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Cautions

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 nortriptyline, other dibenzazepine-derivative TCAs, or any ingredient in the formulation.

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, 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 nortriptyline 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.

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) or nonpsychiatric disorders.

Bipolar Disorder

May unmask bipolar disorder. (See Activation of Mania or Hypomania under Cautions.) Nortriptyline 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 arrhythmias, sinus tachycardia, prolongation of the conduction time, MI, and stroke.

Patients with preexisting cardiac disease and patients with disturbed eating behaviors (e.g., purging) that result in inadequate hydration and/or compromised cardiac status most at risk; monitor closely.

Interactions

May block hypotensive actions of guanethidine and similar agents.

May enhance effects of alcohol. Use with caution in patients with a history of excessive alcohol consumption. (See Interactions.)

Possible pharmacokinetic (increased systemic exposure to nortriptyline) interaction with quinidine.

Anticholinergic Effects

Use with 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 caution in patients with a history of seizures.

Hyperthyroidism

Possible development of cardiac arrhythmias; use with caution and under close supervision in hyperthyroid patients 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, desipramine, trimipramine).

Photosensitivity

Avoid excessive exposure to sunlight.

General Precautions

Activation of Mania or Hypomania

Possible activation of mania and hypomania, particularly in patients with bipolar disorder; decrease dosage and/or administer an antipsychotic agent (e.g., perphenazine) concomitantly. (See Bipolar Disorder under Cautions.)

Increased anxiety, agitation, and hostility also may occur, particularly when administered to overactive or agitated patients.

Psychosis

Risk of manifestations of psychosis in patients with schizophrenia.

Electroconvulsive Therapy (ECT)

Possible increased ECT risks; limit to patients for whom concomitant use is essential.

Elective Surgery

Discontinue therapy several days prior to surgery whenever possible.

Blood Glucose Effects

Possible alterations in blood glucose concentrations.

Specific Populations

Pregnancy

Category D. Possible cardiovascular or limb reduction anomalies.

Lactation

Distributes into milk; use not recommended.

Pediatric Use

Not effective in management of depression in children† or adolescents in clinical studies; manufacturer states not recommended for use in children <18 years of age.

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 nortriptyline in a child or adolescent for any clinical use. (See Worsening of Depression and Suicidality Risk under Cautions.)

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; select dosage with caution.

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, hepatic (e.g., elevated liver enzymes, jaundice), orthostatic hypotension, and sedative effects of TCAs. Monitor carefully, particularly for cardiovascular toxicity (e.g., arrhythmias, fluctuations in BP).

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

Hepatic Impairment

Use with caution.

Common Adverse Effects

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