinetic muscle activity (children and adolescents: ≥2%), muscle spasm (<2%)
Ophthalmic: Blurred vision (<2%), mydriasis (<2%), visual disturbance (4%)
Otic: Tinnitus (<2%)
Respiratory: Bronchospasm (<2%)
Frequency not defined:
Nervous system: Aggressive behavior
Neuromuscular & skeletal: Arthralgia, muscle twitching
Respiratory: Epistaxis
Miscellaneous: Fever
Postmarketing:
Cardiovascular: Atrial arrhythmia, atrioventricular block, bradycardia, prolonged QT interval on ECG (Beach 2014; Funk 2013), torsades de pointes (Danielsson 2016), vasculitis, ventricular tachycardia (Patel 2013)
Dermatologic: Erythema multiforme (Khan 2012), skin photosensitivity, Stevens-Johnson syndrome (Jan 1999), toxic epidermal necrolysis
Endocrine & metabolic: Gynecomastia (Kaufman 2013), hyperglycemia (Khoza 2011), hyperprolactinemia, hyponatremia (literature suggests incidence of hyponatremia among SSRIs ranging from <1% to as high as 32%) (Jacob 2006; Varela Piñón 2017), menstrual disease, secondary amenorrhea (Ekinci 2019), SIADH (Jacob 2006), weight gain (slight increase, primarily in adults with long-term therapy) (Fava 2000)
Gastrointestinal: Burning sensation of mouth (Purohith 2022), oromandibular dystonia (Doruk 2021), pancreatitis (Malbergier 2004)
Genitourinary: Abnormal orgasm (Jing 2016), decreased penile sensation (Bolton 2006)
Hematologic & oncologic: Agranulocytosis (Trescoli-Serrano 1996), aplastic anemia, coagulation time increased (altered platelet function) (Apseloff 1997), Henoch-Schönlein purpura (Fatima 2022), immune thrombocytopenia (Krivy 1995), leukopenia, neutropenia (Ozcanli 2005), pancytopenia, purpuric disease (periorbital) (Kayhan 2015)
Hepatic: Hepatic failure, hepatitis (Persky 2003), hepatotoxicity (Persky 2003), jaundice (Verrico 2000)
Hypersensitivity: Angioedema (Gales 1994), hypersensitivity reaction (Dadic-Hero 2011), serum sickness
Nervous system: Akathisia (Madhusoodanan 2010), anosmia (including hyposmia), electric shock-like sensation (Viani 2022), hyperactive behavior (including restlessness occurring in children at a two- to threefold higher incidence compared to adolescents [Safer 2006]), hypomania (Kumar 2000), intracranial hemorrhage (Douros 2018), mania (Ghaziuddin 1994), myoclonus (hypnic jerks) (Kumar 2023), neuroleptic malignant syndrome (Stevens 2008), nightmares, psychosis (Popli 1997), reversible cerebral vasoconstriction syndrome (Bain 2013), serotonin syndrome (Duignan 2019), suicidal ideation (children and adolescents) (Hammad 2006), suicidal tendencies (children and adolescents) (Hammad 2006), trismus (Holmberg 2018), withdrawal syndrome (Fava 2015)
Neuromuscular & skeletal: Bone fracture (Rabenda 2013), dystonia (Madhusoodanan 2010), lupus-like syndrome (Hussain 2008), rhabdomyolysis (Gareri 2009)
Ophthalmic: Acute angle-closure glaucoma (Kirkham 2017), blindness, cataract (Erie 2014), maculopathy (Dang 2016), oculogyric crisis, optic nerve damage (with papilledema) (Abuallut 2023), optic neuritis
Renal: Acute kidney injury
Respiratory: Eosinophilic pneumonitis, hypersensitivity pneumonitis (Virdee 2019), pulmonary hypertension
Use of monoamine oxidase inhibitors (MAOIs) including methylene blue (concurrently or within 14 days of stopping an MAOI or sertraline); concurrent use with pimozide; hypersensitivity (eg, anaphylaxis, angioedema) to sertraline or any component of the formulation; concurrent use with disulfiram (oral solution only).
Note: Although sertraline is contraindicated per the manufacturer labeling when used in combination with linezolid, new evidence suggests that the combination is unlikely to cause serotonin syndrome (0.06% to 3% risk), and therefore these agents can be administered concomitantly when necessary. Monitor patients on this combination; average duration of serotonin toxicity is ~4 days; however, risks may be greater with longer durations of concurrent therapy. Educate patients on the signs and symptoms of serotonin syndrome (Bai 2022; Butterfield 2012; Karkow 2017; Kufel 2023; Narita 2007; Taylor 2006).
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• CNS depression: Has a low potential to impair cognitive or motor performance; caution operating hazardous machinery or driving.
• QT prolongation: QTc prolongation and torsades de pointes have been reported with sertraline use. Most reports involved other risk factors; use with caution in patients with risk factors for QTc prolongation. Studies have shown correlations with serum sertraline concentrations.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment; clearance is decreased and half-life and plasma concentrations are increased; dose reduction may be necessary.
• Seizure disorder: Use with caution in patients with a previous seizure disorder or condition predisposing to seizures such as brain damage or alcoholism.
Special populations:
• Pediatric: Monitor growth in pediatric patients. Given their lower body weight, lower doses are advisable in pediatric patients in order to avoid excessive plasma levels, despite slightly greater metabolism efficiency than adults.
Dosage form specific issues:
• Latex sensitivity: Use oral solution formulation with caution in patients with latex sensitivity; dropper dispenser contains dry, natural rubber.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
• Tartrazine: Capsules contain tartrazine (FD&C Yellow No. 5), which may cause allergic-type reactions (including bronchial asthma) in susceptible individuals, particularly those who also have aspirin sensitivity.
Selective serotonin reuptake inhibitor (SSRI)-associated behavioral activation (ie, restlessness, hyperkinesis, hyperactivity, agitation) is two- to threefold more prevalent in children compared to adolescents; it is more prevalent in adolescents compared to adults. Somnolence (including sedation and drowsiness) is more common in adults compared to children and adolescents and SSRI-associated vomiting is two- to threefold more prevalent in children compared to adolescents; it is more prevalent in adolescents compared to adults (Safer 2006).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as hydrochloride:
Generic: 150 mg, 200 mg
Concentrate, Oral:
Zoloft: 20 mg/mL (60 mL) [contains alcohol, usp, menthol]
Generic: 20 mg/mL (60 mL)
Tablet, Oral:
Zoloft: 25 mg [scored; contains fd&c blue #1 (brill blue) aluminum lake, fd&c red #40(allura red ac)aluminum lake, polysorbate 80, quinoline (d&c yellow #10) aluminum lake]
Zoloft: 50 mg [scored; contains fd&c blue #2 (indigo carm) aluminum lake]
Zoloft: 100 mg [scored; contains polysorbate 80]
Generic: 25 mg, 50 mg, 100 mg
Yes
Capsules (Sertraline HCl Oral)
150 mg (per each): $6.17
200 mg (per each): $6.17
Concentrate (Sertraline HCl Oral)
20 mg/mL (per mL): $0.68 - $1.13
Concentrate (Zoloft Oral)
20 mg/mL (per mL): $5.68
Tablets (Sertraline HCl Oral)
25 mg (per each): $0.05 - $2.87
50 mg (per each): $0.06 - $2.87
100 mg (per each): $0.05 - $2.87
Tablets (Zoloft Oral)
25 mg (per each): $17.35
50 mg (per each): $17.35
100 mg (per each): $17.35
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Zoloft: 25 mg, 50 mg [contains corn starch, fd&c yellow #6 (sunset yellow), quinoline yellow (d&c yellow #10)]
Zoloft: 100 mg [contains corn starch, fd&c red #40 (allura red ac dye), quinoline yellow (d&c yellow #10)]
Generic: 25 mg, 50 mg, 100 mg
The following feeding tube recommendations are based upon the best available evidence and clinical expertise. Senior editor panel: Joseph I. Boullata, PharmD, RPh, CNS-S, FASPEN, FACN; Peggi A. Guenter, PhD, RN, FASPEN; Kathleen Gura, PharmD, BCNSP, FASHP, FASPEN, FPPA, FMSHP; Mark G. Klang, MS, RPh, BCNSP, PhD, FASPEN; Linda Lord, NP, ACNP-BC, CNSC, FASPEN.
Note: Recommendations may not account for differences in inactive ingredients, osmolality, or other formulation properties among manufacturers.
Oral:
Capsules: Swallow whole; do not open, crush, or chew. May be administered without regard to food.
Administration via feeding tube: Enteral feeding tube administration utilizing sertraline capsules has not been evaluated; the manufacturer recommends capsules should not be opened or crushed.
Oral solution concentrate (commercially available): Must dilute oral concentrate before use. Direct administration of the undiluted solution is astringent and may numb the tongue/mouth for at least a day, even if the mouth is rinsed extensively (Ref).
Administration via feeding tube: Enteral feeding tube administration of oral solution concentrate is not recommended (Ref).
Tablet: May be administered without regard to food.
Administration via feeding tube:
Gastric (eg, NG, percutaneous endoscopic gastrostomy [PEG]) or post-pyloric (eg, jejunal) tubes (≥8 French): Crush tablet(s) into a fine powder and disperse in ≥10 mL purified water immediately prior to administration; draw up mixture into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: Some tablets may be film coated; administration of film-coated tablets via feeding tube may increase the risk of clogging the tube; if used, ensure tablets are sufficiently dispersed in purified water prior to administration (Ref).
General guidance: Hold enteral nutrition during sertraline administration (Ref). Flush feeding tube with an appropriate volume of purified water before administration (Ref); consult ASPEN recommendations (Ref) or institution-specific protocols for appropriate flush volume. Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water and restart enteral nutrition (Ref).
Oral:
Capsules: Swallow capsules whole; do not open, chew, or crush.
Oral solution: Must be diluted immediately before use to make the preparation more palatable. Direct administration of the pure solution is astringent and may numb the tongue/mouth for at least a day, even if the mouth is rinsed extensively (Ref). Note: Use with caution in patients with latex sensitivity; dropper dispenser contains dry natural rubber.
Enteral feeding tube:
The following recommendations are based upon the best available evidence and clinical expertise. Senior editorial team: Joseph I. Boullata, PharmD, RPh, CNS-S, FASPEN, FACN; Peggi A. Guenter PhD, RN, FASPEN; Kathleen Gura, PharmD, BCNSP, FASHP, FASPEN, FPPA, FMSHP; Mark G. Klang MS, RPh, BCNSP, PhD, FASPEN; Linda Lord, NP, ACNP-BC, CNSC, FASPEN.
Oral capsule: Enteral feeding tube administration utilizing capsules has not been evaluated; the manufacturer recommends capsules should not be opened or crushed.
Oral solution concentrate (commercially available): Enteral feeding tube administration of oral solution concentrate is not recommended (Ref).
Oral tablets:
Gastric (eg, NG, gastrostomy) or post-pyloric (eg, jejunal) tubes (≥8 French): Crush tablet(s) into a fine powder and disperse in ≥10 mL purified water immediately prior to administration; draw up mixture into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: Formulations may be film-coated; administration of film-coated sertraline tablets via feeding tube may increase the risk of clogging the tube; if used, ensure tablets are dispersed sufficiently with an adequate amount of purified water prior to administration (Ref).
General guidance: Hold enteral nutrition during sertraline administration (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) before administration (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 20 mL) and restart enteral nutrition (Ref).
Note: Recommendations may not account for differences in inactive ingredients, osmolality, or other formulation properties among manufacturers.
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/019839s108,20990s062lbl.pdf#page=37, must be dispensed with this medication.
Treatment of obsessive-compulsive disorder (FDA approved in ages ≥6 years and adults); treatment of major depressive disorder, panic disorder (with or without agoraphobia), posttraumatic stress disorder, premenstrual dysphoric disorder, and social anxiety disorder (social phobia) (FDA approved in adults).
Sertraline may be confused with cetirizine, selegiline, Serevent, Soriatane
Zoloft may be confused with Zocor
Beers Criteria: Selective Serotonin Reuptake Inhibitors (SSRIs) are identified in the Beers Criteria as potentially inappropriate medications to be used with caution in patients 65 years and older due to the potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium concentration closely when initiating or adjusting the dose in older adults (Beers Criteria [AGS 2023]).
Substrate of CYP2B6 (minor), CYP2C19 (minor), CYP2C9 (minor), CYP2D6 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (weak)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Abrocitinib: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Abrocitinib. Risk X: Avoid combination
Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Risk C: Monitor therapy
Agents with Blood Glucose Lowering Effects: Selective Serotonin Reuptake Inhibitors may enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Alcohol (Ethyl): May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Management: Patients receiving selective serotonin reuptake inhibitors should be advised to avoid alcohol. Monitor for increased psychomotor impairment in patients who consume alcohol during treatment with selective serotonin reuptake inhibitors. Risk D: Consider therapy modification
Almotriptan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Alosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Amphetamines: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability). Initiate amphetamines at lower doses, monitor frequently, and adjust doses as needed. Risk C: Monitor therapy
Anagrelide: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Antiplatelet Agents (P2Y12 Inhibitors): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Antiplatelet Agents (P2Y12 Inhibitors). Risk C: Monitor therapy
Antipsychotic Agents: Serotonergic Agents (High Risk) may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy
Apixaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely. Risk C: Monitor therapy
Aspirin: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Aspirin. Risk C: Monitor therapy
Bemiparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Brexanolone: Selective Serotonin Reuptake Inhibitors may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Bromopride: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Risk X: Avoid combination
BuPROPion: May enhance the adverse/toxic effect of Sertraline. Risk C: Monitor therapy
BusPIRone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Caplacizumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Caplacizumab. Specifically, the risk of bleeding may be increased. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs. Risk D: Consider therapy modification
CarBAMazepine: May decrease the serum concentration of Sertraline. Risk C: Monitor therapy
Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy
Citalopram: May enhance the antiplatelet effect of Selective Serotonin Reuptake Inhibitors. Citalopram may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor therapy
Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor therapy
Cyclobenzaprine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Sertraline. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Sertraline. Risk C: Monitor therapy
Cyproheptadine: May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy
Dabigatran Etexilate: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Risk C: Monitor therapy
Dapoxetine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Do not use serotonergic agents (high risk) with dapoxetine or within 7 days of serotonergic agent discontinuation. Do not use dapoxetine within 14 days of monoamine oxidase inhibitor use. Dapoxetine labeling lists this combination as contraindicated. Risk X: Avoid combination
Darunavir: May decrease the serum concentration of Sertraline. Risk C: Monitor therapy
Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy
Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
Dexmethylphenidate-Methylphenidate: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Dextromethorphan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Dipyrone: May decrease the serum concentration of Sertraline. Risk C: Monitor therapy
Disulfiram: May enhance the adverse/toxic effect of Products Containing Ethanol. Management: Do not use disulfiram with dosage forms that contain ethanol. Risk X: Avoid combination
DULoxetine: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of DULoxetine. Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of DULoxetine. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor therapy
Edoxaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Risk C: Monitor therapy
Eletriptan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Enoxaparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Epinephrine (Racemic): Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Epinephrine (Racemic). Risk X: Avoid combination
Ergot Derivatives: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Erythromycin (Systemic): May enhance the adverse/toxic effect of Sertraline. Risk C: Monitor therapy
Fenfluramine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy
Fosphenytoin-Phenytoin: Sertraline may increase the serum concentration of Fosphenytoin-Phenytoin. Fosphenytoin-Phenytoin may decrease the serum concentration of Sertraline. Risk C: Monitor therapy
Gepirone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy
Gilteritinib: May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Avoid use of this combination if possible. If the combination cannot be avoided, monitor closely for evidence of reduced response to the selective serotonin reuptake inhibitor. Risk D: Consider therapy modification
Grapefruit Juice: May increase the serum concentration of Sertraline. Risk C: Monitor therapy
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Heparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. Risk D: Consider therapy modification
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk C: Monitor therapy
Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy
Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Icosapent Ethyl: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Ioflupane I 123: Selective Serotonin Reuptake Inhibitors may diminish the diagnostic effect of Ioflupane I 123. Risk C: Monitor therapy
Lasmiditan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Lecanemab: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor therapy
Levoketoconazole: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Levoketoconazole. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Levomethadone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Linezolid: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination
Lipid Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Lorcaserin (Withdrawn From US Market): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Metaxalone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Methadone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Methotrimeprazine: Products Containing Ethanol may enhance the adverse/toxic effect of Methotrimeprazine. Specifically, a disulfiram-like reaction may occur and CNS depressant effects may be increased. Management: Avoid products containing alcohol in patients treated with methotrimeprazine. Risk X: Avoid combination
Methylene Blue: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid combination
Metoclopramide: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Consider monitoring for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Mivacurium: Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Mivacurium. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors (Antidepressant): Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid combination
Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Nefazodone: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents (Nonselective): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider alternatives to NSAIDs. Monitor for evidence of bleeding and diminished antidepressant effects. It is unclear whether COX-2-selective NSAIDs reduce risk. Risk D: Consider therapy modification
Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the antiplatelet effect of Selective Serotonin Reuptake Inhibitors. Risk C: Monitor therapy
Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy
Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Ondansetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Opioid Agonists: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Opioid Agonists (metabolized by CYP3A4 and CYP2D6): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Opioid Agonists (metabolized by CYP3A4): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Ornidazole: May enhance the adverse/toxic effect of Products Containing Ethanol. Specifically, a disulfiram-like reaction may occur. Risk X: Avoid combination
Oxitriptan: Serotonergic Agents (High Risk) may enhance the serotonergic effect of Oxitriptan. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Ozanimod: May enhance the adverse/toxic effect of Serotonergic Agents (High Risk). Risk C: Monitor therapy
Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy
Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Pimozide: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Pimozide. Risk X: Avoid combination
Pirtobrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Psilocybin: Antidepressants may diminish the therapeutic effect of Psilocybin. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Ramosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Rasagiline: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Rasagiline. This could result in serotonin syndrome. Risk X: Avoid combination
Rivaroxaban: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Rivaroxaban. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Risk C: Monitor therapy
Safinamide: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Use the lowest effective dose of SSRIs in patients treated with safinamide and monitor for signs and symptoms of serotonin syndrome/serotonin toxicity. Risk D: Consider therapy modification
Secnidazole: Products Containing Ethanol may enhance the adverse/toxic effect of Secnidazole. Risk X: Avoid combination
Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of other Selective Serotonin Reuptake Inhibitors. Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of other Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor therapy
Selegiline: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Selegiline. This could result in serotonin syndrome. Risk X: Avoid combination
Selumetinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Serotonergic Agents (High Risk, Miscellaneous): May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Serotonergic Non-Opioid CNS Depressants: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Serotonergic Opioids (High Risk): May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) if these agents are combined. Risk C: Monitor therapy
Serotonin 5-HT1D Receptor Agonists (Triptans): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Serotonin/Norepinephrine Reuptake Inhibitors: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Serotonin/Norepinephrine Reuptake Inhibitors. Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor therapy
St John's Wort: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease the serum concentration of Serotonergic Agents (High Risk). Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Succinylcholine: Sertraline may increase the serum concentration of Succinylcholine. Risk C: Monitor therapy
Syrian Rue: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Thiazide and Thiazide-Like Diuretics: Selective Serotonin Reuptake Inhibitors may enhance the hyponatremic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy
Thioridazine: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Thioridazine. Management: Consider avoiding concomitant use of thioridazine and weak CYP2D6 inhibitors. If combined, monitor closely for QTc interval prolongation and arrhythmias. Some weak CYP2D6 inhibitors list use with thioridazine as a contraindication. Risk D: Consider therapy modification
Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Thyroid Products: Selective Serotonin Reuptake Inhibitors may diminish the therapeutic effect of Thyroid Products. Thyroid product dose requirements may be increased. Risk C: Monitor therapy
Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
TraMADol: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk for serotonin syndrome/serotonin toxicity and seizures may be increased. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and seizures when these agents are combined. Risk C: Monitor therapy
Tricyclic Antidepressants: Sertraline may enhance the serotonergic effect of Tricyclic Antidepressants. Sertraline may increase the serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined. Risk C: Monitor therapy
Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Risk X: Avoid combination
Vasopressin: Drugs Suspected of Causing SIADH may enhance the therapeutic effect of Vasopressin. Specifically, the pressor and antidiuretic effects of vasopressin may be increased. Risk C: Monitor therapy
Venlafaxine: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Venlafaxine. Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Venlafaxine. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor therapy
Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Selective Serotonin Reuptake Inhibitors may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Volanesorsen: May enhance the antiplatelet effect of Agents with Antiplatelet Effects. Risk C: Monitor therapy
Vortioxetine: May enhance the antiplatelet effect of Selective Serotonin Reuptake Inhibitors. Vortioxetine may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, mental status changes) when these agents are combined. In addition, monitor for signs and symptoms of bleeding. Risk C: Monitor therapy
Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Zolpidem: Sertraline may increase the serum concentration of Zolpidem. Risk C: Monitor therapy
Sertraline is approved for the treatment of unipolar major depressive disorder. If treatment for major depressive disorder is initiated for the first time in patients planning to become pregnant, sertraline is one of the preferred selective serotonin reuptake inhibitors (SSRIs) (Larsen 2015).
Sertraline is also approved for the treatment of premenstrual dysphoric disorder. For patients attempting to conceive, symptom-onset dosing may be beneficial to minimize potential fetal exposure (Ismaili 2016; Lanza di Scalea 2019).
SSRIs may be associated with male and female treatment-emergent sexual dysfunction (Coskuner 2018; WFSBP [Bauer 2013]). Decreased libido has been reported in females and males; ejaculation failure, ejaculation dysfunction, and ejaculation disorders have been reported in males with sertraline use. This may also be a manifestation of the psychiatric disorder. The actual risk associated with sertraline is not known. SSRI-related sexual dysfunction may resolve with dose reduction or discontinuation of the SSRI; in some cases, sexual dysfunction may persist once therapy is discontinued (Coskuner 2018; Jing 2016; Waldinger 2015).
Sertraline is used off label for the treatment of premature ejaculation. Although data are limited, some studies have shown SSRIs may impair the motility of spermatozoa; therefore, use of other treatments may be preferred in patients planning to father a child (Althof 2014; Siroosbakht 2019; Sylvester 2019).
Sertraline crosses the human placenta. Cord blood and amniotic fluid concentrations are less than those in the maternal serum; concentrations in the amniotic fluid correlate with maternal dose (Newport 2003; Paulzen 2017).
As a class, selective serotonin reuptake inhibitors (SSRIs) have been evaluated extensively in pregnant patients. Studies focusing on newborn outcomes following first trimester exposure often have inconsistent results due to differences in study design and confounders such as maternal disease and social factors (Anderson 2020; Biffi 2020; Fitton 2020; Reefhuis 2015; Womersley 2017). Adverse effects in the newborn following SSRI exposure late in the third trimester can include apnea, constant crying, cyanosis, feeding difficulty, hyperreflexia, hypo- or hypertonia, hypoglycemia, irritability, jitteriness, respiratory distress, seizures, temperature instability, tremor, and vomiting. Prolonged hospitalization, respiratory support, or tube feedings may be required. Symptoms may be due to the toxicity of the SSRIs or a discontinuation syndrome and may be consistent with serotonin syndrome associated with SSRI treatment. Persistent pulmonary hypertension of the newborn has been reported with SSRI exposure; although the absolute risk is small, monitoring of infants exposed to SSRIs late in pregnancy is recommended (Masarwa 2019; Ng 2019). The long-term effects of in utero SSRI exposure on infant neurodevelopment and behavior are not known (CANMAT [MacQueen 2016]).
Due to pregnancy-induced physiologic changes some pharmacokinetic parameters of sertraline may be altered. Serum concentrations may be decreased in the third trimester; however, due to the wide therapeutic reference range, dose adjustments may not be needed. Close clinical monitoring as pregnancy progresses and therapeutic drug monitoring to detect patterns of changing plasma concentrations is recommended to assist dose-adjustment when needed (Schoretsanitis 2020).
If treatment for major depressive disorder is initiated for the first time during pregnancy, sertraline is one of the preferred SSRIs (CANMAT [MacQueen 2016]; Larsen 2015; WFSBP [Bauer 2013]). Untreated or inadequately treated psychiatric illness may lead to poor adherence with prenatal care and adverse pregnancy outcomes. Therapy with antidepressants during pregnancy should be individualized; treatment with antidepressant medication is recommended for pregnant patients with severe major depressive disorder (ACOG 2008; CANMAT [MacQueen 2016]). Patients treated for major depression and who are euthymic prior to pregnancy are more likely to experience a relapse when medication is discontinued (68%) as compared to pregnant patients who continue taking antidepressant medications (26%) (Cohen 2006).
Data collection to monitor pregnancy and infant outcomes following exposure to antidepressant medications is ongoing. Patients exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants. Pregnant patients 18 to 45 years of age or their health care providers may contact the registry to enroll; enrollment should be done as early in pregnancy as possible (1-866-961-2388 or https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/).
Weight, height, BMI (longitudinal monitoring); closely monitor patients for depression, clinical worsening, suicidality, psychosis, or unusual changes in behavior (eg, anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, mania, social functioning), particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); signs/symptoms of serotonin syndrome such as mental status changes (eg, agitation, hallucinations, delirium, coma), autonomic instability (eg, tachycardia, labile BP, diaphoresis), neuromuscular changes (eg, tremor, rigidity, myoclonus), GI symptoms (eg, nausea, vomiting, diarrhea), and/or seizures; serum sodium in at-risk populations.
Antidepressant with selective inhibitory effects on presynaptic serotonin (5-HT) reuptake and only very weak effects on norepinephrine and dopamine neuronal uptake. In vitro studies demonstrate no significant affinity for adrenergic, cholinergic, GABA, dopaminergic, histaminergic, serotonergic, or benzodiazepine receptors.
Onset of action:
Anxiety disorders (generalized anxiety, obsessive-compulsive, panic, and posttraumatic stress disorder): Initial effects may be observed within 2 weeks of treatment, with continued improvements through 4 to 6 weeks (Issari 2016; Varigonda 2016; WFSBP [Bandelow 2023a]); some experts suggest up to 12 weeks of treatment may be necessary for response, particularly in patients with obsessive-compulsive disorder and posttraumatic stress disorder (BAP [Baldwin 2014]; Katzman 2014; WFSBP [Bandelow 2023a]; WFSBP [Bandelow 2023b]).
Body dysmorphic disorder: Initial effects may be observed within 2 weeks; some experts suggest up to 12 to 16 weeks of treatment may be necessary for response in some patients (Phillips 2008).
Depression: Initial effects may be observed within 1 to 2 weeks of treatment, with continued improvements through 4 to 6 weeks (Papakostas 2006; Posternak 2005; Szegedi 2009; Taylor 2006).
Premenstrual dysphoric disorder: Initial effects may be observed within the first few days of treatment, with response at the first menstrual cycle of treatment (ISPMD [Nevatte 2013]).
Protein binding: 98%.
Metabolism: Hepatic; may involve CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 (Chen 2020; Markowitz 2000; Rajasingham 2018); extensive first pass metabolism; forms metabolite N-desmethylsertraline (APA [Gelenberg 2010]); Note: Children 6 to 17 years may metabolize sertraline slightly better than adults, as pediatric AUCs and peak concentrations were 22% lower than adults when adjusted for weight; however, lower doses are recommended for younger pediatric patients to avoid excessive drug levels).
Bioavailability: Bioavailability of tablets and solution are equivalent.
Half-life elimination: Sertraline: Mean: 26 hours; N-desmethylsertraline (not as active as parent drug): 62 to 104 hours.
Children 6 to 12 years: Mean: 26.2 hours (Alderman 1998).
Children 13 to 17 years: Mean: 27.8 hours (Alderman 1998).
Adults 18 to 45 years: Mean: 27.2 hours (Alderman 1998).
Time to peak, plasma: Sertraline: 4.5 to 8.4 hours.
Excretion: Urine (40% to 45% as metabolites); feces (40% to 45%; 12% to 14% as unchanged drug).
Hepatic function impairment: Sertraline clearance was reduced in patients with chronic mild liver impairment resulting in a 3-fold greater exposure. Sertraline Cmax, AUC and half-life were 1.7-fold, 4-fold, and 2.5-fold higher following a single dose of sertraline in patients with stable chronic cirrhosis (Démolis 1996).
Pediatric: Children 6 to 17 years may metabolize sertraline slightly better than adults, as pediatric AUCs and peak concentrations were 22% lower than adults when adjusted for weight; however, lower doses are recommended for younger pediatric patients to avoid excessive drug levels)
Older adult: Plasma clearance 40% lower; steady state achieved after 2 to 3 weeks
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