Skip to main content

Nortriptyline (Monograph)

Brand name: Pamelor
Drug class: Tricyclics and Other Norepinephrine-reuptake Inhibitors
- Smoking Deterrents
- Deterrents, Smoking
VA class: CN601
CAS number: 894-71-3

Medically reviewed by on Apr 10, 2023. Written by ASHP.


  • 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. Nortriptyline 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 nortriptyline 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.)


Tricyclic antidepressant (TCA); active metabolite of amitriptyline.

Uses for Nortriptyline

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.

Attention Deficit Hyperactivity Disorder

Second-line agent in attention deficit hyperactivity disorder [off-label] (ADHD) patients unable to tolerate or unresponsive to stimulants; should be used only under close supervision.

Associated with a narrower margin of safety than some other therapeutic agents; use only if clearly indicated and with careful monitoring, including baseline and subsequent determinations of ECG and other parameters.

Eating Disorders

Has been used for management of eating disorder [off-label] (e.g., bulimia [off-label], anorexia nervosa [off-label]) with equivocal results; avoid use in underweight individuals and in those exhibiting suicidal ideation.

Smoking Cessation

US Public Health Service (USPHS) guideline for the treatment of tobacco use and dependence recommends nortriptyline as a second-line drug for smoking cessation [off-label] after first-line drugs (i.e., bupropion [as extended-release tablets], nicotine polacrilex gum or lozenge, transdermal nicotine, nicotine nasal spray, nicotine oral inhaler, varenicline) have been used without success or are contraindicated.

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).


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

Anxiety Disorders

Has been used for the management of anxiety (in combination with anxiolytics, sedatives, or antipsychotics) in patients with depression.

Postherpetic Neuralgia

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


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

Nortriptyline Dosage and Administration



Oral Administration

Administer orally in up to 4 divided doses or as a single daily dose.


Available as nortriptyline hydrochloride; dosage is expressed in terms of nortriptyline.


Major Depressive Disorder

Initially, 25 mg daily. Gradually adjust to level that produces maximal therapeutic effects (up to 200 mg daily).

Usual dosage: Manufacturer recommends 75–100 mg daily, but some experts state usual dosage range is 50–200 mg daily. After symptoms are controlled, dosage should be gradually reduced to the lowest level that will maintain relief of symptoms.

Hospitalized patients under close supervision may generally be given higher dosages than outpatients.

Smoking Cessation†

25 mg daily, and then gradually increase to a target dosage of 75–100 mg daily.

Initiate nortriptyline therapy 10–28 days before date set for cessation of smoking.

Nortriptyline was continued for approximately 12 weeks in clinical studies.

Prescribing Limits


Major Depressive Disorder

Manufacturer does not recommend dosages >150 mg daily, but higher dosages (e.g., 200 mg daily) have been used.

Special Populations

Geriatric Patients

30–50 mg daily.

Cautions for Nortriptyline




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.


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).


Risk of seizures; use with caution in patients with a history of seizures.


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


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


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.


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


Category D. Possible cardiovascular or limb reduction anomalies.


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.

Drug Interactions

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 nortriptyline concentrations). Adjust nortriptyline dosage whenever a CYP2D6 inhibitor is added or discontinued.

Specific Drugs





Potentiates the effects of alcohol

Increased risks if overdose or suicide attempt occurs

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

Potential for decreased nortriptyline metabolism

Possible increased plasma nortriptyline concentrations and prolonged half-life when quinidine administered concomitantly

Monitor for TCA toxicity

Anticholinergic agents

Hyperthermia, particularly during hot weather, and paralytic ileus

Use with caution; dosage adjustment may be needed

Anticoagulants (e.g., warfarin)

Possible increased PT

Antipsychotics (e.g., phenothiazines)

Potential for decreased nortriptyline metabolism

Use with caution


Substantial hypoglycemia possible


Potential for decreased nortriptyline metabolism

Hypotensive agents (e.g., guanethidine)

Antagonizes the antihypertensive effects of guanethidine


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


Possible stimulating effect in depressed patients

SSRIs (e.g., fluoxetine, paroxetine, sertraline)

Possible serotonin syndrome

Potential for decreased nortriptyline metabolism and increased plasma concentrations

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 cardiac arrhythmias

Use with caution and under close supervision

Nortriptyline Pharmacokinetics



Peak plasma concentrations occur within 7–8.5 hours after oral administration.


Antidepressant effects may not be evident for ≥2 weeks.

Plasma Concentrations

Optimal antidepressant effect may be associated with plasma concentrations of 50–150 ng/mL.



Distributes into milk; nortriptyline concentrations in milk appear to be similar to or slightly greater than those present in maternal serum.



Extensively metabolized in the liver via demethylation by various CYP isoenzymes (e.g., CYP1A2, CYP2D6, CYP3A4, CYP2C).

Elimination Route

Excreted principally in urine (33% within 24 hours) as inactive metabolites; small amounts are also excreted in feces via biliary elimination.


Plasma half-life ranges from 16 to >90 hours.




Capsules and Oral Solution

Tight, light-resistant containers at 25°C (may be exposed to 15–30°C).


Advice to Patients


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

Nortriptyline Hydrochloride


Dosage Forms


Brand Names




10 mg (of nortriptyline)*

Nortriptyline Hydrochloride Capsules


Pamelor (with benzyl alcohol and parabens)


25 mg (of nortriptyline)*

Nortriptyline Hydrochloride Capsules


Pamelor (with benzyl alcohol and parabens)


50 mg (of nortriptyline)*

Nortriptyline Hydrochloride Capsules


Pamelor (with benzyl alcohol parabens and sodium bisulfite)


75 mg (of nortriptyline)*

Nortriptyline Hydrochloride Capsules


Pamelor (with benzyl alcohol and parabens)



10 mg (of nortriptyline) per 5 mL*

Nortriptyline Hydrochloride Oral Solution

Pharmaceutical Associates

Pamelor (with alcohol 4%)


AHFS DI Essentials™. © Copyright 2024, Selected Revisions April 20, 2016. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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

Reload page with references included

Frequently asked questions