Version July 2025
Antidepressants increase the risk of suicidal thoughts and behaviors 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. Trazodone is not approved for use in pediatric patients.
Aggressive or agitated behavior associated with dementia (alternative agent) (off-label use): Based on limited data: Oral: Initial: 25 to 50 mg once daily at bedtime; may increase dose gradually based on response and tolerability up to 300 mg/day in 1 to 3 divided doses (Ref). Some experts target doses in the lower end of the dosing range, rarely using doses as high as 100 to 150 mg/day (Ref).
Insomnia, sleep onset and sleep maintenance (alternative agent) (off-label use):
Note: Limit long-term use (>4 weeks) to cases for which nonpharmacologic treatments are not available or not effective and benefits are felt to outweigh risks (Ref).
Oral: Usual dose: 50 mg to 100 mg at bedtime (Ref). Note: Lower initial doses of 12.5 to 50 mg at bedtime may be considered (eg, in palliative care patients) (Ref). May consider increasing dose based on response and tolerability up to 200 mg at bedtime (eg, in patients with substance use disorder) (Ref). In patients with substance use disorder, trazodone may be preferred due to its low abuse potential (Ref).
Insomnia in patients with depression (as adjunct to other appropriate antidepressant treatment [eg SSRI]): Oral: Usual dose: 50 to 300 mg at bedtime. Doses up to 600 mg/day have been evaluated; however, evidence of greater benefit is uncertain and adverse effects may be increased (Ref).
Major depressive disorder (unipolar) (alternative agent): Oral:
Initial: 50 mg twice daily; may increase in increments of 50 mg/day every 3 to 7 days to a target dose of 75 to 150 mg twice daily. Thereafter may further increase by 50 to 100 mg/day every 2 to 4 weeks based on response and tolerability; usual dosage range 200 to 400 mg/day; maximum 600 mg/day. Note: Adverse effects are increased with doses >400 mg/day and are not recommended in patients with cardiovascular disease; sedative effects may be better tolerated by dividing the daily dose to give a smaller dose in daytime and larger dose before bedtime (Ref).
Manufacturer’s labeling: Dosing in prescribing information may not reflect current clinical practice. Initial: 150 mg/day in divided doses; maximum dose: 600 mg/day (inpatients); 400 mg/day (outpatients).
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 treatment generally does not warrant taper (Ref). Reasons for a slower taper (eg, over 4 weeks) include 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 (Shelton 2001). 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).
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 trazodone.
Allow 14 days to elapse between discontinuing trazodone 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; titrate with caution (Ref).
Hemodialysis, Intermittent (thrice weekly): Not significantly dialyzed (Ref); no dosage adjustment necessary; titrate with caution (Ref).
Peritoneal dialysis: No dosage adjustment necessary; titrate with caution (Ref).
The hepatic 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: The effects of trazodone in patients with hepatic impairment have not been studied.
Hepatic impairment prior to treatment initiation:
Initial dose or dose titration in patients with preexisting liver cirrhosis:
Child-Turcotte-Pugh class A through C: Initial: Use the lowest recommended indication-specific dose; may gradually titrate based on response and tolerability with frequent monitoring for dose-related adverse effects (eg, oversedation) that may appear similar or additive to the presentation of hepatic encephalopathy (Ref). Do not exceed the usual indication-specific maximum recommended dose or 400 mg/day, whichever is less (Ref).
Dosage adjustment in patients with chronic, worsening hepatic function during treatment (eg progression from Child-Turcotte-Pugh Class A to B):
Progression from baseline to new Child-Turcotte-Pugh class A through C:
If underlying oversedation/encephalopathy is not present: No dosage adjustment necessary; monitor frequently for dose-related adverse effects (eg, oversedation) that may appear similar or additive to the presentation of hepatic encephalopathy (Ref).
If oversedation/encephalopathy is present: Consider 50% dose reduction weekly until symptoms resolve or stop therapy immediately if it is considered safe (Ref).
Acute worsening of hepatic function (eg requiring hospitalization):
Child-Turcotte-Pugh class A through C: Permanently discontinue therapy if trazodone-induced liver injury is suspected. If trazodone-induced liver injury has been ruled out, may continue trazodone therapy with no dosage adjustment necessary (Ref). However, if trazodone-related adverse effects (eg, oversedation, QT prolongation, orthostasis) and/or new or worsening encephalopathy are observed (Ref), consider permanent discontinuation of trazodone or use of alternative therapy as appropriate after acute event resolves (Ref).
Major depressive disorder (unipolar) (alternative agent): Oral: Initial: 25 to 50 mg at bedtime; may increase in increments of 25 to 50 mg/day every 3 days for inpatients and weekly for outpatients, if tolerated; usual dose: 75 to 150 mg/day.
Discontinuation of therapy: Refer to adult dosing.
Switching antidepressants: Refer to adult dosing.
(For additional information see "Trazodone: Pediatric drug information")
Insomnia; sleep disturbances: Limited data available; frequently used clinically in children with comorbid neuropsychiatric disorders (eg, autistic spectrum disorders [ASDs], neurogenetic disorders, mood disorders, anxiety disorders, developmental delay with attention-deficit hyperactivity disorder) (Ref). Due to possible risk of QT prolongation, it is suggested to avoid or use with caution in patients with Rett syndrome (Ref).
Children 18 months to <3 years: Oral: Initial: 1 to 2 mg/kg/dose at bedtime; maximum dose: 25 mg/dose; may increase dose at 2-week intervals in 12.5 to 25 mg increments up to 3 mg/kg/dose once daily at bedtime, not to exceed a maximum dose: 100 mg/dose (Ref). Note: Pharmacokinetic analysis based on simulation reported that the following age-dependent pediatric doses resulted in exposures similar to adult doses of 30 to 150 mg/day: Children 2 to 6 years: 0.35 to 1.6 mg/kg/day; experiential data are needed to fully assess (Ref).
Children 3 to 5 years: Oral: Initial: 1 to 2 mg/kg/dose at bedtime; maximum dose: 50 mg/dose; may increase dose at 2-week intervals in 12.5 to 25 mg increments up to 3 mg/kg/dose once daily at bedtime, not to exceed a maximum dose: 150 mg/dose (Ref). Note: Pharmacokinetic analysis based on simulation reported that the following age-dependent pediatric doses resulted in exposures similar to adult doses of 30 to 150 mg/day: Children 2 to 6 years: 0.35 to 1.6 mg/kg/day; experiential data are needed to fully assess (Ref).
Children >5 years and Adolescents: Oral: Initial: 0.75 to 1 mg/kg/dose or 25 to 50 mg at bedtime; may increase at 2-week intervals in 12.5 to 25 mg increments up to a maximum dose of 200 mg/dose; reported range: 0.5 to 2 mg/kg/day (Ref). When used for palliative care, multiple daily doses may be necessary; in patients >18 years of age, 25 to 50 mg/dose increased gradually to twice or 3 times daily as needed (do not exceed adult dosing) (Ref). Note: Pharmacokinetic analysis based on simulation reported that the following age-dependent pediatric doses resulted in exposures similar to adult doses of 30 to 150 mg/day: Children >6 to 12 years: 0.4 to 1.9 mg/kg/day and Adolescents: 0.4 to 2.1 mg/kg/day (Ref); experiential data are needed to fully assess.
Migraine, prophylaxis: Limited data available: Note: Efficacy results variable; expert recommendations for migraine prevention in children and adolescents do not suggest trazodone as a routine therapeutic option (Ref).
Children ≥7 years and Adolescents: Oral: 1 mg/kg/day in 3 divided doses; maximum dose: 150 mg/dose (Ref).
Discontinuation of therapy: Due to short half-life of trazodone, avoid abrupt discontinuation to minimize the incidence of withdrawal symptoms, rebound insomnia, or increased nightmares as a result of REM sleep rebound. Evidence supporting ideal taper rates is limited. APA and NICE guidelines suggest tapering therapy over at least several weeks with consideration to the half-life of the drug; drugs with a shorter half-life may need to be tapered more conservatively. If intolerable withdrawal symptoms occur following a dose reduction, consider resuming the previously prescribed dose and/or decrease dose at a more gradual rate (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 specific pediatric dosage adjustments; in adult patients, no dosage adjustment is necessary for mild to moderate kidney impairment, and titration should be done with caution. Not significantly dialyzed (Ref).
There are no dosage adjustments provided in the manufacturer's labeling. Use with caution.
Antidepressants may precipitate a mixed/manic episode in patients with bipolar disorder. Treatment-emergent mania or hypomania in patients with unipolar major depressive disorder (MDD) have been reported, as many cases of bipolar disorder present in episodes of MDD (Ref).
Mechanism: Non-dose-related; idiosyncratic; unclear to what extent mood switches represent an uncovering of unrecognized bipolar disorder or a more direct pharmacologic effect independent of diagnosis (Ref). May interfere with the balance of neurotransmitter systems when trazodone is added to other antidepressant therapies, like selective serotonin reuptake inhibitors (SSRIs) (eg, sertraline) (Ref).
Onset: Varied; onset may vary from 4 days to 4 weeks (Ref). A systematic review observed that the risk of switching increased significantly within the initial 2 years of antidepressant treatment in patients with unipolar MDD receiving an antidepressant as monotherapy but not thereafter (up to 4.6 years) (Ref).
Risk factors:
• Family history of bipolar disorder (Ref)
• Depressive episode with psychotic symptoms (Ref)
• Younger age at onset of depression (Ref)
• Antidepressant resistance (Ref)
• Female sex (Ref)
Trazodone may increase the risk of bleeding, particularly if used concomitantly with antiplatelet and/or anticoagulants. Multiple observational studies with other drugs that interfere with serotonin reuptake (eg, selective serotonin reuptake inhibitors [SSRIs]) have found an association with use and a variety of bleeding complications. Similar to these agents, trazodone may increase the risk of bleeding; however, the risk may be lower (Ref).
Mechanism: Possibly via inhibition of serotonin-mediated platelet activation and subsequent platelet dysfunction (Ref).
Onset : Varied; per SSRI-derived literature (ie, trazodone not included), bleeding risk is likely delayed for several weeks until SSRI-induced platelet serotonin depletion becomes clinically significant (Ref).
Risk factors:
• Concomitant use of antiplatelets and/or anticoagulants (based on SSRI-derived literature) (Ref)
• Preexisting platelet dysfunction or coagulation disorders (eg, von Willebrand factor) (Ref)
Cardiac arrhythmias, including prolonged QT interval on ECG (with or without torsades de pointes [TdP]) and ventricular tachycardia, have been reported. Other arrhythmias identified include ventricular premature contractions, ventricular couplets, tachycardia with syncope, sinus bradycardia, first-degree atrioventricular block, and complete atrioventricular block (Ref).
Mechanism: Dose-related (generally, although may also occur at low to moderate doses); QT prolongation may be a result of the concentration-dependent inhibition of human ether-à-go-go (hERG) channel current (Ref).
Risk factors:
Risk factors for drug-induced QT prolongation (in general):
• Females (Ref)
• Age >65 years (Ref)
• Structural heart disease (eg, history of myocardial infarction or heart failure with reduced ejection fraction) (Ref)
• History of drug-induced TdP (Ref)
• Genetic defects of cardiac ion channels (Ref)
• Congenital long QT syndrome (Ref)
• Baseline QTc interval prolongation (eg, >500 msec or lengthening of the QTc by ≥60 msec) (Ref)
• Electrolyte disturbances (eg, hypokalemia, hypocalcemia, hypomagnesemia) (Ref)
• Bradycardia (Ref)
• Hepatic impairment (Ref)
• Kidney impairment (Ref)
• Coadministration of multiple medications (≥2) that prolong the QT interval or increase drug interactions that increase serum drug concentrations of QTc prolonging medications (Ref)
• Substance use (Ref)
Trazodone can cause acute hepatitis, including transaminitis, elevated bilirubin, and symptomatic jaundice, consistent with mixed hepatocellular-cholestatic injury (Ref). Trazodone-induced hepatotoxicity is limited to case reports that resolved after cessation of therapy; however, there are cases that resulted in liver transplant and death (Ref). Two cases describe components of autoimmune hepatitis (eg, eosinophilia, eosinophils on liver biopsy) (Ref). Liver biochemistries normalization was delayed for weeks (eg, ≥2 to 4 weeks) following cessation of therapy (Ref).
Mechanism: Non–dose-related; idiosyncratic, non–dose-related (Ref).
Onset: Varied; 4 days to 18 months; quicker onset has also been observed with unintentional rechallenge (Ref).
Risk factors:
• Hypersensitivity to tricyclic antidepressants (Ref)
• Concurrent hepatotoxins (eg, phenothiazines) (Ref)
Trazodone may cause significant orthostatic hypotension, which may lead to syncope and subsequent falls and fracture (Ref).
Mechanism: Orthostatic hypotension is due to alpha-1 adrenergic receptor blockade (Ref).
Risk factors:
• Cerebrovascular disease
• Cardiovascular disease
• Hypovolemia/dehydration (Ref)
• Concurrent medication use that may predispose to hypotension/bradycardia (Ref)
• Older adults, especially in those with preexisting heart conditions (Ref)
Priapism has been reported rarely (Ref).
Mechanism: Related to the blockade of alpha receptors in the absence of sufficient antimuscarinic activity (Ref).
Onset: Intermediate; usually evident within 28 days of beginning treatment (Ref).
Risk factors:
• Sickle cell anemia
• Multiple myeloma
• Leukemia
• Anatomical deformation of the penis (eg, angulation, cavernosal fibrosis, Peyronie disease)
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, monoamine oxidase inhibitors [MAOIs]). Of note, concomitant use of some serotonergic agents, such as MAOIs, is contraindicated.
Antidepressants are associated with an increased risk of suicidal ideation and suicidal tendencies in pediatric and young adult patients (18 to 24 years) in short-term studies. In adults >24 years, 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 the risk extends to longer-term use (>4 months).
Risk factors:
• Children and adolescents (Ref)
• Depression (risk of suicide associated with major depression and may persist until remission occurs)
Withdrawal syndrome, consisting of both somatic symptoms (eg, dizziness, chills, lightheadedness, vertigo, shock-like sensations, paresthesia, fatigue, headache, nausea, tremor, diarrhea, visual disturbances) and psychological symptoms (eg, anxiety, agitation, confusion, insomnia, irritability), has been reported, primarily following the abrupt discontinuation of selective serotonin reuptake inhibitors (SSRIs) (including case reports with trazodone). 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 serotonergic agent. Other neurotransmission systems, including increased glutamine and dopamine, may also be affected, as well as effects on 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: Nausea and vomiting (10% to 13%), xerostomia (15% to 34%)
Nervous system: Dizziness (20% to 28%), drowsiness (24% to 41%), fatigue (6% to 11%), headache (10% to 20%), nervousness (15%)
Ophthalmic: Blurred vision (6% to 15%)
1% to 10%:
Cardiovascular: Chest pain (<2%), hypotension (4% to 7%) (table 1), palpitations (<2%), syncope (3% to 5%) (table 2), tachycardia (<2%)
|
Drug (Trazodone) |
Placebo |
Population |
Number of Patients (Trazodone) |
Number of Patients (Placebo) |
|---|---|---|---|---|
|
7% |
1% |
Inpatients |
142 |
95 |
|
4% |
0% |
Outpatients |
157 |
158 |
|
Drug (Trazodone) |
Placebo |
Population |
Number of Patients (Trazodone) |
Number of Patients (Placebo) |
|---|---|---|---|---|
|
3% |
2% |
Inpatients |
142 |
95 |
|
5% |
1% |
Outpatients |
157 |
158 |
Dermatologic: Dermatologic disorder (3% to 7%; including skin edema)
Endocrine & metabolic: Change in menstrual flow (missed menstrual periods: <2%), increased libido (<2%), weight gain (1% to 5%), weight loss (6%)
Gastrointestinal: Constipation (7% to 8%), diarrhea (5%), flatulence (<2%), gastrointestinal disease (6%), increased appetite (<2%), sialorrhea (<2%)
Genitourinary: Early menses (<2%), erectile dysfunction (<2%), hematuria (<2%), retrograde ejaculation (<2%), urinary frequency (<2%), urinary hesitancy (<2%)
Hematologic & oncologic: Anemia (<2%)
Hypersensitivity: Hypersensitivity reaction (<2%)
Nervous system: Akathisia (<2%), ataxia (2% to 5%), confusion (5%), delusion (<2%), disorientation (2%), hallucination (<2%), heavy headedness (3%), hypomania (<2%), lack of concentration (1% to 3%), malaise (3%), memory impairment (<2%), numbness (<2%), paresthesia (<2%), speech disturbance (<2%), tremor (3% to 5%)
Neuromuscular & skeletal: Muscle twitching (<2%), musculoskeletal pain (5% to 6%)
Ophthalmic: Asthenopia (≤3%), eye pruritus (≤3%), eye redness (≤3%)
Respiratory: Dyspnea (<2%), nasal congestion (≤6%), paranasal sinus congestion (≤6%)
Frequency not defined:
Cardiovascular: Hypertension, premature ventricular contractions, sinus bradycardia
Nervous system: Suicidal ideation, suicidal tendencies
Postmarketing:
Cardiovascular: Acute myocardial infarction, atrial fibrillation (Ref), bradycardia (Ref), cardiac arrhythmia, cardiac conduction disorder (conduction block), complete atrioventricular block (Ref), edema (Ref), first-degree atrioventricular block (Ref), heart failure, orthostatic hypotension (Ref), prolonged QT interval on ECG (Ref), torsades de pointes (Ref), ventricular ectopy, ventricular tachycardia (Ref)
Dermatologic: Alopecia, fixed drug eruption (lesions [including bullous]) (Ref), leukonychia (Ref), psoriasis (Ref), skin rash, urticaria
Endocrine & metabolic: Hirsutism, SIADH
Gastrointestinal: Cholestasis (Ref), esophageal achalasia
Genitourinary: Breast engorgement, breast hypertrophy, female sexual disorder (including clitoromegaly) (Ref), lactation, priapism (Ref), urinary incontinence, urinary retention
Hematologic & oncologic: Hemolytic anemia, leukocytosis, methemoglobinemia
Hepatic: Hepatotoxicity (Ref), increased serum alanine aminotransferase (Ref)
Nervous system: Abnormal dreams, anxiety, aphasia, cerebrovascular accident, delirium (Ref), extrapyramidal reaction (Ref), insomnia, mania (Ref), paranoid ideation, parkinsonism (Ref), psychosis (Ref), restless leg syndrome (Ref), seizure (Ref), serotonin syndrome (Ref), stupor, vertigo
Neuromuscular & skeletal: Orofacial dyskinesia (Ref), tardive dyskinesia (Ref)
Ophthalmic: Diplopia
Respiratory: Apnea
Hypersensitivity to trazodone or any component of the formulation; use of monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders (concurrently or within 14 days of discontinuing either trazodone or the MAOI); initiation of trazodone in a patient receiving IV methylene blue.
Note: Although trazodone 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:
• Bariatric surgery: Presurgical assessment of the indication for use, symptoms, and goals of therapy should be documented to enable postsurgical assessment. A small pharmacokinetic study shows wide interpatient variability with a trend toward decreased concentrations of trazodone after bariatric surgery (Garin 2023). Monitor for continued efficacy after bariatric surgery and consider switching to an alternate medication if symptoms worsen.
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).
• Falls: May cause falls and major osteoporotic fractures (eg, hip, pelvis, humerus, forearm) when used in elderly patients. The fall rate was found to be similar to the rates associated with antipsychotics and benzodiazepines (Bronskill 2018; Watt 2018).
• Ocular effects: May cause mild pupillary dilation, which can lead to an episode of narrow-angle glaucoma in susceptible individuals. Consider evaluating patients who have not had an iridectomy for narrow-angle glaucoma risk factors.
Disease-related concerns:
• Coronary artery disease: Not recommended for use in a patient during the acute recovery phase of MI due to exacerbation of arrhythmias.
• Hepatic impairment: Use with caution in patients with hepatic impairment; has not been studied in hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment.
• Seizure disorder: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications that may lower seizure threshold (Hill 2015).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Oral, as hydrochloride:
Raldesy: 10 mg/mL (150 mL, 300 mL) [contains edetate (edta) disodium, propylene glycol, sodium benzoate]
Tablet, Oral, as hydrochloride:
Generic: 50 mg, 100 mg, 150 mg, 300 mg
May be product dependent
Solution (Raldesy Oral)
10 mg/mL (per mL): $3.09
Tablets (traZODone HCl Oral)
50 mg (per each): $0.08 - $1.07
100 mg (per each): $0.15 - $1.39
150 mg (per each): $0.43 - $2.79
300 mg (per each): $5.44 - $12.56
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.
Tablet, Oral:
Generic: 75 mg
Tablet, Oral, as hydrochloride:
Generic: 50 mg, 100 mg, 150 mg
Oral: Administer shortly after a meal or light snack; swallow tablet whole or as a half tablet by breaking along the score line. Administer oral solution using the provided adapter and oral dosing syringe only.
Oral: Administer after meals or a snack to decrease lightheadedness, sedation, and postural hypotension; swallow whole or as a half tablet by breaking along the score line.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Desyrel: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018207s032lbl.pdf#page=13
Raldesy: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/218637s000lbl.pdf#page=12
Antidepressant medications: http://www.fda.gov/downloads/Drugs/DrugSafety/InformationbyDrugClass/ucm100211.pdf
Major depressive disorder (unipolar): Treatment of unipolar major depressive disorder
Aggressive or agitated behavior associated with dementia; Insomnia, sleep onset and sleep maintenance
Desyrel may be confused with deferoxamine, Demerol, Delsym, Seroquel, Zestril
TraZODone may be confused with traMADol, ziprasidone
Trazodone 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 recurrent falls (O’Mahony 2023).
Substrate of CYP2D6 (Minor), CYP3A4 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
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
Acrivastine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Alcohol (Ethyl): May increase adverse/toxic effects of TraZODone. Specifically, effects on sleepiness, dizziness, and manual dexterity may be enhanced. Risk C: Monitor
Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
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
Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. 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
Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification
Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Blonanserin: CNS Depressants may increase CNS depressant effects of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider Therapy Modification
Brexanolone: CNS Depressants may increase CNS depressant effects of Brexanolone. Risk C: Monitor
Brexanolone: Serotonin Reuptake Inhibitor/Antagonists may increase CNS depressant effects of Brexanolone. Risk C: Monitor
Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromopride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Buprenorphine: CNS Depressants may increase CNS depressant effects of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider Therapy Modification
BusPIRone: May increase CNS depressant effects of CNS Depressants. 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
Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. 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 TraZODone. TraZODone may increase serum concentration of CarBAMazepine. Management: Consider increasing the trazodone dose during coadministration with strong CYP3A4 inducers, such as carbamazepine. In addition, monitor for increased carbamazepine concentrations and effects during coadministration with trazodone. Risk D: Consider Therapy Modification
Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification
Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification
Chlormethiazole: May increase CNS depressant effects of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider Therapy Modification
Chlorphenesin Carbamate: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
CNS Depressants: May increase adverse/toxic effects of CNS Depressants. 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 TraZODone. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of TraZODone. Management: Consider increasing the trazodone dose during coadministration with strong CYP3A4 inducers. Risk D: Consider Therapy Modification
CYP3A4 Inhibitors (Moderate): May increase serum concentration of TraZODone. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of TraZODone. Management: Consider the use of a lower trazodone dose and monitor for increased trazodone effects (eg, sedation, QTc prolongation) if combined with strong CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Dantrolene: May increase CNS depressant effects of CNS Depressants. 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
Daridorexant: May increase CNS depressant effects of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
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
DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider Therapy Modification
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
Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Difenoxin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor
Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Direct Oral Anticoagulants (DOACs): Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Direct Oral Anticoagulants (DOACs). Risk C: Monitor
Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Doxylamine: CNS Depressants may increase CNS depressant effects of Doxylamine. Risk C: Monitor
DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification
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
Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor
Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Epinephrine (Racemic): Serotonin Reuptake Inhibitor/Antagonists 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
Esketamine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Fenfluramine: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor
Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid
Flunitrazepam: CNS Depressants may increase CNS depressant effects of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider Therapy Modification
Fondaparinux: Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Fondaparinux. Risk C: Monitor
Fosphenytoin: May decrease serum concentration of TraZODone. TraZODone may increase serum concentration of Fosphenytoin. Management: Consider increasing the trazodone dose during coadministration with strong CYP3A4 inducers, such as fosphenytoin. In addition, monitor for increased phenytoin concentrations and effects during coadministration with trazodone. Risk D: Consider Therapy Modification
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Gepirone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor
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 TraZODone. 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
HydrOXYzine: May increase CNS depressant effects of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider Therapy Modification
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
Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
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
Lemborexant: May increase CNS depressant effects of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider Therapy Modification
Levocetirizine: May increase CNS depressant effects of CNS Depressants. 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 Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Risk X: Avoid
Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofepramine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification
Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Melitracen [INT]: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
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
Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider Therapy Modification
Methoxyflurane: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methylene Blue: Serotonergic Non-Opioid CNS Depressants may increase serotonergic effects of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid
Metoclopramide: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
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
MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor
Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mirtazapine: TraZODone may increase serotonergic effects of Mirtazapine. This could result in serotonin syndrome. TraZODone may increase CNS depressant effects of Mirtazapine. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and CNS depression when these agents are combined. Risk C: Monitor
Miscellaneous Antiplatelets: Agents with Antiplatelet Effects may increase antiplatelet effects of Miscellaneous Antiplatelets. Risk C: Monitor
Monoamine Oxidase Inhibitors (Antidepressant): Serotonergic Non-Opioid CNS Depressants may increase serotonergic effects of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid
Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nefazodone: TraZODone may increase serotonergic effects of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase serum concentration of TraZODone. Management: Consider the use of a lower trazodone dose and monitor for increased trazodone effects such as sedation, QTc prolongation, and signs and symptoms of serotonin syndrome/serotonin toxicity when these agents are combined. Risk D: Consider Therapy Modification
Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid
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
Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
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
Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Opioid Agonists: CNS Depressants may increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Opipramol: May increase CNS depressant effects of CNS Depressants. 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
Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid
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
Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Oxybate Salt Products: CNS Depressants may increase CNS depressant effects of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider Therapy Modification
OxyCODONE: CNS Depressants may increase CNS depressant effects of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Paliperidone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid
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
Perampanel: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Phenytoin: May decrease serum concentration of TraZODone. TraZODone may increase serum concentration of Phenytoin. Management: Consider increasing the trazodone dose during coadministration with strong CYP3A4 inducers, such as phenytoin. In addition, monitor for increased phenytoin concentrations and effects during coadministration with trazodone. Risk D: Consider Therapy Modification
Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor
Pirtobrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Pizotifen: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor
Procarbazine: May increase CNS depressant effects of CNS Depressants. 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: May increase serotonergic effects of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Risk X: Avoid
Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider Therapy Modification
ROPINIRole: CNS Depressants may increase sedative effects of ROPINIRole. Risk C: Monitor
Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor
Safinamide: May increase serotonergic effects of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Risk X: Avoid
Saquinavir: May increase QTc-prolonging effects of TraZODone. Saquinavir may increase serum concentration of TraZODone. Risk X: Avoid
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
Selegiline: May increase serotonergic effects of Serotonergic Non-Opioid CNS Depressants. 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 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): Serotonergic Non-Opioid CNS Depressants may increase serotonergic effects of Serotonergic Opioids (High Risk). This could result in serotonin syndrome. Serotonergic Non-Opioid CNS Depressants may increase CNS depressant effects of Serotonergic Opioids (High Risk). Management: Consider alternatives to this drug combination. If combined, monitor for signs and symptoms of serotonin syndrome/serotonin toxicity and CNS depression. Risk D: Consider Therapy Modification
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: TraZODone may increase serotonergic effects of Serotonin/Norepinephrine 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
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
Suvorexant: CNS Depressants may increase CNS depressant effects of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
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
Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid
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
Tipranavir: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Tricyclic Antidepressants: May increase serotonergic effects of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Tricyclic Antidepressants may increase CNS depressant effects of Serotonergic Non-Opioid CNS Depressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and CNS depression when these agents are combined. Risk C: Monitor
Trimeprazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Vitamin E (Systemic): May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Vitamin K Antagonists: TraZODone may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor
Volanesorsen: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Warfarin: TraZODone may decrease anticoagulant effects of Warfarin. TraZODone may increase anticoagulant effects of Warfarin. 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: CNS Depressants may increase CNS depressant effects of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider Therapy Modification
Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification
Time to peak serum levels may be increased if taken with food. Management: Administer after a meal or light snack.
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, trazodone is not a first line medication 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]).
Trazodone and the active metabolite 1-m-chlorophenylpiperazine cross the placenta and can be detected in cord blood at delivery (Saito 2021).
Outcome data following maternal use of trazodone during pregnancy are limited. Based on available data, an increased risk of adverse pregnancy outcomes has not been observed following use of trazodone during pregnancy (Anderson 2020; Dao 2023; Einarson 2003; Einarson 2009). Long-term effects on neurodevelopment are not known (Korade 2021).
Untreated and undertreated mental health conditions are associated with adverse pregnancy outcomes. Untreated or undertreated depression is associated with preterm birth, low birth weight, preeclampsia, postpartum depression, and impaired infant attachment (associated with long-term developmental effects). Discontinuing effective medications during pregnancy increases the risk of relapse. Management should be made as part of a shared decision-making process (ACOG 2023). Patients effectively treated for depression prepregnancy may use the same medication during pregnancy unless contraindications exist (ACOG 2023; CANMAT [MacQueen 2016]; BAP [McAllister-Williams 2017]). Treatment should not be withheld or discontinued based only on pregnancy status. Trazodone is not a first line medication for pregnant patients who are treatment naive or who do not have a history of effective treatment with another medication. 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).
Trazodone has also been evaluated for the treatment of insomnia. A randomized, placebo-controlled study in pregnant patients found trazodone (n = 18) to improve total sleep duration and sleep efficacy after 6 weeks of treatment compared to placebo (n = 17). In addition, the risk of postpartum depression was decreased. Treatment began during the third trimester and patients had no underlying sleep or mood disorders prior to pregnancy. Daytime sleepiness was a common adverse event (Khazaie 2013). In nonpregnant patients, trazodone is not the preferred treatment when cognitive behavioral therapies are not adequate because harm outweighs benefit (AASM [Sateia 2017]). Cognitive behavioral therapy is also effective in pregnant patients and is the currently preferred treatment (Bacaro 2020).
Data collection to monitor pregnancy and infant outcomes following exposure to antidepressant medications is ongoing. Pregnant patients 45 years 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).
Trazodone and the active metabolite 1-m-chlorophenylpiperazine (mCPP) are present in breast milk (Saito 2021).
Data related to the presence of trazodone in breast milk are available from a study that administered a single dose of trazodone 50 mg to 6 otherwise healthy breastfeeding women, 3 to 8 months postpartum. Breast milk was sampled over 24 hours. The presence of trazodone metabolites was not evaluated. Trazodone concentrations in breast milk peaked about 2 hours following administration, approximately the same time as in the plasma (Verbeeck 1986). Using data from this study, the relative infant dose (RID) of trazodone was calculated to be 2% of the weight-adjusted maternal dose, based on the highest breast milk concentration (100 ng/mL), providing an estimated daily infant dose via breast milk of 0.015 mg/kg/day.
Data related to the presence of trazodone and mCPP in breast milk are available from a patient following use of trazodone 50 mg daily during pregnancy and postpartum. Breast milk was sampled after 5 days of therapy. The highest concentrations of trazodone (50.2 ng/mL) and mCPP (3.2 ng/mL) in breast milk were in the sample obtained 7.2 hours after a maternal dose. Using the highest breast milk concentration of trazodone, authors of this study calculated the RID to be 0.8% of the weight-adjusted maternal dose, providing an estimated daily infant dose via breast milk of 0.008 mg/kg/day. The infant was partially breastfed with >50% of nutrition from breast milk. Trazodone and mCPP were detected in infant serum 14.2 hours after birth (156.6 ng/mL and 9.8 ng/mL, respectively) and decreased significantly by postpartum day 5 (1.3 ng/mL and <0.2 ng/mL, respectively). This infant required oxygen due to a persistent respiratory disturbance for the first 4 days after birth (mother also taking etizolam); however, no drug-related adverse events were observed in the infant up to 6 months of age (Saito 2021).
In general, breastfeeding is considered acceptable when the RID 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).
Additional data related to the use of trazodone in patients who are breastfeeding are limited (Misri 1991; Misri 2006). Infants exposed to psychotropic medication via breast milk should be monitored for adverse effects (eg, over sedation, poor feeding) (BAP [McAllister-Williams 2017]).
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 benefits of treatment to the mother. Patients effectively treated for depression 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, an agent other than trazodone may be preferred (ABM [Sriraman 2015]; CANMAT [MacQueen 2016]).
Baseline liver function prior to and periodically during therapy; 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, and mania), particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); signs/symptoms of hypotension or orthostasis.
Inhibits reuptake of serotonin, causes adrenoreceptor subsensitivity, acts as a 5HT2a receptor antagonist and induces significant changes in 5-HT presynaptic receptor adrenoreceptors. Trazodone also significantly blocks histamine (H1) and alpha1-adrenergic receptors.
Onset of action: 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).
Absorption: Well absorbed. Food increases absorption, decreases peak concentration and delays time to peak concentration.
Protein binding: 89% to 95%.
Metabolism: Hepatic via CYP3A4 (extensive) to an active metabolite (mCPP).
Bioavailability: 100% (Hiemke 2018).
Half-life elimination: Oral solution: ~18 hours (fed state); tablet: 5 to 9 hours, prolonged in obese patients.
Time to peak, serum: Oral solution: ~60 minutes (fed state); tablet: 30 to 100 minutes; delayed with food (up to 2.5 hours).
Excretion: Primarily urine (74%, <1% excreted unchanged); secondarily feces (~21%).
