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Desipramine

Class: Tricyclics and Other Norepinephrine-reuptake Inhibitors
VA Class: CN601
CAS Number: 58-28-6
Brands: Norpramin

Medically reviewed by Drugs.com on Jan 22, 2021. Written by ASHP.

Warning

    Suicidality
  • Antidepressants may increase risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (18–24 years of age) with major depressive disorder and other psychiatric disorders; balance this risk with clinical need. Desipramine is not approved for use in pediatric patients. (See Pediatric Use under Cautions.)

  • In pooled data analyses, risk of suicidality was not increased in adults >24 years of age and apparently was reduced in adults ≥65 years of age with antidepressant therapy compared with placebo.

  • Depression and certain other psychiatric disorders are themselves associated with an increased risk of suicide.

  • Appropriately monitor and closely observe all patients who are started on desipramine therapy for clinical worsening, suicidality, or unusual changes in behavior; involve family members and/or caregivers in this process. (See Worsening of Depression and Suicidality Risk under Cautions.)

Introduction

Tricyclic antidepressant (TCA); active metabolite of imipramine.

Uses for Desipramine

Major Depressive Disorder

Management of major depressive disorder.

Results of several studies of TCAs in preadolescent and adolescent patients with major depression indicate lack of overall efficacy in this age group.

Panic Disorder

Has been used for the management of panic disorder with or without agoraphobia.

Eating Disorders

Has been used for the management of eating disorders (e.g., bulimia, anorexia nervosa) with equivocal results; avoid use in underweight individuals and in those exhibiting suicidal ideation.

Bipolar Disorder

Has been used for the short-term management of acute depressive episodes in bipolar disorder.

TCAs associated with a greater risk of precipitating hypomania or manic episodes than other classes of antidepressants; should always be used in combination with a mood stabilizer (e.g., lithium).

Schizophrenia

Has been used for the management of acute depressive episodes (in combination with an antipsychotic) in patients with schizophrenia.

Postherpetic Neuralgia

Among the drugs of choice for the symptomatic treatment of postherpetic neuralgia.

Insomnia

Less effective for insomnia and associated with more serious adverse reactions than conventional hypnotics.

Attention Deficit Hyperactivity Disorder (ADHD)

Not recommended for use in children with ADHD. (See Pediatric Use under Cautions.)

Desipramine Dosage and Administration

General

  • Allow at least 2 weeks to elapse between discontinuance of therapy with an MAO inhibitor and initiation of desipramine and vice versa. Also allow at least 5 weeks to elapse when switching from fluoxetine.

  • Monitor for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustments. (See Worsening of Depression and Suicidality Risk under Cautions.)

  • Sustained therapy may be required; administer lowest effective dosage and monitor periodically for need for continued therapy.

  • Avoid abrupt discontinuance in patients receiving high dosages for prolonged periods. To avoid withdrawal reactions, taper dosage gradually.

Administration

Oral Administration

Initially, administer in up to 3 divided doses or as a single daily dose at bedtime (to avoid daytime sedation) or in the morning (to avoid insomnia and/or stimulation from the drug); for maintenance therapy, may be given as a single daily dose for patient compliance and convenience.

Administer desipramine hydrochloride dosages of 300 mg daily in a hospital setting, where regular visits by the physician, skilled nursing care, and frequent ECGs are available.

Dosage

Available as desipramine hydrochloride; dosage is expressed in terms of the salt.

Pediatric Patients

Major Depressive Disorder
Oral

Adolescents ≥12 years of age: Initially, 25–50 mg daily. Increase dosage gradually until maximal therapeutic effect with minimal toxicity is achieved or up to a maximum dosage of 100 mg daily. (See Pediatric Use under Cautions.)

Usual dosage: 25–100 mg daily. Dosage may be further increased to 150 mg daily, if necessary, in more seriously ill patients.

After symptoms are controlled, gradually reduce dosage to the lowest level that will maintain relief of symptoms.

Adults

Major Depressive Disorder
Oral

Initially, 75–150 mg daily, depending on the severity of the condition being treated. Increase dosage gradually until maximal therapeutic effect with minimal toxicity is achieved.

Usual dosage: 100–200 mg daily. Dosage may be further increased to 300 mg daily, if necessary, in more seriously ill patients.

After symptoms are controlled, gradually reduce dosage to the lowest level that will maintain relief of symptoms.

Prescribing Limits

Pediatric Patients

Major Depressive Disorder
Oral

Adolescents ≥12 years of age: Maximum 150 mg daily.

Adults

Major Depressive Disorder
Oral

Maximum 300 mg daily.

Special Populations

Geriatric Patients

Initially, 25–50 mg daily. Increase dosage gradually until maximal therapeutic effect with minimal toxicity is achieved or up to a usual maximum dosage of 100 mg daily.

Usual dosage: 25–100 mg daily. Dosage may be further increased to 150 mg daily, if necessary, in more seriously ill patients.

After symptoms are controlled, gradually reduce dosage to the lowest level that will maintain relief of symptoms.

Cautions for Desipramine

Contraindications

  • Concurrent or recent (i.e., within 2 weeks) therapy with an MAO inhibitor. (See Specific Drugs under Interactions.)

  • During the acute recovery phase following MI.

  • Known hypersensitivity to desipramine. (See Cross-Hypersensitivity under Cautions.)

Warnings/Precautions

Warnings

Worsening of Depression and Suicidality Risk

Possible worsening of depression and/or emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior in both adult and pediatric patients with major depressive disorder, whether or not they are taking antidepressants; may persist until clinically important remission occurs. However, suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.

Appropriately monitor and closely observe patients receiving desipramine for any reason, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments. (See Boxed Warning and also see Pediatric Use under Cautions.)

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania may be precursors to emerging suicidality. Consider changing or discontinuing therapy in patients whose depression is persistently worse or in those with emerging suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if severe, abrupt in onset, or not part of patient’s presenting symptoms. (See General under Dosage and Administration.)

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.

Observe these precautions for patients with psychiatric (e.g., major depressive disorder, obsessive-compulsive disorder [OCD]) or nonpsychiatric disorders.

Bipolar Disorder

May unmask bipolar disorder. (See Activation of Mania or Hypomania under Cautions.) Desipramine is not approved for use in treating bipolar depression.

Screen for risk of bipolar disorder by obtaining detailed psychiatric history (e.g., family history of suicide, bipolar disorder, depression) prior to initiating therapy.

Cardiovascular Effects

Possible conduction defects, arrhythmias, tachycardia, strokes, and acute MI; use with extreme caution in patients with preexisting cardiovascular disease. Monitor such patients closely (e.g., perform ECG at baseline and as appropriate during therapy). Also use with extreme caution in patients with a family history of sudden death, cardiac dysrhythmias, or cardiac conduction disturbances.

Use with caution in patients with disturbed eating behaviors (e.g., purging) that result in inadequate hydration and/or compromised cardiac status.

Toxicity in Overdosage

Overdosage of desipramine has resulted in a higher death rate compared with overdosages of other tricyclic antidepressants.

Interactions

May block hypotensive actions of guanethidine and similar agents.

May enhance effects of alcohol, sedative/hypnotics, and other CNS depressants. Use with caution in patients with a history of excessive alcohol consumption.

Anticholinergic Effects

Use with extreme caution in patients for whom excess anticholinergic activity could be harmful (e.g., history of urinary retention, increased intraocular pressure, angle-closure glaucoma).

Seizures

Risk of seizures; use with extreme caution in patients with a history of seizure disorder. In some patients, seizures precede cardiac dysrhythmias and death.

Hyperthyroidism

Possible cardiovascular toxicity (e.g., arrhythmias); use with extreme caution in patients with thyroid disease or patients receiving thyroid agents.

Cognitive/Physical Impairment

Performance of activities requiring mental alertness and physical coordination may be impaired.

Sensitivity Reactions

Cross-Hypersensitivity

Possible cross sensitivity to other dibenzazepine-derivative TCAs (e.g., clomipramine, imipramine, trimipramine).

Photosensitivity

Avoid excessive exposure to sunlight.

General Precautions

Activation of Mania or Hypomania

Possible activation of hypomania in patients with bipolar disorder.

Psychosis

Possible exacerbation of psychosis in patients with schizophrenia.

Hematologic Effects

Perform leukocyte and differential counts in any patient who develops symptoms of blood dyscrasias (e.g., fever, sore throat). If evidence of pathologic neutrophil depression is found, discontinue the drug.

Electroconvulsive Therapy (ECT)

Possible increased ECT risks.

Elective Surgery

Discontinue therapy several days prior to surgery whenever possible. Hypertensive episodes have occurred during surgery in patients receiving desipramine.

Blood Glucose Effects

Possible alterations in blood glucose concentrations.

Storage

Keep out of reach of children. If possible, dispense in containers with child-resistant safety closures.

Specific Populations

Pregnancy

Category C.

Lactation

Distributes into milk; discontinue nursing or the drug.

Pediatric Use

Not effective in management of depression in children or adolescents in clinical studies.

Collapse and/or sudden death reported in children, some of whom received the drug for the treatment of ADHD; not recommended for use in children.

FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during first few months of antidepressant treatment (4%) compared with placebo (2%) in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and others). However, a more recent meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients <19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation. No suicides occurred in these pediatric trials.

Carefully consider these findings when assessing potential benefits and risks of desipramine in a child or adolescent for any clinical use. (See Worsening of Depression and Suicidality Risk under Cautions.)

Geriatric Use

In pooled data analyses, a reduced risk of suicidality was observed in adults ≥65 years of age with antidepressant therapy compared with placebo. (See Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Possible increased sensitivity to anticholinergic (e.g., dry mouth, constipation, vision disturbance), cardiovascular, orthostatic hypotension, and sedative effects of TCAs and increased risk for falls and/or other desipramine-induced toxicity. Monitor renal function.

Titrate dosage carefully. (See Geriatric Patients under Dosage and Administration.)

Renal Impairment

Use with caution.

Common Adverse Effects

Anticholinergic effects (e.g., dry mouth, constipation, vision disturbance), orthostatic hypotension, sedation, weakness, lethargy, fatigue.

Interactions for Desipramine

Metabolized in the liver by various CYP isoenzymes (e.g., CYP1A2, CYP2C, CYP2D6, CYP3A4).

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP2D6: potential pharmacokinetic interaction (increased plasma desipramine concentrations). Adjust desipramine dosage whenever a CYP2D6 inhibitor is added or discontinued.

Specific Drugs

Drug

Interaction

Comments

Alcohol

Potentiates CNS depressant effects of alcohol

Increased risks if overdose or suicide attempt occurs

Antiarrhythmics: class 1C (e.g., flecainide, propafenone); quinidine

Potential for decreased desipramine metabolism

Monitor for TCA toxicity

Anticholinergic agents

Hyperthermia, particularly during hot weather, and paralytic ileus

Use with caution; dosage adjustment may be needed

Antipsychotics (e.g., phenothiazines)

Potential for decreased desipramine metabolism

Use with caution

Benzodiazepines (e.g., chlordiazepoxide, diazepam)

Additive sedative effects

Use with caution

Cimetidine

Potential for decreased desipramine metabolism

CNS depressants

Potentiates the effects of CNS depressants

Use with caution

Guanethidine

Antagonizes the antihypertensive effects of guanethidine

Levodopa

May interfere with levodopa absorption

Monitor levodopa dosage carefully

MAO inhibitors

Potentially life-threatening serotonin syndrome

Concomitant use contraindicated

Allow at least 14 days to elapse when switching to or from these drugs

Methylphenidate

Potential for decreased desipramine metabolism

SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline)

Possible serotonin syndrome

Potential for decreased desipramine metabolism

Use with caution; monitor for TCA toxicity

Allow at least 5 weeks to elapse when switching from fluoxetine

Sympathomimetic agents (e.g., amphetamines, epinephrine, isoproterenol, norepinephrine, phenylephrine)

Increased vasopressor, cardiac effects

Use with caution; dosage adjustment may be required

Thyroid agents

Possible cardiovascular toxicity, including arrhythmias

Use with extreme caution and under close supervision

Desipramine Pharmacokinetics

Absorption

Bioavailability

Well absorbed from the GI tract following oral administration, with peak plasma concentration usually attained within 4–6 hours.

Onset

Antidepressant effects may occasionally be seen in 2–5 days, but full therapeutic effect may not be evident for up to 3 weeks.

Distribution

Extent

Distributed into milk; concentrations in milk may be greater than or equal to those in maternal serum.

Elimination

Metabolism

Extensively metabolized in the liver via oxidation to pharmacologically active metabolite, 2-hydroxydesipramine, by various CYP isoenzymes (e.g., CYP1A2, CYP2D6, CYP3A4, and CYP2C).

Elimination Route

Excreted principally in urine (70%).

Half-life

Plasma half-life of desipramine ranges from 7 to >60 hours.

Special Populations

In geriatric patients, the ratio of the principal metabolite, 2-hydroxydesipramine, to desipramine appears to be increased, most likely because of decreased renal elimination that occurs with aging.

Stability

Storage

Oral

Tablets

Tight containers at room temperature, preferably <30°C. Protect from excessive heat.

Actions

  • Mechanism of action in the management of depression unknown but may involve inhibition of reuptake of norepinephrine and/or serotonin.

  • Associated with more frequent anticholinergic, sedative, and cardiovascular effects and weight gain than SSRIs.

Advice to Patients

  • Risk of suicidality; importance of patients, family, and caregivers being alert to and immediately reporting emergence of suicidality, worsening depression, or unusual changes in behavior, especially during the first few months of therapy or during periods of dosage adjustment. FDA recommends providing written patient information (medication guide) explaining risks of suicidality each time the drug is dispensed.

  • Importance of considering possible impaired ability to perform hazardous activities (e.g., operating machinery, driving a motor vehicle).

  • Importance of patients understanding that it may take up to 3 weeks before the full effects are apparent.

  • Importance of avoiding alcohol-containing beverages or products.

  • Importance of patients or caregivers supervising storage of the drug in the home and of keeping it out of reach of children.

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses or planned surgery.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Desipramine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

10 mg*

Desipramine Hydrochloride Tablets

25 mg*

Desipramine Hydrochloride Tablets

50 mg*

Desipramine Hydrochloride Tablets

75 mg*

Desipramine Hydrochloride Tablets

100 mg*

Desipramine Hydrochloride Tablets

150 mg*

Desipramine Hydrochloride Tablets

Tablets, film-coated

10 mg

Norpramin

Sanofi-Aventis

25 mg

Norpramin

Sanofi-Aventis

50 mg

Norpramin

Sanofi-Aventis

75 mg

Norpramin

Sanofi-Aventis

100 mg

Norpramin

Sanofi-Aventis

150 mg

Norpramin

Sanofi-Aventis

AHFS DI Essentials™. © Copyright 2021, Selected Revisions February 1, 2011. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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