Nortriptyline: 7 things you should know

Medically reviewed by Carmen Pope, BPharm. Last updated on Jan 3, 2024.

1. How it works

• Nortriptyline may be used to relieve the symptoms of depression and off-label to treat conditions such as ADHD, eating disorders, anxiety, insomnia, and smoking cessation.
• Experts are unsure exactly how nortriptyline works, although historically it was believed that nortriptyline’s effects on depression were due to its ability to rebalance chemicals in the brain, such as serotonin, that were thought to be imbalanced in people with anxiety, depression, and other mood disorders. Studies confirm that nortriptyline is still effective for treating mood disorders, such as depression, even though the way it works is unknown.
• Nortriptyline belongs to the class of medicines known as tricyclic antidepressants.

2. Upsides

• May be used to treat the symptoms of depression in people diagnosed with Major Depressive Disorder (MDD).
• May be used off-label to treat other conditions, such as ADHD, eating disorders, anxiety, insomnia, and smoking cessation.
• Is considered a second-line agent for the treatment of ADHD but is associated with a lower margin of safety compared with some agents and should only be used under close supervision.
• May be given as a second-line agent for the treatment of tobacco use and dependence but should only be considered when first-line agents, such as bupropion, nicotine replacement products, and varenicline, have been used without success or are contraindicated.
• May be used short-term in bipolar disorder for the management of acute depressive episodes.
• May be used in combination with an antipsychotic for the management of acute depressive episodes.
• An agent of choice to relieve symptoms of postherpetic neuralgia.
• May be administered as a single daily dose or up to 4 divided doses daily.
• Generic nortriptyline is available.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Dizziness, headache, blurred vision, trouble with eye focusing or vision problems, dry mouth, constipation, heart palpitations, tiredness, and a drop in blood pressure on standing. May increase the risk of heart attacks or glaucoma.
• Not recommended for children under the age of 18 years.
• May increase the risk of suicidal thoughts or behavior in young adults (similar to other antidepressants). An increased risk of suicide was not reported in adults aged over 24 and the risk appeared reduced in adults aged 65 years and older who were taking antidepressants. Monitor the behavior of all patients who have started on nortriptyline for clinical worsening, suicidality, or unusual changes in behavior.
• May cause drowsiness and affect a person's ability to drive or operate machinery. Some people may develop tolerance to this effect. Avoid alcohol.
• May not be suitable for some people including those with pre-existing cardiovascular disease, undiagnosed bipolar disorder, history of urinary retention, history of seizures, increased intraocular pressure or angle-closure glaucoma, or taking other medications such as cimetidine, chlorpropamide, and SSRIs.
• People who are poor metabolizers of CYP 2D6 may experience higher than expected concentrations of nortriptyline. Tell your doctor if your side effects are excessive.
• May interact with some other medications including monoamine oxidase inhibitors (a type of antidepressant), ketoconazole, rifampicin, linezolid, and methylene blue. Interaction or overdosage may cause serotonin syndrome (symptoms include agitation, hallucinations, fast heart rate, dizziness, muscle tremors, nausea, vomiting, or diarrhea).
• May cause withdrawal symptoms with abrupt discontinuation (symptoms include nausea, headache, and generalized tiredness). These are not indicative of addiction. Taper dosage off slowly under medical supervision.
• Clinical trials that have been conducted in preadolescent and adolescent patients have indicated a lack of overall efficacy in this age group.
• When used off-label to treat eating disorders, use should be avoided in those who are underweight or with suicidal ideation.
• Less effective and associated with more side effects than conventional agents when used for insomnia.
• May unmask bipolar disorder and people should be screened for risk of bipolar disorder by obtaining a detailed psychiatric history that includes a family history of suicide, bipolar depression, or depression.
• Not recommended for children. Lower initial dosages should be used in the elderly or adolescents.
• Possible association with limb reduction anomalies and cardiovascular effects in the fetus when given to pregnant women. Avoid during pregnancy. Distributes into breastmilk and use is not recommended during breastfeeding.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Nortriptyline is an effective antidepressant but it may cause drowsiness initially and a withdrawal syndrome with abrupt discontinuation. It may be used off-label to treat other conditions, such as ADHD, eating disorders, anxiety, insomnia, and smoking cessation.

5. Tips

• Take higher dosages late afternoon or in the evening to minimize daytime sedation. Take exactly as your doctor has told you to.
• Do not stop suddenly as withdrawal symptoms may occur. Slow dosage reduction over weeks to months is recommended.
• Tell your doctor if you experience any new or worsening mood symptoms or suicidal thoughts, have trouble sleeping, have symptoms of serotonin syndrome, or develop eye pain or vision problems.
• May increase the risk of sunburn; protect yourself from the sun when outdoors and avoid exposure to tanning beds.
• Do not take any other medication (including those brought over-the-counter) before checking with your doctor or pharmacist that it is safe to take with nortriptyline. If you have surgery scheduled, tell your doctor that you are taking nortriptyline because they may consider discontinuing treatment with nortriptyline several days before surgery.
• Nortriptyline is not recommended during pregnancy or breastfeeding. If you inadvertently become pregnant while taking Nortriptyline, tell your doctor immediately.

6. Response and effectiveness

• Peak concentrations of nortriptyline are reached within 7 to 9 hours; however, it may take several weeks for the full antidepressant effect to develop.

7. Interactions

Medicines that interact with nortriptyline may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with nortriptyline. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with nortriptyline include:

• anticoagulants (blood thinners), such as warfarin, or other drugs that have blood-thinning effects such as aspirin or NSAIDs
• anticholinergics, such as benztropine (may increase the risk of hyperthermia, particularly during hot weather, and increase the risk of paralytic ileus)
• anticonvulsants, such as phenytoin, phenobarbital, or primidone
• antipsychotics (such as butyrophenones, phenothiazines, or thioxanthenes) and atypical antipsychotics (eg, olanzapine, quetiapine, ziprasidone)
• any medication that may cause drowsiness, such as benzodiazepines (eg, diazepam, lorazepam), first-generation antihistamines (such as doxylamine or promethazine), metoclopramide, or opioids (such as codeine, morphine)
• bupropion
• buspirone
• chlorpropamide (may cause severe hypoglycemia)
• cimetidine
• diuretics, such as furosemide
• disulfiram
• hydroxyzine
• ipratropium and other anticholinergics
• levodopa
• lithium
• medications that may affect the heartbeat by prolonging the QT interval, such as quinidine or fexinidazole
• medications that induce or inhibit CYP2D6 such as amiodarone or duloxetine
• other antidepressants, such as tricyclic antidepressants (eg, clomipramine), monoamine oxidase inhibitors (MAOI) (eg, isocarboxazid, phenelzine, and tranylcypromine), venlafaxine, and SSRIs (eg, paroxetine, sertraline)
• metoclopramide
• reserpine
• thyroid agents (may cause cardiac arrhythmias)
• other medications that affect serotonin, such as amphetamines, fentanyl, lithium, ondansetron, tramadol, triptans (eg, almotriptan, eletriptan, or sumatriptan), or St. John's Wort
• others, such as HIV medications (fosamprenavir, ritonavir), fluconazole, or procyclidine.

Avoid drinking alcohol or taking illegal or recreational drugs while taking nortriptyline.

Allow at least two weeks to elapse between discontinuing treatment with an MAOI and initiation of nortriptyline and vice versa.

Note that this list is not all-inclusive and includes only common medications that may interact with nortriptyline. You should refer to the prescribing information for nortriptyline for a complete list of interactions.

References

• Nortriptyline. Revised 11/2023. Dr. Reddy's. https://www.drugs.com/pro/nortriptyline.html

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use nortriptyline only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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