Version July 2025
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:
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 liver dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST, FCCP; 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 liver impairment as dosage adjustments are not possible with the available strengths (Ref).
Liver impairment prior to treatment initiation:
Initial or dose adjustment 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).
Liver impairment developing in patients already receiving sertraline:
Chronic disease progression (eg, outpatient):
Baseline to Child-Turcotte-Pugh class A to 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 of liver function (eg, requiring hospitalization):
Baseline to Child-Turcotte-Pugh class A to B: Consider a 50% reduction in dose during acute worsening of liver function (Ref). May resume previous dose if liver function returns to pre-event baseline (Ref); if liver function does not improve to pre-event baseline consider dose reduction to ≤100 mg/day (Ref).
Progression to 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).
Refer to adult dosing; however, lower initial doses (25 mg once daily) may be better tolerated in older adults (Ref).
Discontinuation of therapy: Refer to adult dosing.
Switching antidepressants: Refer to adult dosing.
(For additional information see "Sertraline: Pediatric drug information")
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.
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). In addition, treatment-emergent mania or hypomania has been described in patients receiving antidepressants, including selective serotonin reuptake inhibitors, for the treatment of obsessive-compulsive disorder (OCD) without a history of bipolar disorder (with or without comorbid 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). In a systematic review of patients with OCD who experienced switching, the manic/hypomanic episodes were more common within 12 weeks of antidepressant treatment initiation; however, episodes occurred up to 9 months in these patients (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)
• Females (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 (exposure during late gestation), 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). In addition, several trials and subsequent meta-analyses have found an increased risk of bone fracture with the use of SSRIs in stroke survivors (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). Conversely, the increased risk of bone fracture in stroke survivors who received an SSRI (fluoxetine) was no longer statistically significant at 12 months post-stroke (Ref).
Risk factors:
• Long-term use may be a risk factor (Ref)
Hypersensitivity reactions have been reported rarely with sertraline, including severe systemic reactions; reactions include acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS), acneiform eruption, lichenoid eruption and maculopapular rash (Ref). Sertraline has also been associated with lung diseases (eg, hypersensitivity pneumonitis, pulmonary fibrosis) and cutaneous lupus erythematosus have also been documented (Ref).
Mechanism: Non–dose-related; immunologic. Severe cutaneous adverse reactions, namely SJS/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, AGEP), are delayed type IV hypersensitivity reactions involving a T-cell mediated drug-specific immune response (Ref).
Onset: Intermediate; in the majority of cases, onset of symptoms generally occurred from 3 to 7 weeks after initiation of therapy (Ref).
Risk factors:
• Females (Ref)
• Cross-reactivity between selective serotonin reuptake inhibitors has not been established, but has been reported between paroxetine and sertraline (Ref)
Selective serotonin reuptake inhibitors (SSRIs) are associated with syndrome of inappropriate antidiuretic hormone secretion (SIADH) and/or hyponatremia (including severe cases), predominantly in older adults (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 with an SSRI (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 [MAO inhibitors]). Of note, concomitant use of some serotonergic agents, such as MAO inhibitors, 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). The impact on sexual health may be lessened with drug holidays; in an open-label trial, patients taking an SSRI (other than fluoxetine) who were instructed to not take their medication on the weekends (n=63) reported improved erection, ejaculation, satisfaction, and overall sexual health without significant worsening in their mental health status (Ref)
Mechanism: Dose-related (Ref); 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. 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 (Ref)), 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 (Ref))
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% (Ref)) (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, 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, 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 (Ref), torsades de pointes (Ref), vasculitis, ventricular tachycardia (Ref)
Dermatologic: Acneiform eruption (Ref), acute generalized exanthematous pustulosis (Ref), cutaneous lupus erythematosus (Ref), erythema multiforme (Ref), lichenoid eruption (Ref), skin photosensitivity, Stevens-Johnson syndrome (Ref), toxic epidermal necrolysis
Endocrine & metabolic: Gynecomastia (Ref), hyperglycemia (Ref), hyperprolactinemia, hyponatremia (literature suggests incidence of hyponatremia among SSRIs ranging from <1% to as high as 32%) (Ref), menstrual disease, secondary amenorrhea (Ref), SIADH (Ref), weight gain (slight increase, primarily in adults with long-term therapy) (Ref)
Gastrointestinal: Burning sensation of mouth (Ref), oromandibular dystonia (Ref), pancreatitis (Ref)
Genitourinary: Abnormal orgasm (Ref), decreased penile sensation (Ref)
Hematologic & oncologic: Agranulocytosis (Ref), aplastic anemia, coagulation time increased (altered platelet function) (Ref), Henoch-Schönlein purpura (Ref), immune thrombocytopenia (Ref), leukopenia, neutropenia (Ref), pancytopenia, purpuric disease (periorbital) (Ref)
Hepatic: Hepatic failure, hepatitis (Ref), hepatotoxicity (Ref), jaundice (Ref)
Hypersensitivity: Angioedema (Ref), hypersensitivity reaction (Ref), serum sickness
Nervous system: Akathisia (Ref), anosmia (including hyposmia), electric shock-like sensation (Ref), hyperactive behavior (including restlessness occurring in children at a two- to threefold higher incidence compared to adolescents (Ref)), hypomania (Ref), intracranial hemorrhage (Ref), mania (Ref), myoclonus (hypnic jerks) (Ref), neuroleptic malignant syndrome (Ref), nightmares, psychosis (Ref), reversible cerebral vasoconstriction syndrome (Ref), serotonin syndrome (Ref), suicidal ideation (children, adolescents) (Ref), suicidal tendencies (children, adolescents) (Ref), trismus (Ref), withdrawal syndrome (Ref)
Neuromuscular & skeletal: Bone fracture (Ref), dystonia (Ref), lupus-like syndrome (Ref), rhabdomyolysis (Ref)
Ophthalmic: Acute angle-closure glaucoma (Ref), blindness, cataract (Ref), maculopathy (Ref), oculogyric crisis, optic nerve damage (with papilledema) (Ref), optic neuritis
Renal: Acute kidney injury
Respiratory: Eosinophilic pneumonitis (Ref), hypersensitivity pneumonitis (Ref), 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:
• Bariatric surgery: Presurgical assessment of the indication for use, symptoms, and goals of therapy should be documented to enable postsurgical assessment. Small pharmacokinetic studies show wide interpatient variability with statistically significant decreases in sertraline exposure after bariatric surgery (Hamad 2012; Roerig 2012; Wallerstedt 2021). Monitor for continued efficacy after bariatric surgery and consider switching to an alternate medication if symptoms worsen.
• 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: 25 mg [scored; contains fd&c blue #1 (brill blue) aluminum lake, fd&c red #40(allura red ac)aluminum lake, quinoline (d&c yellow #10) aluminum lake]
Zoloft: 50 mg [scored; contains fd&c blue #2 (indigo carm) aluminum lake]
Zoloft: 100 mg [scored]
Zoloft: 100 mg [scored; contains polysorbate 80]
Generic: 25 mg, 50 mg, 100 mg
Yes
Capsules (Sertraline HCl Oral)
150 mg (per each): $6.48
200 mg (per each): $6.48
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): $17.88
50 mg (per each): $17.88
100 mg (per each): $17.88
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
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.
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).
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.
Major depressive disorder (unipolar): Treatment of unipolar major depressive disorder (MDD) in adults.
Obsessive-compulsive disorder: Treatment of obsessions and compulsions in patients with obsessive-compulsive disorder (OCD).
Panic disorder: Treatment of panic disorder with or without agoraphobia in adults.
Posttraumatic stress disorder: Treatment of posttraumatic stress disorder (PTSD) in adults.
Premenstrual dysphoric disorder: Treatment of premenstrual dysphoric disorder (PMDD) in adults.
Social anxiety disorder: Treatment of social anxiety disorder (social phobia) in adults.
Binge eating disorder; Body dysmorphic disorder; Bulimia nervosa; Generalized anxiety disorder; Premature ejaculation
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]).
Sertraline is identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age) with a history of recurrent falls due to an increased risk of falls. In addition, some disease states of concern include hyponatremia and recent or current significant bleeding (O’Mahony 2023).
Substrate of CYP2B6 (Minor), CYP2C19 (Minor), CYP2C9 (Minor), CYP2D6 (Minor), CYP3A4 (Major with inducers), CYP3A4 (Minor with inhibitors); 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.
Abciximab: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Abrocitinib: Agents with Antiplatelet Effects may increase antiplatelet effects of Abrocitinib. Risk X: Avoid
Acalabrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Agents with Blood Glucose Lowering Effects: Selective Serotonin Reuptake Inhibitor may increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Alcohol (Ethyl): May increase adverse/toxic effects of Selective Serotonin Reuptake Inhibitor. 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 increase serotonergic effects 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
Alosetron: May increase serotonergic effects 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
Amphetamines: May increase serotonergic effects 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
Anagrelide: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Anticoagulants (Miscellaneous Agents): Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Anticoagulants (Miscellaneous Agents). Risk C: Monitor
Antiemetics (5HT3 Antagonists): May increase serotonergic effects 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
Antiplatelet Agents (P2Y12 Inhibitors): Agents with Antiplatelet Effects may increase antiplatelet effects of Antiplatelet Agents (P2Y12 Inhibitors). Risk C: Monitor
Antipsychotic Agents: Serotonergic Agents (High Risk) may increase adverse/toxic effects of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor
Aspirin: Selective Serotonin Reuptake Inhibitor may increase antiplatelet effects of Aspirin. Risk C: Monitor
Brexanolone: Selective Serotonin Reuptake Inhibitor may increase CNS depressant effects of Brexanolone. Risk C: Monitor
Bromopride: May increase adverse/toxic effects of Selective Serotonin Reuptake Inhibitor. Risk X: Avoid
BuPROPion: May increase adverse/toxic effects of Sertraline. Risk C: Monitor
BusPIRone: May increase serotonergic effects 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
Caplacizumab: Agents with Antiplatelet Effects may increase adverse/toxic effects of Caplacizumab. Specifically, the risk of bleeding may be increased. Risk C: Monitor
CarBAMazepine: May decrease serum concentration of Sertraline. Risk C: Monitor
Citalopram: May increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. This could result in serotonin syndrome. Citalopram may increase antiplatelet effects of Selective Serotonin Reuptake Inhibitor. 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
Collagenase (Systemic): Agents with Antiplatelet Effects may increase adverse/toxic effects of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor
Cyclobenzaprine: May increase serotonergic effects 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
CYP3A4 Inducers (Moderate): May decrease serum concentration of Sertraline. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Sertraline. Risk C: Monitor
Cyproheptadine: May decrease therapeutic effects of Selective Serotonin Reuptake Inhibitor. Risk C: Monitor
Dapoxetine: May increase serotonergic effects 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
Darunavir: May decrease serum concentration of Sertraline. Risk C: Monitor
Dasatinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Deoxycholic Acid: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Desmopressin: Hyponatremia-Associated Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor
Dexmethylphenidate-Methylphenidate: May increase serotonergic effects 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
Dextromethorphan: May increase serotonergic effects 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
Dipyrone: May decrease serum concentration of Sertraline. Risk C: Monitor
Direct Oral Anticoagulants (DOACs): Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Direct Oral Anticoagulants (DOACs). Risk C: Monitor
Disulfiram: May increase adverse/toxic effects of Products Containing Ethanol. Management: Do not use disulfiram with dosage forms that contain ethanol. Risk X: Avoid
DULoxetine: Selective Serotonin Reuptake Inhibitor may increase serotonergic effects of DULoxetine. This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitor may increase antiplatelet effects of DULoxetine. 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
Eletriptan: May increase serotonergic effects 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
Epinephrine (Racemic): Selective Serotonin Reuptake Inhibitor may increase adverse/toxic effects of Epinephrine (Racemic). Risk X: Avoid
Ergot Derivatives: May increase serotonergic effects 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
Erythromycin (Systemic): May increase adverse/toxic effects of Sertraline. Risk C: Monitor
Fenfluramine: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor
Fondaparinux: Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Fondaparinux. Risk C: Monitor
Fosphenytoin-Phenytoin: Sertraline may increase serum concentration of Fosphenytoin-Phenytoin. Fosphenytoin-Phenytoin may decrease serum concentration of Sertraline. Risk C: Monitor
Gepirone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor
Gilteritinib: May decrease therapeutic effects of Selective Serotonin Reuptake Inhibitor. 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
Glycoprotein IIb/IIIa Inhibitors: Agents with Antiplatelet Effects may increase antiplatelet effects of Glycoprotein IIb/IIIa Inhibitors. Risk C: Monitor
Grapefruit Juice: May increase serum concentration of Sertraline. Risk C: Monitor
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may increase QTc-prolonging effects of Haloperidol. Risk C: Monitor
Heparin: Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Heparin. Risk C: Monitor
Heparins (Low Molecular Weight): Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Heparins (Low Molecular Weight). Risk C: Monitor
Herbal Products with Anticoagulant/Antiplatelet Effects: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Ibritumomab Tiuxetan: Agents with Antiplatelet Effects may increase antiplatelet effects of Ibritumomab Tiuxetan. Risk C: Monitor
Ibrutinib: Agents with Antiplatelet Effects may increase adverse/toxic effects of Ibrutinib. Specifically, the risk of bleeding and hemorrhage may be increased. Risk C: Monitor
Inotersen: Agents with Antiplatelet Effects may increase adverse/toxic effects of Inotersen. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Ioflupane I 123: Coadministration of Selective Serotonin Reuptake Inhibitor and Ioflupane I 123 may alter diagnostic results. Risk C: Monitor
Lasmiditan: May increase serotonergic effects 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
Levoketoconazole: QT-prolonging Agents (Indeterminate Risk - Avoid) may increase QTc-prolonging effects 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
Levomethadone: May increase serotonergic effects 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
Limaprost: May increase adverse/toxic effects of Agents with Antiplatelet Effects. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Linezolid: May increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. This could result in serotonin syndrome. Risk X: Avoid
Metaxalone: May increase serotonergic effects 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
Methadone: May increase serotonergic effects 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
Methotrimeprazine: May increase CNS depressant effects of Products Containing Ethanol. Management: Avoid products containing alcohol in patients treated with methotrimeprazine. Risk X: Avoid
Methylene Blue: Selective Serotonin Reuptake Inhibitor may increase serotonergic effects of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid
Metoclopramide: May increase serotonergic effects 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
MetroNIDAZOLE (Systemic): May increase adverse/toxic effects of Products Containing Ethanol. A disulfiram-like reaction may occur. Risk X: Avoid
MetroNIDAZOLE (Topical): May increase adverse/toxic effects of Products Containing Ethanol. A disulfiram-like reaction may occur. Risk C: Monitor
Miscellaneous Antiplatelets: Agents with Antiplatelet Effects may increase antiplatelet effects of Miscellaneous Antiplatelets. Risk C: Monitor
Mivacurium: Selective Serotonin Reuptake Inhibitor may increase serum concentration of Mivacurium. Risk C: Monitor
Monoamine Oxidase Inhibitors (Antidepressant): Selective Serotonin Reuptake Inhibitor may increase serotonergic effects of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid
Nefazodone: May increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. 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
Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Selective Serotonin Reuptake Inhibitor may increase antiplatelet effects of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective) may decrease therapeutic effects of Selective Serotonin Reuptake Inhibitor. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents (Nonselective): Selective Serotonin Reuptake Inhibitor may increase antiplatelet effects of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may decrease therapeutic effects of Selective Serotonin Reuptake Inhibitor. 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 increase antiplatelet effects of Selective Serotonin Reuptake Inhibitor. Risk C: Monitor
Obinutuzumab: Agents with Antiplatelet Effects may increase adverse/toxic effects of Obinutuzumab. Specifically, the risk of bleeding may be increased. Management: Consider avoiding coadministration of obinutuzumab and agents with antiplatelet effects, especially during the first cycle of obinutuzumab therapy. Risk D: Consider Therapy Modification
Ondansetron: May increase serotonergic effects 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
Opioid Agonists (metabolized by CYP3A4 and CYP2D6): May increase serotonergic effects 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
Opioid Agonists (metabolized by CYP3A4): May increase serotonergic effects 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
Opioid Agonists: May increase serotonergic effects 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
Opipramol: May increase serotonergic effects 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
Oxitriptan: Serotonergic Agents (High Risk) may increase serotonergic effects 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
OxyCODONE: May increase serotonergic effects 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
Pentosan Polysulfate Sodium: Agents with Antiplatelet Effects may increase adverse/toxic effects of Pentosan Polysulfate Sodium. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor
Pimozide: Selective Serotonin Reuptake Inhibitor may increase adverse/toxic effects of Pimozide. Risk X: Avoid
Pirtobrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Psilocybin: Antidepressants may decrease therapeutic effects of Psilocybin. Risk C: Monitor
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may increase QTc-prolonging effects 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
Ramosetron: May increase serotonergic effects 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
Rasagiline: Selective Serotonin Reuptake Inhibitor may increase serotonergic effects of Rasagiline. This could result in serotonin syndrome. Risk X: Avoid
Safinamide: May increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. This could result in serotonin syndrome. Risk X: Avoid
Secnidazole: Products Containing Ethanol may increase adverse/toxic effects of Secnidazole. Risk X: Avoid
Selective Serotonin Reuptake Inhibitor: May increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitor may increase antiplatelet effects of Selective Serotonin Reuptake Inhibitor. 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
Selegiline: Selective Serotonin Reuptake Inhibitor may increase serotonergic effects of Selegiline. This could result in serotonin syndrome. Risk X: Avoid
Selumetinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Serotonergic Agents (High Risk, Miscellaneous): May increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. 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
Serotonergic Non-Opioid CNS Depressants: Selective Serotonin Reuptake Inhibitor may increase serotonergic effects 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
Serotonergic Opioids (High Risk): May increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. 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
Serotonin 5-HT1D Receptor Agonists (Triptans): May increase serotonergic effects 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
Serotonin/Norepinephrine Reuptake Inhibitor: Selective Serotonin Reuptake Inhibitor may increase serotonergic effects of Serotonin/Norepinephrine Reuptake Inhibitor. This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitor may increase antiplatelet effects of Serotonin/Norepinephrine Reuptake Inhibitor. 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
St John's Wort: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease 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
Succinylcholine: Sertraline may increase serum concentration of Succinylcholine. Risk C: Monitor
Syrian Rue: May increase serotonergic effects 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
Thiazide and Thiazide-Like Diuretics: Selective Serotonin Reuptake Inhibitor may increase hyponatremic effects of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor
Thioridazine: CYP2D6 Inhibitors (Weak) may increase 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 Effects may increase adverse/toxic effects of Thrombolytic Agents. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Thyroid Products: Selective Serotonin Reuptake Inhibitor may decrease therapeutic effects of Thyroid Products. Thyroid product dose requirements may be increased. Risk C: Monitor
Tilidine: May increase serotonergic effects 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
Tipranavir: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
TraMADol: May increase adverse/toxic effects of Selective Serotonin Reuptake Inhibitor. 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
Tricyclic Antidepressants: Sertraline may increase serotonergic effects of Tricyclic Antidepressants. Sertraline may increase 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
Vasopressin: Drugs Suspected of Causing SIADH may increase therapeutic effects of Vasopressin. Specifically, the pressor and antidiuretic effects of vasopressin may be increased. Risk C: Monitor
Venlafaxine: Selective Serotonin Reuptake Inhibitor may increase antiplatelet effects of Venlafaxine. Selective Serotonin Reuptake Inhibitor may increase serotonergic effects 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
Vitamin E (Systemic): May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Vitamin K Antagonists: Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor
Volanesorsen: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Vortioxetine: May increase serotonergic effects of Selective Serotonin Reuptake Inhibitor. This could result in serotonin syndrome. Vortioxetine may increase antiplatelet effects of Selective Serotonin Reuptake Inhibitor. 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
Zanubrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Ziprasidone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor
Zolpidem: Sertraline may increase serum concentration of Zolpidem. Risk C: Monitor
Evaluate pregnancy status prior to initiating treatment in patients who could become pregnant. Treatment should not be withheld, but pharmacologic management may vary based on reproductive status, severity of illness, and history of antidepressant response (ACOG 2023, WFSBP [Dodd 2018]). When treating depression, anxiety, obsessive-compulsive disorder (OCD), or post-traumatic stress disorder, selective serotonin reuptake inhibitors (SSRIs) are preferred for use prior to conception in patients who are treatment naive or who do not have a history of effective treatment. Patients effectively treated may continue their current medication when planning a pregnancy unless contraindications exist (BAP [McAllister-Williams 2017]). Management of mental health conditions in patients who could become pregnant should be based on a shared decision-making process that considers the possibility of pregnancy during treatment (ACOG 2023; BAP [McAllister-Williams 2017]; CANMAT [MacQueen 2016]).
Sertraline is also approved for the treatment of premenstrual dysphoric disorder. Symptom-onset dosing, which is initiated on the day of symptom onset and continued until after the start of menses, may be beneficial in patients attempting to conceive (Lanza di Scalea 2019; Yonkers 2015).
Menstrual irregularities, including amenorrhea have been reported following use of sertraline (Ekinci 2019; Peritogiannis 2007). SSRI use may cause hyperprolactinemia and rarely changes in thyroid function, both of which can be associated with menstrual irregularities. Depression is also associated with menstrual changes (Padda 2021).
Some studies suggest SSRIs may reversibly impair semen parameters, including the motility of spermatozoa; use of other treatments may be preferred in male patients planning a pregnancy (ISSM [Althof 2014]; Sylvester 2019). SSRIs are associated with an increased risk of sexual dysfunction (Tarchi 2023). Sertraline may delay ejaculation and is used off label for the treatment of premature ejaculation (ISSM [Althof 2014]; Sathianathen 2021).
Sertraline and the active metabolite desmethylsertraline (DCT) can be detected in cord blood and amniotic fluid (Phogole 2023; Yue 2023).
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. Overall, an increased risk of major congenital malformations has not been observed with sertraline when considering differences in study design and confounders ; data evaluating the risk of specific defects are inconclusive (ACOG 2023; Anderson 2020; BAP [McAllister-Williams 2017]; Biffi 2020; Fitton 2020; Gao 2018; Lebin 2022).
Adverse effects in the newborn following SSRI exposure in the third trimester include neonatal adaptation syndrome and persistent pulmonary hypertension of the newborn (PPHN). Neonatal adaptation syndrome can occur shortly after birth and typically resolves within 2 weeks. Mechanisms of neonatal adaptation syndrome are not well understood but may be due to either SSRI toxicity or withdrawal. Reducing the dose or discontinuing the SSRI prior to delivery to reduce the risk of neonatal adaptation syndrome is not recommended (ACOG 2023). Symptoms 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.
PPHN is a rare complication of SSRI use during pregnancy with symptoms of respiratory distress within the first hours of life and an increased risk of neonatal mortality (ACOG 2023). Monitoring of infants exposed to SSRIs late in pregnancy is recommended (Masarwa 2019; Ng 2019). Data related to the long-term effects of in utero SSRI exposure on infant neurodevelopment and behavior are limited (CANMAT [MacQueen 2016]; Lebin 2022).
SSRIs may increase the risk of bleeding. Exposure late in pregnancy is associated with less than a 2-fold increase in postpartum hemorrhage. The clinical significance of this is uncertain (BAP [McAllister-Williams 2017]; Lebin 2022).
Due to pregnancy-induced physiologic changes some pharmacokinetic parameters of sertraline may be altered. Serum concentrations may be decreased in the third trimester; however, sertraline has a wide therapeutic reference range, and dose adjustments may not always 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; Stika 2022).
Untreated and undertreated mental health conditions are associated with adverse pregnancy outcomes. Untreated or undertreated depression is associated with preterm birth, low birth weight (LBW), preeclampsia, postpartum depression, and impaired infant attachment (associated with long-term developmental effects). Anxiety disorders during pregnancy are associated with LBW, preterm birth, and adverse behavioral outcomes in the offspring. Untreated bipolar disorder is associated with fetal growth restriction, preterm birth, adverse neurodevelopment, and may increase the risk of postpartum psychosis. Discontinuing effective medications during pregnancy increases the risk of symptom relapse. Management should be made as part of a shared decision-making process (ACOG 2023). Patients effectively treated for depression, anxiety, obsessive-compulsive disorder or post-traumatic stress disorder prepregnancy may use the same medication during pregnancy unless contraindications exist (ACOG 2023; BAP [McAllister-Williams 2017]; CANMAT [MacQueen 2016]). Treatment should not be withheld or discontinued based only on pregnancy status (ACOG 2023).
SSRIs are preferred for use in pregnant patients who are treatment naive or who do not have a history of effective treatment with another medication. Sertraline is a preferred option for pregnant patients with no prior medication history (ACOG 2023). SSRI dosing should be initiated with half the lowest recommended dose and titrated gradually over 4 to 10 days. Dose adjustments may be required as pregnancy progresses to keep symptoms in remission (ACOG 2023).
When medications are used, the lowest effective dose of a single agent is recommended. Optimize dosing prior to changing a medication or adding additional agents whenever possible. Monthly monitoring for symptom improvement with a validated screening tool during pregnancy is recommended. Manage side effects as needed (ACOG 2023).
Data collection to monitor pregnancy and infant outcomes following exposure to antidepressant medications is ongoing. Pregnant patients 45 years of age and younger with a history of psychiatric illness are encouraged to enroll in the National Pregnancy Registry for Antidepressants (1-866-961-2388 or https://womensmentalhealth.org/research/pregnancyregistry/antidepressants).
Sertraline and the active metabolite desmethylsertraline (DCT) are present in breast milk.
Multiple reports summarize data related to the presence of sertraline in breast milk:
• Using data from 53 mother-infant pairs, the manufacturer notes sertraline concentrations in exclusively breastfed infants is 2% (range: 0% to 15%) of the mother's serum concentration.
• The relative infant dose (RID) of sertraline has been calculated in review articles to be 0.05% to 3.7% of the weight-adjusted maternal dose (Berle 2011; Orsolini 2015). In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000). However, some sources note breastfeeding should only be considered if the RID is <5% for psychotropic agents (Anderson 2021).
• A review article used pooled data from 145 mother/infant pairs to calculate the estimated daily infant dose of sertraline via breast milk to be 0.4 mg/day, providing a RID of 0.5% to 3%. The maternal dose and actual breast milk concentrations for the calculation were not provided (Berle 2011).
• A second review included information from 279 cases; maternal daily doses of sertraline were 25 to 300 mg/day. The highest breast milk concentrations of sertraline presented were 670 to 4,640 ng/mL following maternal doses of 50 to 200 mg/day from a study of 8 women 5 to 58 weeks postpartum, providing a RID of 2.2%; the DCT metabolite was also present in breast milk. Sertraline and DCT were detected in the serum of some infants (Orsolini 2015).
• A study published since these reviews included 9 lactating women taking sertraline 25 to 75 mg/day; the sertraline breast milk concentrations and RID fell within the ranges presented in the earlier reviews (Pogliani 2019).
• Data are available from 6 lactating patients evaluated for sertraline breast milk levels 1 to 7 days postpartum. All were at steady state when sampling occurred. The median sertraline dose was 50 mg/day (range 25 to 100 mg). Median concentrations of sertraline were 11.3 ng/mL (breast milk, range 3.6 to 35.7 ng/mL) and 9.55 ng/mL (maternal serum, range 3.3 to 17.8 ng/mL). Authors of the study calculated the absolute infant dose of sertraline via breast milk to be 0.0016 mg/kg/day (range 0.0005 to 0.0054 mg/kg/day) (Schoretsanitis 2019).
• Peak milk concentrations occurred 7 to 8 hours (sertraline) and 5 to 11 hours (DCT) after the maternal dose (Stowe 1997). However, avoiding breastfeeding during the expected peak concentrations will generally not decrease infant exposure significantly for antidepressants with long half-lives (Berle 2011). DCT milk concentrations were higher than sertraline in some cases (Orsolini 2015; Pinheiro 2015).
• Concentrations of sertraline in breast milk are lower than other preferred antidepressants (ACOG 2023).
• A significant relationship between maternal and infant sertraline serum concentrations has not been observed (Pinheiro 2015; Schoretsanitis 2019).
Adverse events following exposure to selective serotonin reuptake inhibitors (SSRIs) via breast milk have been reported in some infants (Lanza di Scalea 2009; Orsolini 2015). Adverse events to the infant following exposure to sertraline via breast milk are limited in comparison to other SSRIs (Orsolini 2015). Infants exposed to an SSRI via breast milk should be monitored for irritability and changes in sleep, feeding patterns, and behavior as well as growth and development (ABM [Sriraman 2015]; BAP [McAllister-Williams 2017]; Weissman 2004).
Maternal use of an SSRI during pregnancy may delay lactogenesis (Marshall 2010); however, the underlying maternal illness and various other factors may also influence this outcome. Patients who wish to breastfeed during treatment with an SSRI may need additional assistance to initiate and maintain breastfeeding (Anderson 2021).
According to the manufacturer the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Patients effectively treated for depression, anxiety, obsessive-compulsive disorder, or post-traumatic stress disorder during pregnancy may continue their medication postpartum unless contraindications to breastfeeding exist. The presence and concentration of the drug in breast milk, efficacy of maternal treatment, and infant age should be considered when initiating a medication for the first-time postpartum. When first initiating an antidepressant in a patient who is treatment naive and breastfeeding, sertraline is one of the preferred SSRIs (ABM [Sriraman 2015]; CANMAT [MacQueen 2016). Breastfeeding may be continued in patients treated with an SSRI during pregnancy (ABM [Sriraman 2015], ACOG 2023). Treatment should not be withheld or discontinued based only on breastfeeding status (ACOG 2023).
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); 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
