Yes

Antidepressant, Tricyclic (Tertiary Amine)

Treatment of depression

C

Hypersensitivity to this drug or other dibenzodiazepines; use of monoamine oxidase inhibitors within 14 days; use in a patient during the acute recovery phase of MI

Often causes sedation, resulting in impaired performance of tasks requiring alertness (ie, operating machinery or driving). Sedative effects may be additive with other CNS depressants and/or ethanol. The degree of sedation is very high relative to other antidepressants. May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disease. May increase the risks associated with electroconvulsive therapy. This agent should be discontinued, when possible, prior to elective surgery. Therapy should not be abruptly discontinued in patients receiving high doses for prolonged periods. Use with caution in patients with hepatic or renal dysfunction and in elderly patients.

Use caution in patients with depression, particularly if suicidal risk may be present. 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. Use caution in patients with a previous seizure disorder or condition predisposing to seizures such as brain damage, alcoholism, or concurrent therapy with other drugs which lower the seizure threshold. Use with caution in hyperthyroid patients or those receiving thyroid supplementation.

Cardiovascular: Arrhythmias, hypotension, hypertension, tachycardia, palpitations, heart block, stroke, myocardial infarction

Central nervous system: Headache, exacerbation of psychosis, confusion, delirium, hallucinations, nervousness, restlessness, delusions, agitation, insomnia, nightmares, anxiety, seizures

Dermatologic: Photosensitivity, rash, petechiae, itching

Endocrine & metabolic: Sexual dysfunction, breast enlargement, galactorrhea, SIADH

Gastrointestinal: Xerostomia, constipation, increased appetite, nausea, unpleasant taste, weight gain, diarrhea, heartburn, vomiting, anorexia, trouble with gums, decreased lower esophageal sphincter tone may cause GE reflux

Genitourinary: Difficult urination, urinary retention, testicular edema

Hematologic: Agranulocytosis, eosinophilia, purpura, thrombocytopenia

Hepatic: Cholestatic jaundice, increased liver enzymes

Neuromuscular & skeletal: Tremors, numbness, tingling, paresthesia, incoordination, ataxia, peripheral neuropathy, extrapyramidal symptoms

Ocular: Blurred vision, eye pain, disturbances in accommodation, mydriasis, increased intraocular pressure

Otic: Tinnitus

Miscellaneous: Allergic reactions

Symptoms of overdose include agitation, confusion, hallucinations, urinary retention, hypothermia, hypotension, tachycardia, cardiac arrhythmias

Following initiation of essential overdose management, toxic symptoms should be treated. Sodium bicarbonate is indicated when QRS interval is >0.10 seconds or QT_c >0.42 seconds. Ventricular arrhythmias and EKG changes (QRS widening) often respond to systemic alkalinization (sodium bicarbonate 0.5-2 mEq/kg I.V.). Arrhythmias unresponsive to this therapy may respond to lidocaine 1 mg/kg I.V. followed by a titrated infusion. Physostigmine (1-2 mg I.V. slowly for adults or 0.5 mg I.V. slowly for children) may be indicated in reversing cardiac arrhythmias that are life-threatening. Seizures usually respond to diazepam I.V. boluses (5-10 mg for adults up to 30 mg or 0.25-0.4 mg/kg/dose for children up to 10 mg/dose). If seizures are unresponsive or recur, phenytoin or phenobarbital may be required.

CYP2D6 enzyme substrate

Trimipramine inhibits the antihypertensive response to bethanidine, clonidine, debrisoquin, guanadrel, guanethidine, guanabenz, guanfacine; monitor BP; consider alternate antihypertensive agent

Abrupt discontinuation of clonidine may cause hypertensive crisis, trimipramine may enhance the response

Use with altretamine may cause orthostatic hypertension

Trimipramine may be additive with or may potentiate the action of other CNS depressants (sedatives, hypnotics, or ethanol); with MAO inhibitors, hyperpyrexia, hypertension, tachycardia, confusion, seizures, and deaths have been reported (serotonin syndrome), this combination should be avoided

Trimipramine may increase the prothrombin time in patients stabilized on warfarin

Cimetidine and methylphenidate may decrease the metabolism of trimipramine

Additive anticholinergic effects seen with other anticholinergic agents

The SSRIs, to varying degrees, inhibit the metabolism of TCAs and clinical toxicity may result

Use of lithium with a TCA may increase the risk for neurotoxicity

Phenothiazines may increase concentration of some TCAs and TCAs may increase concentration of phenothiazines; monitor for altered clinical response

TCAs may enhance the hypoglycemic effects of tolazamide, chlorpropamide, or insulin; monitor for changes in blood glucose levels

Cholestyramine and colestipol may bind TCAs and reduce their absorption; monitor for altered response

TCAs may enhance the effect of amphetamines; monitor for adverse CV effects

Verapamil and diltiazem appear to decrease the metabolism of imipramine and potentially other TCAs; monitor for increased TCA concentrations. The pressor response to I.V. epinephrine, norepinephrine, and phenylephrine may be enhanced in patients receiving TCAs, this combination is best avoided.

Grapefruit juice, amprenavir, indinavir, ritonavir may inhibit the metabolism of clomipramine and potentially other TCAs; monitor for altered effects; a decrease in TCA dosage may be required

Quinidine may inhibit the metabolism of TCAs; monitor for altered effect

Combined use of anticholinergics with TCAs may produce additive anticholinergic effects; combined use of beta-agonists with TCAs may predispose patients to cardiac arrhythmias

Solutions stable at a pH of 4-5; turns yellowish or reddish on exposure to light. Slight discoloration does not affect potency; marked discoloration is associated with loss of potency. Capsules stable for 3 years following date of manufacture.

Increases the synaptic concentration of serotonin and/or norepinephrine in the central nervous system by inhibition of their reuptake by the presynaptic neuronal membrane

Onset of action: Oral: Therapeutic effects require >2 weeks

Therapeutic plasma levels: Oral: Occurs within 6 hours

Protein binding: 95%

Metabolism: Undergoes significant first-pass metabolism; metabolized in the liver

Half-life: 20-26 hours

Elimination: In urine

Adults: Oral: 50-150 mg/day as a single bedtime dose up to a maximum of 200 mg/day outpatient and 300 mg/day inpatient

Alcohol: Avoid use

Blood pressure and pulse rate prior to and during initial therapy; evaluate mental status; monitor weight

glucose

Use with caution; epinephrine, norepinephrine and levonordefrin have been shown to have an increased pressor response in combination with TCAs

>10% of patients experience dry mouth; long-term treatment with TCAs such as trimipramine increases the risk of caries by reducing salivation and salivary buffer capacity

Take exactly as directed (do not increase dose or frequency); may take 2-3 weeks to achieve desired results; may cause physical and/or psychological dependence. Take at bedtime. Avoid excessive alcohol, caffeine, and other prescription or OTC medications not approved by prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience drowsiness, lightheadedness, dizziness, or blurred vision (use caution when driving or engaging in tasks requiring alertness until response to drug is known); nausea, altered taste, dry mouth (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); constipation (increased exercise, fluids, or dietary fruit and fiber may help); diarrhea (buttermilk, yogurt, or boiled milk may help); increased appetite (monitor dietary intake to avoid excess weight gain); postural hypotension (use caution when climbing stairs or changing position from lying or sitting to standing); urinary retention (void before taking medication); or sexual dysfunction (reversible). Report persistent CNS effects (eg, insomnia, restlessness, fatigue, anxiety, impaired cognitive function, seizures); muscle cramping or tremors; chest pain, palpitations, rapid heartbeat, swelling of extremities, or severe dizziness; unresolved urinary retention; vision changes or eye pain; yellowing of eyes or skin; pale stools/dark urine; or worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Do not breast-feed.

May increase appetite; may cause drowsiness, raise bed rails, institute safety precautions

Capsule, as maleate: 25 mg, 50 mg, 100 mg

Druid H and Holmgren P, "Fatal Seizures Associated With Trimipramine Overdose," Forensic Sci Int, 1991, 49(1):75-9.

Nebinger P and Koel M, "Specificity Data of the Tricyclic Antidepressants Assay by Fluorescent Polarization Immunoassay," J Anal Toxicol, 1990, 14(4):219-21.

Remy AJ, Larrey D, Pageaux GP, et al, "Cross Hepatotoxicity Between Tricyclic Antidepressants and Phenothiazines," Eur J Gastroenterol Hepatol, 1995, 7(4):373-6.

Roose SP, Glassman AH, Attia E, et al, "Comparative Efficacy of Selective Serotonin Reuptake Inhibitors and Tricyclics in the Treatment of Melancholia," Am J Psychiatry, 1994, 151(12):1735-9.