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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(des IP ra meen)
Generic Available (U.S.)
Yes
Index Terms
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088665.pdf, must be dispensed with this medication.
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of depression
Use: Unlabeled
Analgesic adjunct in chronic pain; peripheral neuropathies (including diabetic neuropathy); attention-deficit/hyperactivity disorder (ADHD); depression in children ≤12 years of age
Pregnancy Considerations
Animal reproduction studies are inconclusive.
Lactation
Enters breast milk (AAP rates “of concern”; AAP 2001 update pending)
Breast-Feeding Considerations
Based on information from one mother-infant pair, following maternal use of desipramine 300 mg/day, the estimated exposure to the breast-feeding infant would be 2% of the weight-adjusted maternal dose. Adverse events were not reported. Infants should be monitored for signs of adverse events; routine monitoring of infant serum concentrations is not recommended.
Contraindications
Hypersensitivity to desipramine, drugs of similar chemical class, or any component of the formulation; use of MAO inhibitors with or within 14 days; use in a patient during the acute recovery phase of MI
Warnings/Precautions
Boxed warnings:
• Suicidal thinking/behavior: See “Major psychiatric warnings” below.
Major psychiatric warnings:
• Suicidal thinking/behavior: [U.S. Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 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 1-2 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 healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Desipramine is FDA approved for the treatment of depression in adolescents.
• The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Patients treated with antidepressants should be observed for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. 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 healthcare 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 extreme caution in patients with decreased gastrointestinal motility, paralytic ileus, urinary retention, BPH, xerostomia, or visual problems. The degree of anticholinergic blockade produced by this agent is low relative to other antidepressants.
• 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.
• 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 which may predispose to hypotension/bradycardia).
• Sedation: May cause sedation, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). The degree of sedation is low-moderate relative to other antidepressants.
Disease-related concerns:
• Cardiovascular disease: Due to risk of conduction abnormalities, use with extreme caution in patients with a history of cardiovascular disease (including previous MI, stroke, tachycardia, or conduction abnormalities) or in patients with a family history of sudden death, dysrhythmias, or conduction abnormalities.
• Diabetes: Use with caution in patients with diabetes mellitus; may alter glucose regulation.
• Glaucoma: Use with caution in patients with glaucoma; condition may be exacerbated by cholinergic blockade.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Mania/hypomania: May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder. Desipramine is not FDA approved for the treatment of bipolar depression.
• Renal impairment: Use with caution in patients with renal impairment.
• Seizure disorder: Use with extreme caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold. In some patients, seizures may precede cardiac dysrhythmias and death.
• Thyroid dysfunction: Use with extreme caution in patients with hyperthyroidism or those receiving thyroid supplementation due to concerns of pro-arrhythmogenesis.
Concurrent drug therapy issues:
• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations:
• Elderly: Use caution in elderly patients; may cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion or hyponatremia; monitor sodium closely with initiation or dosage adjustments in older adults. May be inappropriate in older adults depending on comorbidities (eg, dementia, delirium) due to its potent anticholinergic effects (Beers Criteria). May also increase risk of falling or confusional states.
Other warnings/precautions:
• Discontinuation of therapy: Recommended to discontinue prior to elective surgery requiring general anesthesia. Therapy should not be abruptly discontinued.
• Electroconvulsive therapy: May increase the risks associated with electroconvulsive therapy; consider discontinuing, when possible, prior to ECT treatment.
Adverse Reactions
Frequency not defined.
Cardiovascular: Arrhythmias, edema, flushing, heart block, hyper-/hypotension, MI, palpitation, stroke, tachycardia
Central nervous system: Agitation, anxiety, ataxia, confusion, delusions, disorientation, dizziness, drowsiness, EEG alterations, exacerbation of psychosis, extrapyramidal symptoms, fatigue, fever, hallucinations, headache, hypomania, incoordination, insomnia, neuroleptic malignant syndrome, nightmares, restlessness, seizure, suicidal thinking and behavior
Dermatologic: Alopecia, itching, petechiae, photosensitivity, skin rash, urticaria
Endocrine & metabolic: Breast enlargement, galactorrhea, gynecomastia, hyper-/hypoglycemia, impotence, libido changes, SIADH
Gastrointestinal: Abdominal cramps, anorexia, black tongue, constipation, diarrhea, epigastric distress, nausea, parotid edema, paralytic ileus, stomatitis, sublingual adenitis, unpleasant taste, vomiting, weight gain/loss, xerostomia
Genitourinary: Micturition delayed, nocturia, painful ejaculation, polyuria, testicular edema, urinary retention
Hematologic: Agranulocytosis, eosinophilia, purpura, thrombocytopenia
Hepatic: Alkaline phosphatase increased, cholestatic jaundice, hepatitis, liver enzymes increased
Neuromuscular & skeletal: Falling, numbness, paresthesia of extremities, peripheral neuropathy, tingling, tremor, weakness
Ocular: Blurred vision, disturbances of accommodation, intraocular pressure increased, mydriasis
Otic: Tinnitus
Miscellaneous: Allergic reaction, diaphoresis (excessive), withdrawal symptoms
Metabolism/Transport Effects
Substrate of CYP1A2 (minor), CYP2D6 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2A6 (moderate), CYP2B6 (moderate), CYP2D6 (moderate), CYP2E1 (weak), CYP3A4 (moderate)
Drug Interactions
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Risk D: Consider therapy modification
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy
Alfuzosin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Alpha-/Beta-Agonists (Direct-Acting): Tricyclic Antidepressants may enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Exceptions: Dipivefrin. Risk D: Consider therapy modification
Alpha1-Agonists: Tricyclic Antidepressants may enhance the vasopressor effect of Alpha1-Agonists. Risk D: Consider therapy modification
Alpha2-Agonists: Tricyclic Antidepressants may diminish the antihypertensive effect of Alpha2-Agonists. Exceptions: Apraclonidine; Brimonidine. Risk D: Consider therapy modification
Altretamine: May enhance the orthostatic hypotensive effect of Tricyclic Antidepressants. Risk C: Monitor therapy
Amphetamines: Tricyclic Antidepressants may enhance the stimulatory effect of Amphetamines. Tricyclic Antidepressants may also potentiate the cardiovascular effects of Amphetamines. Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Levocabastine (Nasal); Paliperidone. Risk C: Monitor therapy
Antipsychotics: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Risk C: Monitor therapy
Artemether: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Barbiturates: May increase the metabolism of Tricyclic Antidepressants. Risk D: Consider therapy modification
Beta2-Agonists: Tricyclic Antidepressants may enhance the adverse/toxic effect of Beta2-Agonists. Risk C: Monitor therapy
Boceprevir: May increase the serum concentration of Desipramine. Management: Consider lower doses of desipramine in patients treated with boceprevir and monitor for symptoms of desipramine toxicity (including dizziness, hypotension and syncope), due to a possible increase in desipramine concentrations. Risk D: Consider therapy modification
Budesonide (Systemic, Oral Inhalation): CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Budesonide (Systemic, Oral Inhalation). Management: Consider reducing the oral budesonide dose when used together with a CYP3A4 inhibitor. This interaction is likely less severe with orally inhaled budesonide. Monitor patients closely for signs/symptoms of corticosteroid excess. Risk D: Consider therapy modification
BuPROPion: May decrease the metabolism of Tricyclic Antidepressants. Risk C: Monitor therapy
CarBAMazepine: May increase the metabolism of Tricyclic Antidepressants. Risk C: Monitor therapy
Chloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Cimetidine: May decrease the metabolism of Tricyclic Antidepressants. Risk C: Monitor therapy
Cinacalcet: May increase the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy
Ciprofloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Ciprofloxacin (Systemic): May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Codeine: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor therapy
Colchicine: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Colchicine. Management: Reduce colchicine dose as directed when using with a moderate CYP3A4 inhibitor, and increase monitoring for colchicine-related toxicity. Use extra caution in patients with impaired renal and/or hepatic function. Risk D: Consider therapy modification
CYP2A6 Substrates: CYP2A6 Inhibitors (Moderate) may decrease the metabolism of CYP2A6 Substrates. Risk C: Monitor therapy
CYP2B6 Substrates: CYP2B6 Inhibitors (Moderate) may decrease the metabolism of CYP2B6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification
CYP2D6 Substrates: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of CYP2D6 Substrates. Exceptions: Tamoxifen. Risk C: Monitor therapy
CYP3A4 Substrates: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Cyproterone: May decrease the serum concentration of CYP1A2 Substrates. Risk C: Monitor therapy
Desmopressin: Tricyclic Antidepressants may enhance the adverse/toxic effect of Desmopressin. Risk C: Monitor therapy
Dexmethylphenidate: May enhance the adverse/toxic effect of Tricyclic Antidepressants. Dexmethylphenidate may increase the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy
Divalproex: May increase the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy
Dronedarone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Dronedarone. Risk X: Avoid combination
DULoxetine: May decrease the metabolism of Tricyclic Antidepressants. Risk C: Monitor therapy
Eplerenone: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Eplerenone. Management: A lower starting dose of eplerenone (25 mg once daily for adults) is recommended in patients with hypertension who are also taking drugs that are moderate inhibitors of CYP3A4. Risk D: Consider therapy modification
Everolimus: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Everolimus. Management: Everolimus dose reductions are required for patients being treated for subependymal giant cell astrocytoma or renal cell carcinoma. See prescribing information for specific dose adjustment and monitoring recommendations. Risk D: Consider therapy modification
FentaNYL: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of FentaNYL. Management: Monitor patients extra closely for several days following initiation of the combination, and fentanyl dosage reductions should be made as appropriate. Risk D: Consider therapy modification
Fesoterodine: CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine. Risk C: Monitor therapy
Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification
Indacaterol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Iobenguane I 123: Tricyclic Antidepressants may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
Ivacaftor: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ivacaftor. Management: Decrease ivacaftor dose to 150 mg daily in patients also receiving moderate CYP3A4 inhibitors. Risk D: Consider therapy modification
Linezolid: May enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. Management: Consider alternatives. When this combination is indicated, closely monitor for signs/symptoms of serotonin toxicity/serotonin syndrome. If such symptoms occur, consider discontinuation of one or both agents. Risk D: Consider therapy modification
Lithium: May enhance the neurotoxic effect of Tricyclic Antidepressants. Risk C: Monitor therapy
Lumefantrine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
MAO Inhibitors: May enhance the serotonergic effect of Tricyclic Antidepressants. This may cause serotonin syndrome. Risk X: Avoid combination
MAO Inhibitors: May enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing Agents. Risk C: Monitor therapy
Methylene Blue: Tricyclic Antidepressants may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid combination
Methylphenidate: May enhance the adverse/toxic effect of Tricyclic Antidepressants. Methylphenidate may increase the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy
Metoclopramide: May enhance the adverse/toxic effect of Tricyclic Antidepressants. Management: Seek alternatives to this combination when possible. Monitor patients receiving metoclopramide with tricyclic antidepressants for signs of extrapyramidal symptoms, neuroleptic malignant syndrome, and serotonin syndrome. Risk D: Consider therapy modification
Metoclopramide: Serotonin Modulators may enhance the adverse/toxic effect of Metoclopramide. This may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Risk C: Monitor therapy
Metyrosine: May enhance the adverse/toxic effect of Tricyclic Antidepressants. Risk C: Monitor therapy
Mifepristone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Management: Avoid use of mifepristone for treatment of hyperglycemia in Cushing's syndrome in patients receiving QT interval prolonging agents. Avoid initiation of QT prolonging agents for 2 weeks following mifepristone discontinuation. Risk X: Avoid combination
Nebivolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol. Risk C: Monitor therapy
Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Pimecrolimus: CYP3A4 Inhibitors (Moderate) may decrease the metabolism of Pimecrolimus. Risk C: Monitor therapy
Pimozide: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Pimozide. Risk X: Avoid combination
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
Protease Inhibitors: May increase the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy
QTc-Prolonging Agents: May enhance the adverse/toxic effect of other QTc-Prolonging Agents. Their effects can be additive, causing life-threatening ventricular arrhythmias. Risk D: Consider therapy modification
QUEtiapine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
QuiNIDine: Tricyclic Antidepressants may enhance the QTc-prolonging effect of QuiNIDine. QuiNIDine may increase the serum concentration of Tricyclic Antidepressants. Risk D: Consider therapy modification
QuiNINE: QTc-Prolonging Agents may enhance the QTc-prolonging effect of QuiNINE. QuiNINE may enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Saxagliptin: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Saxagliptin. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May decrease the metabolism of Tricyclic Antidepressants. Risk D: Consider therapy modification
Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Risk D: Consider therapy modification
Sodium Phosphates: Tricyclic Antidepressants may enhance the adverse/toxic effect of Sodium Phosphates. Specifically, the risk of seizure and/or loss of consciousness may be increased in patients with significant sodium phosphate induced fluid/electrolyte abnormalities. Risk C: Monitor therapy
St Johns Wort: May increase the metabolism of Tricyclic Antidepressants. The risk of serotonin syndrome may theoretically be increased. Risk D: Consider therapy modification
Sulfonylureas: Cyclic Antidepressants may enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy
Tamoxifen: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the formation of highly potent active metabolites. Management: Consider alternatives with less of an inhibitory effect on CYP2D6 activity when possible. Risk D: Consider therapy modification
Telaprevir: May increase the serum concentration of Desipramine. Risk C: Monitor therapy
Terbinafine: May decrease the metabolism of Tricyclic Antidepressants. Risk D: Consider therapy modification
Terbinafine (Systemic): May decrease the metabolism of Tricyclic Antidepressants. Risk D: Consider therapy modification
Tetrabenazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Tetrabenazine. Risk X: Avoid combination
Thioridazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination
Tolvaptan: CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Tolvaptan. Risk X: Avoid combination
Toremifene: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Toremifene. The risk for potentially dangerous arrhythmias may be increased. Risk X: Avoid combination
TraMADol: Tricyclic Antidepressants may enhance the neuroexcitatory and/or seizure-potentiating effect of TraMADol. Risk C: Monitor therapy
Valproic Acid: May increase the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy
Vandetanib: QTc-Prolonging Agents may enhance the arrhythmogenic effect of Vandetanib. Risk X: Avoid combination
Vemurafenib: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Vemurafenib. Risk X: Avoid combination
Vitamin K Antagonists (eg, warfarin): Tricyclic Antidepressants may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Yohimbine: Tricyclic Antidepressants may increase the serum concentration of Yohimbine. Risk C: Monitor therapy
Ziprasidone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Ziprasidone. The risk of a severe arrhythmia may be increased. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Ethanol: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Food: Grapefruit juice may inhibit the metabolism of some TCAs and clinical toxicity may result.
Herb/Nutraceutical: Avoid valerian, St John's wort, SAMe, kava kava (may increase risk of serotonin syndrome and/or excessive sedation).
Storage
Store at 20°C to 25°C (68°F to 77°F).
Mechanism of Action
Traditionally believed to increase the synaptic concentration of norepinephrine (and to a lesser extent, serotonin) in the central nervous system by inhibition of its reuptake by the presynaptic neuronal membrane. However, additional receptor effects have been found including desensitization of adenyl cyclase, down regulation of beta-adrenergic receptors, and down regulation of serotonin receptors.
Pharmacodynamics/Kinetics
Onset of action: Earliest therapeutic effects: 2-5 days; Maximum antidepressant effect: >2 weeks
Metabolism: Hepatic
Half-life elimination: Adults: 15-24 hours (Weiner, 1981)
Time to peak, plasma: ~6 hours (Weiner, 1981)
Excretion: Urine (~70%)
Dosage
Note: Not FDA approved for use in pediatric patients; controlled clinical trials have not shown tricyclic antidepressants to be superior to placebo for the treatment of depression in children and adolescents (Dopheide, 2006; Wagner, 2005).
Oral:
Children 6-12 years: Depression (unlabeled use): 1-3 mg/kg/day in divided doses; monitor carefully with doses >3 mg/kg/day; maximum dose: 5 mg/kg/day.
Adolescents: Depression: Initial dose: Start at the lower range and increase based on tolerance and response to 100 mg/day in divided or single dose; usual maintenance dose: 25-100 mg/day, but doses up to 150 mg/day may be necessary in severely depressed patients
Adults:
Depression: Initial dose: Start at the lower range and increase based on tolerance and response; usual maintenance dose: 100-200 mg/day, but doses up to 300 mg/day may be necessary in severely depressed patients
Neuropathic pain (unlabeled use): Initial: 10-25 mg/day; increase dose every 3 days as necessary until the desired effect is obtained; usual effective dose: 50-150 mg/day (maximum dose: 150 mg/day)
Elderly: Depression: Initial dose: Start at the lower range and increase based on tolerance and response to 100 mg/day in as single or divided doses; usual maintenance dose: 25-100 mg/day, but doses up to 150 mg/day may be necessary in severely depressed patients
Hemodialysis/peritoneal dialysis: Supplemental dose is not necessary
Monitoring Parameters
Monitor blood pressure and pulse rate prior to and during initial therapy; evaluate mental status, suicide ideation (especially at the beginning of therapy or when doses are increased or decreased); monitor weight; ECG in older adults and those patients with cardiac disease
When used for the treatment of ADHD, thoroughly evaluate for cardiovascular risk. Monitor heart rate, blood pressure, and consider obtaining ECG prior to initiation (Vetter, 2008); ensure PR interval ≤200 ms, QRS duration ≤120 ms, and QTc ≤460 ms.
Test Interactions
Increased glucose; decreased glucose has also been reported. May interfere with urine detection of amphetamines/methamphetamines (false-positive).
Patient Education
It may take 2-3 weeks to achieve desired results. Avoid alcohol. Maintain adequate hydration, unless instructed to restrict fluid intake. May cause drowsiness, lightheadedness, impaired coordination, dizziness, blurred vision, loss of appetite or disturbed taste, constipation, urinary retention, postural hypotension, altered sexual drive or ability (reversible), or photosensitivity. Report chest pain, palpitations, or rapid heartbeat; persistent adverse CNS effects (eg, suicide ideation, nervousness, restlessness, insomnia, anxiety, excitation, headache, agitation, impaired coordination, changes in cognition); muscle cramping, weakness, tremors, or rigidity; seizures; blurred vision or eye pain; breast enlargement or swelling; yellowing of skin or eyes; or worsening of condition.
Geriatric Considerations
Preferred tricyclic antidepressant because of its milder side effect profile; patients may experience excitation or stimulation; in such cases, administer as a single morning dose or divided dose.
A systematic review and meta-analysis of antidepressant placebo-controlled trials in persons with depression and dementia found evidence "suggestive" of efficacy but not of sufficient strength to "confirm" efficacy. Antidepressant trials in this patient population are small and underpowered. Older patients with depression being treated with an antidepressant should be closely monitored for response and adverse effects. Treatment should be switched or augmented when response is inadequate with a therapeutic dose. Antidepressants that are not tolerated should be discontinued and an alternative agent should be started.
This medication is considered to be potentially inappropriate in this patient population (Beers Criteria: SIADH: Quality of evidence - moderate; Strength of recommendation - strong).
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: Desipramine causes less sedation and anticholinergic effects than with amitriptyline or imipramine.
Cardiovascular Considerations
In an effort to reduce the rate of sudden cardiac death especially in pediatric patients receiving stimulant medications for the treatment of attention-deficit/hyperactivity disorder (ADHD), the American Heart Association (AHA) issued a statement in April 2008 (Vetter, 2008) recommending that all children diagnosed with ADHD who may be candidates for stimulant medications have a thorough cardiovascular assessment (including a combination of a thorough medical history, family history, and physical examination with the intent to identify risk factors for sudden death) prior to initiation of drug therapy. Although not mandatory, physicians should consider obtaining an ECG. These recommendations are based on the Food and Drug Administration (FDA) reports of serious cardiovascular adverse events (including sudden death) in patients (both children and adults) taking usual doses of stimulant medications. Most of these patients were found to have underlying structural heart disease (eg, hypertrophic obstructive cardiomyopathy). Stimulant medications theoretically increase cardiovascular risk due to potential effects on blood pressure elevation and increased heart rate. These effects have generally been considered clinically insignificant in most children, however, may be detrimental in certain patients with underlying cardiovascular disease. None of the medications have been shown to cause heart conditions or proven to have caused sudden cardiac death.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia and changes in salivation (normal salivary flow resumes upon discontinuation), unpleasant taste, stomatitis, and black tongue. Long-term treatment with TCAs increases the risk of caries by reducing salivation and salivary buffer capacity.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
Use with caution; epinephrine and levonordefrin have been shown to have an increased pressor response in combination with TCAs. Desipramine is one of the drugs confirmed to prolong the QT interval and is accepted as having a risk of causing torsade de pointes. The risk of drug-induced torsade de pointes is extremely low when a single QT interval prolonging drug is prescribed. In terms of epinephrine, it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval. Until more information is obtained, it is suggested that the clinician consult with the physician prior to the use of a vasoconstrictor in suspected patients, and that the vasoconstrictor (epinephrine, mepivacaine and levonordefrin [Carbocaine® 2% with Neo-Cobefrin®]) be used with caution.
Dental Comment
Desipramine is known to prolong the QT interval. The QT interval is measured as the time and distance between the Q point of the QRS complex and the end of the T wave in the ECG tracing. After adjustment for heart rate, the QT interval is defined as prolonged if it is more than 450 msec in men and 460 msec in women. A long QT syndrome was first described in the 1950s and 60s as a congenital syndrome involving QT interval prolongation and syncope and sudden death. Some of the congenital long QT syndromes were characterized by a peculiar electrocardiographic appearance of the QRS complex involving a premature atria beat followed by a pause, then a subsequent sinus beat showing marked QT prolongation and deformity. This type of cardiac arrhythmia was originally termed “torsade de pointes” (translated from the French as “twisting of the points”). Desipramine is considered as having a risk of causing torsade de pointes. Since it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval, a medical consult is suggested.
Mental Health: Comment
Tricyclic antidepressants may be classified as tertiary (amitriptyline, doxepin, clomipramine, imipramine, trimipramine) or secondary amines (nortriptyline, desipramine, protriptyline). The tertiary amines are not recommended to treat depression in the elderly. If a TCA is used in the elderly, it should be a secondary amine. The tertiary amines are commonly used in low dosages for various conditions associated with pain. Plasma concentrations correlate with clinical response. A linear relationship appears to exist. Toxicity is generally dose dependent. Relatively small overdoses (1-week supply) can be potentially fatal.
Nursing: Physical Assessment/Monitoring
Monitor CNS status. Assess cardiac and seizure history prior to initiating therapy. Assess for suicidal tendencies before beginning therapy, during initiation of therapy, or following an increase or decrease of dosage. Caution patients with diabetes to monitor glucose levels closely; may increase or decrease serum glucose levels. Taper dose slowly when discontinuing.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral, as hydrochloride: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg
Norpramin®: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg [contains soybean oil]
Pricing: U.S. (www.drugstore.com)
Tablets (Desipramine HCl)
10 mg (60): $60.46
25 mg (60): $74.99
Tablets (Norpramin)
10 mg (60): $71.27
25 mg (60): $86.39
50 mg (60): $161.99
75 mg (60): $205.18
100 mg (30): $134.99
150 mg (30): $194.40
References
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International Brand Names
Lexi-Comp.com
Last full review/revision April 2012
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