Version July 2025
Compared with placebo, antidepressants increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of clomipramine or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared with placebo in adults older than 24 years; there was a reduction in risk with antidepressants compared with placebo in adults 65 years and older. Depression and certain other psychiatric disorders are associated with increased risk of suicide. Appropriately monitor patients of all ages who are started on antidepressant therapy and observe closely for clinical worsening, suicidality, or unusual changes in behavior. Advise families and caregivers of the need for close observation and communication with the prescriber. Clomipramine is not approved for use in pediatric patients except for patients with obsessive-compulsive disorder (OCD).
Obsessive-compulsive disorder (OCD), treatment:
Initial: Oral: 25 mg once daily; may gradually increase as tolerated over the first 2 weeks to ~100 mg/day in divided doses.
After the initial titration, wait 2 to 3 weeks between dosing adjustments to assess tolerability and effectiveness. May further increase over next several weeks up to a maximum of 250 mg/day; after titration, may give as a single dose once daily at bedtime.
Major depressive disorder (unipolar) (off-label use): Oral: Initial: 25 to 50 mg once daily at bedtime; titrate every 1 to 3 days in 50 mg increments to an effective dose (usual dose: 150 mg/day); doses as high as 250 mg/day have been studied (Ref).
Panic disorder (off-label use): Oral: Initial: 10 to 25 mg daily; increase by 10 to 25 mg every 2 to 3 days based on efficacy and tolerability to a target dose of 50 to 150 mg/day, in 1 to 3 divided doses; guidelines recommend doses ranging from 50 to 250 mg/day (Ref).
Discontinuation of therapy:When discontinuing antidepressant treatment that has lasted for ≥4 weeks, gradually taper the dose (eg, over 2 to 4 weeks) to minimize withdrawal symptoms and detect reemerging symptoms (Ref). For brief treatment (eg, 2 to 3 weeks) may taper over 1 to 2 weeks; <2 weeks treatment generally does not warrant tapering (Ref). Reasons for a slower taper (eg, over 4 weeks) include prior history of antidepressant withdrawal symptoms or high doses of antidepressants (Ref). If intolerable withdrawal symptoms occur, resume the previously prescribed dose and/or decrease dose at a more gradual rate (Ref). Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months (Ref). Evidence supporting ideal taper rates is limited (Ref).
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 a monoamine oxidase inhibitor. A direct switch may be an appropriate approach when switching to another agent in the same or similar class (eg, when switching between 2 selective serotonin reuptake inhibitors), when the antidepressant to be discontinued has been used for <1 week, or when the discontinuation is for adverse effects. When choosing the switch strategy, consider the risk of discontinuation symptoms, potential for drug interactions, other antidepressant properties (eg, half-life, adverse effects, pharmacodynamics), and the degree of symptom control desired (Ref).
Switching to or from a monoamine oxidase inhibitor (MAOI):
Allow 14 days to elapse between discontinuing an MAOI and initiation of clomipramine.
Allow 14 days to elapse between discontinuing clomipramine 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.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Use with caution in patients with significantly impaired renal function.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, hepatically metabolized. Use with caution in patients with hepatic impairment. Some experts recommended reducing initial and maintenance doses by 50% in patients with hepatic impairment, with cautious dose adjustments based on response and tolerability (Ref).
Note: Avoid use (Ref).
(For additional information see "Clomipramine: Pediatric drug information")
Obsessive-compulsive disorder (OCD), treatment: Children ≥10 years and Adolescents: Oral:
Initial: 25 mg daily; gradually increase as tolerated over the first 2 weeks to 3 mg/kg/day or 100 mg daily (whichever is less) in divided doses (may be divided with meals)
Maintenance: May further increase over next several weeks up to maximum daily dose: 3 mg/kg/day or 200 mg/day (whichever is less); after titration, may give as a single once daily dose at bedtime
Discontinuation of therapy: Upon discontinuation of antidepressant therapy, gradually taper the dose to minimize the incidence of withdrawal symptoms and allow for the detection of reemerging symptoms. 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 antidepressant; antidepressants with a shorter half-life may need to be tapered more conservatively. In addition for long-term treated patients, WFSBP guidelines recommend tapering over 4 to 6 months. 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.
MAO inhibitor recommendations:
Switching to or from an MAO inhibitor intended to treat psychiatric disorders:
Allow 14 days to elapse between discontinuing an MAO inhibitor intended to treat psychiatric disorders and initiation of clomipramine.
Allow 14 days to elapse between discontinuing clomipramine and initiation of an MAO inhibitor intended to treat psychiatric disorders.
Use with other MAO inhibitors (linezolid or IV methylene blue):
Do not initiate clomipramine in patients receiving linezolid or IV methylene blue; consider other interventions for psychiatric condition.
If urgent treatment with linezolid or IV methylene blue is required in a patient already receiving clomipramine and potential benefits outweigh potential risks, discontinue clomipramine promptly and administer linezolid or IV methylene blue. Monitor for serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or IV methylene blue, whichever comes first. May resume clomipramine 24 hours after the last dose of linezolid or IV methylene blue.
Children ≥10 years and Adolescents: There are no dosage adjustments provided in manufacturer's labeling (has not been studied). Use with caution in patients with significantly impaired renal function.
Children ≥10 years and Adolescents: There are no dosage adjustments provided in manufacturer's labeling; clomipramine is hepatically metabolized; use with caution in patients with hepatic impairment. In adult patients, initial dose reductions suggested.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in children, adolescents, and adults unless otherwise indicated.
>10%:
Dermatologic: Diaphoresis (children and adolescents: 9%; adults: 29%)
Endocrine & metabolic: Change in libido (adults: 21%), weight gain (children and adolescents: 2%; adults: 18%)
Gastrointestinal: Abdominal pain (adults: 11%), anorexia (12% to 22%), constipation (children and adolescents: 22%; adults: 47%), diarrhea (7% to 13%), dyspepsia (13% to 22%), increased appetite (adults: 11%), nausea (adults: 33%), xerostomia (children and adolescents: 63%; adults: 84%)
Genitourinary: Difficulty in micturition (children and adolescents: 4%; adults: 14%), ejaculation failure (children and adolescents: 6%; adults: 42%), erectile dysfunction (adults: 20%)
Nervous system: Dizziness (children and adolescents: 41%; adults: 54%), drowsiness (46% to 54%), fatigue (35% to 39%), headache (adults: 52%), insomnia (children and adolescents: 11%; adults: 25%), myoclonus (children and adolescents: 2%; adults: 13%), nervousness (children and adolescents: 4%; adults: 18%), tremor (children and adolescents: 33%; adults: 54%)
Neuromuscular & skeletal: Myalgia (adults: 13%)
Ophthalmic: Visual disturbance (children and adolescents: 7%; adults: 18%)
Respiratory: Pharyngitis (adults: 14%), rhinitis (adults: 12%)
1% to 10%:
Cardiovascular: Chest pain (children and adolescents: 7%), ECG abnormality (2%), flushing (7% to 8%), orthostatic hypotension (4% to 6%), palpitations (4%), syncope (children and adolescents: 2%), tachycardia (2% to 4%)
Dermatologic: Body odor (children and adolescents: 2%), dermatitis (adults: 2%), pruritus (adults: 6%), skin rash (4% to 8%), urticaria (adults: 1%), xeroderma (adults: 2%)
Endocrine & metabolic: Amenorrhea (adults: 1%), hot flash (2% to 5%), menstrual disease (adults: 4%), weight loss (children and adolescents: 7%)
Gastrointestinal: Aphthous stomatitis (children and adolescents: 2%), dysgeusia (4% to 8%), dysphagia (adults: 2%), esophagitis (adults: 1%), flatulence (adults: 6%), halitosis (children and adolescents: 2%), vomiting (7%)
Genitourinary: Breast hypertrophy (adults: 2%), cystitis (adults: 2%), lactation (nonpuerperal; adults: 4%), leukorrhea (adults: 2%), mastalgia (adults: 1%), urinary frequency (adults: 5%), urinary retention (children and adolescents: 7%; adults: 2%), urinary tract infection (adults: 6%), vaginitis (adults: 2%)
Hematologic & oncologic: Purpuric disease (adults: 3%)
Hepatic: Increased serum alanine aminotransferase (>3 × ULN: 3%), increased serum aspartate aminotransferase (>3 × ULN: 1%)
Hypersensitivity: Hypersensitivity reaction (children and adolescents: 7%)
Nervous system: Abnormal dreams (adults: 3%), aggressive behavior (children and adolescents: 2%), agitation (adults: 3%), anxiety (children and adolescents: 2%; adults: 9%), asthenia (children and adolescents: 2%), changes in thinking (≥1%), chills (adults: 2%), confusion (2% to 3%), depersonalization (2%), depression (adults: 5%), emotional lability (adults: 2%), hypertonia (2% to 4%), irritability (children and adolescents: 2%), lack of concentration (adults: 5%), memory impairment (7% to 9%), migraine (adults: 3%), myasthenia (1% to 2%), pain (3% to 4%), panic attack (1% to 2%), paresis (children and adolescents: 2%), paresthesia (adults: 9%), psychosomatic disorder (adults: 3%), seizure (≤1%), sleep disorder (4% to 9%), speech disturbance (adults: 3%), twitching (adults: 7%), vertigo (≥1%), yawning (adults: 3%)
Ophthalmic: Abnormal lacrimation (adults: 3%), anisocoria (children and adolescents: 2%), blepharospasm (children and adolescents: 2%), conjunctivitis (adults: 1%), mydriasis (adults: 2%), ocular allergy (children and adolescents: 2%)
Otic: Tinnitus (4% to 6%)
Respiratory: Bronchospasm (children and adolescents: 7%; adults: 2%), dyspnea (children and adolescents: 2%), epistaxis (adults: 2%), laryngitis (children and adolescents: 2%), sinusitis (adults: 6%)
Miscellaneous: Fever (adults: 4%)
<1%:
Cardiovascular: Acute myocardial infarction, aneurysm, atrial flutter, bradycardia, bundle branch block, cardiac arrhythmia, edema (including dependent edema and oral edema), extrasystoles, heart block, heart failure, ischemic heart disease, peripheral ischemia, polyarteritis nodosa, thrombophlebitis, vasospasm, ventricular tachycardia
Dermatologic: Alopecia, cellulitis, cheilitis, chloasma, dermal ulcer, eczema, erythematous rash, folliculitis, hypertrichosis, maculopapular rash, pallor, piloerection, psoriasis, pustular rash, seborrhea, skin discoloration, skin hypertrophy, skin photosensitivity
Endocrine & metabolic: Albuminuria, dehydration, diabetes mellitus, goiter, gynecomastia, hypercholesterolemia, hyperglycemia, hyperthyroidism, hyperuricemia, hypokalemia, hypothyroidism
Gastrointestinal: Ageusia, blood in stool, chronic enteritis, colitis, dental caries, duodenitis, enlargement of salivary glands, fecal discoloration, gastric dilation, gastric ulcer, gastritis, gastroesophageal reflux disease, gingival hemorrhage, gingivitis, glossitis, hemorrhoids, hiccups, intestinal obstruction, irritable bowel syndrome, malabsorption (fat intolerance), paralytic ileus, peptic ulcer, rectal hemorrhage, sialorrhea, teeth clenching, tongue ulcer
Genitourinary: Anorgasmia, breast engorgement, breast fibroadenosis, cervical dysplasia, endometrial hyperplasia, endometriosis, endometritis, epididymitis, genital pruritus, glycosuria, hematuria, nocturia, oliguria, ovarian cyst, perineal pain, premature ejaculation, prostatic disease, pyuria, urethral disease, urinary incontinence, uterine hemorrhage, vaginal hemorrhage, vulvar disease
Hematologic & oncologic: Bone marrow depression, bruise, leukemoid reaction, lymphadenopathy, pseudolymphoma
Hepatic: Abnormal liver function, hepatitis
Infection: Increased susceptibility to infection
Nervous system: Abnormal electroencephalogram, abnormal gait, abnormal sensory symptoms, altered sense of smell, anticholinergic syndrome, apathy, aphasia, apraxia, ataxia, catatonic-like state, cerebral hemorrhage, cholinergic syndrome, choreoathetosis, coma, delirium, delusion, encephalopathy, euphoria, extrapyramidal reaction, hallucination, hemiparesis, hostility, hyperacusis, hyperesthesia, hyperreflexia, hypnogenic hallucinations, hypoesthesia, illusion, impulse control disorder, malaise, manic reaction, mutism, neuralgia, neuropathy, paranoid ideation, phobia, psychosis, schizophreniform disorder, sense of stimulation, somnambulism, stupor, suicidal ideation, suicidal tendencies, voice disorder, withdrawal syndrome
Neuromuscular & skeletal: Dyskinesia, dystonia, exostosis, gout, hyperkinetic muscle activity, hypokinesia, lower limb cramp, lupus erythematous-like rash, muscle spasm, myopathy, myositis, osteoarthritis, torticollis
Ophthalmic: Accommodation disturbance, blepharitis, chromatopsia, conjunctival hemorrhage, diplopia, exophthalmos, eye pain, foreign body sensation of eye, glaucoma, keratitis, night blindness, nystagmus disorder, oculogyric crisis, oculomotor nerve paralysis, photophobia, retinopathy, scleritis, strabismus, visual field defect
Otic: Deafness, labyrinth disease
Renal: Nephrolithiasis, polyuria, pyelonephritis, renal cyst, renal pain
Respiratory: Bronchitis, cyanosis, hemoptysis, hyperventilation, hypoventilation, increased bronchial secretions, laryngismus, pharyngeal edema, pneumonia
Miscellaneous: Cyst
Postmarketing:
Endocrine & metabolic: Hyponatremia (Sommer 1997), SIADH (Sommer 1997)
Hematologic & oncologic: Agranulocytosis (Souhami 1976), anemia, leukopenia, pancytopenia, thrombocytopenia
Hepatic: Hepatic injury (severe)
Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms
Nervous system: Hyperthermia, neuroleptic malignant syndrome (Haddow 2004), serotonin syndrome
Ophthalmic: Angle-closure glaucoma
Hypersensitivity to clomipramine, other tricyclic agents, 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 clomipramine or the MAOI); initiation of clomipramine in a patient receiving IV methylene blue; use in a patient during the acute recovery phase of myocardial infarction.
Note: Although clomipramine is contraindicated per 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.
Canadian labeling: Additional contraindications (not in US labeling): Acute heart failure; hepatic impairment; renal impairment; history of blood dyscrasias; glaucoma.
Major psychiatric warnings:
• Suicidal thinking/behavior: [US Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient's family or caregiver should be instructed to closely observe the patient and communicate condition with health care provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Clomipramine is FDA approved for the treatment of OCD in children ≥10 years of age.
- The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.
- Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their health care provider if any of these symptoms or worsening depression or psychosis occur.
Concerns related to adverse effects:
• Anticholinergic effects: May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention); use with caution in patients with decreased GI motility, paralytic ileus, urinary retention, BPH, xerostomia, or visual problems. The degree of anticholinergic blockade produced by this agent is very high relative to other antidepressants.
• 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). The degree of sedation is very high relative to other antidepressants.
• Drug rash with eosinophilia and systemic syndrome (DRESS): DRESS has been reported with the use of clomipramine. If a severe, acute reaction such as DRESS occurs, discontinue clomipramine immediately.
• Fractures: Bone fractures have been associated with antidepressant treatment. Consider the possibility of a fragility fracture if an antidepressant-treated patient presents with unexplained bone pain, point tenderness, swelling, or bruising (Rabenda 2013; Rizzoli 2012).
• Hematologic effects: TCAs may rarely cause bone marrow suppression; monitor for any signs of infection and obtain CBC if symptoms (eg, fever, sore throat) evident.
• Hepatotoxicity: Increases in ALT/AST have occurred, including rare reports of severe hepatic injury (some fatal).
• Ocular effects: May cause mild pupillary dilation, which, in susceptible individuals, can lead to an episode of narrow-angle glaucoma. Consider evaluating patients who have not had an iridectomy for narrow-angle glaucoma risk factors.
• Orthostatic hypotension: May cause orthostatic hypotension (risk is moderate relative to other antidepressants); use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use that may predispose to hypotension/bradycardia).
• Seizures: May cause seizures (relationship to dose and/or duration of therapy); do not exceed maximum doses. Use with caution in patients with a previous seizure disorder or condition predisposing to seizures such as brain damage, alcoholism, or concurrent therapy with other drugs that lower the seizure threshold.
• Serotonin syndrome: Potentially life-threatening serotonin syndrome has occurred with serotonergic agents (eg, SSRIs, SNRIs), particularly when used in combination with other serotonergic agents (eg, triptans, TCAs, fentanyl, lithium, tramadol, buspirone, St. John's wort, tryptophan) or agents that impair metabolism of serotonin (eg, monoamine oxidase inhibitors [MAOIs] intended to treat psychiatric disorders and other MAOIs, including IV methylene blue). Monitor patients closely for signs of serotonin syndrome such as mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile blood pressure, diaphoresis); neuromuscular changes (eg, tremor, rigidity, myoclonus); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. Discontinue treatment (and any concomitant serotonergic agent) immediately if signs/symptoms arise.
• Sexual dysfunction: Has been associated with a high incidence of male sexual dysfunction.
• SIADH and hyponatremia: Antidepressant agents have been associated with the development of SIADH and hyponatremia, predominately in elderly patients. Other risk factors include volume depletion, concurrent use of diuretics, female gender, low body weight, and severe physical illness. TCAs have a lower risk for hyponatremia in comparison to SSRIs (De Picker 2014).
• Weight gain: May cause weight gain.
Disease-related concerns:
• Adrenal tumor: Use with caution in patients with tumors of the adrenal medulla (eg, pheochromocytoma, neuroblastoma); may cause hypertensive crises.
• Cardiovascular disease: Use with caution in patients with a history of cardiovascular disease (including previous MI, stroke, tachycardia, or conduction abnormalities); the risk of conduction abnormalities with this agent is high relative to other antidepressants. In a scientific statement from the American Heart Association, clomipramine has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: moderate) (AHA [Page 2016]).
• GI motility: Use with caution in patients with decreased GI motility (eg, paralytic ileus) as anticholinergic effects may exacerbate underlying condition.
• Hepatic impairment: Use caution in patients with hepatic impairment; clearance is decreased. Due to the narrow therapeutic index, use lower initial and maintenance doses of tricyclic antidepressants. Use caution in patients with hepatic encephalopathy due to the risk of neurocognitive effects (Mullish 2014). Monitor hepatic transaminases periodically in patients with hepatic impairment.
• Mania/hypomania: May precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Combination therapy with an antidepressant and a mood stabilizer should also be avoided in acute mania or mixed episodes, as well as maintenance treatment in bipolar disorder due to the mood-destabilizing effects of antidepressants (CANMAT [Yatham 2018]; WFSBP [Grunze 2018]). Patients presenting with depressive symptoms should be screened for bipolar disorder. Clomipramine is not FDA approved for the treatment of bipolar depression.
• Renal impairment: Use with caution in patients with renal impairment.
Other warnings/precautions:
• Discontinuation syndrome: Abrupt discontinuation or interruption of antidepressant therapy has been associated with a discontinuation syndrome. Symptoms arising may vary with antidepressant however commonly include nausea, vomiting, diarrhea, headaches, light-headedness, dizziness, diminished appetite, sweating, chills, tremors, paresthesias, fatigue, somnolence, and sleep disturbances (eg, vivid dreams, insomnia). Less common symptoms include electric shock-like sensations, cardiac arrhythmias (more common with tricyclic antidepressants), myalgias, parkinsonism, arthralgias, and balance difficulties. Psychological symptoms may also emerge such as agitation, anxiety, akathisia, panic attacks, irritability, aggressiveness, worsening of mood, dysphoria, mood lability, hyperactivity, mania/hypomania, depersonalization, decreased concentration, slowed thinking, confusion, and memory or concentration difficulties. Greater risks for developing a discontinuation syndrome have been associated with antidepressants with shorter half-lives, longer durations of treatment, and abrupt discontinuation. For antidepressants of short or intermediate half-lives, symptoms may emerge within 2 to 5 days after treatment discontinuation and last 7 to 14 days (APA 2010; Fava 2006; Haddad 2001; Shelton 2001; Warner 2006).
• Electroconvulsive therapy: May increase the risks associated with electroconvulsive therapy; consider discontinuing, when possible, prior to ECT treatment.
• Surgery: Recommended by the manufacturer to discontinue prior to elective surgery; risks exist for drug interactions with anesthesia and for cardiac arrhythmias. However, some experts recommend continuing tricyclic antidepressants prior to surgery (Pass 2004). Therapy should not be abruptly discontinued in patients receiving high doses for prolonged periods.
Vomiting is two- to threefold more prevalent in children compared to adolescents and is more prevalent in adolescents compared to adults; to help minimize, divide the dose and give with food initially. Once titrated to maintenance therapy, can consolidate to once daily dosing at bedtime.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as hydrochloride:
Anafranil: 25 mg, 50 mg, 75 mg
Generic: 25 mg, 50 mg, 75 mg
Yes
Capsules (Anafranil Oral)
25 mg (per each): $42.36
50 mg (per each): $43.16
75 mg (per each): $43.96
Capsules (clomiPRAMINE HCl Oral)
25 mg (per each): $0.61 - $11.24
50 mg (per each): $0.65 - $11.24
75 mg (per each): $0.86 - $11.24
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as hydrochloride:
Generic: 25 mg, 50 mg
Tablet, Oral:
Anafranil: 10 mg, 25 mg, 50 mg
Generic: 10 mg
Oral: During titration, may divide doses and administer with meals to decrease gastrointestinal side effects. After titration, may administer total daily dose at bedtime to decrease daytime sedation.
Oral: May administer with food to decrease GI upset.
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019906s043lbl.pdf#page=27, must be dispensed with this medication.
Obsessive-compulsive disorder: Treatment of obsessive-compulsive disorder
Major depressive disorder (unipolar); Panic disorder
ClomiPRAMINE may be confused with chlorproMAZINE, clevidipine, clomiPHENE, desipramine, Norpramin
Anafranil may be confused with ALfentanil, enalapril, nafarelin
Beers Criteria: Clomipramine is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to its strong anticholinergic properties and potential for sedation and orthostatic hypotension. In addition, use TCAs with caution due to their potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium closely with initiation or dosage adjustments in older adults (Beers Criteria [AGS 2023]).
Substrate of CYP1A2 (Major), CYP2C19 (Minor), CYP2D6 (Major), CYP3A4 (Minor); 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
Acetylcholinesterase Inhibitors: May decrease therapeutic effects of Agents with Clinically Relevant Anticholinergic Effects. Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Acetylcholinesterase Inhibitors. Risk C: Monitor
Aclidinium: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Acrivastine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Acrivastine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Adagrasib: May increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate Risk). Adagrasib may increase serum concentration of QT-prolonging Antidepressants (Moderate Risk). Management: Consider alternatives to this combination. If combined, monitor for increased antidepressant toxicities including QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider Therapy Modification
Agents with Clinically Relevant Anticholinergic Effects: May increase anticholinergic effects of Tricyclic Antidepressants. Risk C: Monitor
Alcohol (Ethyl): CNS Depressants may increase CNS depressant effects of Alcohol (Ethyl). Risk C: Monitor
Alfuzosin: May increase hypotensive effects of Blood Pressure Lowering Agents. 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
Alpha-/Beta-Agonists: Tricyclic Antidepressants may increase vasopressor effects of Alpha-/Beta-Agonists. Management: Avoid, if possible, the use of alpha-/beta-agonists in patients receiving tricyclic antidepressants. If combined, monitor for evidence of increased pressor effects and consider reductions in initial dosages of the alpha-/beta-agonist. Risk D: Consider Therapy Modification
Alpha1-Agonists: Tricyclic Antidepressants may increase therapeutic effects of Alpha1-Agonists. Tricyclic Antidepressants may decrease therapeutic effects of Alpha1-Agonists. Risk C: Monitor
Alpha2-Agonists (Ophthalmic): Tricyclic Antidepressants may decrease therapeutic effects of Alpha2-Agonists (Ophthalmic). Risk C: Monitor
Alpha2-Agonists: Tricyclic Antidepressants may decrease antihypertensive effects of Alpha2-Agonists. Management: Consider avoiding this combination. If used, monitor for decreased effects of the alpha2-agonist. Exercise great caution if discontinuing an alpha2-agonist in a patient receiving a TCA. Risk D: Consider Therapy Modification
Amantadine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Amifampridine: Agents With Seizure Threshold Lowering Potential may increase neuroexcitatory and/or seizure-potentiating effects of Amifampridine. Risk C: Monitor
Amifostine: Blood Pressure Lowering Agents may increase hypotensive effects of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider Therapy Modification
Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Amisulpride (Oral). Specifically, the risk of seizures may be increased. Risk C: Monitor
Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Amisulpride (Oral): May increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Amisulpride (Oral): May increase QTc-prolonging effects of QT-prolonging Agents (Moderate Risk). Risk C: Monitor
Amphetamines: Tricyclic Antidepressants may increase adverse/toxic effects of Amphetamines. Tricyclic Antidepressants may potentiate the cardiovascular effects of Amphetamines. Amphetamines may increase serotonergic effects of Tricyclic Antidepressants. 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 increased cardiovascular effects when these agents are combined. 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
Arginine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
ARIPiprazole Lauroxil: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor
ARIPiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Artemether and Lumefantrine: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). 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
Asenapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Asenapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Aspirin: ClomiPRAMINE may increase antiplatelet effects of Aspirin. Risk C: Monitor
Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Baclofen: Tricyclic Antidepressants may increase adverse neuromuscular effects of Baclofen. Baclofen may increase CNS depressant effects of Tricyclic Antidepressants. Risk C: Monitor
Barbiturates: May increase metabolism of Tricyclic Antidepressants. Management: Monitor for decreased efficacy of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. Tricyclic antidepressant dose adjustments are likely required. Risk D: Consider Therapy Modification
Benperidol: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Benperidol. Risk C: Monitor
Benperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Benperidol: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Benztropine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Benztropine. Risk C: Monitor
Beta-Acetyldigoxin: Tricyclic Antidepressants may increase arrhythmogenic effects of Beta-Acetyldigoxin. Risk C: Monitor
Beta2-Agonists: Tricyclic Antidepressants may increase adverse/toxic effects of Beta2-Agonists. Risk C: Monitor
Biperiden: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Biperiden. 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
Blood Pressure Lowering Agents: May increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Bornaprine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Bornaprine. Risk C: Monitor
Botulinum Toxin-Containing Products: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Brexanolone: CNS Depressants may increase CNS depressant effects of Brexanolone. Risk C: Monitor
Brexpiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Brexpiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Brimonidine (Topical): May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Broccoli: May decrease serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor
Bromopride: May increase adverse/toxic effects of Tricyclic Antidepressants. Risk X: Avoid
Bromperidol: May decrease hypotensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase hypotensive effects of Bromperidol. Risk X: Avoid
Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Buclizine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Buclizine. Risk C: Monitor
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
BuPROPion: Tricyclic Antidepressants may increase neuroexcitatory and/or seizure-potentiating effects of BuPROPion. BuPROPion may increase serum concentration of Tricyclic Antidepressants. Risk C: Monitor
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: Agents with Clinically Relevant Anticholinergic Effects may increase tachycardic effects of Cannabinoid-Containing Products. Risk C: Monitor
Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor
Cannabis: May decrease serum concentration of CYP1A2 Substrates (High risk with Inducers). 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 ClomiPRAMINE. Risk C: Monitor
Cariprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
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
Chlorprothixene: May increase QTc-prolonging effects of Tricyclic Antidepressants. Risk X: Avoid
Cimetidine: May increase serum concentration of Tricyclic Antidepressants. Risk C: Monitor
Cimetropium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Cimetropium. Risk X: Avoid
Citalopram: May increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate Risk). Citalopram may increase serotonergic effects of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. Citalopram may increase serum concentration of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Citalopram: Tricyclic Antidepressants may increase serotonergic effects of Citalopram. Tricyclic Antidepressants may increase serum concentration of Citalopram. Citalopram may increase serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA and citalopram concentrations/effects. Risk C: Monitor
Clothiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
CloZAPine: QT-prolonging Antidepressants (Moderate Risk) may increase constipating effects of CloZAPine. CloZAPine may increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate Risk). Management: Consider alternatives to this combination whenever possible. If combined, consider prophylactic laxatives and monitor closely for signs and symptoms of gastrointestinal hypomotility, QTc prolongation, and serotonin syndrome. Risk D: Consider Therapy Modification
CNS Depressants: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Cocaine (Topical): May increase adverse/toxic effects of Tricyclic Antidepressants. 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
Cyclizine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. 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
CYP1A2 Inducers (Moderate): May decrease serum concentration of ClomiPRAMINE. Risk C: Monitor
CYP1A2 Inhibitors (Moderate): May increase serum concentration of ClomiPRAMINE. Risk C: Monitor
CYP1A2 Inhibitors (Strong): May increase serum concentration of ClomiPRAMINE. Risk C: Monitor
CYP2D6 Inhibitors (Moderate): May increase serum concentration of ClomiPRAMINE. CYP2D6 Inhibitors (Moderate) may increase active metabolite exposure of ClomiPRAMINE. Risk C: Monitor
CYP2D6 Inhibitors (Strong): May increase serum concentration of ClomiPRAMINE. CYP2D6 Inhibitors (Strong) may increase active metabolite exposure of ClomiPRAMINE. Risk C: Monitor
Dabrafenib: May increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
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
Darifenacin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Darifenacin. Risk C: Monitor
Dasatinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Deoxycholic Acid: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Desmopressin: Tricyclic Antidepressants may increase hyponatremic effects of Desmopressin. 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
Diazoxide Choline: May increase serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk X: Avoid
Diazoxide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Dicyclomine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Dicyclomine. 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 (Systemic): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Dimethindene (Systemic). 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
Domperidone: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Domperidone. Risk X: Avoid
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
DroNABinol: Agents with Clinically Relevant Anticholinergic Effects may increase tachycardic effects of DroNABinol. Risk X: Avoid
Dronedarone: QT-prolonging Antidepressants (Moderate Risk) may increase QTc-prolonging effects of Dronedarone. Risk X: Avoid
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
DULoxetine: Blood Pressure Lowering Agents may increase hypotensive effects of DULoxetine. Risk C: Monitor
DULoxetine: May increase serotonergic effects of Tricyclic Antidepressants. This could result in serotonin syndrome. DULoxetine may increase serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations and effects if these agents are combined. Risk C: Monitor
Eletriptan: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Eluxadoline: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of Eluxadoline. Risk X: Avoid
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
Encorafenib: May increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate 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
Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Epinephrine (Racemic): Tricyclic Antidepressants 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
Escitalopram: May increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate Risk). Escitalopram may increase serotonergic effects of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. Risk C: Monitor
Escitalopram: Tricyclic Antidepressants may increase serotonergic effects of Escitalopram. Escitalopram may increase serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined. Risk C: Monitor
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
Fesoterodine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Fesoterodine. Risk C: Monitor
Fexinidazole: QT-prolonging Antidepressants (Moderate Risk) may increase QTc-prolonging effects of Fexinidazole. 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
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
Fluorouracil Products: May increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
FLUoxetine: May increase serotonergic effects of Tricyclic Antidepressants. FLUoxetine may increase serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined. Risk D: Consider Therapy Modification
Flupentixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Flupentixol. Specifically, the risk of seizures may be increased. Risk C: Monitor
FluPHENAZine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor
FluPHENAZine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
FluvoxaMINE: May increase serotonergic effects of Tricyclic Antidepressants. FluvoxaMINE may increase serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined. Risk C: Monitor
Fondaparinux: Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Fondaparinux. Risk C: Monitor
Gastrointestinal Agents (Prokinetic): Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Gastrointestinal Agents (Prokinetic). Risk C: Monitor
Gepirone: May increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate Risk). Gepirone may increase serotonergic effects of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. Risk C: Monitor
Gepotidacin: May decrease anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Gilteritinib: QT-prolonging Antidepressants (Moderate Risk) may increase QTc-prolonging effects of Gilteritinib. 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
Glucagon: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor
Glycoprotein IIb/IIIa Inhibitors: Agents with Antiplatelet Effects may increase antiplatelet effects of Glycoprotein IIb/IIIa Inhibitors. Risk C: Monitor
Glycopyrrolate (Oral Inhalation): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Glycopyrrolate (Oral Inhalation). Risk X: Avoid
Glycopyrrolate (Systemic): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Glycopyrrolate (Systemic). Risk C: Monitor
Glycopyrronium (Topical): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Grapefruit Juice: May increase serum concentration of ClomiPRAMINE. Risk C: Monitor
Guanethidine: Tricyclic Antidepressants may decrease therapeutic effects of Guanethidine. Risk C: Monitor
Haloperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Haloperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Haloperidol: QT-prolonging Antidepressants (Moderate Risk) may increase QTc-prolonging effects of Haloperidol. Haloperidol may increase serotonergic effects of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome/serotonin toxicity (SS/ST) or NMS when these agents are combined. Patients with additional risk factors for QTc prolongation or SS/ST may be at even higher risk. 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
Herbal Products with Blood Pressure Lowering Effects: May increase hypotensive effects of Blood Pressure Lowering Agents. 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
Hypotension-Associated Agents: Blood Pressure Lowering Agents may increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Ibritumomab Tiuxetan: Agents with Antiplatelet Effects may increase antiplatelet effects of Ibritumomab Tiuxetan. Risk C: Monitor
Ibrutinib: Agents with Antiplatelet Effects may increase adverse/toxic effects of Ibrutinib. Specifically, the risk of bleeding and hemorrhage may be increased. Risk C: Monitor
Iloperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iloperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Iloperidone: May increase hypotensive effects of Blood Pressure Lowering Agents. 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
Iobenguane Radiopharmaceutical Products: Tricyclic Antidepressants may decrease therapeutic effects of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. Risk X: Avoid
Iohexol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Iomeprol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Iopamidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Ipratropium (Nasal): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Ipratropium (Oral Inhalation): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Itopride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Itopride. 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
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may increase hypotensive effects of Levodopa-Foslevodopa. Risk C: Monitor
Levoketoconazole: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Levoketoconazole. Risk X: Avoid
Levosulpiride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Levosulpiride. Risk X: Avoid
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 Tricyclic Antidepressants. 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 QTc-prolonging effects of QT-prolonging Antidepressants (Moderate Risk). QT-prolonging Antidepressants (Moderate Risk) may increase QTc-prolonging effects of Lofexidine. QT-prolonging Antidepressants (Moderate Risk) may decrease therapeutic effects of Lofexidine. Management: Consider avoiding this combination when possible. 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 D: Consider Therapy Modification
Lormetazepam: May increase hypotensive effects of Blood Pressure Lowering Agents. 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
Lumateperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Lurasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Maprotiline: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Maprotiline. Risk C: Monitor
Mavorixafor: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk X: Avoid
Melitracen [INT]: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Melperone: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Melperone: Tricyclic Antidepressants may increase adverse/toxic effects of Melperone. Melperone may increase adverse/toxic effects of Tricyclic Antidepressants. Melperone may increase serum concentration of Tricyclic Antidepressants. 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 decrease antihypertensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase orthostatic hypotensive effects of Metergoline. 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
Methscopolamine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Methscopolamine. Risk C: Monitor
Methylene Blue: Tricyclic Antidepressants 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
Mirabegron: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Mirabegron. Risk C: Monitor
Miscellaneous Antiplatelets: Agents with Antiplatelet Effects may increase antiplatelet effects of Miscellaneous Antiplatelets. Risk C: Monitor
Molindone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Molsidomine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Monoamine Oxidase Inhibitors (Antidepressant): May increase serotonergic effects of Tricyclic Antidepressants. This could result in serotonin syndrome. Risk X: Avoid
Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Naftopidil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nefazodone: Tricyclic Antidepressants may increase serotonergic effects of Nefazodone. 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
Nicergoline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicorandil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicorandil: Tricyclic Antidepressants may increase hypotensive effects of Nicorandil. Risk C: Monitor
Nitroglycerin: Agents with Clinically Relevant Anticholinergic Effects may decrease absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor
Nitroprusside: Blood Pressure Lowering Agents may increase hypotensive effects of Nitroprusside. Risk C: Monitor
Nonsteroidal Anti-Inflammatory Agents: Tricyclic Antidepressants may increase antiplatelet effects of Nonsteroidal Anti-Inflammatory Agents. Tricyclic Antidepressants may increase adverse/toxic effects of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of major adverse cardiac events (MACE), hemorrhagic stroke, ischemic stroke, and heart failure may be increased. Risk C: Monitor
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
Obinutuzumab: May increase hypotensive effects of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider Therapy Modification
OLANZapine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of OLANZapine. Risk C: Monitor
OLANZapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of OLANZapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Ondansetron: May increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate Risk). Ondansetron may increase serotonergic effects of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome when these agents are combined. Patients with additional risk factors for QTc prolongation or serotonin syndrome may be at even higher risk. 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 anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
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
Oxatomide: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. 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
OxyBUTYnin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of OxyBUTYnin. Risk C: Monitor
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: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
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
PARoxetine: May increase serotonergic effects of Tricyclic Antidepressants. PARoxetine may increase serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined. Risk D: Consider Therapy Modification
Peginterferon Alfa-2b: May decrease serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Pentamidine (Systemic): May increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate 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
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
Pentoxifylline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Perampanel: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Perazine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Periciazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Perphenazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Perphenazine. Risk C: Monitor
Perphenazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Pholcodine: Blood Pressure Lowering Agents may increase hypotensive effects of Pholcodine. Risk C: Monitor
Phosphodiesterase 5 Inhibitors: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Pimozide: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pimozide. Specifically, the risk of seizures may be increased. Risk C: Monitor
Pipamperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pipamperone. Specifically, the risk of seizures may be increased. Risk X: Avoid
Piperaquine: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Piperaquine. Risk X: Avoid
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
Pitolisant: Tricyclic Antidepressants may decrease therapeutic effects of Pitolisant. Risk X: Avoid
Pizotifen: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor
Potassium Chloride: Agents with Clinically Relevant Anticholinergic Effects may increase ulcerogenic effects of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid
Potassium Citrate: Agents with Clinically Relevant Anticholinergic Effects may increase ulcerogenic effects of Potassium Citrate. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium citrate. Risk X: Avoid
Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor
Pramlintide: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. These effects are specific to the GI tract. Risk X: Avoid
Primaquine: May increase serum concentration of CYP1A2 Substrates (High risk with Inhibitors). Risk C: Monitor
Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Prochlorperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Promazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Promethazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Promethazine. Risk C: Monitor
Propantheline: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Propantheline. Risk C: Monitor
Propiverine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Prostacyclin Analogues: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Psilocybin: Antidepressants may decrease therapeutic effects of Psilocybin. Risk C: Monitor
QT-prolonging Agents (Highest Risk): ClomiPRAMINE may increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider Therapy Modification
QT-prolonging Antidepressants (Moderate Risk): May increase anticholinergic effects of QT-prolonging Antidepressants (Moderate Risk). QT-prolonging Antidepressants (Moderate Risk) may increase CNS depressant effects of QT-prolonging Antidepressants (Moderate Risk). QT-prolonging Antidepressants (Moderate Risk) may increase serotonergic effects of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. QT-prolonging Antidepressants (Moderate Risk) may increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
QT-prolonging Antipsychotics (Moderate Risk): May increase QTc-prolonging effects of ClomiPRAMINE. QT-prolonging Antipsychotics (Moderate Risk) may increase serotonergic effects of ClomiPRAMINE. This could result in serotonin syndrome. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome/serotonin toxicity (SS/ST) or NMS when these agents are combined. Patients with additional risk factors for QTc prolongation or SS/ST may be at even higher risk. Risk C: Monitor
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate 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
QT-Prolonging Inhalational Anesthetics (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
QT-prolonging Kinase Inhibitors (Moderate Risk): QT-prolonging Antidepressants (Moderate Risk) may increase QTc-prolonging effects of QT-prolonging Kinase Inhibitors (Moderate 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
QT-prolonging Miscellaneous Agents (Moderate Risk): QT-prolonging Antidepressants (Moderate Risk) may increase QTc-prolonging effects of QT-prolonging Miscellaneous Agents (Moderate 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
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): QT-prolonging Antidepressants (Moderate Risk) may increase QTc-prolonging effects of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Risk C: Monitor
QT-prolonging Quinolone Antibiotics (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate 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
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging Antidepressants (Moderate Risk). Risk C: Monitor
Quinagolide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Ramosetron: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of Ramosetron. 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 Tricyclic Antidepressants. This could result in serotonin syndrome. Risk X: Avoid
Revefenacin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Revefenacin. Risk X: Avoid
RisperiDONE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of RisperiDONE. Specifically, the risk of seizures may be increased. Risk C: Monitor
Rivastigmine: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Rivastigmine. Rivastigmine may decrease therapeutic effects of Agents with Clinically Relevant Anticholinergic Effects. Management: Use of rivastigmine with an anticholinergic agent is not recommended unless clinically necessary. If the combination is necessary, monitor for reduced anticholinergic effects. Risk D: Consider Therapy Modification
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 Tricyclic Antidepressants. This could result in serotonin syndrome. Risk X: Avoid
Scopolamine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Scopolamine. Risk C: Monitor
Secretin: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider Therapy Modification
Selegiline: May increase serotonergic effects of ClomiPRAMINE. 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): Tricyclic Antidepressants may increase serotonergic effects of Serotonergic Agents (High Risk, Miscellaneous). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Serotonergic Non-Opioid CNS Depressants: 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
Serotonergic Opioids (High Risk): May increase serotonergic effects of Tricyclic Antidepressants. This could result in serotonin syndrome. Tricyclic Antidepressants 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: May increase serotonergic effects of Tricyclic Antidepressants. 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
Sertindole: May increase QTc-prolonging effects of QT-prolonging Agents (Moderate Risk). Risk X: Avoid
Sertraline: May increase serotonergic effects of Tricyclic Antidepressants. Sertraline may increase serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined. Risk C: Monitor
Silodosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor
Sofpironium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Sofpironium. Risk X: Avoid
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
Sulpiride: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sulpiride. Specifically, the risk of seizures may be increased. 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
Thiazide and Thiazide-Like Diuretics: Agents with Clinically Relevant Anticholinergic Effects may increase serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor
Thioridazine: ClomiPRAMINE may increase QTc-prolonging effects of Thioridazine. Thioridazine may increase serum concentration of ClomiPRAMINE. Thioridazine may increase active metabolite exposure of ClomiPRAMINE. Risk X: Avoid
Thiothixene: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Thiothixene. Risk C: Monitor
Thiothixene: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor
Thrombolytic Agents: Agents with Antiplatelet Effects may increase adverse/toxic effects of Thrombolytic Agents. Specifically, the risk of bleeding may be increased. Risk C: Monitor
Thyroid Products: May increase arrhythmogenic effects of Tricyclic Antidepressants. Thyroid Products may increase stimulatory effects of Tricyclic Antidepressants. Risk C: Monitor
Tiapride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Tiapride. Risk C: Monitor
Tiotropium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tiotropium. Risk X: Avoid
Tipranavir: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Tobacco (Smoked): May decrease serum concentration of ClomiPRAMINE. Risk C: Monitor
Tolterodine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tolterodine. Risk C: Monitor
Topiramate: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Topiramate. Risk C: Monitor
Tricyclic Antidepressants: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tricyclic Antidepressants. Risk C: Monitor
Tricyclic Antidepressants: May increase anticholinergic effects of Tricyclic Antidepressants. Tricyclic Antidepressants may increase CNS depressant effects of Tricyclic Antidepressants. Tricyclic Antidepressants may increase serotonergic effects of Tricyclic Antidepressants. This could result in serotonin syndrome. Management: Monitor closely for increased TCA adverse effects, including serotonin syndrome/serotonin toxicity, CNS depression, and anticholinergic effects. Risk C: Monitor
Trifluoperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Trimeprazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Trimethobenzamide: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Trimethobenzamide. Risk C: Monitor
Triptorelin: Hyperprolactinemic Agents may decrease therapeutic effects of Triptorelin. Risk X: Avoid
Trospium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Trospium. Risk C: Monitor
Umeclidinium: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Valproic Acid and Derivatives: May increase serum concentration of Tricyclic Antidepressants. Risk C: Monitor
Vasopressin: Drugs Suspected of Causing SIADH may increase therapeutic effects of Vasopressin. Specifically, the pressor and antidiuretic effects of vasopressin may be increased. Risk C: Monitor
Vilazodone: Tricyclic Antidepressants may increase serotonergic effects of Vilazodone. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) if these agents are combined. Risk C: Monitor
Vitamin E (Systemic): May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Vitamin K Antagonists: Antidepressants with Antiplatelet Effects may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor
Volanesorsen: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Vortioxetine: Tricyclic Antidepressants may increase serotonergic effects of Vortioxetine. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) if these agents are combined. Risk C: Monitor
Zanubrutinib: May increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Ziprasidone: May increase serotonergic effects of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. QT-prolonging Antidepressants (Moderate Risk) may increase QTc-prolonging effects of Ziprasidone. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider Therapy Modification
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
Zuclopenthixol: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Zuclopenthixol. Risk C: Monitor
Zuclopenthixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Zuclopenthixol. Specifically, the risk of seizures may be increased. Risk C: Monitor
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
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 obsessive compulsive disorder or depression, tricyclic antidepressants are not first-line medications 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]).
Sexual dysfunction has been reported with clomipramine (Drobnis 2017). Because clomipramine may delay ejaculation it has been used off label for the treatment of premature ejaculation (ISSM [Althof 2014].
Clomipramine and its metabolite desmethylclomipramine cross the placenta and can be detected in cord blood and neonatal serum at birth (Loughhead 2006; ter Horst 2012).
Outcome data following maternal use of tricyclic antidepressants (TCAs), including clomipramine, during pregnancy are available (Bérard 2017; Cantarutti 2017; De Vries 2021; Ericson 1999; Huybrechts 2015; Källén 2003, Källén 2004; McDonagh 2014; McElhatton 1996). Study outcomes vary due to limited data, differences in study design, and confounders (Gentile 2014; Yonkers 2014), however clomipramine may be associated with an increased risk of fetal cardiovascular malformations (CANMAT [MacQueen 2016]; Gentile 2014). Withdrawal symptoms (including jitteriness, tremor, and seizures) have been observed in neonates whose mothers took clomipramine up to delivery.
Due to pregnancy-induced physiologic changes some pharmacokinetic parameters of clomipramine may be altered. Clearance may be decreased during the third trimester. Data are insufficient to make dosing recommendations because clomipramine is metabolized by multiple liver enzymes; however, therapeutic drug monitoring of TCAs can be considered during pregnancy and postpartum to avoid toxicity and monitor efficacy (Deligiannidis 2014; Yue 2023). Data from 5 newborns found the half-life for clomipramine in the neonate to be 42 ± 16 hours following in utero exposure. Serum concentrations were not found to correlate to withdrawal symptoms (ter Horst 2012).
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). Anxiety disorders during pregnancy are associated with low-birth-weight, preterm birth, and adverse behavioral outcomes in the offspring. 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 pre-pregnancy may use the same medication during pregnancy unless contraindications exist (ACOG 2023; BAP [McAllister-Williams 2017]; CANMAT [MacQueen 2016]). Treatment should not be withheld or discontinued based only on pregnancy status (ACOG 2023). TCAs are not considered first-line medications for treating depression or obsessive compulsive disorder (OCD) in pregnant patients who are treatment naive or who do not have a history of effective treatment with another medication (ACOG 2023; BAP [McAllister-Williams 2017]; CANMAT [MacQueen 2016]). Clomipramine is not considered an alternative for treating depression during pregnancy (CANMAT [MacQueen 2016]), but could be considered as an option for OCD when other therapies are not effective (Hudepohl 2022; Mulcahy 2023). When medications are used, the lowest effective dose of a single agent is recommended. Optimize dosing prior to changing a medication or adding additional agents whenever possible. Close monitoring for symptom improvement with a validated screening tool during pregnancy is recommended. Manage side effects as needed (ACOG 2023).
Data collection to monitor pregnancy and infant outcomes following exposure to antidepressant medications is ongoing. Encourage pregnant patients 45 years of age and younger with a history of psychiatric illness to enroll in the National Pregnancy Registry for Antidepressants (1-866-961-2388 or https://womensmentalhealth.org/research/pregnancyregistry/antidepressants).
Clomipramine is present in breast milk (Schimmell 1991; Yonkers 1997).
Data related to the presence of clomipramine in breast milk are available from 2 lactating patients in a study that compared the gas chromatography (GC) and enzyme immunoassay (EIA) assay methods. Both mothers gave birth at 42 weeks' gestation. Fore and hind milk samples were obtained ~12 to 15 hours after the last dose. Breast milk concentrations were generally related to maternal serum concentration; the level of detection varied by assay method (the clomipramine concentrations presented also include metabolites):
• The first mother began clomipramine at 1 week postpartum and continued breastfeeding for 20 weeks. The initial clomipramine dose was 75 mg/day and was increased to 125 mg/day during the study period. Clomipramine concentrations were 32 ng/mL in the fore and hind milk at the 75 mg dose using the GC assay (EIA fore milk 200 ng/mL, hind milk 61ng/L). The highest concentration (436 ng/mL) was detected in the hind milk following clomipramine 100 mg/day (GC; not tested using EIA). Clomipramine and metabolite concentrations following a maternal dose of 125 mg/day were evaluated on three occasions and were variable (GC fore milk: 98 to 212 ng/mL, hind milk 136 to 250 ng/mL; EIA fore milk 48 to 167 ng/mL, hind milk 100 to 263 ng/mL).
• The second mother started clomipramine 100 mg/day at 3 weeks postpartum and breastfed during therapy for 53 weeks. Breast milk was sampled once. Clomipramine concentrations were 60 ng/mL and 226 ng/mL in the fore- and hind milk, respectively, using the GC assay (EIA: fore milk 43 ng/mL, hind milk 283 ng/mL).
Clomipramine was present in the urine and plasma of both infants using the EIA method. Adverse events were not observed in either infant. Concentrations of tricyclic antidepressants were also found to vary by fat content of breast milk (Yoshida 1997).
Plasma concentrations of clomipramine decreased over time in a newborn exposed in utero and via breast milk. Symptoms of withdrawal were present at birth and resolved spontaneously at 6 days of life. The maternal dose of clomipramine was 125 mg/day during pregnancy and postpartum, then increased to 150 mg/day 10 days after delivery. Breastfeeding was initiated at 7 days of age. At birth, clomipramine concentrations in the newborn plasma were 266 ng/mL. By 35 days of age, they decreased to 9.8 ng/mL (Schimmell 1991). Clomipramine or its metabolites were not detected in the plasma of 4 breastfed infants whose mothers were taking clomipramine, three with no prior in utero exposure (Wisner 1995).
Monitor infants exposed to psychotropic medication via breast milk for adverse effects (eg, over sedation, poor feeding) (BAP [McAllister-Williams 2017]).
Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends a decision be made to discontinue breastfeeding or to discontinue the drug, considering the importance of treatment to the mother. Patients effectively treated for depression with a TCA 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, agents other than TCAs are preferred (ABM [Sriraman 2015]), but may be considered as an alternative (CANMAT [MacQueen 2016]).
Serum sodium in at-risk populations (as clinically indicated) (De Picker 2014); pulse rate and blood pressure prior to and during therapy; ECG/cardiac status in older adults and patients with cardiac disease; suicidal ideation (especially at the beginning of therapy, after initiation, or when doses are increased or decreased); signs/symptoms of serotonin syndrome; hepatic transaminases (periodically during therapy in patients with preexisting hepatic impairment); electrolyte panel (to assess risk of conduction abnormalities).
Depression:
Timing of serum samples: Draw trough just before next dose
Therapeutic reference range: 230 to 450 ng/mL (as clomipramine PLUS norclomipramine)
Laboratory alert level: 450 ng/mL (Hiemke 2018)
Clomipramine appears to affect serotonin uptake while its active metabolite, desmethylclomipramine, affects norepinephrine uptake
Onset of action:
Anxiety disorders (obsessive-compulsive, panic disorder): Initial effects may be observed within 2 weeks of treatment, with continued improvements through 4 to 6 weeks (Varigonda 2016; WFSBP [Bandelow 2023a]); some experts suggest up to 12 weeks of treatment may be necessary for response, particularly in patients with obsessive-compulsive disorder (BAP [Baldwin 2014]; Katzman 2014; WFSBP [Bandelow 2023a]; WFSBP [Bandelow 2023b]).
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).
Duration of action: 1 to 2 days.
Absorption: Rapid.
Distribution: Distributes into CSF and brain, active metabolite (desmethylclomipramine) also distributes into CSF with average CSF to plasma ratio: 2.6.
Protein binding: 97%, primarily to albumin.
Metabolism: Hepatic to desmethylclomipramine (DMI; active); extensive first-pass effect; metabolites undergo glucuronide conjugation; metabolism of clomipramine and DMI may be capacity limited (ie, may display nonlinear pharmacokinetics); with multiple dosing, plasma concentrations of DMI are greater than clomipramine.
Bioavailability: 50% (Hiemke 2018).
Half-life elimination: Adults (following a 150 mg dose): Clomipramine 19 to 37 hours (mean: 32 hours); DMI: 54 to 77 hours (mean: 69 hours).
Time to peak, plasma: 2 to 6 hours.
Excretion: Urine (50% to 60%; 0.8% to 1.3% as parent drug and active metabolite (combined amount); feces (24% to 32%).
