Nortriptyline, commonly known as Pamelor, is a tricyclic antidepressant available only through prescription. Medical monitoring is needed while taking this medication due to the risk of serious side effects and adverse interactions with other medicines.

Nortriptyline brand names

Nortriptyline is available under the following brand names:

  • Aventyl
  • Pamelor
  • Allegron

What is nortriptyline prescribed for?

The U.S. Food and Drug Administration (FDA) approved nortriptyline for the treatment of depression symptoms. Additionally, nortriptyline has been found helpful in treating other medical conditions through off-label use. 

This medication is more likely to reduce depression symptoms that are not a result of a traumatic experience or complex psychological disorder [1].

 Off-label nortriptyline uses include [4][2]:

  • Panic disorders
  • Nerve pain disorders: trigeminal neuralgia, postherpetic neuralgia, myofascial pain
  • Diabetic neuropathy
  • Migraines
  • Neurogenic cough

Some people have had success using nortriptyline for smoking cessation.

How does nortriptyline work?

Nortriptyline affects neurotransmitters and receptors within the brain including norepinephrine, serotonin, and several others. Studies have not yet determined how or why these changes result in clinical effects.

Some animal studies suggest that nortriptyline has both stimulant and depressant properties [1]. Additional studies are needed to gain deeper insight into how this medication works. 

It can take several weeks for nortriptyline's clinical benefits to be felt.

How is nortriptyline usually taken?

Nortriptyline is taken orally in either a capsule or liquid solution form. It is usually started at a low dose and gradually increased until clinical benefits are reached [4].

It is typically taken three to four times daily but can be prescribed once daily [2][4].

Nortriptyline capsules are available in several strengths and should not be cut or altered. If taking the oral solution, measure the liquid using the measurement tool supplied for accuracy. 

Be consistent in taking this medication at the exact times daily as prescribed. This medicine can be taken with or without food. 

Do not stop taking nortriptyline without medical advice. Suddenly stopping this medication can cause withdrawal symptoms.

Take missed doses as soon as possible unless it is near time for the next dose. Do not take two doses at the same time.

How long does nortriptyline stay in your system?

Nortriptyline has a half-life of 36 hours, meaning it takes approximately 72 hours for the drug to be eliminated from the body [3]. The body primarily excretes this medication through urine [NCBI]. 

Several factors impact how quickly nortriptyline is metabolized, including overall health, liver functioning, age, the last time the person ate, the amount of times it has been taken, and the dosage.

Withdrawal symptoms are associated with suddenly stopping nortriptyline use. These can be avoided by titrating the dose down over a period of time [2].

Withdrawal symptoms from nortriptyline include [2]:

  • Headache
  • Nausea 
  • Vomiting
  • Anxiety and restlessness 

Nortriptyline side effects

Nortriptyline side effects range from mild to severe. Adverse effects should be discussed with the doctor as changes to the dosage or a change in medication may be needed.

Nortriptyline common side effects include [4][2]:

  • Drowsiness
  • Weakness
  • Dizziness
  • Excitability 
  • Feeling anxious
  • Sleep changes, including nightmares
  • Dry mouth
  • Nausea
  • Appetite and weight changes 
  • Constipation
  • Changes in urination including difficulty and frequency
  • Changes in sex drive
  • Sexual dysfunction
  • Sweating
  • Itching

More severe side effects, which should immediately be reported to the doctor, include:

  • Muscle spasms 
  • Slowed speech or difficulty with speaking
  • Shuffling walk
  • Uncontrollable movements or shaking
  • Fever
  • Jaundice
  • Irregular heart rate

If any signs of an allergic reaction occur, seek emergency medical care. Symptoms of an allergic reaction include:

  • Rash/Hives
  • Itching
  • Trouble breathing or swallowing
  • Changes in heart rate
  • Fever
  • Swelling in the face, mouth, throat, or tongue 

Some people, especially children, teens, and young adults, experience suicidal thoughts or sudden mood changes when first taking an antidepressant.

Nortriptyline precautions

Nortriptyline is not the right medication for everyone. Adverse reactions have occurred in people with certain other medical conditions. 

Discuss current medications, personal and familial medical and mental health history, and alcohol or substance use with the doctor before taking this medication. The medical provider may request additional lab work or evaluation before prescribing this medication. 

Medical conditions to disclose before taking nortriptyline include [4]:

  • Enlarged prostate
  • Urinary retention
  • Diabetes
  • Seizures
  • Schizophrenia
  • Thyroid problems
  • Liver disease
  • Kidney disease
  • Heart disease
  • Bipolar disorder 

People with previous heart conditions should only take nortriptyline under close monitoring by their doctor [6].

Cardiotoxicity is one of the most dangerous adverse reactions from nortriptyline [1]. The doctor may request an EKG, or other heart monitoring test, before prescribing nortriptyline. Continued tracking of heart functioning may be advised while taking this drug.

This medicine can lead to drowsiness. Avoid operating heavy machinery, including driving a vehicle, until its effects are known.

Consuming alcohol while taking nortriptyline may worsen the side effects, including drowsiness.

Nortriptyline causes some people to become sensitive to sunlight. Avoid prolonged sun exposure and take extra precautions until the effects of this medication are known.

Antidepressant medications can trigger manic or hypomanic symptoms in people with bipolar disorder. Discuss with the doctor any changes in mood, such as agitation or irritability, and behavior changes while taking nortriptyline [1].

Studies have not shown whether nortriptyline use during pregnancy or while breastfeeding is safe. If pregnant or trying to become pregnant, do not stop taking this medication without first consulting with the doctor.

Nortriptyline interactions

Nortriptyline can cause dangerous, potentially life-threatening interactions when used with other medications. Therefore, it is critical to discuss with the doctor all current prescriptions, including over-the-counter medicines, vitamins, and herbal supplements.

Other antidepressant drugs used with nortriptyline can cause serotonin syndrome, a potentially life-threatening situation caused by serotonin levels becoming too high. This includes other tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), and selective serotonin reuptake inhibitors (SSRIs).

Two antidepressant medications should only be used when the benefits outweigh the risks and under close medical monitoring [1].  

St. John's Wort, a commonly used herbal supplement, should not be taken with nortriptyline due to the risk of serotonin syndrome [2].

Symptoms of serotonin syndrome include [4]:

  • Changes in mood such as increased agitation
  • Psychosis
  • Loss of consciousness, coma
  • Tachycardia
  • Sudden changes in blood pressure
  • Dizziness
  • Hyperthermia
  • Tremors
  • Body rigidity
  • Incoordination
  • Seizures
  • Gastrointestinal upset 

If signs of serotonin syndrome occur, seek immediate emergency medical attention to prevent permanent damage to bodily systems or death. 

To lower the risk of serotonin syndrome when switching medications there should be a period of up to 6 weeks before starting nortriptyline [2].

In addition to the risk of serotonin syndrome, using two antidepressant medications concurrently carries a risk of convulsions, sudden dangerous increase in body temperature (known as hyperpyrexia), and even death [2].

There have been reports of adverse interactions between nortriptyline and the following medications [FDA]:

  • Warfarin and other blood thinners
  • Antihistamines
  • Diabinese
  • Tagamet
  • Tambocor
  • Ismelin
  • Lithium
  • Blood pressure medications
  • Paroxetine (Paxil)
  • Sertraline (Zoloft)
  • Sleeping pills
  • Thyroid medications
  • Tranquilizers
  • Dibenzazepines 

People taking heart medications may be at a higher risk of experiencing severe reactions. Some people who have taken nortriptyline have experienced serious cardiac events or the unmasking of Brugada syndrome, a rare cardiac disorder involving abnormal heart rhythms and risk of sudden death [1].

Nortriptyline storage

Nortriptyline should be stored at room temperature in a closed container away from moisture. 

Use child-safety containers to prevent accidental overdose by children, teens, and pets. Remember that most pill reminder containers are not child safe. Store all medications in a safe location away from the reach of adolescents and teens to prevent prescription misuse. 

Speak with a medical provider for the best way to dispose of unused nortriptyline. Avoid flushing this medication down the toilet.

What to do if you overdose on nortriptyline

An overdose on nortriptyline is a medical emergency. Nortriptyline overdoses can be fatal.

Symptoms of a nortriptyline overdose include [4]:

  • Irregular heart rate
  • Breathing difficulty or inability to breathe 
  • Confusion
  • Hallucinations or delusions
  • Widened pupils
  • Drowsiness
  • Agitation
  • Abnormal body temperature
  • Rigidor stiff muscles
  • Vomiting
  • Seizure
  • Loss of consciousness  

Seek immediate emergency medical care if an overdose has occurred or is suspected. Information is also available from the poison control hotline at 1-800-222-1222.

Frequently asked questions about nortiptyline

How long does it take for nortriptyline to kick in? 

The clinical effects of nortriptyline can take up to 6 weeks as therapeutic levels build in the body. Generally, people notice benefits starting at week 4 when used consistently. 

Is nortriptyline addictive? 

Nortriptyline is not considered to be addictive, however, stopping its use suddenly can lead to withdrawal symptoms as the body adjusts to the changes in biochemicals.

However, using nortriptyline while taking illicit substances can cause serious medical complications. It is important to have an honest conversation with a medical provider if there are any concerns about substance use disorder or misuse of this medication. 

Nortriptyline vs Amitriptyline: What’s the difference? 

Nortriptyline and amitriptyline are from the same group of medications, tricyclic antidepressants, and have similar effects.

Amitriptyline is an older medication. Some people tolerate nortriptyline better than amitriptyline, but both carry similar risk factors and side effects.

Resources:

  1. Mallinckrodt Inc. (2014). Pamelor. U.S. Food And Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018013s064lbl.pdf
  2. Merwar G, Gibbons JR, Hosseini SA, et al. Nortriptyline. [Updated 2022 Jun 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482214/
  3. (2020). Antidepressants. Retrieved October 28, 2022, from https://www.mind.org.uk/information-support/drugs-and-treatments/antidepressants/comparing-antidepressants/
  4. Nortriptyline: MedlinePlus Drug Information. (n.d.). Retrieved October 28, 2022, from https://medlineplus.gov/druginfo/meds/a682620.html