Version October 2024
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.
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.
(For additional information see "Trazodone: Drug information")
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, 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).
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 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, hypotension (4% to 7%) (table 1), palpitations, sinus bradycardia, syncope (3% to 5%) (table 2), tachycardia (may include syncope)
|
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 |
Endocrine & metabolic: Change in menstrual flow, increased libido, weight gain (1% to 5%), weight loss (6%)
Gastrointestinal: Constipation (7% to 8%), diarrhea (5%), flatulence, gastrointestinal disease (6%), increased appetite, sialorrhea
Genitourinary: Early menses, erectile dysfunction, hematuria, retrograde ejaculation, urinary frequency, urinary hesitancy
Hematologic & oncologic: Anemia
Hypersensitivity: Hypersensitivity reaction
Nervous system: Akathisia, ataxia (2% to 5%), confusion (5%), delusion, disorientation (2%), hallucination, heavy headedness (3%), hypomania, lack of concentration (1% to 3%), malaise (3%), memory impairment, numbness, paresthesia, speech disturbance, tremor (3% to 5%)
Neuromuscular & skeletal: Muscle twitching, myalgia (5% to 6%)
Ophthalmic: Asthenopia, eye pruritus, eye redness
Respiratory: Dyspnea, nasal congestion (≤6%), paranasal sinus congestion (≤6%)
Frequency not defined:
Cardiovascular: Hypertension, ventricular premature contractions
Nervous system: Suicidal ideation, suicidal tendencies
Postmarketing:
Cardiovascular: Acute myocardial infarction, atrial fibrillation (Ref), bradycardia (Ref), cardiac arrhythmia, cardiac conduction disorder, 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 (Ref), lactation, priapism (Ref), urinary incontinence, urinary retention
Hematologic & oncologic: Hemolytic anemia, leukocytosis, methemoglobinemia
Hepatic: Hepatotoxicity (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, tardive dyskinesia (Ref), vertigo
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:
• 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.
Tablet, Oral, as hydrochloride:
Generic: 50 mg, 100 mg, 150 mg, 300 mg
Yes
Tablets (traZODone HCl Oral)
50 mg (per each): $0.15 - $1.07
100 mg (per each): $0.21 - $1.39
150 mg (per each): $0.52 - $2.79
300 mg (per each): $5.44
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 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.
Oral: Administer shortly after a meal or light snack; swallow whole or as a half tablet by breaking along the score line.
Store at 20ºC to 25ºC (68ºF to 77ºF); excursions permitted between 15ºC to 30ºC (59ºF to 86ºF). Protect from light.
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
Antidepressant medications: http://www.fda.gov/downloads/Drugs/DrugSafety/InformationbyDrugClass/ucm100211.pdf
Treatment of depression, including major depressive disorder (FDA approved in adults); has also been used for treatment of insomnia (sleep disturbances) and prevention of migraines.
Desyrel may be confused with deferoxamine, Demerol, Delsym, Seroquel, Zestril
TraZODone may be confused with traMADol, ziprasidone
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.
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
Alcohol (Ethyl): May enhance the adverse/toxic effect of TraZODone. Specifically, effects on sleepiness, dizziness, and manual dexterity may be enhanced. Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Almotriptan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Alosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Amphetamines: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability). Initiate amphetamines at lower doses, monitor frequently, and adjust doses as needed. Risk C: Monitor therapy
Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Antipsychotic Agents: Serotonergic Agents (High Risk) may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect 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 enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brexanolone: Serotonin Reuptake Inhibitor/Antagonists may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect 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 enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
CarBAMazepine: May decrease the serum concentration of TraZODone. TraZODone may increase the 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
Chlormethiazole: May enhance the CNS depressant effect 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 enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Cyclobenzaprine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of TraZODone. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the 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 the serum concentration of TraZODone. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the 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
Dapoxetine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Do not use serotonergic agents (high risk) with dapoxetine or within 7 days of serotonergic agent discontinuation. Do not use dapoxetine within 14 days of monoamine oxidase inhibitor use. Dapoxetine labeling lists this combination as contraindicated. Risk X: Avoid combination
Daridorexant: May enhance the CNS depressant effect 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
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect 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 enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Dextromethorphan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy
DroPERidol: May enhance the CNS depressant effect 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 enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Epinephrine (Racemic): Serotonin Reuptake Inhibitor/Antagonists may enhance the adverse/toxic effect of Epinephrine (Racemic). Risk X: Avoid combination
Ergot Derivatives: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Fenfluramine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect 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
Fosphenytoin: May decrease the serum concentration of TraZODone. TraZODone may increase the 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 the 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 enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect 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
Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lasmiditan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Lemborexant: May enhance the CNS depressant effect 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
Linezolid: May enhance the serotonergic effect of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Risk X: Avoid combination
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lorcaserin (Withdrawn From US Market): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Loxapine: CNS Depressants may enhance the CNS depressant effect of Loxapine. Risk D: Consider therapy modification
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Metaxalone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect 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
Methylene Blue: Serotonergic Non-Opioid CNS Depressants may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid combination
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Metoclopramide: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Consider monitoring for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Mirtazapine: TraZODone may enhance the CNS depressant effect of Mirtazapine. TraZODone may enhance the serotonergic effect of Mirtazapine. 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) and CNS depression when these agents are combined. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors (Antidepressant): Serotonergic Non-Opioid CNS Depressants may enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid combination
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Nefazodone: TraZODone may enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the 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
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Ondansetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect 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
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxitriptan: Serotonergic Agents (High Risk) may enhance the serotonergic effect of Oxitriptan. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect 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 enhance the CNS depressant effect 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
Ozanimod: May enhance the adverse/toxic effect of Serotonergic Agents (High Risk). Risk C: Monitor therapy
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Phenytoin: May decrease the serum concentration of TraZODone. TraZODone may increase the 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
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Psilocybin: Antidepressants may diminish the therapeutic effect of Psilocybin. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Ramosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Rasagiline: May enhance the serotonergic effect of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Risk X: Avoid combination
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect 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 enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Safinamide: May enhance the serotonergic effect of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Risk X: Avoid combination
Saquinavir: May enhance the QTc-prolonging effect of TraZODone. Saquinavir may increase the serum concentration of TraZODone. Risk X: Avoid combination
Selective Serotonin Reuptake Inhibitors: May enhance the serotonergic effect of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Selegiline: May enhance the serotonergic effect of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Risk X: Avoid combination
Serotonergic Agents (High Risk, Miscellaneous): May enhance the serotonergic effect of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Serotonergic Opioids (High Risk): Serotonergic Non-Opioid CNS Depressants may enhance the CNS depressant effect of Serotonergic Opioids (High Risk). Serotonergic Non-Opioid CNS Depressants may enhance the serotonergic effect of Serotonergic Opioids (High Risk). This could result in serotonin syndrome. 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 enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Serotonin/Norepinephrine Reuptake Inhibitors: TraZODone may enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
St John's Wort: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease the serum concentration of Serotonergic Agents (High Risk). Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Suvorexant: CNS Depressants may enhance the CNS depressant effect 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 enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Tricyclic Antidepressants: May enhance the CNS depressant effect of Serotonergic Non-Opioid CNS Depressants. Tricyclic Antidepressants may enhance the serotonergic effect of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and CNS depression when these agents are combined. Risk C: Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Warfarin: TraZODone may diminish the anticoagulant effect of Warfarin. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect 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 enhance the CNS depressant effect 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.
Trazodone and the active metabolite 1-m-chlorophenylpiperazine cross the placenta and can be detected in cord blood at delivery (Saito 2021).
Based on available data, an increased risk of adverse pregnancy outcomes has not been observed following use of trazodone during pregnancy (Anderson 2020; Einarson 2003; Einarson 2009). Long-term effects on neurodevelopment are not known (Korade 2021).
Untreated or inadequately treated psychiatric illness may lead to poor adherence with prenatal care and adverse pregnancy outcomes. Therapy with antidepressants during pregnancy should be individualized; treatment with antidepressant medication is recommended for pregnant patients with severe major depressive disorder (ACOG 2008; CANMAT [MacQueen 2016]). Patients treated for major depression and who are euthymic prior to pregnancy are more likely to experience a relapse when medication is discontinued (68%) as compared to pregnant patients who continue taking antidepressant medications (26%) (Cohen 2006). However, if treatment for major depressive disorder is initiated for the first time during pregnancy, trazodone is not one of the preferred medications (CANMAT [MacQueen 2016]; Larsen 2015; WFSBP [Bauer 2013]).
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. Patients exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants. Pregnant patients 18 to 45 years of age or their health care providers may contact the registry by calling 1-844-405-6185. Enrollment should be done as early in pregnancy as possible.
Blood pressure (signs/symptoms of hypotension or orthostasis), ECG (for QT changes), liver function (baseline and periodically); daytime sedation, priapism. Monitor patient periodically for symptom resolution; monitor for worsening depression, suicidality, and associated behaviors (especially at the beginning of therapy or when doses are increased or decreased). Monitor for the emergence of serotonin syndrome.
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: 5 to 9 hours, prolonged in obese patients.
Time to peak, serum: 30 to 100 minutes; delayed with food (up to 2.5 hours).
Excretion: Primarily urine (74%, <1% excreted unchanged); secondarily feces (~21%).
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